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  1. Article ; Online: Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex.

    Mann, Beth / Crawford, Jeremy Chase / Reddy, Kavya / Lott, Josi / Youn, Yong Ha / Gao, Geli / Guy, Cliff / Chou, Ching-Heng / Darnell, Daniel / Trivedi, Sanchit / Bomme, Perrine / Loughran, Allister J / Thomas, Paul G / Han, Young-Goo / Tuomanen, Elaine I

    mBio

    2023  Volume 14, Issue 3, Page(s) e0051023

    Abstract: Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain ...

    Abstract Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. We identify ventricular radial glia (vRG), the primary NPC, as the target of bacterial cell wall (BCW) generated during the antibiotic treatment of maternal pneumonia. BCW enhanced proliferative potential of vRGs by shortening the cell cycle and increasing self-renewal. Expanded vRGs propagated to increase neuronal output in all cortical layers. Remarkably, Toll-like receptor 2 (TLR2), which recognizes BCW, localized at the base of primary cilia in vRGs and the BCW-TLR2 interaction suppressed ciliogenesis leading to derepression of Hedgehog (HH) signaling and expansion of vRGs. We also show that TLR6 is an essential partner of TLR2 in this process. Surprisingly, TLR6 alone was required to set the number of cortical neurons under healthy conditions. These findings suggest that an endogenous signal from TLRs suppresses cortical expansion during normal development of the neocortex and that BCW antagonizes that signal through the TLR2/cilia/HH signaling axis changing brain structure and function.
    MeSH term(s) Pregnancy ; Female ; Humans ; Hedgehog Proteins/metabolism ; Neocortex/metabolism ; Toll-Like Receptor 2/metabolism ; Ligands ; Toll-Like Receptor 6/metabolism
    Chemical Substances Hedgehog Proteins ; Toll-Like Receptor 2 ; Ligands ; Toll-Like Receptor 6 ; TLR2 protein, human
    Language English
    Publishing date 2023-04-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00510-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Evolutionary Action Score of

    Michikawa, Chieko / Torres-Saavedra, Pedro A / Silver, Natalie L / Harari, Paul M / Kies, Merrill S / Rosenthal, David I / Le, Quynh-Thu / Jordan, Richard C / Duose, Dzifa Y / Mallampati, Saradhi / Trivedi, Sanchit / Luthra, Rajyalakshmi / Wistuba, Ignacio I / Osman, Abdullah A / Lichtarge, Olivier / Foote, Robert L / Parvathaneni, Upendra / Hayes, D Neil / Pickering, Curtis R /
    Myers, Jeffrey N

    Advances in radiation oncology

    2022  Volume 7, Issue 6, Page(s) 100989

    Abstract: Purpose: An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies patients with head and neck squamous cell carcinoma (HNSCC) bearing : Methods and materials: Eighty-one resection samples from patients ... ...

    Abstract Purpose: An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies patients with head and neck squamous cell carcinoma (HNSCC) bearing
    Methods and materials: Eighty-one resection samples from patients treated surgically for stage III or IV human papillomavirus-negative HNSCC with high-risk pathologic features, who received either radiation therapy + cetuximab + cisplatin (cisplatin) or radiation therapy + cetuximab + docetaxel (docetaxel) as adjuvant treatment in a phase 2 study were subjected to
    Results: At a median follow-up of 9.8 years, there was a significant interaction between EAp53 group and treatment for overall survival (
    Conclusions: The docetaxel arm was associated with better survival than the cisplatin arm for patients with wild-type or low-risk EAp53. These benefits appear to be largely driven by a reduction in DM.
    Language English
    Publishing date 2022-05-18
    Publishing country United States
    Document type Journal Article
    ISSN 2452-1094
    ISSN 2452-1094
    DOI 10.1016/j.adro.2022.100989
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  3. Article: SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells.

    Minervina, Anastasia A / Pogorelyy, Mikhail V / Kirk, Allison M / Crawford, Jeremy Chase / Allen, E Kaitlynn / Chou, Ching-Heng / Mettelman, Robert C / Allison, Kim J / Lin, Chun-Yang / Brice, David C / Zhu, Xun / Vegesana, Kasi / Wu, Gang / Trivedi, Sanchit / Kottapalli, Pratibha / Darnell, Daniel / McNeely, Suzanne / Olsen, Scott R / Schultz-Cherry, Stacey /
    Estepp, Jeremie H / McGargill, Maureen A / Wolf, Joshua / Thomas, Paul G

    medRxiv : the preprint server for health sciences

    2022  

    Abstract: Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 ... ...

