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71.
3 novel pyridinylidene arylurea derivatives were found to lower arterial pressure in spontaneously hypertensive rats. Their relative oral potency ranged from 6 to 32 times that of guanethidine. The onset of antihypertensive action following their oral administration was less than 1 h and the duration of action ranged from 8 to over 24 h. The antihypertensive activity of the pyridinylidene arylureas was found to be assoicated with depletion of tissue catecholamines. Compound C depleted cardiac norepinephrine with little or no effect on total brain norepinephrine levels. It is suggested that compound C may have useful antihypertensive properties without CNS depressant activity. 相似文献
72.
73.
The accessible chromatin landscape of the human genome 总被引:2,自引:0,他引:2
RE Thurman E Rynes R Humbert J Vierstra MT Maurano E Haugen NC Sheffield AB Stergachis H Wang B Vernot K Garg S John R Sandstrom D Bates L Boatman TK Canfield M Diegel D Dunn AK Ebersol T Frum E Giste AK Johnson EM Johnson T Kutyavin B Lajoie BK Lee K Lee D London D Lotakis S Neph F Neri ED Nguyen H Qu AP Reynolds V Roach A Safi ME Sanchez A Sanyal A Shafer JM Simon L Song S Vong M Weaver Y Yan Z Zhang Z Zhang B Lenhard M Tewari MO Dorschner RS Hansen PA Navas G Stamatoyannopoulos VR Iyer 《Nature》2012,489(7414):75-82
74.
Moreno JA Radford H Peretti D Steinert JR Verity N Martin MG Halliday M Morgan J Dinsdale D Ortori CA Barrett DA Tsaytler P Bertolotti A Willis AE Bushell M Mallucci GR 《Nature》2012,485(7399):507-511
The mechanisms leading to neuronal death in neurodegenerative disease are poorly understood. Many of these disorders, including Alzheimer's, Parkinson's and prion diseases, are associated with the accumulation of misfolded disease-specific proteins. The unfolded protein response is a protective cellular mechanism triggered by rising levels of misfolded proteins. One arm of this pathway results in the transient shutdown of protein translation, through phosphorylation of the α-subunit of eukaryotic translation initiation factor, eIF2. Activation of the unfolded protein response and/or increased eIF2α-P levels are seen in patients with Alzheimer's, Parkinson's and prion diseases, but how this links to neurodegeneration is unknown. Here we show that accumulation of prion protein during prion replication causes persistent translational repression of global protein synthesis by eIF2α-P, associated with synaptic failure and neuronal loss in prion-diseased mice. Further, we show that promoting translational recovery in hippocampi of prion-infected mice is neuroprotective. Overexpression of GADD34, a specific eIF2α-P phosphatase, as well as reduction of levels of prion protein by lentivirally mediated RNA interference, reduced eIF2α-P levels. As a result, both approaches restored vital translation rates during prion disease, rescuing synaptic deficits and neuronal loss, thereby significantly increasing survival. In contrast, salubrinal, an inhibitor of eIF2α-P dephosphorylation, increased eIF2α-P levels, exacerbating neurotoxicity and significantly reducing survival in prion-diseased mice. Given the prevalence of protein misfolding and activation of the unfolded protein response in several neurodegenerative diseases, our results suggest that manipulation of common pathways such as translational control, rather than disease-specific approaches, may lead to new therapies preventing synaptic failure and neuronal loss across the spectrum of these disorders. 相似文献
75.
用脸谱图对太子河本溪市区段河流沉积物中重金属污染进行评价的研究 总被引:9,自引:0,他引:9
本文将沉积学原理及国际上新发展的两种重金属污染评价方法与多变量的图表示法——脸谱图相结合,对太子河本溪市区段河道沉积物中重金属的污染状况及潜在生态危害进行了综合性的评价研究。从脸谱图上可以直观地看出各采样点重金属的污染情况和潜在生态危害程度。从研究结果可以看出,太子河本溪市区段河道沉积物中重金属的污染是很严重的。 相似文献
76.
贾巍巍 《山西师范大学学报:自然科学版》2004,18(3):6-11
本文讨论F4上n维线性空间的k维子空间W,这些子空间都有特定的自同构群(实际上是典型群GLn(F4)的一个子群),根据群中元素形式的不同可将子空间W分为两类,并对寻找n维空间中形如这两类的n/2维自对偶子空间提供了一种采用降低维数寻找的方法。 相似文献
77.
B. D. Jackson P. J. Wright E. D. Morgan 《Cellular and molecular life sciences : CMLS》1989,45(5):487-489
Summary 3-Ethyl-2,5-dimethylpyrazine, found in the poison gland of workers, induces trail following in the Mediterranean harvester antMessor bouvieri. The poison gland contains on average 9 ng of this trail pheromone component. The alkaloids anabasine and anabaseine are also present in this gland, but induce no reaction in workers. Trail following is also induced by substances present in the Dufour gland, but the combined effect of both glands shows no synergism. 相似文献
78.
Epstein-Barr (EB) virus is one of the five herpesviruses of man. Strong links between this agent and the chain of events causing two human cancers, endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, have long been evident (reviewed in ref. 1). Because of this, and because of the very high incidence of nasopharyngeal carcinoma in certain large populations, it was suggested in 1976 that a vaccine should be developed against EB virus to prevent infection and thereby reduce tumour incidence amongst those at risk. The virus-determined membrane antigen (MA) was proposed as immunogen because it was known to elicit naturally occurring virus-neutralizing antibodies in man and because analogous antigens had been shown to act as effective experimental vaccines for preventing the herpesvirus-induced lymphomas of Marek's disease in chickens. Progress has been achieved in defining, quantifying and preparing MA molecules, and in enhancing their immunogenicity; a sensitive assay for antibodies to MA has been elaborated. Here we report that isolated cell membranes expressing MA, or purified MA glycoprotein of relative molecular mass (Mr) 340,000 (gp340), have been used to vaccinate cottontop tamarins (Saguinus oedipus oedipus), and that animals receiving either preparation were protected against the effects of a 100% tumour-inducing challenge dose of EB virus. 相似文献
79.
A Scriabine C T Ludden L S Watson J M Stavorski G Morgan J J Baldwin 《Experientia》1979,35(5):653-655
2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator durgs. 相似文献
80.
Coitus, which precedes internal fertilisation, is a unique physiological event which allows motile allogeneic spermatozoa to enter the female host and invade her tissues. The cyclic cellular proliferation observed in the thymus of the female rat may be an important preparation of her immune system for this event. 相似文献