Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
  • American Association for the Advancement of Science (AAAS)  (14)
  • Nature Publishing Group (NPG)  (8)
  • The American Association for Cancer Research (AACR)  (5)
  • 1
    Publication Date: 2018-12-11
    Description: To determine the effects of diet, rats were placed on a standard diet (4% fat) or on a modified Western (high-fat diet, HFD) diet (21% fat) at 43 days of age (DOA) and administered methylnitrosourea (MNU) at 50 DOA. Rats were administered effective (tamoxifen, vorozole, and Targretin) or ineffective (metformin and Lipitor) chemopreventive agents either by daily gavage or in the diet beginning at 57 DOA and continuing until sacrifice (190 DOA). Latency period of the tumors was determined by palpation, and multiplicity and cancer weights per rat were determined at final sacrifice. Rats on the HFD versus standard diet had: (i) a 6% increase in final body weights; (ii) significant decreases in tumor latency; and (iii) significant increases in final tumor multiplicity and average tumor weight. Tamoxifen, vorozole, and Targretin were highly effective preventive agents, whereas Lipitor and metformin were ineffective in rats on either diet. Serum was collected at 78 DOA and at sacrifice (190 DOA), and metabolomics were determined to identify the metabolite changes due to diets and effective agents. Rats given the HFD had increased levels of saturated free fatty acids (including myristate) and decreased levels of 2-aminooctanoate. Furthermore, rats on the HFD diet had increased levels of 2-aminobutyrate and decreases in glycine markers previously identified as indicators of prediabetes. Targretin increased long-chain glycophospholipids (e.g., oleyl-linoleoyl-glycerophosphocholine) and decreased primary bile acids (e.g., taurocholate). Tamoxifen increased palmitoyl-linoleoyl-glycophosphocholine and decreased stearoyl-arachidonyl glycophosphocholine. Finally, increased levels of methylated nucleotides (5-methylcytidine) and decreased levels of urea cycle metabolites (N-acetylcitrulline) were associated with the presence of mammary cancers.
    Print ISSN: 1940-6207
    Electronic ISSN: 1940-6215
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2018-03-29
    Description: The Earth-Moon system likely formed as a result of a collision between two large planetary objects. Debate about their relative masses, the impact energy involved, and the extent of isotopic homogenization continues. We present the results of a high-precision oxygen isotope study of an extensive suite of lunar and terrestrial samples. We demonstrate that lunar rocks and terrestrial basalts show a 3 to 4 ppm (parts per million), statistically resolvable, difference in 17 O. Taking aubrite meteorites as a candidate impactor material, we show that the giant impact scenario involved nearly complete mixing between the target and impactor. Alternatively, the degree of similarity between the 17 O values of the impactor and the proto-Earth must have been significantly closer than that between Earth and aubrites. If the Earth-Moon system evolved from an initially highly vaporized and isotopically homogenized state, as indicated by recent dynamical models, then the terrestrial basalt-lunar oxygen isotope difference detected by our study may be a reflection of post–giant impact additions to Earth. On the basis of this assumption, our data indicate that post–giant impact additions to Earth could have contributed between 5 and 30% of Earth’s water, depending on global water estimates. Consequently, our data indicate that the bulk of Earth’s water was accreted before the giant impact and not later, as often proposed.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2018-03-06
    Description: Tumor-selective delivery of cytotoxic agents in the form of antibody–drug conjugates (ADCs) is now a clinically validated approach for cancer treatment. In an attempt to improve the clinical success rate of ADCs, emphasis has been recently placed on the use of DNA–cross-linking pyrrolobenzodiazepine compounds as the payload. Despite promising early clinical results with this class of ADCs, doses achievable have been low due to systemic toxicity. Here, we describe the development of a new class of potent DNA-interacting agents wherein changing the mechanism of action from a cross-linker to a DNA alkylator improves the tolerability of the ADC. ADCs containing the DNA alkylator displayed similar in vitro potency, but improved bystander killing and in vivo efficacy, compared with those of the cross-linker. Thus, the improved in vivo tolerability and antitumor activity achieved in rodent models with ADCs of the novel DNA alkylator could provide an efficacious, yet safer option for cancer treatment. Mol Cancer Ther; 17(3); 650–60. ©2018 AACR .
