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261.
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Ahmad I Paterson WF Lin L Adlard P Duncan P Tolmie J Achermann JC Donaldson MD 《Hormone research》2007,68(1):32-37
A male presented at age 2.2 years with a 6-week history of intermittent vomiting and hyperpigmentation. Investigations showed salt wasting with hyperkalaemia, a grossly impaired cortisol response to ACTH stimulation, elevated renin and ACTH. Family history revealed that two maternal uncles had died soon after birth. A third uncle failed to thrive during infancy but improved with a course of cortisone, then being untreated until further investigation revealed adrenal insufficiency. A fourth uncle died aged 10 days, with urinary salt loss and hypoplastic adrenal glands at postmortem. Molecular studies on the proband, his mother, maternal grandmother, and surviving uncle showed a novel C to G substitution at nucleotide position 794 (missense mutation T265R) in the DAX1 (NR0B1) gene. The proband has responded well to steroid replacement but has proved sensitive to 9alpha-fludrocortisone treatment, developing hypertension on a dose of 133 microg/m(2)/day. At 8.8 years he was noted to have testicular volumes of 4 ml, despite no other evidence of secondary sexual development and prepubertal gonadotrophin levels. Novel features of this family include a novel DAX1 mutation, marked variability in age of presentation, hypertension on 'standard' doses of 9alpha-fludrocortisone and mild testicular enlargement. 相似文献
263.
Norbury R Travis MJ Erlandsson K Waddington W Ell PJ Murphy DG 《Hormones and behavior》2007,51(2):249-257
Estrogen Therapy (ET) may protect against age-related cognitive decline and neuropsychiatric disorders (e.g. Alzheimer's disease). The biological basis for this putative neuroprotective effect is not fully understood, but may include modulation of cholinergic systems. Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimer's disease. However, to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging, and related this to cognitive function. We used Single Photon Emission Tomography (SPET) and (R,R)[(123)I]-I-QNB, a novel ligand with high affinity for m(1)/m(4) muscarinic receptors, to examine the effect of long-term ET and age on brain m(1)/m(4) receptors in healthy females. We included 10 younger premenopausal subjects and 22 postmenopausal women; 11 long-term ET users (all treated following surgical menopause) and 11 ET never-users (surgical menopause, n=2). Also, verbal memory and executive function was assessed in all postmenopausal subjects. Compared to young women, postmenopausal women (ET users and never-users combined) had significantly lower muscarinic receptor density in all brain regions examined. ET users also had higher muscarinic receptor density than ET never-users in all the brain regions, and this reached statistical significance in left striatum and hippocampus, lateral frontal cortex and thalamus. Moreover, in ET users, (R,R)[(123)I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels. We also found evidence for improved executive function in ET users as compared to ET never-users. However, there was no significant relationship between receptor binding and cognitive function within any of the groups. In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding, and this may be related to serum estradiol levels. 相似文献
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265.
Two strategies can guide walking to a stationary goal: (1) the optic-flow strategy, in which one aligns the direction of locomotion or "heading" specified by optic flow with the visual goal; and (2) the egocentric-direction strategy, in which one aligns the locomotor axis with the perceived egocentric direction of the goal and in which error results in optical target drift. Optic flow appears to dominate steering control in richly structured visual environments, whereas the egocentric- direction strategy prevails in visually sparse environments. Here we determine whether optic flow also drives visuo-locomotor adaptation in visually structured environments. Participants adapted to walking with the virtual-heading direction displaced 10 degrees to the right of the actual walking direction and were then tested with a normally aligned heading. Two environments, one visually structured and one visually sparse, were crossed in adaptation and test phases. Adaptation of the walking path was more rapid and complete in the structured environment; the negative aftereffect on path deviation was twice that in the sparse environment, indicating that optic flow contributes over and above target drift alone. Optic flow thus plays a central role in both online control of walking and adaptation of the visuo-locomotor mapping. 相似文献
266.
Powell NA Ciske FL Cai C Holsworth DD Mennen K Van Huis CA Jalaie M Day J Mastronardi M McConnell P Mochalkin I Zhang E Ryan MJ Bryant J Collard W Ferreira S Gu C Collins R Edmunds JJ 《Bioorganic & medicinal chemistry》2007,15(17):5912-5949
We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3(sp) subsite. 相似文献
267.
Barclay WS Jones IM Osborn HM Phillipson L Ren J Talevera GA Thompson CI 《Bioorganic & medicinal chemistry》2007,15(12):4038-4047
Influenza viruses attach to host cells by binding to terminal sialic acid (Neu5Ac) on glycoproteins or glycolipids. Both the linkage of Neu5Ac and the identity of other carbohydrates within the oligosaccharide are thought to play roles in restricting the host range of the virus. In this study, the receptor specificity of an H5 avian influenza virus haemagglutinin protein that has recently infected man (influenza strain A/Vietnam/1194/04) has been probed using carbohydrate functionalised poly(acrylic acid) polymers. A baculovirus expression system that allows facile and safe analysis of the Neu5Ac binding specificity of mutants of H5 HA engineered at sites that are predicted to effect a switch in host range has also been developed. 相似文献
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269.
Loiselle Bette A.; Ryder Thomas B.; Duraes Renata; Tori Wendy; Blake John G.; Parker Patricia G. 《Behavioral ecology》2007,18(2):287-291
In lek-mating systems, males aggregate at display arenas andfemales visit solely for the purpose of mating. This breedingsystem is characterized by high variance in male mating successwith one male often receiving most copulations. High reproductiveskew among males has led to question why males join leks whentheir chances of reproductive success are so low. Kin selectionhas been invoked as a mechanism to explain the evolution oflekking behavior, whereby nonreproducing but genetically relatedmales gain indirect inclusive-fitness benefits. Evidence forkin selection among lek-mating birds is, however, mixed. Here,we show that kin selection is unlikely to be an important explanationfor evolution of lekking behavior in manakins (Aves: Pipridae).We found that for 4 species chosen from several major cladeswithin Pipridae, males within leks were not significantly morerelated than expected from random assortment of males in thepopulation. This means that nonreproducing males do not gainindirect inclusive-fitness benefits by joining leks. This resultsuggests alternative mechanisms must be invoked to explain theevolution of lek-mating systems in manakins. 相似文献
270.