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951.
Jodie N. Painter Susanne Kaufmann Tracy A. O’Mara Kristine M. Hillman Haran Sivakumaran Hatef Darabi Timothy H.T. Cheng John Pearson Stephen Kazakoff Nicola Waddell Erling A. Hoivik Ellen L. Goode Rodney J. Scott Ian Tomlinson Alison M. Dunning Douglas F. Easton Juliet D. French Helga B. Salvesen Pamela M. Pollock Deborah J. Thompson Amanda B. Spurdle Stacey L. Edwards 《American journal of human genetics》2016,98(6):1159-1169
952.
Brian DeChristopher Soo-Hee Park Linh Vong Derek Bamford Hyun-Hee Cho Rohit Duvadie Allison Fedolak Christopher Hogan Toshiyuki Honda Pramod Pandey Olga Rozhitskaya Liansheng Su Elizabeth Tomlinson Iain Wallace 《Bioorganic & medicinal chemistry letters》2019,29(8):991-994
The relaxin family peptide receptors have been implicated in numerous physiological processes including energy homeostasis, cardiac function, wound healing, and reproductive function. Two family members, RXFP3 and RXFP4, are class A GPCRs with endogenous peptide ligands (relaxin-3 and insulin-like peptide 5 (INSL5), respectively). Polymorphisms in relaxin-3 and RXFP3 have been associated with obesity, diabetes, and hypercholesterolemia. Moreover, central administration of relaxin-3 in rats has been shown to increase food intake, leading to body weight gain. Reported RXFP3 and RXFP4 ligands have been restricted to peptides (both endogenous and synthetic) as well as a low molecular weight positive allosteric modulator requiring a non-endogenous orthosteric ligand. Described here is the discovery of the first potent low molecular weight dual agonists of RXFP3/4. The scaffold identified is competitive with a chimeric relaxin-3/INSL5 peptide for RXFP3 binding, elicits similar downstream signaling as relaxin-3, and increases food intake in rats following acute central administration. This is the first report of small molecule RXFP3/4 agonism. 相似文献
953.
The seroprevalence against heartwater for maure zebus coming from Mali and Mauritania is analysed by indirect ELISA using the major antigenic protein number 1-B (MAP1-B). Sero-epidemiological results realized on maure zebu cattle give a good adequation between the abundance or absence of the vector tick in the two countries for 98% of prevalence in Mali (infected area) and 0% of prevalence in Mauritania (non infected area). 相似文献
954.
Tomlinson S Withers PC Cooper C 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,148(3):645-650
This study compared torpor as a response to food deprivation and low ambient temperature for the introduced house mouse (Mus musculus) and the Australian endemic sandy inland mouse (Pseudomys hermannsburgensis). The house mouse (mass 13.0+/-0.48 g) had a normothermic body temperature of 34.0+/-0.20 degrees C at ambient temperatures from 5 degrees C to 30 degrees C and a basal metabolic rate at 30 degrees C of 2.29+/-0.07 mL O2 g(-1) h(-1). It used torpor with spontaneous arousal at low ambient temperatures; body temperature during torpor was 20.5+/-3.30 degrees C at 15 degrees C. The sandy inland mouse (mass 11.7+/-0.16 g) had a normothermic T(b) of 33.0+/-0.38 degrees C between T(a) of 5 degrees C to 30 degrees C, and a BMR of 1.45+/-0.26 mL O2 g(-1) h(-1) at 30 degrees C. They became hypothermic at low T(a) (T(b) about 17.3 degrees C at T(a)=15 degrees C), but did not spontaneously arouse. They did, however, survive and become normothermic if returned to room temperature (23 degrees C). We conclude that this is hypothermia, not torpor. Consequently, house mice (Subfamily Murinae) appear to use torpor as an energy conservation strategy whereas sandy inland mice (Subfamily Conilurinae) do not, but can survive hypothermia. This may reflect a general phylogenetic pattern of metabolic reduction in rodents. On the other hand, this may be related to differences in the social structure of house mice (solitary) and sandy inland mice (communal). 相似文献
955.
From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis 总被引:1,自引:0,他引:1
Springthorpe B Bailey A Barton P Birkinshaw TN Bonnert RV Brown RC Chapman D Dixon J Guile SD Humphries RG Hunt SF Ince F Ingall AH Kirk IP Leeson PD Leff P Lewis RJ Martin BP McGinnity DF Mortimore MP Paine SW Pairaudeau G Patel A Rigby AJ Riley RJ Teobald BJ Tomlinson W Webborn PJ Willis PA 《Bioorganic & medicinal chemistry letters》2007,17(21):6013-6018
Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y(12) receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae. 相似文献
956.
