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1.
Goats and some sheep synthesize a juvenile hemoglobin, Hb C (alpha 2 beta
C2), at birth and produce this hemoglobin exclusively during severe anemia.
Sheep that synthesize this juvenile hemoglobin are of the A haplotype.
Other sheep, belonging to a separate group, the B haplotype, do not
synthesize hemoglobin C and during anemia continue to produce their adult
hemoglobin. To understand the basis for this difference we have determined
the structural organization of the beta- globin locus of B-type sheep by
constructing and isolating overlapping genomic clones. These clones have
allowed us to establish the linkage map 5' epsilon I-epsilon II-psi beta
I-beta B-epsilon III-epsilon IV- psi beta II-beta F3' in this haplotype.
Thus, B sheep lack four genes, including the BC gene, and have only eight
genes, compared with the 12 found in the goat globin locus. The goat
beta-globin locus is as follows: 5' epsilon I-epsilon II-psi beta X-beta
C-epsilon III-epsilon IV-psi beta Z-beta A-epsilon V-epsilon VI-psi beta
Y-beta F3'. Southern blot analysis of A-type sheep reveals that these
animals have a beta- globin locus similar to that of goat, i.e., 12 globin
genes. Thus, the beta-globin locus of B-haplotype sheep resembles that of
cows and may have retained the duplicated locus of the ancestor of cows and
sheep. Alternatively, the B-sheep locus arrangement may be the result of a
deletion of a four-gene set from the triplicated locus.
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2.
Topical applications of MEA (beta-mercaptoethylamine or cysteamine), WR-2721 [S-2-(3-aminopropylamino)-ethylphosphorothioic acid], and N-acetylcysteine (NAC) were tested for their ability to protect the normal skin of the hind legs of mice against acute and late damage from single doses of 137Cs radiation. No significant protection was observed with either WR-2721 or NAC. MEA was shown to offer significant protection against acute skin damage in both buffered and unbuffered forms, but no significant protection against late contraction. The use of topical MEA on unanesthetized animals breathing carbogen (95% O2, 5% CO2) appears to give an enhanced level of radioprotection over that shown for anesthetized, air-breathing animals. 相似文献
3.
Gold salts and phenylbutazone selectively inhibit the synthesis of PGF2α and PGE2 respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE2 and PGF2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action
and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function. 相似文献
4.
Lyzel S. Elias-Sonnenschein Seppo Helisalmi Teemu Natunen Anette Hall Teemu Paajanen Sanna-Kaisa Herukka Marjo Laitinen Anne M. Remes Anne M. Koivisto Kari M. Mattila Terho Lehtim?ki Frans R. J. Verhey Pieter Jelle Visser Hilkka Soininen Mikko Hiltunen 《PloS one》2013,8(4)
Objectives
To understand the relation between risk genes for Alzheimer’s disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers Aβ1–42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF).Methods
We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland.Results
APOE-ε4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased Aβ1–42 (corrected p<0.05). At an uncorrected p<0.05, PPP3R1 rs1868402 and MAPT rs2435211 were related with increased t-tau; while SORL1 rs73595277 and MAPT rs16940758, with increased p-tau. Only TOMM40 rs2075650 showed association with clinical AD after adjusting for APOE-ε4 (p = 0.007), but not after multiple test correction (p>0.05).Conclusions
We provide evidence that APOE-ε4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF Aβ1–42 in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-ε4, CLU and MS4A4A influence both AD risk and CSF Aβ1–42. 相似文献5.
Two silicone coatings have been evaluated for barnacle adhesion. One coating is an unfilled hydrosilation cured polydimethylsiloxane (PDMS) network, while the other is a room temperature vulcanized (RTV), filled, ethoxysiloxane cured PDMS elastomer, RTV11?. The adhesion strength of one species of barnacle, Balanus eburneus, to the hydrosilation coatings is in the range of 0.37–0.60 kg cm‐2 while the corresponding range for RTV11 is 0.64–0.90 kg cm‐2. The easier release of B. eburneus from the hydrosilation cured network compared to RTV11 is discussed in relationship to differences in bulk and surface properties. Preliminary results suggest bulk modulus may be the most important parameter in determining barnacle adhesion strength. In light or mechanical property analysis, a re‐evaluation of surface properties and chemical stability is presented. 相似文献
6.
Background
Finite element method (FEM) analysis for intraoperative modeling of the left ventricle (LV) is presently not possible. Since 3D structural data of the LV is now obtainable using standard transesophageal echocardiography (TEE) devices intraoperatively, the present study describes a method to transfer this data into a commercially available FEM analysis system: ABAQUS?. 相似文献7.
8.
Jacobsen RB Koch ED Lange-Malecki B Stocker M Verhey J Van Wagoner RM Vyazovkina A Olivera BM Terlau H 《The Journal of biological chemistry》2000,275(32):24639-24644
kappa-Conotoxin PVIIA (kappa-PVIIA), a 27-amino acid peptide with three disulfide cross-links, isolated from the venom of Conus purpurascens, is the first conopeptide shown to inhibit the Shaker K(+) channel (Terlau, H., Shon, K., Grilley, M., Stocker, M., Stühmer, W., and Olivera, B. M. (1996) Nature 381, 148-151). Recently, two groups independently determined the solution structure for kappa-PVIIA using NMR; although the structures reported were similar, two mutually exclusive models for the interaction of the peptide with the Shaker channel were proposed. We carried out a structure/function analysis of kappa-PVIIA, with alanine substitutions for all amino acids postulated to be key residues by both groups. Our data are consistent with the critical dyad model developed by Ménez and co-workers (Dauplais, M., Lecoq, A., Song, J. , Cotton, J., Jamin, N., Gilquin, B., Roumestand, C., Vita, C., de Medeiros, C., Rowan, E. G., Harvey, A. L., and Ménez, A. (1997) J. Biol. Chem. 272, 4802-4809) for polypeptide antagonists of K(+) channels. In the case of kappa-PVIIA, Lys(7) and Phe(9) are essential for activity as predicted by Savarin et al. (Savarin, P., Guenneugues, M., Gilquin, B., Lamthanh, H., Gasparini, S., Zinn-Justin, S., and Ménez, A. (1998) Biochemistry 37, 5407-5416); these workers also correctly predicted an important role for Lys(25). Thus, although kappa-conotoxin PVIIA has no obvious sequence homology to polypeptide toxins from other venomous animals that interact with voltage-gated K(+) channels, there may be convergent functional features in diverse K(+) channel polypeptide antagonists. 相似文献
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10.
Kinesin-1 structural organization and conformational changes revealed by FRET stoichiometry in live cells 下载免费PDF全文
Kinesin motor proteins drive the transport of cellular cargoes along microtubule tracks. How motor protein activity is controlled in cells is unresolved, but it is likely coupled to changes in protein conformation and cargo association. By applying the quantitative method fluorescence resonance energy transfer (FRET) stoichiometry to fluorescent protein (FP)-labeled kinesin heavy chain (KHC) and kinesin light chain (KLC) subunits in live cells, we studied the overall structural organization and conformation of Kinesin-1 in the active and inactive states. Inactive Kinesin-1 molecules are folded and autoinhibited such that the KHC tail blocks the initial interaction of the KHC motor with the microtubule. In addition, in the inactive state, the KHC motor domains are pushed apart by the KLC subunit. Thus, FRET stoichiometry reveals conformational changes of a protein complex in live cells. For Kinesin-1, activation requires a global conformational change that separates the KHC motor and tail domains and a local conformational change that moves the KHC motor domains closer together. 相似文献