GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Vol. 379, No. 6637 ( 2023-03-17)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6637 ( 2023-03-17)
    Abstract: Autoimmune diseases such as ankylosing spondylitis (AS) can be caused by emerging neoantigens that break immune tolerance in humans. Posttranslational modifications (PTMs) have been shown to be a critical mechanism that alters protein structure and function to generate neoantigens and induce subsequent autoimmune responses. Previous studies have confirmed that citrulline-modified peptides are a critical source of neoantigens in rheumatoid arthritis. However, the molecular mechanisms underlying neoantigen formation and pathogenic autoreactive responses for AS are largely unknown. There is an urgent need to develop a systematic approach to profiling the possible PTMs in patients with AS and identifying AS-associated PTMs responsible for autoreactive neoantigen production to better understand the etiology of autoimmune diseases. RATIONALE AS has been suggested to be an autoimmune disease because of its clear correlation with certain major histocompatibility complex (MHC) alleles, including HLA-B27. Neoantigens have been hypothesized to induce an aberrant immune response, leading to pathogenic autoreactive T cell responses and autoantibody generation in AS. Here, we developed a systematic open search approach to identify any possible amino acid residues and derivatives in the proteins that are different from the genomic coding sequences. We then applied this information to identify AS-related neoantigens with PTMs within a possible pool of PTM autoantigens and elucidate the pathogenesis of AS. RESULTS An open search approach was applied to identify any possible amino acid derivatives across the proteome of patients with AS. This approach generated a large set of noncoded amino acids representing the mass differences between the coded amino acids and actual residues. Among these, an amino acid derivative with a delta mass of 72.021 showed the greatest increase in patients with AS and resulted from a PTM called cysteine carboxyethylation. In vitro and in vivo experiments demonstrated that carboxyethylation at a cysteine residue of integrin αIIb [ITGA2B (CD41)] was catalyzed by cystathionine beta synthase (CBS) in a process that required 3-hydroxypropionic acid (3-HPA), a metabolite commonly released from gut microbes. Cysteine carboxyethylation induced the lysosomal degradation of ITGA2B and produced neoantigens that triggered MHC-II–dependent CD4 + T cell responses. Fluorescence polarization and enzyme-linked immunosorbent assay (ELISA) demonstrated that the identified carboxyethylated peptide (ITGA2B-ceC96) specifically interacted with HLA-DRA*01/HLA-DRB1*04 and was associated with autoantibody production and T cell responses in HLA-DRB1*04 patients. Additional in vitro assays showed that the neoantigen ITGA2B-ceC96 correlated with 3-HPA levels but was independent of CBS expression. HLA-DRB1 haplotype, the carboxyethylated peptide, specific autoantibodies, and 3-HPA levels in patients with AS all correlated with one another. 3-HPA–treated and ITGA2B-ceC96–immunized HLA-DR4 transgenic mice developed colitis and vertebral bone erosion. Thus, cysteine carboxyethylation induced by the metabolite 3-HPA generates a neoantigen that appears to be critical for autoimmune responses in patients with AS. CONCLUSION Cysteine carboxyethylation is an in vivo protein modification induced by the metabolite 3-HPA, which is commonly released from gut microbes. Carboxyethylated ITGA2B then induces autoantibody production and autoimmune response in AS. Our work provides a systematic workflow to identify differentially modified proteins that are important for neoantigen production in immune disorders. This approach furthers our understanding of AS pathogenesis and may aid in the development of neoantigen-based diagnosis and treatment for AS and other autoimmune diseases. Metabolite-induced cysteine carboxyethylation provokes HLA-restricted autoimmune responses in ankylosing spondylitis. 3-HPA, which is commonly obtained from food and gut microbes, induces carboxyethylation of cysteine residues in integrin αIIb (ITGA2B). Cysteine carboxyethylation requires CBS, and carboxyethylated ITGA2B (ITGA2B-ceC96) peptides are recruited to the HLA-DR4 complex and thereby stimulate CD4 + T cell responses closely related to AS.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abg2482
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    “Perfect” designer chromosome V and behavior of a ring derivative
    American Association for the Advancement of Science (AAAS) ; 2017
    In:  Science Vol. 355, No. 6329 ( 2017-03-10)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 355, No. 6329 ( 2017-03-10)
    Abstract: Perfect matching of an assembled physical sequence to a specified designed sequence is crucial to verify design principles in genome synthesis. We designed and de novo synthesized 536,024–base pair chromosome synV in the “Build-A-Genome China” course. We corrected an initial isolate of synV to perfectly match the designed sequence using integrative cotransformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)–mediated editing in 22 steps; synV strains exhibit high fitness under a variety of culture conditions, compared with that of wild-type V strains. A ring synV derivative was constructed, which is fully functional in Saccharomyces cerevisiae under all conditions tested and exhibits lower spore viability during meiosis. Ring synV chromosome can extends Sc2.0 design principles and provides a model with which to study genomic rearrangement, ring chromosome evolution, and human ring chromosome disorders.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaf4704
