Biology subjects

Yamamoto, J.

Publications and source records attributed to Yamamoto, J..

8 recordsLinked to original sources

bioRxiv2026

Hippocampal consummatory reward ensembles dynamically engage theta-SWR states during spatial working memory

Reward consumption consists of temporally structured sensory and behavioral episodes critical for memory-guided behavior. However, how hippocampal circuits organize consummatory episodes and their associated oscillatory activity remains poorly understood. Recording dorsal hippocampal CA1 activity during a delayed nonmatch-to-place T-maze task, we identified a sparse population of reward-ensemble neurons with sustained firing aligned to distinct phases of reward consumption and spatially centered on reward locations. Reward consumption was accompanied by chewing-linked, atropine-sensitive 6-Hz theta oscillations that coexisted with intermittent sharp-wave ripples (SWRs). Notably, coupling of reward-ensemble spiking to theta and SWRs differed across sample and test phases of the task, suggesting state-dependent coordination of hippocampal reward ensembles during spatial working memory. Together, these findings identify reward consumption as a distinct hippocampal state characterized by coordinated theta-SWR dynamics during mnemonic behavior.

neuroscience↗

bioRxiv2026

A macrocyclic peptide-based fusion inhibitor targeting SARS-CoV-2 Spike S2 subunit

Continuous emergence of SARS-CoV-2 variants carrying mutations in Spike presents a significant challenge for durable antiviral agents. Here we screen for random 13-amino acid non-mimetic macrocyclic peptides that bind to Spike and identify PA-001 that inhibits SARS-CoV-2 infection with high potency at 0.23-2.9 nM as 50% inhibitory concentration (IC50). PA-001 bound to Spike S2 subunit and inhibited the membrane fusion during virus entry. Through drug-resistant selection, we revealed that PA-001 targeted the fusion peptide proximal region (FPPR) in S2, which has not been recognized as a drug target to date. Consistent with its highly conserved amino acid sequences beyond strains, PA-001 exhibited broad antiviral activity against all tested SARS-CoV-2 variants, in contrast to clinically-approved S1-targeting antibodies that lost activity to Omicron variants. PA-001 suppressed SARS-CoV-2 propagation and disease progression in mouse- and hamster-infection models, both by administration prophylactically and therapeutically. Combination therapy with remdesivir further enhanced antiviral profiles. In clinical phase-I trial, PA-001 was well-tolerated and showed high systemic exposure, with 4,300-10,300-fold concentration of IC50 as maximum plasma concentration by single administration to healthy volunteers. These evidence propose FPPR as an unexpected antiviral drug target accessible by macrocyclic peptides and identify PA-001 as a potent anti-SARS-CoV-2 fusion inhibitor.

microbiology↗

bioRxiv2022

Extracting electromyographic signals from multi-channel local-field-potentials using independent component analysis without direct muscular recording

Electromyography (EMG) has been commonly used for precise identification of animal behavior. However, they are often not recorded together with in vivo electrophysiology due to the need for additional surgeries and setups and the high risk of mechanical wire disconnection. While independent component analysis (ICA) has been used to reduce noise from field potential data, there has been no attempt to proactively use the removed "noise", of which EMG signals are thought to be one of the major sources. Here, we demonstrate that EMG signals can be reconstructed without direct EMG recording, using the "noise" ICA component from local field potentials. The extracted component is highly correlated with directly measured EMG, termed as IC-EMG. IC-EMG is useful for measuring an animals sleep/wake, freezing response and NREM/REM sleep states consistently with actual EMG. Our method has advantages in precise and long-term behavioral measurement in wide-ranged in vivo electrophysiology experiments. Highlights- EMG signals can be extracted from LFP signals without direct muscular recording - The extracted signal is highly correlated with direct EMG recording signals - The extracted signal is useful in measuring animal behaviors as well as actual EMG - This method contributes to precise and stable long-term behavior measurement In briefOsanai et al. demonstrate electromyography (EMG) signals can be extracted from multi-channel local field potential (LFP) recordings using blind-source-separation technique without direct measurement of muscle activity. The proposed method adds precise and long-term behavioral measurements with EMG information in wide-ranged in vivo electrophysiology experiments.

neuroscience↗

bioRxiv2021

A triple-negative matrix-producing breast carcinoma is arrested by tumor-targeting Salmonella typhimurium A1-R in a PDOX model

Background/AimMatrix-producing breast carcinoma (MPBC), is a rare, recalcitrant and highly aggressive. The present study aimed to determine the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R on a triple-negative MPBC in a patient-derived orthotopic xenograft (PDOX) model. MethodsThe PDOX model was established in the left second mammary gland of a nude mouse by surgical orthotopic implantation (SOI) of the patient triple-negative MPBC PDOX models were randomized into two groups: G1, control group (n=6); G2, tumor-targeting S. typhimurium A1-R group (n=7, intravenous (i.v.) injection via tail vein, weekly, for two weeks). All mice were sacrificed on day 15. Tumor volume and body weight were measured one time per week. ResultsS. typhimurium A1-R arrested tumor growth compared to the control group (P = 0.016). ConclusionThe results of the present study suggest that S. typhimurium A1-R has future clinical potential in triple-negative MPBC patients.

