GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 3 ( 2023-01-17)
    Abstract: There is an urgent need to develop novel drugs to reduce the mortality from severe infectious diseases with the emergence of new pathogens, including Coronavirus disease 2019 (COVID-19). Although current drugs effectively suppress the proliferation of pathogens, immune cell activation, and inflammatory cytokine functions, they cannot completely reduce mortality from severe infections and sepsis. In this study, we focused on the endothelial cell-specific protein, Roundabout 4 (Robo4), which suppresses vascular permeability by stabilizing endothelial cells, and investigated whether enhanced Robo4 expression could be a novel therapeutic strategy against severe infectious diseases. Endothelial-specific overexpression of Robo4 suppresses vascular permeability and reduces mortality in lipopolysaccharide (LPS)-treated mice. Screening of small molecules that regulate Robo4 expression and subsequent analysis revealed that two competitive small mothers against decapentaplegic (SMAD) signaling pathways, activin receptor-like kinase 5 (ALK5)-SMAD2/3 and ALK1-SMAD1/5, positively and negatively regulate Robo4 expression, respectively. An ALK1 inhibitor was found to increase Robo4 expression in mouse lungs, suppress vascular permeability, prevent extravasation of melanoma cells, and decrease mortality in LPS-treated mice. The inhibitor suppressed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced endothelial barrier disruption and decreased mortality in mice infected with SARS-CoV-2. These results indicate that enhancing Robo4 expression is an efficient strategy to suppress vascular permeability and mortality in severe infectious diseases, including COVID-19, and that small molecules that upregulate Robo4 can be potential therapeutic agents against these diseases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    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 ...
  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 10 ( 2000-05-09), p. 5405-5410
    Abstract: Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1; also known as suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative feedback regulator of Janus kinase-STAT signaling. We previously generated mice lacking the SSI-1 gene (SSI-1 −/−) and showed that thymocytes and splenocytes in SSI-1 −/− mice underwent accelerated apoptosis. In this paper, we show that murine embryonic fibroblasts lacking the SSI-1 gene are more sensitive than their littermate controls to tumor necrosis factor-α (TNF-α)-induced cell death. In addition, L929 cells forced to express SSI-1 (L929/SSI-1), but not SSI-3 or SOCS-5, are resistant to TNF-α-induced cell death. Furthermore L929/SSI-1 cells treated with TNF-α sustain the activation of p38 mitogen-activated protein (MAP) kinase. In contrast, SSI-1 −/− murine embryonic fibroblasts treated with TNF-α show hardly any activation of p38 MAP kinase. These findings suggest that SSI-1 suppresses TNF-α-induced cell death, which is mediated by p38 MAP kinase signaling.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2000
    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 ...
  • 3
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1998
    In:  Proceedings of the National Academy of Sciences Vol. 95, No. 22 ( 1998-10-27), p. 13130-13134
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 95, No. 22 ( 1998-10-27), p. 13130-13134
    Abstract: Cytokine-inducible protein SSI-1 [signal transducers and activators of transcription (STAT)-induced STAT inhibitor 1, also referred to as SOCS-1 (suppressor of cytokine signaling 1) or JAB (Janus kinase-binding protein)] negatively regulates cytokine receptor signaling by inhibition of JAK kinases. The SSI family of proteins includes eight members that are structurally characterized by an SH2 domain and a C-terminal conserved region that we have called the SC-motif. In this study, we investigated the roles of these domains in the function of SSI-1. Results of reporter assays demonstrated that the pre-SH2 domain (24 aa in front of the SH2 domain) and the SH2 domain of SSI-1 were required for the suppression by SSI-1 of interleukin 6 signaling. Coexpression studies of COS7 cells revealed that these domains also were required for inhibition of three JAKs (JAK1, JAK2, and TYK2). Furthermore, deletion of the SH2 domain, but not the pre-SH2 domain, resulted in loss of association of SSI-1 with TYK2. Thus, SSI-1 associates with JAK family kinase via its SH2 domain, and the pre-SH2 domain is required for the function of SSI-1. Deletion of the SC-motif markedly reduced expression of SSI-1 protein in M1 cells, and this reduction was reversed by treatment with proteasome inhibitors, suggesting that this motif is required to protect the SSI-1 molecule from proteolytic degradation. Based on these findings, we concluded that three distinct domains of SSI-1 (the pre-SH2 domain, the SH2 domain, and the SC-motif) cooperate in the suppression of interleukin 6 signaling.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1998
    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 ...
