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71.
Kevin K.-C. Liu Bruce A. Lefker Mark A. Dombroski Phoebe Chiang Peter Cornelius Terrell A. Patterson Yuan Zeng Stephanie Santucci Elizabeth Tomlinson Colleen P. Gibbons Ravi Marala Janice A. Brown Jimmy X. Kong Eunsun Lee Wendy Werner Zane Wenzel Craig Giragossian Hou Chen Steven B. Coffey 《Bioorganic & medicinal chemistry letters》2010,20(7):2365-2369
Brain-penetrable proline amides were developed as 5HT2c agonists with more than 1000-fold binding selectivity against 5HT2b receptor. After medicinal chemistry optimization and SAR studies, orally active proline amides with robust efficacy in a rodent food intake inhibition model were uncovered. 相似文献
72.
Muscle ring finger protein-1 inhibits PKC{epsilon} activation and prevents cardiomyocyte hypertrophy 总被引:2,自引:0,他引:2
Arya R Kedar V Hwang JR McDonough H Li HH Taylor J Patterson C 《The Journal of cell biology》2004,167(6):1147-1159
Much effort has focused on characterizing the signal transduction cascades that are associated with cardiac hypertrophy. In spite of this, we still know little about the mechanisms that inhibit hypertrophic growth. We define a novel anti-hypertrophic signaling pathway regulated by muscle ring finger protein-1 (MURF1) that inhibits the agonist-stimulated PKC-mediated signaling response in neonatal rat ventricular myocytes. MURF1 interacts with receptor for activated protein kinase C (RACK1) and colocalizes with RACK1 after activation with phenylephrine or PMA. Coincident with this agonist-stimulated interaction, MURF1 blocks PKCepsilon translocation to focal adhesions, which is a critical event in the hypertrophic signaling cascade. MURF1 inhibits focal adhesion formation, and the activity of downstream effector ERK1/2 is also inhibited in the presence of MURF1. MURF1 inhibits phenylephrine-induced (but not IGF-1-induced) increases in cell size. These findings establish that MURF1 is a key regulator of the PKC-dependent hypertrophic response and can blunt cardiomyocyte hypertrophy, which may have important implications in the pathophysiology of clinical cardiac hypertrophy. 相似文献
73.
Background
This paper describes a microarray study including data quality control, data analysis and the analysis of the mechanism of toxicity (MOT) induced by 1-methyl-4-phenylpyridinium (MPP+) in a rat adrenal pheochromocytoma cell line (PC12 cells) using bioinformatics tools. MPP+ depletes dopamine content and elicits cell death in PC12 cells. However, the mechanism of MPP+-induced neurotoxicity is still unclear.Results
In this study, Agilent rat oligo 22K microarrays were used to examine alterations in gene expression of PC12 cells after 500 μM MPP+ treatment. Relative gene expression of control and treated cells represented by spot intensities on the array chips was analyzed using bioinformatics tools. Raw data from each array were input into the NCTR ArrayTrack database, and normalized using a Lowess normalization method. Data quality was monitored in ArrayTrack. The means of the averaged log ratio of the paired samples were used to identify the fold changes of gene expression in PC12 cells after MPP+ treatment. Our data showed that 106 genes and ESTs (Expressed Sequence Tags) were changed 2-fold and above with MPP+ treatment; among these, 75 genes had gene symbols and 59 genes had known functions according to the Agilent gene Refguide and ArrayTrack-linked gene library. The mechanism of MPP+-induced toxicity in PC12 cells was analyzed based on their genes functions, biological process, pathways and previous published literatures.Conclusion
Multiple pathways were suggested to be involved in the mechanism of MPP+-induced toxicity, including oxidative stress, DNA and protein damage, cell cycling arrest, and apoptosis.74.
Marlys Hammond David G. Washburn Tram H. Hoang Sharada Manns James S. Frazee Hiroko Nakamura Jaclyn R. Patterson Walter Trizna Charlene Wu Leonard M. Azzarano Rakesh Nagilla Melanie Nord Rebecca Trejo Martha S. Head Baoguang Zhao Angela M. Smallwood Kendra Hightower Nicholas J. Laping Christine G. Schnackenberg Scott K. Thompson 《Bioorganic & medicinal chemistry letters》2009,19(15):4441-4445
The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. 相似文献
75.
