711 results match your criteria: "Institute for Comprehensive Medical Science[Affiliation]"

Chickpea cultivated on marginal lands in arid and semiarid tropics is one of the food legumes, and its growth is reduced by flooding stress. Millimeter-wave irradiation has influences on organisms, and it improves the growth of plants such as soybean. To reveal the dynamic effects of millimeter-wave irradiation on chickpea under flooding, gel- and label-free proteomic analysis was conducted.

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To investigate the mechanism of flooding tolerance of soybean, flooding-tolerant mutants derived from gamma-ray irradiated soybean were crossed with parent cultivar Enrei for removal of other factors besides the genes related to flooding tolerance in primary generated mutant soybean. Although the growth of the wild type was significantly suppressed by flooding compared with the non-flooding condition, that of the mutant lines was better than that of the wild type even if it was treated with flooding. A two-day-old mutant line was subjected to flooding for 2 days and proteins were analyzed using a gel-free/label-free proteomic technique.

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Background: The International Reporting Items for Practice Guidelines in Health Care (RIGHT) statement is a set of recommendations for the reporting in clinical practice guidelines (CPGs). We aimed to assess the reporting quality of CPGs for pancreatic cancer following the RIGHT checklist.

Methods: Guidelines for pancreatic cancer were identified by searching electronic databases, guideline databases, and medical society websites.

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SPF45/RBM17-dependent, but not U2AF-dependent, splicing in a distinct subset of human short introns.

Nat Commun

August 2021

Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.

Human pre-mRNA introns vary in size from under fifty to over a million nucleotides. We searched for essential factors involved in the splicing of human short introns by screening siRNAs against 154 human nuclear proteins. The splicing activity was assayed with a model HNRNPH1 pre-mRNA containing short 56-nucleotide intron.

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Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice.

Stem Cell Res Ther

August 2021

Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Mesenchymal stromal cells (MSCs) function as supportive cells on skeletal muscle homeostasis through several secretory factors including type 6 collagen (COL6). Several mutations of COL6A1, 2, and 3 genes cause Ullrich congenital muscular dystrophy (UCMD). Skeletal muscle regeneration deficiency has been reported as a characteristic phenotype in muscle biopsy samples of human UCMD patients and UCMD model mice.

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ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.

iScience

July 2021

Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.

Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of or in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits.

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Altered serum soluble furin and prorenin receptor levels in pregnancies with pre-eclampsia and fetal growth restriction.

J Gynecol Obstet Hum Reprod

December 2021

Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.

Objective: The proprotein convertase furin is known to be involved in the processing of pro-B-type natriuretic peptide (proBNP) and prorenin receptor (PRR), suggesting that it has a potential function in blood pressure regulation. We investigated the role of furin in the etiology of pre-eclampsia and its related disorder, unexplained fetal growth restriction (FGR) without hypertension.

Methods: We evaluated serum and placental furin levels in pre-eclampsia, FGR and uncomplicated pregnancy.

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A Turner syndrome case associated with dic(Y;22).

Mol Cytogenet

July 2021

Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake-shi, Aichi, 470-1192, Japan.

Article Synopsis
  • The study discusses a rare case of Turner syndrome in a female with a complex karyotype involving both a normal and an abnormal chromosome structure.
  • It highlights the confusion surrounding the development of this mosaicism, suggesting it may stem from the separation of a dicentric chromosome (dic(Y;22)) leading to the loss of the Y chromosome while retaining chromosome 22.
  • The authors introduce a new mechanism called "pulled apart," which reflects instability in telomeric associations that could result in such unique chromosomal patterns.
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The Exon Junction Complex Core Represses Cancer-Specific Mature mRNA Re-splicing: A Potential Key Role in Terminating Splicing.

Int J Mol Sci

June 2021

Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake 470-1192, Aichi, Japan.

Using TSG101 pre-mRNA, we previously discovered cancer-specific re-splicing of mature mRNA that generates aberrant transcripts/proteins. The fact that mRNA is aberrantly re-spliced in various cancer cells implies there must be an important mechanism to prevent deleterious re-splicing on the spliced mRNA in normal cells. We thus postulated that mRNA re-splicing is controlled by specific repressors, and we searched for repressor candidates by siRNA-based screening for mRNA re-splicing activity.

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Structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar. However, whereas pMHC-II complexes include similar-sized IIα and IIβ chains, pMHC-I complexes include a heavy chain (HC) and a single domain molecule β-microglobulin (β-m). Recently, we elucidated several pMHC-I and pMHC-II structures of primitive vertebrate species.

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Article Synopsis
  • Cartilaginous fish, like nurse sharks, have special molecules called MHC that help their immune system, and this study is the first to look closely at how these molecules are built.
  • The research found that the structure of these MHC molecules is similar to those in bony fish, showing that certain parts work together in a similar way.
  • The scientists discovered important details about how different parts of the MHC bind together, which could help us understand how these immune systems work better in the future.
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A report of a family of Darier's disease with mood disorders drew attention when the causative gene was identified as ATP2A2 (or SERCA2), which encodes a Ca2+ pump on the endoplasmic reticulum (ER) membrane and is important for intracellular Ca2+ signaling. Recently, it was found that loss-of-function mutations of ATP2A2 confer a risk of neuropsychiatric disorders including depression, bipolar disorder and schizophrenia. In addition, a genome-wide association study found an association between ATP2A2 and schizophrenia.

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The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia.