  • 4
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1998
    In:  Proceedings of the National Academy of Sciences Vol. 95, No. 26 ( 1998-12-22), p. 15577-15582
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 95, No. 26 ( 1998-12-22), p. 15577-15582
    Abstract: Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase–signal transducers and activators of transcription (JAK-STAT) signal pathway is an important component of cytokine signaling. We have previously shown that STAT3 induces a molecule designated as SSI-1, which inhibits STAT3 functions. To clarify the physiological roles of SSI-1 in vivo , we generated, here, mice lacking SSI-1. These SSI-1−/− mice displayed growth retardation and died within 3 weeks after birth. Lymphocytes in the thymus and spleen of the SSI-1−/− mice exhibited accelerated apoptosis with aging, and their number was 20–25% of that in SSI-1+/+ mice at 10 days of age. However, the differentiation of lymphocytes lacking SSI-1 appeared to be normal. Among various pro- and anti-apoptotic molecules examined, an up-regulation of Bax was found in lymphocytes of the spleen and thymus of SSI-1−/− mice. These findings suggest that SSI-1 prevents apoptosis by inhibiting the expression of Bax.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1998
    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 ...
  • 5
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24)
    Abstract: The Hayabusa2 spacecraft made two landings on the asteroid (162173) Ryugu in 2019, during which it collected samples of the surface material. Those samples were delivered to Earth in December 2020. The colors, shapes, and morphologies of the returned samples are consistent with those observed on Ryugu by Hayabusa2, indicating that they are representative of the asteroid. Laboratory analysis of the samples can determine the chemical composition of Ryugu and provide information on its formation and history. RATIONALE We used laboratory analysis to inform the following questions: (i) What are the elemental abundances of Ryugu? (ii) What are the isotopic compositions of Ryugu? (iii) Does Ryugu consist of primary materials produced in the disk from which the Solar System formed or of secondary materials produced in the asteroid or on a parent asteroid? (iv) When were Ryugu’s constituent materials formed? (v) What, if any, relationship does Ryugu have with meteorites? RESULTS We quantified the abundances of 66 elements in the Ryugu samples: H, Li, Be, C, O, Na, Mg, Al, Si, P, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Cd, In, Sn, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Ta, W, Tl, Pb, Bi, Th, and U. There is a slight variation in chemical compositions between samples from the first and second touchdown sites, but the variations could be due to heterogeneity among the samples that were analyzed. The Cr-Ti isotopes and abundance of volatile elements are similar to those of carbonaceous meteorites in the CI (Ivuna-like) chondrite group. The Ryugu samples consist of the minerals magnetite, breunnerite, dolomite, and pyrrhotite as grains embedded in a matrix composed of serpentine and saponite. This mineral assemblage and the texture are also similar to those of CI meteorites. Anhydrous silicates are almost absent, which indicates extensive liquid water–rock reactions (aqueous alteration) in the material. We conclude that the samples mainly consist of secondary materials that were formed by aqueous alteration in a parent body, from which Ryugu later formed. The oxygen isotopes in the bulk Ryugu samples are also similar to those in CI chondrites. We used oxygen isotope thermometry to determine the temperature at which the dolomite and magnetite precipitated from an aqueous solution, which we found to be 37° ± 10°C. The 53 Mn- 53 Cr isotopes date the aqueous alteration at 5.2 − 0.7 + 0.8 million (statistical) or 5.2 − 2.1 + 1.6 million (systematic) years after the birth of the Solar System. Phyllosilicate minerals are the main host of water in the Ryugu samples. The amount of structural water in Ryugu is similar to that in CI chondrites, but interlayer water is largely absent in Ryugu, which suggests a loss of interlayer water to space. The abundance of structural water and results from dehydration experiments indicate that the Ryugu samples remained below ~100°C from the time of aqueous alteration until the present. We ascribe the removal of interlayer water to a combination of impact heating, solar heating, solar wind irradiation, and long-term exposure to the ultrahigh vacuum of