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排序方式: 共有1347条查询结果,搜索用时 125 毫秒
31.
Holly M. Nguyen Nazanin Ruppender Xiaotun Zhang Lisha G. Brown Ted S. Gross Colm Morrissey Roman Gulati Robert L. Vessella Frauke Schimmoller Dana T. Aftab Eva Corey 《PloS one》2013,8(10)
Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease. 相似文献
32.
Birds rarely hybridize: A citizen science approach to estimating rates of hybridization in the wild*
Nicholas M. Justyn Corey T. Callaghan Geoffrey E. Hill 《Evolution; international journal of organic evolution》2020,74(6):1216-1223
The rate of hybridization among taxa is a central consideration in any discussion of speciation, but rates of hybridization are difficult to estimate in most wild populations of animals. We used a successful citizen science dataset, eBird, to estimate the rates of hybridization for wild birds in the United States. We calculated the frequency at which hybrid individuals belonging to different species, families, and orders of birds were observed. Between 1 January 2010 and 31 December 2018, a total of 334,770,194 species records were reported to eBird within the United States. Of this total, 212,875 or 0.064% were reported as hybrids. This estimate is higher than the rate of hybridization (0.00167%) reported by Mayr based on impressions from a career studying museum specimens. However, if the 10 most influential hybrid species are removed from the eBird dataset, the rate of hybridization decreases substantially to about 0.009%. We conclude that the rate of hybridization for individuals in most bird species is extremely low, even though the potential for birds to produce fertile offspring through hybrid crosses is high. These findings indicate that there is strong prezygotic selection working in most avian species. 相似文献
33.
Laura K. Povlich Jae Cheol Cho Michelle K. Leach Joseph M. Corey Jinsang Kim David C. Martin 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Conjugated polymers have been developed as effective materials for interfacing prosthetic device electrodes with neural tissue. Recent focus has been on the development of conjugated polymers that contain biological components in order to improve the tissue response upon implantation of these electrodes.Methods
Carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) monomer was synthesized in order to covalently bind peptides to the surface of conjugated polymer films. EDOTacid was copolymerized with EDOT monomer to form stable, electrically conductive copolymer films referred to as PEDOT-PEDOTacid. The peptide GGGGRGDS was bound to PEDOT-PEDOTacid to create peptide functionalized PEDOT films.Results
The PEDOT-PEDOTacid-peptide films increased the adhesion of primary rat motor neurons between 3 and 9 times higher than controls, thus demonstrating that the peptide maintained its biological activity.Conclusions
The EDOT-acid monomer can be used to create functionalized PEDOT-PEDOTacid copolymer films that can have controlled bioactivity.General Significance
PEDOT-PEDOTacid-peptide films have the potential to control the behavior of neurons and vastly improve the performance of implanted electrodes. This article is part of a Special Issue entitled Organic Bioelectronics—Novel Applications in Biomedicine. 相似文献34.
Corey Bragg Sam McKechnie Jamie Newman David Fletcher Henrik Moller Darren Scott 《New Zealand journal of zoology.》2013,40(3):275-289
Abstract Sooty shearwater (Puffinus griesus, titi) abundance, harvest levels and chick mass were monitored repeatedly on Putauhinu Island, south‐west of Rakiura (Stewart Island) between 1997 and 2005. Putauhinu is the second largest of the Titi Islands and has a relatively high density of chicks distributed over most of the island, so it supports what is likely the second‐largest population of sooty shearwaters in the Rakiura region (after Taukihepa, Big South Cape Island). Rakiura Maori harvested chicks from five “manu” (family birding areas) that covered 56% of the 128.4 ha of breeding colony of the island. Chick density was lower on the unharvested area in the interior of the island than on harvested areas. Burrow entrance density was higher where there was more ground cover (mainly fern) vegetation, but these areas had lower burrow occupancy, so overall chick density was similar at different levels of ground cover. Twenty‐six harvesters present on Putauhinu in 2005 took 31 280 chicks in total, equivalent to 8.4% (95% CI = 6.6–12%) of the available chicks on the entire island. Seasonal variation in total chicks harvested (CV 15–22%) was not related to chick abundance or mass. Refuges, including impenetrable patches of vegetated ground within manu, the unharvested centre of the island, and even nearby unharvested islands, will ameliorate localised impacts of harvest if density‐dependent immigration is operating. 相似文献
35.