Curr Biol

July 2021

Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Sapporo, Japan. Electronic address:

Article Synopsis
  • Oncogenic mutations lead to the formation of multilayered epithelial structures in early cancer development, but the molecular mechanisms are not fully understood.
  • Research has shown that collagen XVII (COL17A1) and CD44 proteins accumulate in transformed epithelial cells, affecting cell behavior, resistance to cell death, and overall structure.
  • COL17A1 and CD44 play key roles in regulating metabolic pathways and maintaining cell survival, making them potential targets for early cancer diagnosis and treatment.
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Article Synopsis
  • Isocitrate dehydrogenase (IDH) wild-type diffuse astrocytic tumors are commonly diagnosed as glioblastomas (GBMs), with a lower myoinositol to total choline (Ins/Cho) ratio in GBMs compared to IDH-mutant gliomas.
  • A study was conducted to see if a low Ins/Cho ratio correlates with poorer progression-free survival (PFS) and overall survival (OS) in patients with IDH-wild-type GBMs.
  • Results showed that patients with a low Ins/Cho ratio had significantly shorter PFS and OS, suggesting that the Ins/Cho ratio may serve as a useful prognostic marker for these tumors.
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In the spring of 2020, we and others hypothesized that T cells in COVID-19 patients may recognize identical protein fragments shared between the coronaviruses of the common cold and COVID-19 and thereby confer cross-virus immune memory. Here, we look at this issue by screening studies that, since that time, have experimentally addressed COVID-19 associated T cell specificities. Currently, the identical T cell epitope shared between COVID-19 and common cold coronaviruses most convincingly identified as immunogenic is the CD8 T cell epitope VYIGDPAQL if presented by the MHC class I allele HLA-A*24:02.

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Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonist-induced orofacial dyskinesia.

JCI Insight

May 2021

Department of Molecular Pharmacology, Graduate School and Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.

Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the US Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevented the dyskinesia induced by dopamine D2 receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1).

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Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy.

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Forebrain-specific deficiency of the GTPase CRAG/Centaurin-γ3 leads to immature dentate gyri and hyperactivity in mice.

J Biol Chem

August 2021

Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan; Laboratory of Molecular Biochemistry, Department of Life Science, Faculty of Science, Gakushuin University, Toshima-ku, Tokyo, Japan. Electronic address:

Mouse models of various neuropsychiatric disorders, such as schizophrenia, often display an immature dentate gyrus, characterized by increased numbers of immature neurons and neuronal progenitors and a dearth of mature neurons. We previously demonstrated that the CRMP5-associated GTPase (CRAG), a short splice variant of Centaurin-γ3/AGAP3, is highly expressed in the dentate gyrus. CRAG promotes cell survival and antioxidant defense by inducing the activation of serum response factors at promyelocytic leukemia protein bodies, which are nuclear stress-responsive domains, during neuronal development.

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An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy.

Int J Mol Sci

March 2021

Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake 470-1192, Japan.

The loss of skeletal muscle mass (muscle atrophy or wasting) caused by aging, diseases, and injury decreases quality of life, survival rates, and healthy life expectancy in humans. Although long non-coding RNAs (lncRNAs) have been implicated in skeletal muscle formation and differentiation, their precise roles in muscle atrophy remain unclear. In this study, we used RNA-sequencing (RNA-Seq) to examine changes in the expression of lncRNAs in four muscle atrophy conditions (denervation, casting, fasting, and cancer cachexia) in mice.

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Pial arteriovenous fistulas (AVFs) are rare vascular lesions; their exact pathophysiology is largely unknown. Pial AVFs have been reported to develop within capillary malformation-arteriovenous malformation (CM-AVM); however, only a few cases have been reported. Variants in the RASA1 gene have been reported as a cause of CM-AVM.

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Dysfunction of the proteoglycan Tsukushi causes hydrocephalus through altered neurogenesis in the subventricular zone in mice.

Sci Transl Med

March 2021

Department of Developmental Neurobiology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.

The lateral ventricle (LV) is flanked by the subventricular zone (SVZ), a neural stem cell (NSC) niche rich in extrinsic growth factors regulating NSC maintenance, proliferation, and neuronal differentiation. Dysregulation of the SVZ niche causes LV expansion, a condition known as hydrocephalus; however, the underlying pathological mechanisms are unclear. We show that deficiency of the proteoglycan Tsukushi (TSK) in ependymal cells at the LV surface and in the cerebrospinal fluid results in hydrocephalus with neurodevelopmental disorder-like symptoms in mice.

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The 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.

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Spliceostatin A interaction with SF3B limits U1 snRNP availability and causes premature cleavage and polyadenylation.

Cell Chem Biol

September 2021

Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; Department of Biotechnology, Graduate School of Agricultural Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan. Electronic address:

RNA splicing, a highly conserved process in eukaryotic gene expression, is seen as a promising target for anticancer agents. Splicing is associated with other RNA processing steps, such as transcription and nuclear export; however, our understanding of the interaction between splicing and other RNA regulatory mechanisms remains incomplete. Moreover, the impact of chemical splicing inhibition on long non-coding RNAs (lncRNAs) has been poorly understood.

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Drought is one of the severe environmental stresses threatening agriculture around the globe. Nitric oxide plays diverse roles in plant growth and defensive responses. Despite a few studies supporting the role of nitric oxide in plants under drought responses, little is known about its pivotal molecular amendment in the regulation of stress signaling.

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The elevated plus maze test is a widely used test for assessing anxiety-like behavior and screening novel therapeutic agents in rodents. Previous studies have shown that a variety of internal factors and procedural variables can influence elevated plus maze behavior. Although some studies have suggested a link between behavior and plasma corticosterone levels, the relationships between them remain unclear.

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