    Abstract Although mRNA vaccine efficacy against severe COVID-19 remains high, variant emergence and breakthrough infections have changed vaccine policy to include booster immunizations. However, the effect of diverse and repeated antigen exposures on SARS-CoV-2 memory T cells is poorly understood. Here, we utilize DNA-barcoded MHC-multimers combined with scRNAseq and scTCRseq to capture the
    Language English
    Publishing date 2022-01-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.07.12.21260227
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Common Trajectories of Highly Effective CD19-Specific CAR T Cells Identified by Endogenous T-cell Receptor Lineages.

    Wilson, Taylor L / Kim, Hyunjin / Chou, Ching-Heng / Langfitt, Deanna / Mettelman, Robert C / Minervina, Anastasia A / Allen, E Kaitlynn / Métais, Jean-Yves / Pogorelyy, Mikhail V / Riberdy, Janice M / Velasquez, M Paulina / Kottapalli, Pratibha / Trivedi, Sanchit / Olsen, Scott R / Lockey, Timothy / Willis, Catherine / Meagher, Michael M / Triplett, Brandon M / Talleur, Aimee C /
    Gottschalk, Stephen / Crawford, Jeremy Chase / Thomas, Paul G

    Cancer discovery

    2022  Volume 12, Issue 9, Page(s) 2098–2119

    Abstract: Current chimeric antigen receptor-modified (CAR) T-cell products are evaluated in bulk, without assessing functional heterogeneity. We therefore generated a comprehensive single-cell gene expression and T-cell receptor (TCR) sequencing data set using pre- ...

    Abstract Current chimeric antigen receptor-modified (CAR) T-cell products are evaluated in bulk, without assessing functional heterogeneity. We therefore generated a comprehensive single-cell gene expression and T-cell receptor (TCR) sequencing data set using pre- and postinfusion CD19-CAR T cells from blood and bone marrow samples of pediatric patients with B-cell acute lymphoblastic leukemia. We identified cytotoxic postinfusion cells with identical TCRs to a subset of preinfusion CAR T cells. These effector precursor cells exhibited a unique transcriptional profile compared with other preinfusion cells, corresponding to an unexpected surface phenotype (TIGIT+, CD62Llo, CD27-). Upon stimulation, these cells showed functional superiority and decreased expression of the exhaustion-associated transcription factor TOX. Collectively, these results demonstrate diverse effector potentials within preinfusion CAR T-cell products, which can be exploited for therapeutic applications. Furthermore, we provide an integrative experimental and analytic framework for elucidating the mechanisms underlying effector development in CAR T-cell products.
    Significance: Utilizing clonal trajectories to define transcriptional potential, we find a unique signature of CAR T-cell effector precursors present in preinfusion cell products. Functional assessment of cells with this signature indicated early effector potential and resistance to exhaustion, consistent with postinfusion cellular patterns observed in patients. This article is highlighted in the In This Issue feature, p. 2007.
    MeSH term(s) Antigens, CD19 ; Humans ; Immunotherapy, Adoptive/methods ; Receptors, Antigen, T-Cell/genetics ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism ; T-Lymphocytes
    Chemical Substances Antigens, CD19 ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2022-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-21-1508
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6916: Show issues Location:
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  5. Article ; Online: SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8

    Minervina, Anastasia A / Pogorelyy, Mikhail V / Kirk, Allison M / Crawford, Jeremy Chase / Allen, E Kaitlynn / Chou, Ching-Heng / Mettelman, Robert C / Allison, Kim J / Lin, Chun-Yang / Brice, David C / Zhu, Xun / Vegesana, Kasi / Wu, Gang / Trivedi, Sanchit / Kottapalli, Pratibha / Darnell, Daniel / McNeely, Suzanne / Olsen, Scott R / Schultz-Cherry, Stacey /
    Estepp, Jeremie H / McGargill, Maureen A / Wolf, Joshua / Thomas, Paul G

    Nature immunology

    2022  Volume 23, Issue 5, Page(s) 781–790

    Abstract: Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens ...

