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31.
Kristin Kassler Anselm H. C. Horn Heinrich Sticht 《Journal of molecular modeling》2010,16(5):1011-1020
Converging lines of evidence suggest that soluble Aβ-amyloid oligomers play a pivotal role in the pathogenesis of Alzheimer’s
disease, and present direct effectors of synaptic and cognitive dysfunction. Three pathological E22-Aβ-amyloid point mutants
(E22G, E22K, E22Q) and the deletion mutant E22Δ exhibit an enhanced tendency to form prefibrillar aggregates. The present
study assessed the effect of these four mutations using molecular dynamics simulations and subsequent structural and energetic
analyses. Our data shows that E22 plays a unique role in wild type Aβ, since it has a destabilising effect on the oligomer
structure due to electrostatic repulsion between adjacent E22 side chains. Mutations in which E22 is replaced by an uncharged
residue result in higher oligomer stability. This effect is also observed to a lesser extent for the E22K mutation and is
consistent with its lower pathogenicity compared to other mutants. Interestingly, deletion of E22 does not destroy the amyloid
fold but is compensated by local changes in the backbone geometry that allow the preservation of a structurally important
salt bridge. The finding that all mutant oligomers investigated exhibit higher internal stability than the wild type offers
an explanation for the experimentally observed enhanced oligomer formation and stability. 相似文献
32.
33.
Donald R. McCarty Christian B. Carson Mark Lazar S. Caprice Simonds 《Genesis (New York, N.Y. : 2000)》1989,10(6):473-481
The viviparous-1 (vp1) locus in maize is a developmental gene that controls diverse aspects of the maturation phase of seed development. Mutations of vp1 alter embryo sensitivity to the hormone abscisic acid and block formation of anthocyanin pigment. Molecular cloning of a Robertson Mutator-induced mutant allele, vp1-mum-1, by transposable element tagging has allowed analysis of several transposon-induced vp1 mutants. In the vp1-Mc mutation, the gene is disrupted by 4.0 kbp insertion, which results in expression of a 3′ truncated mRNA. Phenotypically, this allele is at least partially functional in causing embryo dormancy, but is ineffective in controlling anthocyanin expression. This result suggests that disruption of the C-terminal domain of the Vp1 protein specifically affects regulation of the anthocyanin pathway. A second Mutator- derived allele, vp1-mum2, exhibits an unusual form of somatic mutability in which endosperm cells revert from wild-type vp1 expression to a mutant condition. The vp1-mum2 allele contains a 1.5 kbp Insertion that has no detectable homology to known Mu elements. This element is retained In wild-type germinal revertants derived from vp1-mum2 An apparent DNA modification affecting cleavage at an internal Sstl restriction site in the element correlates with vp1-mum2 states that exhibit wild-type Vp1 expression. A model involving mitotic assortment of modified and unmodified DNA strands during development is proposed for vp1-mum2 somatic mutation. 相似文献
34.
Christian Paech John Pierce Stephen D. McCurry N.E. Tolbert 《Biochemical and biophysical research communications》1978,83(3):1084-1092
Xylulose-1,5-bisphosphate in preparations of ribulose-1,5-bisphosphate (ribulose-P2) arises from non-enzymic epimerization and inhibits the enzyme. Another inhibitor, a diketo degradation product from ribulose-P2, is also present. Both compounds simulate the substrate inhibition of ribulose-P2 carboxylase/oxygenase previously reported for ribulose-P2. Freshly prepared ribulose-P2 had little inhibitory activity. The instability of ribulose-P2 may be one reason for a high level of ribulose-P2 carboxylase in chloroplasts where the molarity of active sites exceeds that of ribulose-P2. Because the KD of the enzyme/substrate complex is ≤1 μM, all ribulose-P2 generated in situ may be stored as this complex to prevent decomposition. 相似文献
35.
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38.
Differences among immune complexes: association of C1q in SLE immune complexes with renal disease 总被引:3,自引:0,他引:3
S G Greisman P B Redecha R P Kimberly C L Christian 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(3):739-745
Studies that made use of multiple assay systems demonstrated increased levels of immune complexes (IC) in patients with systemic lupus erythematosus (SLE), but no consistent correlations of IC concentration to patterns or activity of disease have been observed. Furthermore, consistent associations between qualitative differences in IC and disease manifestations have been elusive. IC interaction with erythrocytes and mononuclear phagocytic cells is another variable in SLE that may also mediate some of the biological effects of IC. The present report concerns studies of the composition of purified IC obtained from individuals with SLE and other rheumatic diseases; a 64,000 dalton component identified as the A-B subunit of C1q was detected in purified IC from 27 of 51 SLE patients (53%). The presence of this 64,000 dalton component was not related to either IC concentration or to the serum C1q level. However, the presence of the C1q component in isolated SLE IC did correlate with the presence of renal disease (p less than 0.02). These observations are interpreted relative to a recently described kinetic model of IC clearance. 相似文献
39.
Measurement of Acetylcholine Release in Freely Moving Rats by Means of Automated Intracerebral Dialysis 总被引:15,自引:13,他引:2
G. Damsma B. H. C. Westerink J. B. de Vries C. J. Van den Berg A. S. Horn 《Journal of neurochemistry》1987,48(5):1523-1528
The present study demonstrates the feasibility of measuring acetylcholine in perfusion samples collected by means of in vivo brain dialysis in the striata of freely moving rats. The output of the dialysis device was directly connected to an automated sample valve of a HPLC-assay system that comprises a cation exchanger, a post-column enzyme reactor, and an electrochemical detector. The presence of an acetylcholinesterase inhibitor (neostigmine) in the perfusion fluid was required for the detection of acetylcholine in the perfusate. Increasing concentrations of neostigmine induced increasing amounts of acetylcholine. Continuous perfusion with a fixed concentration (2 microM) of neostigmine resulted in gradually increasing amounts of collected acetylcholine over time although a considerable variation between successive samples exists. The brain dialysis technique was further validated by studying the effect of various drugs. Systemically administered atropine increased the output of acetylcholine, whereas the addition of tetrodotoxin to the perfusion fluid resulted in a complete disappearance of the neurotransmitter. 相似文献
40.
Hans Christian Weber 《Plant Systematics and Evolution》1987,156(3-4):127-131
In the parasiticScrophulariaceae andOrobanchaceae, two types of contact organs exist: secondary and primary haustoria. Secondary haustoria are lateral organs, developing in large numbers and only when the seedling is fully established. In contrast, a primary haustorium represents the first developmental stage of the seedling itself. In the root system of the parasiticLesquereuxia syriaca (=Siphonostegia syriaca) there are only secondary haustoria, but a few of them apparently develop in a terminal position. This is achieved by transferring the haustorial initiation region closer to the root apex. One can interpret this as a transformation of the apical meristem into a meristematic haustorial tissue. On the condition that an extreme shortening (abbrevation) of the primary root could happen, we discuss the transformation of the terminal secondary into a primary haustorium. 相似文献