GLORIA

GEOMAR Library Ocean Research Information Access

X

Ihre E-Mail wurde erfolgreich gesendet. Bitte prüfen Sie Ihren Maileingang.

Leider ist ein Fehler beim E-Mail-Versand aufgetreten. Bitte versuchen Sie es erneut.

Vorgang fortführen?

Exportieren
Filter
  • Proceedings of the National Academy of Sciences  (105)
  • 1
    Online-Ressource
    Online-Ressource
    Characterization of HPV and host genome interactions in primary head and neck cancers
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 43 ( 2014-10-28), p. 15544-15549
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 43 ( 2014-10-28), p. 15544-15549
    Kurzfassung: Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1416074111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2014
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    Crop pests and predators exhibit inconsistent responses to surrounding landscape composition
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 33 ( 2018-08-14)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 33 ( 2018-08-14)
    Kurzfassung: The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1800042115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2018
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 4 ( 2023-01-24)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 4 ( 2023-01-24)
    Kurzfassung: Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2209964120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2023
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 44 ( 2017-10-31)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 44 ( 2017-10-31)
    Kurzfassung: The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker ( Atg16l1 , Coro1c , Dmxl2 , and Herc1 ), thinner ( Kif21b and Wdr89 ), or absent corpus callosum ( Wdr47 ), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1713625114
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2017
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 5
    Online-Ressource
    Online-Ressource
    An inclusive Research Education Community (iREC): Impact of the SEA-PHAGES program on research outcomes and student learning
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 51 ( 2017-12-19), p. 13531-13536
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 51 ( 2017-12-19), p. 13531-13536
    Kurzfassung: Engaging undergraduate students in scientific research promises substantial benefits, but it is not accessible to all students and is rarely implemented early in college education, when it will have the greatest impact. An inclusive Research Education Community (iREC) provides a centralized scientific and administrative infrastructure enabling engagement of large numbers of students at different types of institutions. The Science Education Alliance–Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) is an iREC that promotes engagement and continued involvement in science among beginning undergraduate students. The SEA-PHAGES students show strong gains correlated with persistence relative to those in traditional laboratory courses regardless of academic, ethnic, gender, and socioeconomic profiles. This persistent involvement in science is reflected in key measures, including project ownership, scientific community values, science identity, and scientific networking.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1718188115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2017
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 6
    Online-Ressource
    Online-Ressource
    Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 41 ( 2007-10-09), p. 16239-16244
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 41 ( 2007-10-09), p. 16239-16244
    Kurzfassung: Activin A is a member of the transforming growth factor-β superfamily, which we have identified as having a role in inflammatory responses. We show that circulating levels of activin increase rapidly after LPS-induced challenge through activation of Toll-like receptor 4 and the key adaptor protein, MyD88. Treatment with the activin-binding protein, follistatin, alters the profiles of TNF, IL-1β, and IL-6 after LPS stimulation, indicating that activin modulates the release of several key proinflammatory cytokines. Further, mice administered one 10-μg dose of follistatin to block activin effects have increased survival after a lethal dose of LPS, and the circulating levels of activin correlate with survival outcome. These findings demonstrate activin A's crucial role in the inflammatory response and show that blocking its actions by the use of follistatin has significant therapeutic potential to reduce the severity of inflammatory diseases.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0705971104
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2007
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 7
    Online-Ressource
    Online-Ressource
    A regulatory toolbox of MiniPromoters to drive selective expression in the brain
    Proceedings of the National Academy of Sciences ; 2010
    In:  Proceedings of the National Academy of Sciences Vol. 107, No. 38 ( 2010-09-21), p. 16589-16594
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 38 ( 2010-09-21), p. 16589-16594
    Kurzfassung: The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination “knockins” in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5′ of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type–specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1009158107
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2010
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 8