    Abstract Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7
    MeSH term(s) CD8-Positive T-Lymphocytes ; COVID-19 ; Humans ; Phenotype ; Receptors, Antigen, T-Cell/genetics ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/genetics ; Vaccines, Synthetic ; mRNA Vaccines
    Chemical Substances Receptors, Antigen, T-Cell ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic ; mRNA Vaccines ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-04-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-022-01184-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5294: Show issues Location:
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    Zs.MG 42: Show issues

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  6. Article: High-Risk

    Sandulache, Vlad C / Michikawa, Chieko / Kataria, Pranav / Gleber-Netto, Frederico O / Bell, Diana / Trivedi, Sanchit / Rao, Xiayu / Wang, Jing / Zhao, Mei / Jasser, Samar / Myers, Jeffrey N / Pickering, Curtis R

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2018  Volume 24, Issue 7, Page(s) 1727–1733

    Abstract: Purpose: ...

    Abstract Purpose:
    MeSH term(s) Carcinoma, Squamous Cell/genetics ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/genetics ; Lymphatic Metastasis/pathology ; Male ; Mouth/pathology ; Mouth Neoplasms/genetics ; Mutation/genetics ; Prognosis ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics
    Chemical Substances TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2018-01-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-17-0721
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    Zs.A 4223: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  7. Article ; Online: Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma.

    Gleber-Netto, Frederico O / Zhao, Mei / Trivedi, Sanchit / Wang, Jiping / Jasser, Samar / McDowell, Christina / Kadara, Humam / Zhang, Jiexin / Wang, Jing / William, William N / Lee, J Jack / Nguyen, Minh Ly / Pai, Sara I / Walline, Heather M / Shin, Dong M / Ferris, Robert L / Carey, Thomas E / Myers, Jeffrey N / Pickering, Curtis R

    Cancer

    2017  Volume 124, Issue 1, Page(s) 84–94

    Abstract: Background: Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those ... ...

    Abstract Background: Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC.
    Methods: The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non-HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups.
    Results: HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53.
    Conclusions: HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94. © 2017 American Cancer Society.
    MeSH term(s) Adult ; Aged ; Cadherins/genetics ; Carcinoma, Squamous Cell/complications ; Carcinoma, Squamous Cell/genetics ; Case-Control Studies ; Caspase 8/genetics ; Class I Phosphatidylinositol 3-Kinases/genetics ; Cyclin D1/genetics ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/genetics ; ErbB Receptors/genetics ; F-Box-WD Repeat-Containing Protein 7/genetics ; Female ; HIV Infections/complications ; HLA-A Antigens/genetics ; Head and Neck Neoplasms/complications ; Head and Neck Neoplasms/genetics ; Histone Methyltransferases ; Humans ; In Situ Hybridization ; Intracellular Signaling Peptides and Proteins/genetics ; Kelch-Like ECH-Associated Protein 1/genetics ; LIM Domain Proteins/genetics ; Male ; Middle Aged ; NF-E2-Related Factor 2/genetics ; Nuclear Proteins/genetics ; Papillomaviridae/genetics ; Papillomavirus Infections/complications ; Protein-Serine-Threonine Kinases/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; Receptor, Notch1/genetics ; Receptor, Notch2/genetics ; Receptor, Transforming Growth Factor-beta Type II ; Receptors, Transforming Growth Factor beta/genetics ; Squamous Cell Carcinoma of Head and Neck ; Transcription Factors/genetics ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Proteins/genetics
    Chemical Substances AJUBA protein, human ; CCND1 protein, human ; CDKN2A protein, human ; Cadherins ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18 ; F-Box-WD Repeat-Containing Protein 7 ; FAT1 protein, human ; FBXW7 protein, human ; HLA-A Antigens ; Intracellular Signaling Peptides and Proteins ; KEAP1 protein, human ; Kelch-Like ECH-Associated Protein 1 ; LIM Domain Proteins ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; NOTCH1 protein, human ; NOTCH2 protein, human ; Nuclear Proteins ; Receptor, Notch1 ; Receptor, Notch2 ; Receptors, Transforming Growth Factor beta ; TP53 protein, human ; TP63 protein, human ; Transcription Factors ; Tumor Suppressor Protein p53 ; Tumor Suppressor Proteins ; Cyclin D1 (136601-57-5) ; Histone Methyltransferases (EC 2.1.1.-) ; NSD1 protein, human (EC 2.1.1.43) ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; CASP8 protein, human (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-) ; HRAS protein, human (EC 3.6.5.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2017-10-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.31063
    Database MEDical Literature Analysis and Retrieval System OnLINE

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