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Dissecting yield-associated loci in super hybrid rice by resequencing recombinant inbred lines and improving parental genome sequences
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 35 ( 2013-08-27), p. 14492-14497
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 35 ( 2013-08-27), p. 14492-14497
    Abstract: The growing world population and shrinkage of arable land demand yield improvement of rice, one of the most important staple crops. To elucidate the genetic basis of yield and uncover its associated loci in rice, we resequenced the core recombinant inbred lines of Liang–You–Pei–Jiu , the widely cultivated super hybrid rice, and constructed a high-resolution linkage map. We detected 43 yield-associated quantitative trait loci, of which 20 are unique. Based on the high-density physical map, the genome sequences of paternal variety 93–11 and maternal cultivar PA64s of Liang–You–Pei–Jiu were significantly improved. The large recombinant inbred line population combined with plentiful high-quality single nucleotide polymorphisms and insertions/deletions between parental genomes allowed us to fine-map two quantitative trait loci, qSN8 and qSPB1 , and to identify days to heading8 and lax panicle1 as candidate genes, respectively. The quantitative trait locus qSN8 was further confirmed to be days to heading8 by a complementation test. Our study provided an ideal platform for molecular breeding by targeting and dissecting yield-associated loci in rice.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1306579110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 49 ( 2015-12-08), p. 15084-15089
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 49 ( 2015-12-08), p. 15084-15089
    Abstract: Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic. Among the most highly enriched proteins in this set are those in the glycolysis pathway, including the rate-limiting enzyme in glycolysis, hexokinase-1. Detailed biochemical and metabolomics analyses of the highly homologous hexokinase-2 (HK2), which is overexpressed in many cancers, revealed significant inhibition by arsenic. Furthermore, overexpression of HK2 rescued cells from arsenic-induced apoptosis. Our results thus strongly implicate glycolysis, and HK2 in particular, as a key target of arsenic. Moreover, the arsenic-binding proteins identified in this work are expected to serve as a valuable resource for the development of synergistic antitumor therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1521316112
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Molecular basis of differential receptor usage for naturally occurring CD55-binding and -nonbinding coxsackievirus B3 strains
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 4 ( 2022-01-25)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 4 ( 2022-01-25)
    Abstract: Receptor usage defines cell tropism and contributes to cell entry and infection. Coxsackievirus B (CVB) engages coxsackievirus and adenovirus receptor (CAR), and selectively utilizes the decay-accelerating factor (DAF; CD55) to infect cells. However, the differential receptor usage mechanism for CVB remains elusive. This study identified VP3-234 residues (234Q/N/V/D/E) as critical population selection determinants during CVB3 virus evolution, contributing to diverse binding affinities to CD55. Cryoelectron microscopy (cryo-EM) structures of CD55-binding/nonbinding isolates and their complexes with CD55 or CAR were obtained under both neutral and acidic conditions, and the molecular mechanism of VP3-234 residues determining CD55 affinity/specificity for naturally occurring CVB3 strains was elucidated. Structural and biochemical studies in vitro revealed the dynamic entry process of CVB3 and the function of the uncoating receptor CAR with different pH preferences. This work provides detailed insight into the molecular mechanism of CVB infection and contributes to an in-depth understanding of enterovirus attachment receptor usage.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2118590119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Agonistic analog of growth hormone–releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 47 ( 2021-11-23)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 47 ( 2021-11-23)