cancer biology↗

bioRxiv2021

Histone H3K4me3 and H3K9me3 are super over-methylated in soft tissue sarcoma compared to normal muscle in patient-derived xenograft (PDX) mouse models: an indicator of cancer methionine addiction

Methionine addiction is a fundamental and general hallmark of cancer discovered by us almost a half-century ago [Proc Natl Acad Sci U S A 73 (1976) 1523-1527]. Methionine addiction is defined as the requirement, specific for cancer cells of all types, for exogenous methionine despite the normal ability to synthesize methionine from homocysteine. The methionine addiction of cancer is termed the Hoffman-effect, analogous to the Warburg-effect of the high glucose requirement of cancer cells. Methionine addiction is due to excess transmethylation reactions resulting in high methionine flux in cancer cells, which causes them to selectively arrest under methionine restriction due to depletion of free methionine and S-adenosyl methionine. Recently we have shown methionine-addicted cancer cells over-methylate histone H3 lysine marks which are not over-methylated in normal cells or in low-malignancy methionine-independent revertants derived from methionine-addicted cancer cells. In the present report, we show that in patient-derived xenograft (PDX) mouse models of the most common soft tissue sarcomas: myxofibrosarcoma, undifferentiated pleomorphic sarcoma (UPS) and liposarcoma, histone H3K4me3 and H3K9me3 are super over-methylated compared to normal muscle tissue. This new result is discussed along with our previous reports, regarding the potential of histone H3 over-methylation as a basis of malignancy.

cancer biology↗

bioRxiv2020

Cancer-specific overmethylation of histone H3 lysines is necessary for methionine addiction and malignancy

Methionine addiction is a fundamental and general hallmark of cancer and is an area of current intense interest. Methionine addiction results from the overuse of methionine by cancer cells for excess transmethylation reactions. In order to identify excess transmethylation reactions in cancer and further understand the basis of methionine addiction, we compared the histone H3 lysine-methylation status and malignancy between methionine-addicted cancer cells and their methionine-independent revertants which have regained the ability to grow on low levels of methionine or independently of exogenous methionine. The levels of trimethylated histone H3 lysine marks were reduced in methionine-independent revertants compared to parental cancer cells in vitro. Tumorigenicity and experimental metastatic potential in nude mice were also highly reduced in the methionine-independent revertants compared to the parental cells. Our present results demonstrate that overmethylation of histone H3 lysines is linked with methionine addiction of cancer and to malignancy which suggests a possible causal relationship.

cancer biology↗

bioRxiv2020

Multiple types of navigational information is diffusely and independently encoded in the population activities of the dentate gyrus neurons

The dentate gyrus (DG) plays critical roles in cognitive functions such as learning, memory, and spatial coding, and its dysfunction is implicated in various neuropsychiatric disorders. However, it remains largely unknown how information is represented in this region. Here, we recorded neuronal activity in the DG using Ca2+ imaging in freely moving mice and analysed this activity using machine learning. The activity patterns of populations of DG neurons enabled us to successfully decode position, speed, and motion direction in an open field as well as current and future location in a T-maze, and each individual neuron was diversely and independently tuned to these multiple information types. In CaMKII heterozygous knockout mice, which present deficits in spatial remote and working memory, the decoding accuracy of position in the open field and future location in the T-maze were selectively reduced. These results suggest that multiple types of information are independently distributed in DG neurons.

neuroscience↗

bioRxiv2019

Effect of geographic isolation on the nasal virome of indigenous children

The influence of living in small remote villages on the diversity of viruses in the nasal mucosa was investigated in three Colombian villages with increasing levels of geographic isolation. Viral metagenomics was used to characterize viral nucleic acids on nasal swabs of 63 apparently healthy young children. Sequences from human virus members of the families Anelloviridae, Papillomaviridae, Picornaviridae, Herpesviridae, Polyomaviridae, Adenoviridae, and Paramyxoviridae were detected in a decreasing fraction of children. The diversity of human viruses was not reduced in the most isolated indigenous Kogi villages. Multiple viral transmission clusters were also identified as closely related variants of rhinoviruses A or B in 2 to 4 children from each of villages. The number of papillomavirus detected was greater in the village most exposed to outside contacts while conversely more anellovirus infections were detected in the more isolated indigenous villages. Genomes of viruses not known to infect humans, including in the family Parvoviridae (genus densoviruses), Partitiviridae, Dicistroviridae, and Iflaviridae and circular Rep expressing ssDNA genomes (CRESS-DNA) were also detected in nasal swabs likely reflecting environmental contamination from insect, fungal, and unknown sources. Despite the high level of geographic and cultural isolation, the diversity of human viruses in the nasal passages of children was not reduced in indigenous villages indicating ongoing exposure to globally circulating viruses.\n\nImportanceExtreme geographic and cultural isolation can still be found in some indigenous South American villages. Such isolation may be expected to limit the introduction of globally circulating viruses. Very small population size may also result in rapid local viral extinction due to lack of sufficient sero-negative subjects to maintain transmission chains of rapidly cleared viruses. We compared the viruses in the nasal passage of young children in three villages with increasing level of isolation. We find that isolation did not reduce the diversity of viral infections in the most isolated villages. Ongoing viral transmission of rhinoviruses could also be detected within all villages. We conclude that despite their geographic isolation remote villages are continuously exposed to globally circulating respiratory viruses.

epidemiology↗