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Background
While traditional models of Alzheimer's disease focused on large fibrillar deposits of the Aβ42 amyloid peptide in the brain, recent work suggests that the major pathogenic effects may be attributed to SDS-stable oligomers of Aβ42. These Aβ42 oligomers represent a rational target for therapeutic intervention, yet factors governing their assembly are poorly understood. 相似文献23.
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R E Loomis C C Tseng E J Bergey M J Levine 《International journal of peptide and protein research》1988,32(2):130-140
The amino acid sequence G(1)-P(2)-P(3)-P(4)-H(5)-P(6)-G(7)-K(8)-P(9) occurs twice in the proline-rich glycoprotein (PRG) found in human parotid saliva. As part of our efforts to elucidate the structure-function relationships of PRG, this nonapeptide sequence (PRG9) was synthesized for the purpose of conformational analyses by high-resolution proton n.m.r. spectroscopy and computer-modeling. The empirical n.m.r. spectrum differed from the simulated spectrum in that the overall chemical shift locations were displaced from their random coil positions and the five proline residues had non-degenerate C alpha H alpha protons. Other n.m.r. data indicated that no intramolecular hydrogen-bonding was present in the PRG. In conjunction with X-ray crystallographic data on a triproline-containing model compound (Kartha, g., Ashida, T. & Kakudo, M. (1974) Acta Cryst. B30, 1861-1866), four energy-minimized PRG9 structures were obtained. Two of the structures were energetically unfavorable, while the other two conformations were reasonable. The two most likely structures gave all prolines an S-type ring pucker, the P(2)-P(3)-P(4) sequence as a poly-L-proline II helix, the H(5) phi = -90.3 degrees, P(6) and P(9) with trans peptide bond orientation, G(7) in an extended state, and the K(8) phi = -93.2 degrees or -146.8 degrees for structures #1 and #2, respectively. 相似文献
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Caroline van Haaften-Day Peter Russell Susan Carr Lesley Wright 《In vitro cellular & developmental biology. Plant》1988,24(10):965-971
Summary A cell line derived from a human ovarian carcinosarcoma was established in tissue culture and in nude mice. Two sublines,
LDF and HDF, separated by discontinuous density centrifugation were also established from the parent line JoN. The cloning
efficiency of the JoN line was 21%. Morphologic features of adenocarcinoma cells characteristic of the parent JoN cells were
retained in the sublines and clones; all lines showed the same karyotype and DNA content (pseudodiploid and pseudotetraploid).
Keratin, as demonstrated immunohistochemically, was strongly expressed in the parent line JoN and the xenograft tumor, but
not at all in the LDF sublines and only moderately in the HDF sublines. Vimentin, however, was expressed in neither the parent
line JoN nor the xenograft tumor, but was present in both sublines. Transglutaminase and plasminogen activator activity was
high in the parent line JoN. Neither, sublines nor clones showed the same high enzyme activity as the parent line. It is concluded
that this human tumor line JoN is comprised of epithelial cells, capable of multidirectional differentiation. 相似文献
29.
L Levine M N Sawka B E Joyce B S Cadarette K B Pandolf 《European journal of applied physiology and occupational physiology》1984,53(1):12-16
Comparisons of physiological responses to 0, 0.5, 1, and 2 mg atropine (IM) were made in seven males (X +/- SD: age, 24 +/- 3 years; ht, 174 +/- 12 cm; wt, 76 +/- 3 kg) while they exercised (approximately 390 W) in a hot-dry (40 degrees C, 20% rh) environment. Responses to 4 mg, as well as repeatability of responses to 2 mg, were studied in two and six of these subjects, respectively. On 8 test days an intramuscular injection of atropine or saline control was administered 20 min before subjects walked on a treadmill for two 50-min bouts. Heart rate (HR) during exercise did not change in the control trial but by min 50 increased during all atropine trials (P less than 0.01). Rectal temperature (Tre) increased (P less than 0.01) in all trials by min 50 and continued increasing (P less than 0.01) in the 2-mg trial during the second exercise bout. For the two subjects tested with all dosages (0.5 - 4 mg atropine), the change in HR and Tre between the atropine and control trials at 50 min of exercise was regressed against the various atropine dosages. The relationship (r = 0.92) for HR was curvilinear while the relationship (r = 0.99) for Tre was linear. Mean weighted skin temperature (Tsk) was relatively constant during exercise and was warmer (P less than 0.05) with increasing atropine dosage. In a repeat 2 mg trial, HR was 6 bt . min-1 lower (P less than 0.05) on the second exposure but Tre was the same (P greater than 0.05) on both days. For subjects walking in the heat, three new observations were: 1) 0.5 mg of atropine resulted in increased HR and Tsk compared to control values; 2) HR was elevated but the magnitude of change decreased with increasing dosage, while the elevation in Tre was consistent with increasing dosage; and 3) rectal temperatures (in trials with and without atropine) were unaffected by previous days of atropine administration. 相似文献
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