416 results match your criteria: "Genomic Sciences Center[Affiliation]"

BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis.

Front Immunol

November 2024

Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Introduction: The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients.

Materials And Methods: In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages.

Results: Expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients.

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The intraflagellar transport (IFT) machinery plays a crucial role in the bidirectional trafficking of components necessary for ciliary signaling, such as the Hedgehog, Wnt/PCR, and cAMP/PKA systems. Defects in some components of the IFT machinery cause dysfunction, leading to a wide range of human diseases and developmental disorders termed ciliopathies, such as nephronophthisis. The IFT machinery comprises three sub-complexes: BBsome, IFT-A, and IFT-B.

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Using EGFR amplification to stratify recurrent glioblastoma treated with immune checkpoint inhibitors.

Cancer Immunol Immunother

June 2023

Montefiore Einstein Cancer Center, Departments of Hematology-Oncology, Neurosurgery and Microbiology & Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, USA.

Purpose: While immune checkpoint inhibitors (ICI) have had success with various malignancies, their efficacy in brain cancer is still unclear. Retrospective and prospective studies using PD-1 inhibitors for recurrent glioblastoma (GBM) have not established survival benefit. This study evaluated if ICI may be effective for select patients with recurrent GBM.

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Ribosome biogenesis is a complicated, multistage process coordinated by ribosome assembly factors. Ribosome binding factor A (RbfA) is a bacterial one, which possesses a single structural type-II KH domain. By this domain, RbfA binds to a 16S rRNA precursor in small ribosomal subunits to promote its 5'-end processing.

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Multiple strains of the SARS-CoV-2 have arisen and jointly influence the trajectory of the coronavirus disease (COVID-19) pandemic. However, current models rarely account for this multi-strain dynamics and their different transmission rate and response to vaccines. We propose a new mathematical model that accounts for two virus variants and the deployment of a vaccination program.

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Matrin-3 is a multifunctional protein that binds to both DNA and RNA. Its DNA-binding activity is linked to the formation of the nuclear matrix and transcriptional regulation, while its RNA-binding activity is linked to mRNA metabolism including splicing, transport, stabilization, and degradation. Correspondingly, Matrin-3 has two zinc finger domains for DNA binding and two consecutive RNA recognition motif (RRM) domains for RNA binding.

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In humans, YTH (YT521-B homology) domain containing protein 2 (YTHDC2) plays a crucial role in the phase-shift from mitosis to meiosis. YTH domains bind to methylated adenosine nucleotides such as mA. In a phylogenic tree, the YTH domain of YTHDC2 (YTH2) and that of the YTH containing protein YTHDC1 (YTH1) belong to the same sub-group.

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Article Synopsis
  • Translesion synthesis (TLS) polymerases, particularly Rev1, help bypass DNA damage during replication by incorporating nucleotides and assisting other TLS polymerases.
  • Researchers created specific mutants of Rev1 in medaka fish to study its functions, revealing that one mutant was highly sensitive to DNA damage from a chemical called DENA while another showed increased tumor rates despite similar mutation frequencies compared to normal fish.
  • The study found a significant increase in loss of heterozygosity (LOH) in the mutant with reduced dCMP activity, highlighting its role in tumor development, and marking the first link between Rev1's activity and LOH suppression.
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Single amino acid potential (SAAP) would be a prominent factor to determine peptide conformations. To prove this hypothesis, we previously developed SAAP force field for molecular simulation of polypeptides. In this study, the force field was renovated to SAAP3D force field by applying more accurate three-dimensional main-chain parameters, instead of the original two-dimensional ones, for the amino acids having a long side-chain.

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Many metazoans start germ cell development during embryogenesis, while some metazoans possessing pluripotent stem cells undergo postembryonic germ cell development. The latter reproduce asexually but develop germ cells from pluripotent stem cells or dormant primordial germ cells when they reproduce sexually. Sexual induction of the planarian Dugesia ryukyuensis is an important model for postembryonic germ cell development.

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Solution structure of the first RNA recognition motif domain of human spliceosomal protein SF3b49 and its mode of interaction with a SF3b145 fragment.

Protein Sci

February 2017

Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo, 202-8585, Japan.