Bat species diversity and distribution in a disturbed regime at the Lake Bogoria National Reserve,Kenya 下载免费PDF全文
David B. Wechuli Paul W. Webala Bruce D. Patterson Raphael S. Ochieng 《African Journal of Ecology》2017,55(4):465-476
Human population growth drives intrusion and progressive conversion of natural habitats for agriculture. We evaluated human impacts on bat species diversity and distribution among four vegetation types in and around Lake Bogoria National Reserve between November 2012 and July 2013. Plants were surveyed using the Braun–Blanquet cover/abundance method, whereas bats were sampled using standard mist nets erected on poles at ground level. Floristic similarity analysis revealed three broad vegetation assemblages, namely riverine vegetation, farmland and Acacia woodland/Acacia–Commiphora woodland. Two hundred and 33 bats representing eleven species in eleven genera and seven families were recorded. These were Epomophorus minimus, Rhinolophus landeri, Hipposideros caffer, Cardioderma cor, Lavia frons, Nycteris hispida, Chaerephon pumilus, Mops condylurus, Neoromicia capensis, Scotoecus hirundo and Scotophilus dinganii. Species richness estimators indicated that sampling for bats at ground level was exhaustive. Bat species richness and diversity were highest in the more structurally complex Acacia woodland compared to more homogenous farmlands where we recorded only common and generalist species that often occur in open habitats. The higher bat species richness and diversity in the Acacia woodland as compared to farmland underscore the importance of remnant natural savannah woodlands in the conservation of bats and other elements of biodiversity . 相似文献
76.
Jonathan Gottschall Rachel Berkey Mitchell Cawson Carly Drown Matthew Fleischner Melissa Glotzbecker Kimberly Kernan Tyler Magnan Kate Muse Celeste Ogburn Stephen Patterson Christopher Skeels Stephanie St. Joseph Shawna Weeks Alison Welsh Erin Welch 《Human nature (Hawthorne, N.Y.)》2003,14(4):365-382
Literary scholars are generally suspicious of the concept of universals: there are presently no candidates for literary universals
that a high proportion of literary scholars would accept as valid. This paper reports results from a content analysis of patterns
of characterization in folktales from 48 culture areas, aimed at identifying patterns of characterization that apply across
regions of the world and levels of cultural complexity. The search for these patterns was guided by evolutionary theory and
the findings are consistent with previous research on patterns of altruism, sex differences in mate preferences, sex differences
in reproductive strategy, and differing emphases on male and female physical attractiveness. World literature, especially
originally oral literature, represents a vast and neglected repository of information that researchers can use to more precisely
map the contours of human nature.
Jonathan Gottschall received his Ph.D. in English from Binghamton University and now teaches at St. Lawrence University in
Canton, New York. His research focuses on integrating Darwinian approaches to human behavior and psychology with literary
studies. The other authors are undergraduate students at St. Lawrence University. 相似文献
77.
Thomas Patterson 《Primates; journal of primatology》1979,20(3):341-354
A group of captive pygmy chimpanzees (Pan paniscus) was studied in the San Diego Zoological Gardens. The behavior patterns that these animals exhibit are described. Each of
these behavior patterns is compared to those described for wild and captive common chimpanzees (P. troglodytes). Differences in behavior between these two species are attributed to specialization of the pygmy chimpanzee to a rain forest
habitat and to a monogamous social system. 相似文献
78.
79.
McConnachie SH Cook KV Patterson DA Gilmour KM Hinch SG Farrell AP Cooke SJ 《Hormones and behavior》2012,62(1):67-76
Life-history theory predicts that stress responses should be muted to maximize reproductive fitness. Yet, the relationship between stress and reproduction for semelparous salmon is unusual because successfully spawning individuals have elevated plasma cortisol levels. To tease apart the effects of high baseline cortisol levels and stress-induced elevation of cortisol titers, we determined how varying degrees of cortisol elevation (i.e., acute and chronic) affected behavior, reproductive physiology, and reproductive success of adult female pink salmon (Oncorhynchus gorbuscha) relative to different states of ovulation (i.e., ripe and unripe). Exhaustive exercise and air exposure were applied as acute stressors to manipulate plasma cortisol in salmon either confined to a behavioral arena or free-swimming in a spawning channel. Cortisol (eliciting a cortisol elevation to levels similar to those in post-spawn female salmon) and metyrapone (a corticosteroid synthesis inhibitor) implants were also used to chemically manipulate plasma cortisol. Cortisol implants elevated plasma cortisol, and impaired reproductive success; cortisol-treated fish released fewer eggs and died sooner than fish in other treatment groups. In contrast, acute stressors elevated plasma cortisol and the metyrapone implant suppressed plasma cortisol, but neither treatment significantly altered reproductive success, behavior, or physiology. Our results suggest that acute stressors do not influence behavior or reproductive outcome when experienced upon arrival at spawning grounds. Thus, certain critical aspects of salmonid reproduction can become refractory to various stressful conditions on spawning grounds. However, there is a limit to the ability of these fish to tolerate elevated cortisol levels as revealed by experimental elevation of cortisol. 相似文献
80.
Fichtner M Lee E Tomlinson E Scott D Cornelius P Patterson TA Carpino PA 《Bioorganic & medicinal chemistry letters》2012,22(8):2738-2743
A novel series of spirocyclic derivatives was synthesized and evaluated as NPY Y5R antagonists for the treatment of obesity. Cis and trans analogs 7a and 8a were equipotent in a Y5R binding assay (K(i)'s ≤ 1 nM) and displayed good stability in human and rat liver microsome preparations. Compound 7a failed to demonstrate weight loss activity in a diet-induced obese (DIO) rat model at unbound drug levels in the brain that exceeded the Y5R K(i) value by 25-fold over a 24-h time-period. 相似文献