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101.
Chu GH Gu M Cassel JA Belanger S Stabley GJ DeHaven RN Conway-James N Koblish M Little PJ DeHaven-Hudkins DL Dolle RE 《Bioorganic & medicinal chemistry letters》2006,16(3):645-648
A novel series of phenylamino acetamide derivatives was synthesized. These amides were shown to be potent and selective kappa opioid receptor agonists. 相似文献
102.
Jason D. Gillman Ashley Tetlow Katherine Hagely Jeffery G. Boersma Andrea Cardinal Istvan Rajcan Kristin Bilyeu 《Molecular breeding : new strategies in plant improvement》2014,34(2):447-455
The fatty acid composition of vegetable oil is becoming increasingly critical for its ultimate functionality and utilization in foods and industrial products. Partial chemical hydrogenation of soybean [Glycine max (L.) Merr.] oil increases oxidative stability and shelf life but also results in the introduction of trans fats as an unavoidable byproduct. Due to mandatory labeling of consumer products containing trans fats, conventional soybean oil has lost the ability to deliver the most appropriate economical functionality and oxidative stability, particularly for baking applications. Genetic improvement of the fatty acid profile of soybean oil is one method of meeting these new requirements for oil feedstocks. In this report, we characterized three mutant genetic loci controlling the saturated fatty acid content of soybean oil: two genes additively reduce palmitic acid content (fap1 and fap3-ug), and one gene independently elevates stearic acid content (fas). We identified a new null allele of fap3-ug/GmFATB1A (derived from line ELLP2) present in line RG3. The splicing defect mutation in a beta-ketoacyl-[acyl-carrier-protein] synthase III candidate gene located in the region mapped to fap1, derived originally from ethyl methane sulphonate mutant line C1726 (Cardinal et al. in Theor Appl Genet 127:97–111, 2014), was also present in line RG3. We also utilized the elevated stearic acid line RG7, which has previously been shown to contain novel mutant fas/SACPD-C alleles encoding stearoyl-acyl carrier protein desaturase (Boersma et al. in Crop Sci 52:1736–1742, 2012). Molecular marker assays have been developed to track these causative mutations and understand their contributions to seed oil fatty acid profiles in a recombinant inbred line population segregating for fap1, fap3-ug, and fas alleles. 相似文献
103.
Matthew W. VanBrocklin James P. Robinson Kristin J. Lastwika Joseph D. Khoury Sheri L. Holmen 《Pigment cell & melanoma research》2010,23(4):531-541
We have developed a somatic cell gene delivery mouse model of melanoma that allows for the rapid validation of genetic alterations identified in this disease. A major advantage of this system is the ability to model the multi-step process of carcinogenesis in immune-competent mice without the generation and cross breeding of multiple strains. We have used this model to evaluate the role of RAS isoforms in melanoma initiation in the context of conditional Ink4a/Arf loss. Mice expressing the tumor virus A (TVA) receptor specifically in melanocytes under control of the dopachrome tautomerase (DCT) promoter were crossed to Ink4a/Arflox/lox mice and newborn DCT-TVA/Ink4a/Arflox/lox mice were injected with retroviruses containing activated KRAS, NRAS and/or Cre-recombinase. No mice injected with viruses containing KRAS and Cre or NRAS alone developed tumors; however, more than one-third of DCT-TVA/Ink4a/Arflox/lox mice injected with NRAS and Cre viruses developed melanoma and two-thirds developed melanoma when NRAS and Cre expression was linked. 相似文献
104.
Choi YH Della-Fera MA Li C Hartzell DL Little DE Kuhar MJ Baile CA 《Regulatory peptides》2004,121(1-3):155-162
Because of connections between CART peptide containing neurons and the sympathetic nervous system (SNS) and the possible role of the SNS in leptin-induced adipose apoptosis, CART may act as a downstream effector of leptin-induced adipose apoptosis. Male Sprague-Dawley rats received continuous intracerebroventricular (i.c.v.) infusion for 4 days of either artificial cerebrospinal fluid (aCSF, 12 microl/day), leptin (15 microg/day), or CART55-102 at 2.4 microg/day (CART2.4) or 9.6 microg/day (CART9.6). Food intake (FI) was decreased 10.8% for CART2.4, 41.9% for CART9.6 and 33.4% for leptin (p<0.05). CART9.6 and leptin reduced meal size and meal number. Body weight (BW) was reduced by CART9.6 (14.6%) and leptin (11.6%) (p<0.05), but not by CART2.4. CART9.6 and CART2.4, but not leptin, caused hypothermia, and CART9.6 inhibited physical activity (p<0.05). Epididymal, inguinal and retroperitoneal fat pad weights were reduced (p<0.05) by both CART treatments and leptin; CART9.6 also reduced gastrocnemius muscle weight (18.1%, p<0.05). Leptin, but not CART, increased serum free fatty acid concentrations by 31.1% (p<0.05) and increased adipose apoptosis by 48% (p<0.05). These data show that although leptin and CART55-102 have some similar actions, CART55-102 is probably not a mediator for leptin-induced adipose apoptosis in the brain. 相似文献
105.