space. The loss of interlayer water from phyllosilicates could be responsible for the comet-like activity of some carbonaceous asteroids and the ejection of solid material from the surface of asteroid Bennu. CONCLUSION The Ryugu samples are most similar to CI chondrite meteorites but are more chemically pristine. The chemical composition of the Ryugu samples is a closer match to the Sun’s photosphere than to the composition of any other natural samples studied in laboratories. CI chondrites appear to have been modified on Earth or during atmospheric entry. Such modification of CI chondrites could have included the alteration of the structures of organics and phyllosilicates, the adsorption of terrestrial water, and the formation of sulfates and ferrihydrites. Those issues do not affect the Ryugu samples. Those modifications might have changed the albedo, porosity, and density of the CI chondrites, causing the observed differences between CI meteorites, Hayabusa2 measurements of Ryugu’s surface, and the Ryugu samples returned to Earth. Representative petrography of a Ryugu sample, designated C0002-C1001. Colors indicate elemental abundances determined from x-ray spectroscopy. Lines of iron, sulfur, and calcium are shown as red, green, and blue (RGB) color channels in that order. Combinations of these elements are assigned to specific minerals, as indicated in the legend. All visible minerals were formed by aqueous alteration on Ryugu’s parent body.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    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 ...
  • 6
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 3 ( 2021-01-19)
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    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 ...
  • 7
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2008
    In:  Science Vol. 322, No. 5900 ( 2008-10-17), p. 413-417
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 322, No. 5900 ( 2008-10-17), p. 413-417
    Abstract: The ability to incorporate individual atoms in a surface following predetermined arrangements may bring future atom-based technological enterprises closer to reality. Here, we report the assembling of complex atomic patterns at room temperature by the vertical interchange of atoms between the tip apex of an atomic force microscope and a semiconductor surface. At variance with previous methods, these manipulations were produced by exploring the repulsive part of the short-range chemical interaction between the closest tip-surface atoms. By using first-principles calculations, we clarified the basic mechanisms behind the vertical interchange of atoms, characterizing the key atomistic processes involved and estimating the magnitude of the energy barriers between the relevant atomic configurations that leads to these manipulations.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2008
    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 ...
  • 8
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 34 ( 2020-08-25), p. 20696-20705
    Abstract: Regulatory T (Treg) cells, expressing CD25 (interleukin-2 receptor α chain) and Foxp3 transcription factor, maintain immunological self-tolerance and suppress various immune responses. Here we report a feature of skin Treg cells expanded by ultraviolet B (UVB) exposure. We found that skin Treg cells possessing a healing function are expanded by UVB exposure with the expression of an endogenous opioid precursor, proenkephalin (PENK). Upon UVB exposure, skin Treg cells were expanded with a unique TCR repertoire. Also, they highly expressed a distinctive set of genes enriched in “wound healing involved in inflammatory responses” and the “neuropeptide signaling pathway,” as indicated by the high expression of Penk. We found that not only was PENK expression at the protein level detected in the UVB-expanded skin Treg (UVB-skin Treg) cells, but that a PENK-derived neuropeptide, methionine enkephalin (Met-ENK), from Treg cells promoted the outgrowth of epidermal keratinocytes in an ex vivo skin explant assay. Notably, UVB-skin Treg cells also promoted wound healing in an in vivo wound closure assay. In addition, UVB-skin Treg cells produced amphiregulin (AREG), which plays a key role in Treg-mediated tissue repair. Identification of a unique function of PENK + UVB-skin Treg cells provides a mechanism for maintaining skin homeostasis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    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 ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...