The MSS51 gene product is required for the translation of the COX1 mRNA in yeast mitochondria 总被引:6,自引:0,他引:6
Estelle Decoster Michel Simon Didier Hatat Gérard Faye 《Molecular & general genetics : MGG》1990,224(1):111-118
Summary The MSS51 gene product has been previously shown to be involved in the splicing of the mitochondrial pre-mRNA of cytochrome oxidase subunit I (COX1). We show here that it is specifically required for the translation of the COX1 mRNA. Furthermore, the paromomycin-resistance mutation (P
inf454
supR
) which affects the 15 S mitoribosomal RNA, interferes, directly or indirectly, with the action of the MSS51 gene product. Possible roles of the MSS51 protein on the excision of COX1 introns are discussed. 相似文献
957.
Horn JW Fisher JB Tomlinson PB Lewis CE Laubengayer K 《American journal of botany》2009,96(8):1462-1486
The unique properties of tree building in Arecaceae strongly constrain their architectural lability. Potentially compensating for this limitation, the extensive diversification of leaf anatomical structure within palms involves many characters whose alternate states may confer disparate mechanical or physiological capabilities. In the context of a recent global palm phylogeny, we analyzed the evolution of 10 such lamina anatomical characters and leaf morphology of 161 genera, conducting parsimony and maximum likelihood ancestral state reconstructions, as well as tests of correlated evolution. Lamina morphology evolves independently from anatomy. Although many characters do optimize as synapomorphic for major clades, anatomical evolution is highly homoplasious. Nevertheless, it is not random: analyses indicate the recurrent evolution of different cohorts of correlated character states. Notable are two surface layer (epidermis and hypodermis) types: (1) a parallel-laminated type of rectangular epidermal cells with sinuous anticlinal walls, with fibers present in the hypodermis and (2) a cross-laminated type of hexagonal cells in both layers. Correlated with the cross-laminated type is a remarkable decrease in the volume fraction of fibers, accompanied by changes in the architecture and sheath cell type of the transverse veins. We discuss these and other major patterns of anatomical evolution in relation to their biomechanical and ecophysiological significance. 相似文献
958.
959.
Laurence Vernis Céline Facca Emmanuelle Delagoutte Nicolas Soler Roland Chanet Bernard Guiard Gérard Faye Giuseppe Baldacci 《PloS one》2009,4(2)
A mutated allele of the essential gene TAH18 was previously identified in our laboratory in a genetic screen for new proteins interacting with the DNA polymerase delta in yeast [1]. The present work shows that Tah18 plays a role in response to oxidative stress. After exposure to lethal doses of H2O2, GFP-Tah18 relocalizes to the mitochondria and controls mitochondria integrity and cell death. Dre2, an essential Fe/S cluster protein and homologue of human anti-apoptotic Ciapin1, was identified as a molecular partner of Tah18 in the absence of stress. Moreover, Ciapin1 is able to replace yeast Dre2 in vivo and physically interacts with Tah18. Our results are in favour of an oxidative stress-induced cell death in yeast that involves mitochondria and is controlled by the newly identified Dre2-Tah18 complex. 相似文献
960.
Eiram Elahi Nirosha Suraweera Emmanouil Volikos Jackie Haines Natalie Brown Gerovie Davidson Mike Churchman Mohammed Ilyas Ian Tomlinson Andrew Silver 《PloS one》2009,4(2)
Ionising radiation is a carcinogen capable of inducing tumours, including colorectal cancer, in both humans and animals. By backcrossing a recombinant line of ApcMin/+ mice to the inbred BALB/c mouse strain, which is unusually sensitive to radiation–induced tumour development, we obtained panels of 2Gy-irradiated and sham-irradiated N2 ApcMin/+ mice for genotyping with a genome-wide panel of microsatellites at ∼15 cM density and phenotyping by counting adenomas in the small intestine. Interval and composite interval mapping along with permutation testing identified five significant susceptibility quantitative trait loci (QTLs) responsible for radiation induced tumour multiplicity in the small intestine. These were defined as Mom (Modifier of Min) radiation-induced polyposis (Mrip1-5) on chromosome 2 (log of odds, LOD 2.8, p = 0.0003), two regions within chromosome 5 (LOD 5.2, p<0.00001, 6.2, p<0.00001) and two regions within chromosome 16 respectively (LOD 4.1, p = 4×10−5, 4.8, p<0.00001). Suggestive QTLs were found for sham-irradiated mice on chromosomes 3, 6 and 13 (LOD 1.7, 1.5 and 2.0 respectively; p<0.005). Genes containing BALB/c specific non-synonymous polymorphisms were identified within Mrip regions and prediction programming used to locate potentially functional polymorphisms. Our study locates the QTL regions responsible for increased radiation-induced intestinal tumorigenesis in ApcMin/+ mice and identifies candidate genes with predicted functional polymorphisms that are involved in spindle checkpoint and chromosomal stability (Bub1b, Casc5, and Bub1), DNA repair (Recc1 and Prkdc) or inflammation (Duox2, Itgb2l and Cxcl5). Our study demonstrates use of in silico analysis in candidate gene identification as a way of reducing large-scale backcross breeding programmes. 相似文献