    Abstract: Ischemic stroke can induce neurogenesis. However, most stroke-generated newborn neurons cannot survive. It has been shown that MR-409, a potent synthetic agonistic analog of growth hormone–releasing hormone (GHRH), can protect against some life-threatening pathological conditions by promoting cell proliferation and survival. The present study shows that long-term treatment with MR-409 (5 or 10 μg/mouse/d) by subcutaneous (s.c.) injection significantly reduces the mortality, ischemic insult, and hippocampal atrophy, and improves neurological functional recovery in mice operated on for transient middle cerebral artery occlusion (tMCAO). Besides, MR-409 can stimulate endogenous neurogenesis and improve the tMCAO-induced loss of neuroplasticity. MR-409 also enhances the proliferation and inhibits apoptosis of neural stem cells treated with oxygen and glucose deprivation–reperfusion. The neuroprotective effects of MR-409 are closely related to the activation of AKT/CREB and BDNF/TrkB pathways. In conclusion, the present study demonstrates that GHRH agonist MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis in cerebral ischemic mice.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2109600118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury
    Society for Neuroscience ; 2020
    In:  The Journal of Neuroscience Vol. 40, No. 13 ( 2020-03-25), p. 2644-2662
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 40, No. 13 ( 2020-03-25), p. 2644-2662
    Abstract: Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) of yap in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27 Kip1 mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27 Kip1 pathway positively regulates astrocytic proliferation after SCI. SIGNIFICANCE STATEMENT Glial scars play critical roles in neuronal regeneration of CNS injury diseases, such as spinal cord injury (SCI). Here, we provide evidence for the function of Yes-associated protein (YAP) in the formation of glial scars after SCI through regulation of astrocyte proliferation. As a downstream of bFGF (which is upregulated after SCI), YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27 Kip1 mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI. These results suggest that the bFGF-RhoA-YAP-p27 Kip1 axis for the formation of glial scars may be a potential therapeutic strategy for SCI patients.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.2229-19.2020
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2020
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Activation of GPCRs modulates quantal size in chromaffin cells through Gβγ and PKC
    Springer Science and Business Media LLC ; 2005
    In:  Nature Neuroscience Vol. 8, No. 9 ( 2005-9), p. 1160-1168
    Details
    In: Nature Neuroscience, Springer Science and Business Media LLC, Vol. 8, No. 9 ( 2005-9), p. 1160-1168
    Type of Medium: Online Resource
    ISSN: 1097-6256 , 1546-1726
    URL: Article
    DOI: 10.1038/nn1529
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2005
    detail.hit.zdb_id: 1494955-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Quantum metric nonlinear Hall effect in a topological antiferromagnetic heterostructure
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Vol. 381, No. 6654 ( 2023-07-14), p. 181-186
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 381, No. 6654 ( 2023-07-14), p. 181-186
    Abstract: A nonlinear response was observed in a structure consisting of even-layered MnBi 2 Te 4 interfaced with black phosphorus.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.adf1506
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Complementary Interactions between Command-Like Interneurons that Function to Activate and Specify Motor Programs
    Society for Neuroscience ; 2014
    In:  The Journal of Neuroscience Vol. 34, No. 19 ( 2014-05-07), p. 6510-6521
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 34, No. 19 ( 2014-05-07), p. 6510-6521
    Abstract: Motor activity is often initiated by a population of command-like interneurons. Command-like interneurons that reliably drive programs have received the most attention, so little is known about how less reliable command-like interneurons may contribute to program generation. We study two electrically coupled interneurons, cerebral-buccal interneuron-2 (CBI-2) and CBI-11, which activate feeding motor programs in the mollusk Aplysia californica . Earlier work indicated that, in rested preparations, CBI-2, a powerful activator of programs, can trigger ingestive and egestive programs. CBI-2 reliably generated ingestive patterns only when it was repeatedly stimulated. The ability of CBI-2 to trigger motor activity has been attributed to the two program-promoting peptides it contains, FCAP and CP2. Here, we show that CBI-11 differs from CBI-2 in that it contains FCAP but not CP2. Furthermore, it is weak in its ability to drive programs. On its own, CBI-11 is therefore less effective as a program activator. When it is successful, however, CBI-11 is an effective specifier of motor activity; that is, it drives mostly ingestive programs. Importantly, we found that CBI-2 and CBI-11 complement each other's actions. First, prestimulation of CBI-2 enhanced the ability of CBI-11 to drive programs. This effect appears to be partly mediated by CP2. Second, coactivation of CBI-11 with CBI-2 makes CBI-2 programs immediately ingestive. This effect may be mediated by specific actions that CBI-11 exerts on pattern-generating interneurons. Therefore, different classes of command-like neurons in a motor network may make distinct, but potentially complementary, contributions as either activators or specifiers of motor activity.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.5094-13.2014
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2014
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...