1,352 results match your criteria: "Institute for Genetic Medicine[Affiliation]"

Neurobiology of COVID-19-Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling.

Neuropsychopharmacol Rep

March 2025

Molecular Psychoneuroimmunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

COVID-19 exhibits not only respiratory symptoms but also neurological/psychiatric symptoms rarely including delirium/psychosis. Pathological studies on COVID-19 provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role in the progression of viral replication and lung fibrosis. Of note, SARS-CoV-2 virus (specifically, S1 spike domain) mimics EGF and directly transactivates EGFR, preceding the inflammatory process.

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Bulk macroautophagy/autophagy, typically induced by starvation, is generally thought to non-selectively isolate cytosolic components for degradation. However, a detailed analysis of bulk autophagy cargo has not been conducted. We recently employed mass spectrometry to analyze the contents of isolated autophagic bodies.

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Background: The incidence of antipsychotic-induced weight gain (AIWG) is difficult to predict in real-world practice because various factors influence it. This study aimed to explore background and medication-related factors associated with weight gain in patients newly prescribed with antipsychotic medication.

Methods: This nationwide, multicenter, prospective cohort study was conducted in Japan.

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Plasticity and Tumor Microenvironment in Pancreatic Cancer: Genetic, Metabolic, and Immune Perspectives.

Cancers (Basel)

December 2024

Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0818, Japan.

Article Synopsis
  • Cancer is influenced not only by genetic mutations but also by environmental factors like aging, damage, and inflammation, challenging the traditional view of it being solely a genetic disease.
  • Pancreatic cancer develops in a unique microenvironment filled with stromal and immune cells, which can lead cancer cells to alter their metabolism and create conditions that suppress immune responses.
  • Recent research highlights two significant signaling pathways involved in pancreatic cancer's evolution, focusing on ARF6 mutations and the role of inflammatory cytokines mediated by Arid5a, emphasizing the complexity and variety of therapeutic approaches needed for treatment.
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Novel role of zinc-finger protein 518 in heterochromatin formation on α-satellite DNA.

Nucleic Acids Res

December 2024

Laboratory of Chromosome Engineering, Department of Frontier Research and Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu 292-0818, Japan.

Aneuploidy is caused by chromosomal missegregation and is frequently observed in cancers and hematological diseases. Therefore, it is important to understand the molecular mechanisms underlying chromosomal segregation. The centromere's intricate structure is crucial for proper chromosome segregation, with heterochromatin at the pericentromeric α-satellites playing a key role.

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Visualization and Analyses of Cytoplasmic Streaming in C. elegans Zygotes.

Methods Mol Biol

December 2024

Division of Developmental Physiology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.

Cytoplasmic streaming is the bulk flow of cytoplasm observed, not only in plants but also in animal oocytes and embryos. The flow of viscous fluid within the cytoplasm generates forces that re-arrange intracellular organelles, such as mitotic spindles and nuclei, to regulate cell growth, migration, and polarity. Cytoplasmic streaming is established by motor proteins and the viscoelastic cytoskeleton, including the actin filaments and microtubules.

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To understand neocortical function, we must first define its cell types. Recent studies indicate that neurons in the deepest cortical layer play roles in mediating thalamocortical interactions and modulating brain state and are implicated in neuropsychiatric disease. However, understanding the functions of deep layer 6 (L6b) neurons has been hampered by the lack of agreed upon definitions for these cell types.

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Background: Rodent-borne orthohantaviruses are the causative agents of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Apart from the classic rodent-borne hantaviruses, numerous species of hantaviruses have been identified in shrews and bats; however, their antigenicity and pathogenicity are unknown. This study focused on developing a serological method to detect antibodies against bat- and shrew-borne hantaviruses.

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Two amino acid pairs in the Gc glycoprotein of severe fever with thrombocytopenia syndrome virus responsible for the enhanced virulence.

Virology

January 2025

Laboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8511, Japan; Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8511, Japan. Electronic address:

Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern, with a high fatality rate in humans and cats. In this study, we explored the genetic determinants that contribute to the different virulence of SFTS virus (SFTSV) based on Tk-F123 and Ng-F264 strains isolated from cats. Tk-F123 was 100% lethal in type I interferon receptor-knockout mice, whereas Ng-F264 exhibited no fatality.

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Berberine promotes K-linked polyubiquitination of HNF4α, leading to the inhibition of HBV replication.

Antiviral Res

December 2024

Department of Microbiology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan; Division of Hepatitis Virology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, 060-0808, Japan; Center for Life Science Research, University of Yamanashi, Yamanashi, 409-3898, Japan. Electronic address:

The current antiviral agents for the treatment of chronic infection with hepatitis B virus (HBV) do not completely remove covalently closed circular DNA (cccDNA) and integrated viral DNA fragments from patients. Berberine is an isoquinoline alkaloid extracted from various plants and has been reported to inhibit the replication of various types of DNA. In this study, we tested the effects of berberine and its derivatives on HBV infection.

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Background: The discovery of glioblastoma (GBM)-initiating cells (GICs) has impacted GBM research. These cells are not only tumorigenic, but also exhibit resistance to radiotherapy and chemotherapy. Therefore, it is crucial to characterize GICs thoroughly and identify new therapeutic targets.