Alaina A. Brinley Corey A. Theriot Mayra Nelman‐Gonzalez Brian Crucian Raymond P. Stowe Alan D.T. Barrett Duane L. Pierson 《Journal of cellular biochemistry》2013,114(3):616-624
Epstein–Barr virus (EBV) is the causative agent of mononucleosis and is also associated with several malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, among others. EBV reactivates during spaceflight, with EBV shedding in saliva increasing to levels ten times those observed pre‐and post‐flight. Although stress has been shown to increase reactivation of EBV, other factors such as radiation and microgravity have been hypothesized to contribute to reactivation in space. We used a modeled spaceflight environment to evaluate the influence of radiation and microgravity on EBV reactivation. BJAB (EBV‐negative) and Raji (EBV‐positive) cell lines were assessed for viability/apoptosis, viral antigen and reactive oxygen species expression, and DNA damage and repair. EBV‐infected cells did not experience decreased viability and increased apoptosis due to modeled spaceflight, whereas an EBV‐negative cell line did, suggesting that EBV infection provided protection against apoptosis and cell death. Radiation was the major contributor to EBV ZEBRA upregulation. Combining modeled microgravity and radiation increased DNA damage and reactive oxygen species while modeled microgravity alone decreased DNA repair in Raji cells. Additionally, EBV‐infected cells had increased DNA damage compared to EBV‐negative cells. Since EBV‐infected cells do not undergo apoptosis as readily as uninfected cells, it is possible that virus‐infected cells in EBV seropositive individuals may have an increased risk to accumulate DNA damage during spaceflight. More studies are warranted to investigate this possibility. J. Cell. Biochem. 114: 616–624, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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37.
Pingfang Song Stephen S. Rekow Corey‐Ayne Singleton Harmanjatinder S. Sekhon Gregory A. Dissen Minerva Zhou Barbara Campling Jon Lindstrom Eliot R. Spindel 《Journal of neurochemistry》2013,126(4):451-461
Synthesis of acetylcholine (ACh) by non‐neuronal cells is now well established and plays diverse physiologic roles. In neurons, the Na+‐dependent, high affinity choline transporter (CHT1) is absolutely required for ACh synthesis. In contrast, some non‐neuronal cells synthesize ACh in the absence of CHT1 indicating a fundamental difference in ACh synthesis compared to neurons. The aim of this study was to identify choline transporters, other than CHT1, that play a role in non‐neuronal ACh synthesis. ACh synthesis was studied in lung and colon cancer cell lines focusing on the choline transporter‐like proteins, a five gene family choline‐transporter like protein (CTL)1–5. Supporting a role for CTLs in choline transport in lung cancer cells, choline transport was Na+‐independent and CTL1–5 were expressed in all cells examined. CTL1, 2, and 5 were expressed at highest levels and knockdown of CTL1, 2, and 5 decreased choline transport in H82 lung cancer cells. Knockdowns of CTL1, 2, 3, and 5 had no effect on ACh synthesis in H82 cells. In contrast, knockdown of CTL4 significantly decreased ACh secretion by both lung and colon cancer cells. Conversely, increasing expression of CTL4 increased ACh secretion. These results indicate that CTL4 mediates ACh synthesis in non‐neuronal cell lines and presents a mechanism to target non‐neuronal ACh synthesis without affecting neuronal ACh synthesis. 相似文献
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39.
Corey R. Johnson Suresh Kumar Gorla Mandapati Kavitha Minjia Zhang Xiaoping Liu Boris Striepen Jan R. Mead Gregory D. Cuny Lizbeth Hedstrom 《Bioorganic & medicinal chemistry letters》2013,23(4):1004-1007
Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5′-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure–activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented. 相似文献
40.