The spliceosomal protein SF3b49, a component of the splicing factor 3b (SF3b) protein complex in the U2 small nuclear ribonucleoprotein, contains two RNA recognition motif (RRM) domains. In yeast, the first RRM domain (RRM1) of Hsh49 protein (yeast orthologue of human SF3b49) reportedly interacts with another component, Cus1 protein (orthologue of human SF3b145). Here, we solved the solution structure of the RRM1 of human SF3b49 and examined its mode of interaction with a fragment of human SF3b145 using NMR methods.

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Genetic engineering and metabolite profiling for overproduction of polyhydroxybutyrate in cyanobacteria.

J Biosci Bioeng

November 2015

College of Agriculture, Ibaraki University, 3-21-1 Ami, Ibaraki 300-0393, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan. Electronic address:

Genetic engineering and metabolite profiling for the overproduction of polyhydroxybutyrate (PHB), which is a carbon material in biodegradable plastics, were examined in the unicellular cyanobacterium Synechocystis sp. PCC 6803. Transconjugants harboring cyanobacterial expression vectors that carried the pha genes for PHB biosynthesis were constructed.

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Bcl11b SWI/SNF-complex subunit modulates intestinal adenoma and regeneration after γ-irradiation through Wnt/β-catenin pathway.

Carcinogenesis

June 2015

Department of Molecular Genetics, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Chuo-ku, Niigata 951-8510, Japan, Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, 2-11-1 Iwado-kita, Komae-shi, Tokyo, 201-8511, Japan, Brain Research Institute, Niigata University, Asahimachi 1-757, Chuo-ku, Niigata 951-8510, Japan, Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan and RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

SWI/SNF chromatin remodeling complexes constitute a highly related family of multi-subunit complexes to modulate transcription, and SWI/SNF subunit genes are collectively mutated in 20% of all human cancers. Bcl11b is a SWI/SNF subunit and acts as a haploinsufficient tumor suppressor in leukemia/lymphomas. Here, we show expression of Bcl11b in intestinal crypt cells and promotion of intestinal tumorigenesis by Bcl11b attenuation in Apc (min/+) mice.

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Epithelium specific ETS transcription factor, ESE-3, of Protobothrops flavoviridis snake venom gland transactivates the promoters of venom phospholipase A2 isozyme genes.

Toxicon

December 2014

Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan. Electronic address:

Protobothrops flavoviridis (habu) (Crotalinae, Viperidae) is a Japanese venomous snake, and its venom contains the enzymes with a variety of physiological activities. The phospholipases A2 (PLA2s) are the major components and exert various toxic effects. They are expressed abundantly in the venom gland.

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Wnt/β-catenin signalling regulates numerous developmental and homeostatic processes. Ctnnb1 (also known as β-catenin) is the only protein that transmits signals from various Wnt ligands to downstream genes. In this study, we report that our newly established mouse strain, which harbours a Cys429 to Ser missense mutation in the β-catenin gene, exhibited specific organ defects in contrast to mice with broadly functioning Wnt/β-catenin signalling.

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RBFOX and SUP-12 sandwich a G base to cooperatively regulate tissue-specific splicing.

Nat Struct Mol Biol

September 2014

1] RIKEN Systems and Structural Biology Center, Yokohama, Japan. [2] RIKEN Center for Life Science Technologies, Yokohama, Japan. [3] Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University, Nishitokyo, Japan.

Tissue-specific alternative pre-mRNA splicing is often cooperatively regulated by multiple splicing factors, but the structural basis of cooperative RNA recognition is poorly understood. In Caenorhabditis elegans, ligand binding specificity of fibroblast growth factor receptors (FGFRs) is determined by mutually exclusive alternative splicing of the sole FGFR gene, egl-15. Here we determined the solution structure of a ternary complex of the RNA-recognition motif (RRM) domains from the RBFOX protein ASD-1, SUP-12 and their target RNA from egl-15.

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The N (1)-methyladenosine residue at position 58 of tRNA is found in the three domains of life, and contributes to the stability of the three-dimensional L-shaped tRNA structure. In thermophilic bacteria, this modification is important for thermal adaptation, and is catalyzed by the tRNA m(1)A58 methyltransferase TrmI, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. We present the 2.

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Interleukin-1 receptor gene variants are associated with aggressive periodontitis in the Japanese.