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Contact inhibition of proliferation is a critical cell density control mechanism governed by the Hippo signalling pathway. The biochemical signalling underlying cell density-dependent cues regulating Hippo signalling and its downstream effectors, YAP, remains poorly understood. Here, we reveal that the tight junction protein ZO-2 is required for the contact-mediated inhibition of proliferation.

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Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm preferentially involving the upper aerodigestive tract. Here we show that NK-cell-specific Trp53 disruption in mice leads to the development of NK-cell lymphomas after long latency, which involve not only the hematopoietic system but also the salivary glands. Before tumor onset, Trp53 knockout causes extensive gene expression changes, resulting in immature NK-cell expansion, exclusively in the salivary glands.

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We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (H. Kasai, K. Mochizuki, T.

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The Hi-C method has emerged as an indispensable tool for analyzing the 3D organization of the genome, becoming increasingly accessible and frequently utilized in chromatin research. To effectively leverage 3D genomics data obtained through advanced technologies, it is crucial to understand what processes are undertaken and what aspects require special attention within the bioinformatics pipeline. This protocol aims to demystify the Hi-C data analysis process for field newcomers.

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Article Synopsis
  • Flow cytometry is important in biomedical research but faces challenges with fluctuations in fluorescence intensity, which affects its accuracy.
  • A new method has been developed to integrate fluorescence lifetime imaging microscopy (FLIM) into flow cytometry, achieving speeds over 10,000 cells per second.
  • This advanced FLIM system can identify subpopulations of cells and observe changes in the nucleus due to anti-cancer drugs, improving the analysis of cellular functions and interactions.
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Aims: To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU).

Main Methods: Mice were immunized by subcutaneous injection of interphotoreceptor retinoid-binding protein in Freund's complete adjuvant and intravenous injection of pertussis toxin, and were then exposed to high-contrast VS 12 h/day (days 1-14 post-immunization). EAU severity was assessed by examining clinical score, visual acuity, inflammatory markers, and immune cells in the retina.

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Article Synopsis
  • SARS-CoV-2 causes a range of respiratory symptoms, and although research has made strides in understanding the virus, many aspects of its infection process are still not fully understood.
  • The study focuses on the interferon-inducible protein ISG15, which is involved in suppressing viral functions through a process called ISGylation, and how SARS-CoV-2's protease, PLpro, interferes with this process.
  • Results show that ISGylation of the SARS-CoV-2 nucleocapsid protein disrupts viral replication, indicating that the virus has evolved mechanisms to evade ISGylation to enhance its own replication efficiency.
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Sphingomyelin (SM) is a major sphingolipid in mammalian cells. SM is enriched in the extracellular leaflet of the plasma membrane (PM). Besides this localization, recent electron microscopic and biochemical studies suggest the presence of SM in the cytosolic leaflet of the PM.

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Article Synopsis
  • Scientists studied how sleep is regulated in male mice, especially after staying awake for a long time.
  • They found that a special protein called CaMKII helps control certain brain cells (called PV neurons) that are important for sleep.
  • When these PV neurons become more active, it leads to more rebound sleep, which happens after being awake for too long.
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Click3D: Click reaction across deep tissues for whole-organ 3D fluorescence imaging.

Sci Adv

July 2024

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Click chemistry offers various applications through efficient bioorthogonal reactions. In bioimaging, pretargeting strategies have often been used, using click reactions between molecular probes with a click handle and reporter molecules that make them observable. Recent efforts have integrated tissue-clearing techniques with fluorescent labeling through click chemistry, allowing high-resolution three-dimensional fluorescence imaging.

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Development of an entirely cloned cDNA-based reverse genetics system for Tofla virus of orthonairovirus.

Virology

October 2024

Laboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi, 753-8511, Japan; Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, 753-8511, Japan. Electronic address:

Article Synopsis
  • The Orthonairovirus genus includes dangerous tick-borne viruses like the Crimean-Congo hemorrhagic fever virus (CCHFV), and studying their pathogenicity requires advanced tools like reverse genetics.
  • Researchers have recently investigated Tofla orthonairovirus (TFLV), a newly discovered virus from Japan, as a potential model for studying these viruses.
  • In this study, a reliable reverse genetics system for TFLV was developed using T7 RNA polymerase, allowing the creation of both mutant and wild-type TFLV viruses that showed similar growth and harmful effects in lab mice compared to the authentic virus.
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Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.

Microbiol Immunol

September 2024

Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Article Synopsis
  • A new variant of SARS-CoV-2, called EG.5.1, is spreading rapidly and has been studied using various scientific methods to understand its features.
  • Key mutations in EG.5.1, specifically S:F456L and ORF9b:I5T, enhance its viral fitness compared to other variants like XBB.1.5.
  • Structural differences were found in the spike proteins of EG.5.1 versus XBB.1.5, and the research helps us understand the evolution of emerging viruses that can affect human health.
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Trial Analysis of Brain Activity Information for the Presymptomatic Disease Detection of Rheumatoid Arthritis.

Bioengineering (Basel)

May 2024

Faculty of Information Science and Technology, Hokkaido University, N-14, W-9, Kita-ku, Sapporo 060-0814, Japan.

This study presents a trial analysis that uses brain activity information obtained from mice to detect rheumatoid arthritis (RA) in its presymptomatic stages. Specifically, we confirmed that F759 mice, serving as a mouse model of RA that is dependent on the inflammatory cytokine IL-6, and healthy wild-type mice can be classified on the basis of brain activity information. We clarified which brain regions are useful for the presymptomatic detection of RA.

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