    Print ISSN: 1535-7163
    Electronic ISSN: 1538-8514
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2018-10-16
    Description: Purpose: Inflammatory bowel disease–associated colorectal cancers (IBD-CRC) are associated with a higher mortality than sporadic colorectal cancers. The poorly defined molecular pathogenesis of IBD-CRCs limits development of effective prevention, detection, and treatment strategies. We aimed to identify biomarkers using whole-exome sequencing of IBD-CRCs to guide individualized management. Experimental Design: Whole-exome sequencing was performed on 34 formalin-fixed paraffin-embedded primary IBD-CRCs and 31 matched normal lymph nodes. Computational methods were used to identify somatic point mutations, small insertions and deletions, mutational signatures, and somatic copy number alterations. Mismatch repair status was examined. Results: Hypermutation was observed in 27% of IBD-CRCs. All hypermutated cancers were from the proximal colon; all but one of the cancers with hypermutation had defective mismatch repair or somatic mutations in the proofreading domain of DNA POLE . Hypermutated IBD-CRCs had increased numbers of predicted neo-epitopes, which could be exploited using immunotherapy. We identified six distinct mutation signatures in IBD-CRCs, three of which corresponded to known mechanisms of mutagenesis. Driver genes were also identified. Conclusions: IBD-CRCs should be evaluated for hypermutation and defective mismatch repair to identify patients with a higher neo-epitope load who may benefit from immunotherapies. Prospective trials are required to determine whether IHC to detect loss of MLH1 expression in dysplastic colonic tissue could identify patients at increased risk of developing IBD-CRC. We identified mutations in genes in IBD-CRCs with hypermutation that might be targeted therapeutically. These approaches would complement and individualize surveillance and treatment programs. Clin Cancer Res; 24(20); 5133–42. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    facet.materialart.
    facet.materialart.
    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Description: We document rapid and abrupt clearings of large portions of the subtropical marine low cloud deck that have implications for the global radiation balance and climate sensitivity. Over the southeast Atlantic, large areas of stratocumulus are quickly eroded, yielding partial or complete clearing along sharp transitions hundreds to thousands of kilometers in length that move westward at 8 to 12 meters per second and travel as far as 1000+ kilometers from the African coast. The westward-moving cloudiness reductions have an annual peak in occurrence in the period from April through June. The cloud erosion boundaries reduce cloud at 10-kilometer scale in less than 15 minutes, move approximately perpendicular to the mean flow, and are often accompanied by small-scale wave features. Observations suggest that the cloud erosion is caused by atmospheric gravity waves.
    Keywords: Geochemistry, Geophysics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2018-09-05
    Description: Purpose: Previous studies have indicated an important role for pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis. Here we aimed to confirm the role of PHIP copy number in successive stages of melanoma progression. Experimental Design: PHIP copy number was examined using FISH in three independent cohorts by recording the percentage of cells harboring ≥3 copies of PHIP . The impact of PHIP copy number on survival was assessed using Cox regression analysis. The enrichment of PHIP was assessed in various molecular melanoma subtypes. PHIP expression was analyzed in The Cancer Genome Atlas (TCGA) melanoma cohort. Results: Elevated PHIP copy number was significantly predictive of reduced distant metastasis-free survival (DMFS) and disease-specific survival (DSS), and increased prevalence of ulceration in primary melanoma (cohort No. 1). By multivariate analysis, PHIP FISH scores were independently predictive of DMFS and DSS. PHIP copy number was enriched in metastatic melanomas harboring mutant NRAS or expressing PTEN protein (cohort No. 2). PHIP copy number was significantly elevated in metastatic melanomas when compared with matched primary tumors from the same patient (cohort No. 3). Several of these associations were replicated using TCGA cohort analysis. Conclusions: These results underscore the important role of PHIP copy-number elevation in melanoma progression, and identify molecular subtypes of melanoma in which PHIP is enriched. Finally, as elevated PHIP copy number appears to be selected for during the progression of primary to metastatic melanoma, these results confirm PHIP as a promising therapeutic target for melanoma. Clin Cancer Res; 24(17); 4119–25. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2011-01-15
    Description: Long-term population viability of Fraser River sockeye salmon (Oncorhynchus nerka) is threatened by unusually high levels of mortality as they swim to their spawning areas before they spawn. Functional genomic studies on biopsied gill tissue from tagged wild adults that were tracked through ocean and river environments revealed physiological profiles predictive of successful migration and spawning. We identified a common genomic profile that was correlated with survival in each study. In ocean-tagged fish, a mortality-related genomic signature was associated with a 13.5-fold greater chance of dying en route. In river-tagged fish, the same genomic signature was associated with a 50% increase in mortality before reaching the spawning grounds in one of three stocks tested. At the spawning grounds, the same signature was associated with 3.7-fold greater odds of dying without spawning. Functional analysis raises the possibility that the mortality-related signature reflects a viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Kristina M -- Li, Shaorong -- Kaukinen, Karia H -- Ginther, Norma -- Hammill, Edd -- Curtis, Janelle M R -- Patterson, David A -- Sierocinski, Thomas -- Donnison, Louise -- Pavlidis, Paul -- Hinch, Scott G -- Hruska, Kimberly A -- Cooke, Steven J -- English, Karl K -- Farrell, Anthony P -- New York, N.Y. -- Science. 