Arch Oral Biol

July 2014

Comparative Systems Biology Team, Genomic Sciences Center, RIKEN, Yokohama, Japan; Health Support Center, Toyohashi University of Technology, Toyohashi, Japan. Electronic address:

Objective: Previous studies have indicated that type-1 and type-2 interleukin-1 (IL-1) receptors (IL-1R1 and IL-1R2) play important roles in periodontitis progression. We investigated the association between periodontitis and polymorphisms in the IL-1R1 and IL-1R2 genes (IL1R1 and IL1R2).

Design: We searched for genetic variants in IL1R1 and IL1R2 in 24 Japanese patients with aggressive periodontitis (AgP) and 24 periodontally healthy controls.

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Plant-associated symbiotic Burkholderia species lack hallmark strategies required in mammalian pathogenesis.

PLoS One

September 2014

Dept. of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America ; Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America.

Burkholderia is a diverse and dynamic genus, containing pathogenic species as well as species that form complex interactions with plants. Pathogenic strains, such as B. pseudomallei and B.

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Application of plug-plug technique to ACE experiments for discovery of peptides binding to a larger target protein: a model study of calmodulin-binding fragments selected from a digested mixture of reduced BSA.

Electrophoresis

March 2014

Laboratory of Proteomic Sciences, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto, Japan; Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan; Laboratory of Next Generation Drug Development, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan; Protein Research Group, RIKEN Genomic Sciences Center, Tsurumi, Yokohama, Japan.

To discover peptide ligands that bind to a target protein with a higher molecular mass, a concise screening methodology has been established, by applying a "plug-plug" technique to ACE experiments. Exploratory experiments using three mixed peptides, mastoparan-X, β-endorphin, and oxytocin, as candidates for calmodulin-binding ligands, revealed that the technique not only reduces the consumption of the protein sample, but also increases the flexibility of the experimental conditions, by allowing the use of MS detection in the ACE experiments. With the plug-plug technique, the ACE-MS screening methodology successfully selected calmodulin-binding peptides from a random library with diverse constituents, such as protease digests of BSA.

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Comprehensive survey of CNVs influencing gene expression in the human brain and its implications for pathophysiology.

Neurosci Res

February 2014

Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama 351-0198, Japan. Electronic address:

Article Synopsis
  • Copy number variations (CNVs) are linked to neuropsychiatric diseases and influence gene expression in the brain, but few studies have explored this connection.
  • The research surveyed 72 individuals with schizophrenia, bipolar disorder, and healthy controls, identifying 583 significant CNV-expression pairs, highlighting certain CNVs that impact gene expression.
  • Findings indicated that CNVs affecting gene expression were enriched in rare variants and specific chromosomal regions, suggesting that these variations may increase risk for psychiatric disorders by affecting processes like glutathione metabolism and oxidative stress.
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The common marmoset is a new world monkey, which has become a valuable experimental animal for biomedical research. This study developed cDNA libraries for the common marmoset from five different tissues. A total of 290 426 high-quality EST sequences were obtained, where 251 587 sequences (86.

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Animal guts and plant roots have absorption roles for nutrient uptake and converge in harboring large, complex, and dynamic groups of microbes that participate in degradation or modification of nutrients and other substances. Gut and root bacteria regulate host gene expression, provide metabolic capabilities, essential nutrients, and protection against pathogens, and seem to share evolutionary trends.

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Myostatin (MSTN) functions as a negative regulator of skeletal muscle mass. In mammals, MSTN-deficient animals result in an increase of skeletal muscle mass with both hyperplasia and hypertrophy. A MSTN gene is highly conserved within the fish species, allowing speculation that MSTN-deficient fish could exhibit a double-muscled phenotype.

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ADAMTSL6β protein rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly.

J Biol Chem

November 2011

Department of Biological Science and Technology, Faculty of Industrial Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Organ Technologies Inc., Tokyo, Japan.

Marfan syndrome (MFS) is a systemic disorder of the connective tissues caused by insufficient fibrillin-1 microfibril formation and can cause cardiac complications, emphysema, ocular lens dislocation, and severe periodontal disease. ADAMTSL6β (A disintegrin-like metalloprotease domain with thrombospondin type I motifs-like 6β) is a microfibril-associated extracellular matrix protein expressed in various connective tissues that has been implicated in fibrillin-1 microfibril assembly. We here report that ADAMTSL6β plays an essential role in the development and regeneration of connective tissues.

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