Timo Kanzleiter Michaela Rath Sven W. Görgens Jørgen Jensen Daniel S. Tangen Anders J. Kolnes Kristoffer J. Kolnes Sindre Lee Jürgen Eckel Annette Schürmann Kristin Eckardt 《Biochemical and biophysical research communications》2014
The health-promoting effects of regular exercise are well known, and myokines may mediate some of these effects. The small leucine-rich proteoglycan decorin has been described as a myokine for some time. However, its regulation and impact on skeletal muscle has not been investigated in detail. In this study, we report decorin to be differentially expressed and released in response to muscle contraction using different approaches. Decorin is released from contracting human myotubes, and circulating decorin levels are increased in response to acute resistance exercise in humans. Moreover, decorin expression in skeletal muscle is increased in humans and mice after chronic training. Because decorin directly binds myostatin, a potent inhibitor of muscle growth, we investigated a potential function of decorin in the regulation of skeletal muscle growth. In vivo overexpression of decorin in murine skeletal muscle promoted expression of the pro-myogenic factor Mighty, which is negatively regulated by myostatin. We also found Myod1 and follistatin to be increased in response to decorin overexpression. Moreover, muscle-specific ubiquitin ligases atrogin1 and MuRF1, which are involved in atrophic pathways, were reduced by decorin overexpression. In summary, our findings suggest that decorin secreted from myotubes in response to exercise is involved in the regulation of muscle hypertrophy and hence could play a role in exercise-related restructuring processes of skeletal muscle. 相似文献
106.
Anat Melamed Aviva D. Witkover Daniel J. Laydon Rachael Brown Kristin Ladell Kelly Miners Aileen G. Rowan Niall Gormley David A. Price Graham P. Taylor Edward L. Murphy Charles R. M. Bangham 《PLoS pathogens》2014,10(3)
Human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) both cause lifelong persistent infections, but differ in their clinical outcomes. HTLV-1 infection causes a chronic or acute T-lymphocytic malignancy in up to 5% of infected individuals whereas HTLV-2 has not been unequivocally linked to a T-cell malignancy. Virus-driven clonal proliferation of infected cells both in vitro and in vivo has been demonstrated in HTLV-1 infection. However, T-cell clonality in HTLV-2 infection has not been rigorously characterized. In this study we used a high-throughput approach in conjunction with flow cytometric sorting to identify and quantify HTLV-2-infected T-cell clones in 28 individuals with natural infection. We show that while genome-wide integration site preferences in vivo were similar to those found in HTLV-1 infection, expansion of HTLV-2-infected clones did not demonstrate the same significant association with the genomic environment of the integrated provirus. The proviral load in HTLV-2 is almost confined to CD8+ T-cells and is composed of a small number of often highly expanded clones. The HTLV-2 load correlated significantly with the degree of dispersion of the clone frequency distribution, which was highly stable over ∼8 years. These results suggest that there are significant differences in the selection forces that control the clonal expansion of virus-infected cells in HTLV-1 and HTLV-2 infection. In addition, our data demonstrate that strong virus-driven proliferation per se does not predispose to malignant transformation in oncoretroviral infections. 相似文献
107.
Somatic mutations in cancer patients are inherently sparse and potentially high dimensional. Cancer patients may share the same set of deregulated biological processes perturbed by different sets of somatically mutated genes. Therefore, when assessing the associations between somatic mutations and clinical outcomes, gene-by-gene analysis is often under-powered because it does not capture the complex disease mechanisms shared across cancer patients. Rather than testing genes one by one, an intuitive approach is to aggregate somatic mutation data of multiple genes to assess their joint association with clinical outcomes. The challenge is how to aggregate such information. Building on the optimal transport method, we propose a principled approach to estimate the similarity of somatic mutation profiles of multiple genes between tumor samples, while accounting for gene–gene similarities defined by gene annotations or empirical mutational patterns. Using such similarities, we can assess the associations between somatic mutations and clinical outcomes by kernel regression. We have applied our method to analyze somatic mutation data of 17 cancer types and identified at least five cancer types, where somatic mutations are associated with overall survival, progression-free interval, or cytolytic activity. 相似文献
108.
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110.
Burch ML Osman N Getachew R Al-Aryahi S Poronnik P Zheng W Hill MA Little PJ 《The international journal of biochemistry & cell biology》2012,44(5):722-727
The current paradigm of G protein coupled receptor signaling involves a classical pathway being the activation of phospholipase C and the generation of 1,4,5-inositol trisphosphate, signaling through β-arrestin scaffold molecules and the transactivation of tyrosine kinase growth factor receptors. Transactivation greatly expands the range of signaling pathways and responses attributable to the receptor. Recently it has been revealed that G protein coupled receptor agonists can also transactivate the serine/threonine kinase cell surface receptor for transforming growth factor-β (Alk5). This leads to the generation of carboxyl terminal phosphorylated Smad2 which is the immediate downstream product of the activated Alk5. Thus, the current paradigm of G protein coupled signaling can be expanded to include the transactivation of the serine kinase receptor Alk5. These insights expand the possibilities for outcomes of therapeutically targeting GPCRs where more substantive and prolonged actions such as the synthesis of extracellular matrix may be affected. 相似文献