2011 Jan 14;331(6014):214-7. doi: 10.1126/science.1196901.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics Section, Pacific Biological Station, 3190 Hammond Bay Road, Fisheries and Oceans Canada, Nanaimo, BC V9T 6N7, Canada. kristi.miller@dfo-mpo.gc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21233388" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Migration ; Animals ; Canada ; Female ; Fish Diseases/genetics/immunology/mortality ; *Gene Expression ; *Gene Expression Profiling ; Genome ; Gills ; Male ; Mortality ; Oligonucleotide Array Sequence Analysis ; Pacific Ocean ; Population Dynamics ; Principal Component Analysis ; Remote Sensing Technology ; *Reproduction ; Rivers ; Salmon/*genetics/*physiology ; Stress, Physiological ; Survival Analysis ; Virus Diseases/genetics/immunology/mortality/veterinary
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2014-07-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marrero, Juan Carlos Antuna -- Miller, M Meghan -- Mattioli, Glen -- Feaux, Karl -- Anthes, Richard -- Braun, John -- Wang, Guoquan -- Robock, Alan -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):278. doi: 10.1126/science.345.6194.278-a. Epub 2014 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Grupo de Optica Atmosferica de Camaguey, Centro Meteorologico de Camaguey, Instituto de Meteorologia de la Republica de Cuba, Cuba. ; UNAVCO, Boulder, CO 80301, USA. ; UNAVCO, Boulder, CO 80301, USA. mattioli@unavco.org. ; University Corporation for Atmospheric Research, Boulder, CO 80305, USA. ; Department of Earth and Atmospheric Sciences, University of Houston, TX 77004, USA. ; Department of Environmental Sciences, Rutgers University, New Brunswick, NJ 08901, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035480" target="_blank"〉PubMed〈/a〉
    Keywords: *International Cooperation ; Science/*trends
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2015-11-28
    Description: Solar photoconversion in semiconductors is driven by charge separation at the interface of the semiconductor and contacting layers. Here we demonstrate that time-resolved photoinduced reflectance from a semiconductor captures interfacial carrier dynamics. We applied this transient photoreflectance method to study charge transfer at p-type gallium-indium phosphide (p-GaInP2) interfaces critically important to solar-driven water splitting. We monitored the formation and decay of transient electric fields that form upon photoexcitation within bare p-GaInP2, p-GaInP2/platinum (Pt), and p-GaInP2/amorphous titania (TiO2) interfaces. The data show that a field at both the p-GaInP2/Pt and p-GaInP2/TiO2 interfaces drives charge separation. Additionally, the charge recombination rate at the p-GaInP2/TiO2 interface is greatly reduced owing to its p-n nature, compared with the Schottky nature of the p-GaInP2/Pt interface.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Ye -- Gu, Jing -- Young, James L -- Miller, Elisa M -- Turner, John A -- Neale, Nathan R -- Beard, Matthew C -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1061-5. doi: 10.1126/science.aad3459.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Renewable Energy Laboratory, Chemistry and Nanoscience Center, Golden, CO, 80401, USA. ye.yang@nrel.gov matt.beard@nrel.gov. ; National Renewable Energy Laboratory, Chemistry and Nanoscience Center, Golden, CO, 80401, USA. ; National Renewable Energy Laboratory, Chemistry and Nanoscience Center, Golden, CO, 80401, USA. Material Science and Engineering Program, University of Colorado, Boulder, CO, 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612947" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2014-05-07
    Description: In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123747/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123747/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katsimpardi, Lida -- Litterman, Nadia K -- Schein, Pamela A -- Miller, Christine M -- Loffredo, Francesco S -- Wojtkiewicz, Gregory R -- Chen, John W -- Lee, Richard T -- Wagers, Amy J -- Rubin, Lee L -- 1DP2 OD004345/OD/NIH HHS/ -- 1R01 AG033053/AG/NIA NIH HHS/ -- 1R01 AG040019/AG/NIA NIH HHS/ -- 5U01 HL100402/HL/NHLBI NIH HHS/ -- DP2 OD004345/OD/NIH HHS/ -- R01 AG032977/AG/NIA NIH HHS/ -- R01 AG033053/AG/NIA NIH HHS/ -- R01 AG040019/AG/NIA NIH HHS/ -- R01 NS070835/NS/NINDS NIH HHS/ -- R01 NS072167/NS/NINDS NIH HHS/ -- R01NS070835/NS/NINDS NIH HHS/ -- R01NS072167/NS/NINDS NIH HHS/ -- U01 HL100402/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 9;344(6184):630-4. doi: 10.1126/science.1251141. Epub 2014 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24797482" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*drug effects ; Animals ; Bone Morphogenetic Proteins/*administration & dosage/blood/physiology ; Brain/blood supply/*drug effects ; Cerebrovascular Circulation/*drug effects ; Cognition/drug effects ; Endothelium, Vascular/cytology/drug effects ; Growth Differentiation Factors/*administration & dosage/blood/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/cytology/*drug effects ; Neurogenesis/*drug effects ; Olfactory Bulb/cytology/drug effects ; Parabiosis ; Recombinant Proteins/administration & dosage ; *Rejuvenation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...