1,724,562 research outputs found
Scaled biotic disruption during early Eocene global warming events
Get PDFLate Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are natural experiments ideal for exploring the relationship between carbon cycle perturbations, climate change and biotic response. Here we quantify marine biotic variability through three million years of the early Eocene that include five hyperthermals, utilizing a method that allows us to integrate the records of different plankton groups through scenarios ranging from background to major extinction events. Our long time-series calcareous nannoplankton record indicates a scaling of biotic disruption to climate change associated with the amount of carbon released during the various hyperthermals. Critically, only the three largest hyperthermals, the Paleocene–Eocene Thermal Maximum (PETM), Eocene Thermal Maximum 2 (ETM2) and the I1 event, show above-background variance, suggesting that the magnitude of carbon input and associated climate change needs to surpass a threshold value to cause significant biotic disruption.<br/
Abstract 4679: Betulinic acid inhibits deubiquitinases to increase the degradation of pro-survival proteins and enhance prostate cancer-specific apoptosis
No full textAbstract
Inhibition of the ubiquitin proteasome (UPS) pathway is a valid anti-cancer target but the alternative strategy to increase activity in order to degrade pro-survival proteins is much less developed. Betulinic acid (BA) is a naturally occurring small molecule with multiple mechanisms for increasing apoptosis in cancer cells, making it an attractive anti-prostate cancer agent. There is evidence that BA can activate the UPS pathway to degrade multiple pro-survival proteins such as androgen receptor (AR), but the mechanism is not clear. Our western blot data in prostate cancer (PC) cells indicates that 10 μM BA decreases the levels of multiple pro-survival proteins including AR, cyclins, and cyclin-dependent kinases. Inhibition of the UPS pathway with 1 μM MG132 blocks the BA-mediated decrease of AR and AKT proteins and lowers cell death, suggesting a dependence on the UPS pathway. In TRAMP transgenic mice, BA treatment (10 mg/kg) inhibits tumor growth, increases apoptosis, decreases angiogenesis and proliferation, and lowers AR and cyclin D1 protein levels (immunohistochemistry) without toxic side effects to normal tissues. However, BA does not increase UPS activity (Proteasome-Glo Chymotrypsin-like Cell-Based Assay; Promega) in LNCaP PC cells suggesting an alternative mechanism for increasing protein degradation. BA-mediated inhibition of deubiquitinase (DUB) activity, as determined by DUB-Glo Protease Assay (Promega) and DUB labeling with HA-ubiquitin vinyl sulfone, results in the accumulation of poly-ubiquitinated (Ub) proteins that are recognized by the UPS pathway and degraded. The cyclin D1 T286A mutant that cannot be degraded by the UPS pathway is resistant to BA-mediated degradation. In non-cancer BJ fibroblast, however, BA does not inhibit DUB activity nor increases total poly-Ub proteins and this is associated with no effect on cell death. Our data suggests that BA-mediated inhibition of DUBs and induction of apoptotic cell death specifically in PC but not in non-cancer cells will provide an effective non-toxic and clinically selective agent.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4679. doi:1538-7445.AM2012-467
Linked collectors and determiners for: FUEL - Herbário da Universidade Estadual de Londrina.
No full textNatural history specimen data linked to collectors and determiners held within, "FUEL - Herbário da Universidade Estadual de Londrina". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b">https://bionomia.net/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b">https://gbif.org/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b</a>. Formatted as a Frictionless Data package
Linked collectors and determiners for: Linyphiid spiders collected by V. Mahnert in Kenya, with the description of a new genus and two new species (Arachnida: Araneae).
No full textNatural history specimen data linked to collectors and determiners held within, "Linyphiid spiders collected by V. Mahnert in Kenya, with the description of a new genus and two new species (Arachnida: Araneae)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/6efaf7ca-370f-4679-aacb-d77c4232059a">https://bionomia.net/dataset/6efaf7ca-370f-4679-aacb-d77c4232059a</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/6efaf7ca-370f-4679-aacb-d77c4232059a">https://gbif.org/dataset/6efaf7ca-370f-4679-aacb-d77c4232059a</a>. Formatted as a Frictionless Data package
Linked collectors and determiners for: FUEL - Herbário da Universidade Estadual de Londrina.
No full textNatural history specimen data linked to collectors and determiners held within, "FUEL - Herbário da Universidade Estadual de Londrina". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b">https://bionomia.net/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b">https://gbif.org/dataset/78dcee36-b0a2-4679-802d-bc0b5016518b</a>. Formatted as a Frictionless Data package
Linked collectors and determiners for: Diagnostics and updated catalogue of Acalyptris Meyrick, the second largest genus of Nepticulidae (Lepidoptera) in the Americas.
No full textNatural history specimen data linked to collectors and determiners held within, "Diagnostics and updated catalogue of Acalyptris Meyrick, the second largest genus of Nepticulidae (Lepidoptera) in the Americas". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/e15a5b4c-9199-4679-afdf-1a08dd1cd564">https://bionomia.net/dataset/e15a5b4c-9199-4679-afdf-1a08dd1cd564</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/e15a5b4c-9199-4679-afdf-1a08dd1cd564">https://gbif.org/dataset/e15a5b4c-9199-4679-afdf-1a08dd1cd564</a>. Formatted as a Frictionless Data package
Prudent rahonament, que fa "Pepo Canelles" a les dametes de "escalera abaxo", demostrantles los perchuins de les seues modes. Segona part.
Get PDFHay un ejemplar encuadernado con: Romance nuevo y relación curiosa en que se descubren los estraordinarios [sic] medios de que se valen los criados para hacer la sisa, y el modo particular con que en sus reuniones murmuran de sus amos (Carreres/4679)Tít. tomado de la p. [1
Diálogo entre el tabernero y la tabernera
Get PDFHay un ejemplar encuadernado con: Romance nuevo y relación curiosa en que se descubren los estraordinarios [sic] medios de que se valen los criados para hacer la sisa, y el modo particular con que en sus reuniones murmuran de sus amos (Carreres/4679
Diálogo entre Venancio y Bartola sobre la colasa
Get PDFHay un ejemplar encuadernado con: Romance nuevo y relación curiosa en que se descubren los estraordinarios [sic] medios de que se valen los criados para hacer la sisa, y el modo particular con que en sus reuniones murmuran de sus amos (Carreres/4679
Primera parte de los varios lances que acaecieron a una dama llamada Rosaura y a su amante.
Get PDFHay un ejemplar encuadernado con: Romance nuevo y relación curiosa en que se descubren los estraordinarios [sic] medios de que se valen los criados para hacer la sisa, y el modo particular con que en sus reuniones murmuran de sus amos (Carreres/4679)Tít. tomado de la p. [1
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