    Online-Ressource
    Online-Ressource
    Structural requirements of ligands for the oxysterol liver X receptors LXRα and LXRβ
    Proceedings of the National Academy of Sciences ; 1999
    In:  Proceedings of the National Academy of Sciences Vol. 96, No. 1 ( 1999-01-05), p. 266-271
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 1 ( 1999-01-05), p. 266-271
    Kurzfassung: LXRα and -β are nuclear receptors that regulate the metabolism of several important lipids, including cholesterol and bile acids. Previously, we have proposed that LXRs regulate these pathways through their interaction with specific, naturally occurring oxysterols, including 22( R )-hydroxycholesterol, 24( S )-hydroxycholesterol, and 24( S ),25-epoxycholesterol. Using a ligand binding assay that incorporates scintillation proximity technology to circumvent many of the problems associated with assaying extremely hydrophobic ligands, we now demonstrate that these oxysterols bind directly to LXRs at concentrations that occur in vivo . To characterize further the structural determinants required for potent LXR ligands, we synthesized and tested a series of related compounds for binding to LXRs and activation of transcription. These studies revealed that position-specific monooxidation of the sterol side chain is requisite for LXR high-affinity binding and activation. Enhanced binding and activation can also be achieved through the use of 24-oxo ligands that act as hydrogen bond acceptors in the side chain. In addition, introduction of an oxygen on the sterol B-ring results in a ligand with LXRα-subtype selectivity. These results support the hypothesis that naturally occurring oxysterols are physiological ligands for LXRs and show that a rational, structure-based approach can be used to design potent LXR ligands for pharmacologic use.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.96.1.266
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1999
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 9
    Online-Ressource
    Online-Ressource
    Mechanistic studies of the molybdenum-catalyzed asymmetric alkylation reaction
    Proceedings of the National Academy of Sciences ; 2004
    In:  Proceedings of the National Academy of Sciences Vol. 101, No. 15 ( 2004-04-13), p. 5379-5384
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 15 ( 2004-04-13), p. 5379-5384
    Kurzfassung: Enantiomerically enriched, deuterated branched carbonates ( Z )-( S )-PhCH(OCO 2 Me)-CH = CHD (1-D), ( Z )-( R )-PhCH(OCO 2 Me)CH = CHD (2-D), and linear carbonate ( E )-( S )-PhCH = CHCHD(OCO 2 Me) (3-D) were used as probes in the Mo-catalyzed asymmetric allylic alkylation with sodium dimethyl malonate, catalyzed by ligand-complex 11 derived from the mixed benzamide/picolinamide of ( S , S )-transdiaminocyclohexane and (norbornadiene)Mo(CO) 4 . The results of these studies, along with x-ray crystallography and solution NMR structural analysis of the π-allyl intermediate, conclusively established the reaction proceeded by a retention–retention pathway. This mechanism contrasts with that defined for Pd-catalyzed allylic alkylations, which proceed by an inversion–inversion pathway. A proposed rationale for the retention pathway for nucleophilic substitution involves CO-coordination to form a tri-CO intermediate, followed by complexation with the anion of dimethyl malonate to produce a seven-coordinate intermediate, which reductively eliminates to afford product with retention of configuration.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0306918101
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2004
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
  • 10
    Online-Ressource
    Online-Ressource
    Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 8 ( 2003-04-15), p. 4891-4896
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 8 ( 2003-04-15), p. 4891-4896
    Kurzfassung: Congestive heart failure results in cardiovascular dysfunction and diminished vascular nitric oxide (NO) production. We hypothesized that overexpression of endothelial NO synthase (eNOS) within the endothelium would reduce the extent of contractile dysfunction in a murine model of infarct-induced congestive heart failure. We generated transgenic (TG) mice overexpressing the human eNOS gene. The TG mice displayed significantly enhanced eNOS protein levels and eNOS activity levels (10- to 12-fold greater) in the aorta and the coronary vasculature. Non-TG (NTg) and eNOS TG mice were subjected to permanent left anterior descending coronary artery occlusion and then observed for 1 mo. We assessed cardiac function in vivo by using echocardiography and ultraminiature ventricular pressure catheters. Myocardial infarct size was similar between study groups (≈70% of the risk zone). Survival was increased by 43% in the eNOS TG mice compared with NTg ( P 〈 0.05). Fractional shortening and cardiac output were also significantly ( P 〈 0.05) greater in the eNOS TG than in NTg. Interestingly, pulmonary edema was evident only in NTg mice, and no evidence of pulmonary edema was observed in the eNOS TG mice. Thus, targeted overexpression of the eNOS gene within the vascular endothelium in mice attenuates both cardiac and pulmonary dysfunction and dramatically improves survival during severe congestive heart failure.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0837428100
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2003
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Online-Ressource
Schließen ⊗
Diese Webseite nutzt Cookies und das Analyse-Tool Matomo. Weitere Informationen finden Sie hier...