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51.
Expression of human immunodeficiency virus-1 integrase in Escherichia coli, at levels that had no effect on bacterial cell growth, blocked plaque formation by bacteriophages having single-stranded genomic DNA (M13) or RNA (R17, Q, PRR1). Plaque formation by phages having double-stranded genomic DNA (T4, PR4) was unaffected. Integrase also inhibited infection by the phagemid M13KO7, but it had no effect on production of phage once infection by M13KO7 was established. This result indicated that integrase affects an early stage in infection. Integrase also inhibited phage production following transfection by either single-stranded or double-stranded (replicative form) M13 DNA, it blocked M13 DNA replication, as assayed by incorporation of radioactive nucleotides into DNA, and it failed to affect bacterial pilus function. These data suggest that integrase interacts in vivo with phage nucleic acid, a conclusion supported by studies in which integrase was shown to have a DNA-binding activity in its C-terminal portion. This portion of integrase was both necessary and sufficient for interference of plaque formation by M13 in the present study. Expression of the N-terminal portion of integrase at the same level as intact integrase had little effect on phage growth, indicating that expression of foreign protein in general was not responsible for the inhibitory effect. The simple bacteriophage assay described is potentially useful for identifying integrase mutants that lack single-stranded DNA binding activity. 相似文献
52.
53.
Ruth G. Shaw Gerrit A. J. Platenkamp 《Evolution; international journal of organic evolution》1993,47(3):801-812
To determine the potential for adaptation to a local biotic environment, we examined the magnitude and nature of genetic variation in response to neighboring plants within a natural population of the native California annual, Nemophila menziesii. A total of 22 plants from a natural population were crossed in three reciprocal factorials. The progeny were grown in a greenhouse in nine treatments that varied in conspecific density and in the density of a naturally co-occurring grass species, Bromus diandrus. Increasing the density of each species significantly reduced individual survival, fruit number, and dry weight. Among survivors, we found small to moderate heritability of dry weight within treatments. Additive genetic correlations (rA) of dry weight between competitive regimes were generally large and positive. In no case were they significantly different from 1, as expected under the null hypothesis that the relative performance of the genotypes under consideration is the same in all environments. On the basis of these results, we cannot conclude that the structure of genetic covariation within this population would promote genetic differentiation in response to locally varying conditions of density of these two species. Aspects of the experiment that may have compromised our ability to detect rA differing from 1 are discussed. 相似文献
54.
Yonglan Liu Mingzhen Zhang Hyunbum Jang Ruth Nussinov 《Protein science : a publication of the Protein Society》2023,32(1):e4504
Bcr-Abl, a nonreceptor tyrosine kinase, is associated with leukemias, especially chronic myeloid leukemia (CML). Deletion of Abl's N-terminal region, to which myristoyl is linked, renders the Bcr-Abl fusion oncoprotein constitutively active. The substitution of Abl's N-terminal region by Bcr enables Bcr-Abl oligomerization. Oligomerization is critical: it promotes clustering on the membrane, which is essential for potent MAPK signaling and cell proliferation. Here we decipher the Bcr-Abl specific, step-by-step oligomerization process, identify a specific packing surface, determine exactly how the process is structured and identify its key elements. Bcr's coiled coil (CC) domain at the N-terminal controls Bcr-Abl oligomerization. Crystallography validated oligomerization via Bcr-Abl dimerization between two Bcr CC domains, with tetramerization via tight packing between two binary assemblies. However, the structural principles guiding Bcr CC domain oligomerization are unknown, hindering mechanistic understanding and drugs exploiting it. Using molecular dynamics (MD) simulations, we determine that the binary complex of the Bcr CC domain serves as a basic unit in the quaternary complex providing a specific surface for dimer–dimer packing and higher-order oligomerization. We discover that the small α1-helix is the key. In the binary assembly, the helix forms interchain aromatic dimeric packing, and in the quaternary assembly, it contributes to the specific dimer–dimer packing. Our mechanism is supported by the experimental literature. It offers the key elements controlling this process which can expand the drug discovery strategy, including by Bcr CC-derived peptides, and candidate residues for small covalent drugs, toward quenching oligomerization, supplementing competitive and allosteric tyrosine kinase inhibitors. 相似文献
55.
56.
Ohne ZusammenfassungDiese Arbeit wurde durchgeführt mit freundlicher Unterstützung der Gesellschaft von Freunden und Förderern der Universität Bonn (Geffrub) 相似文献
57.
Ruth G. Shaw 《Evolution; international journal of organic evolution》1991,45(1):143-151
A statistical method for comparing matrices of genetic variation and covariation between groups (e.g., species, populations, a single population grown in distinct environments) is proposed. This maximum-likelihood method provides a test of the overall null hypothesis that two covariance component matrices are identical. Moreover, when the overall null hypothesis is rejected, the method provides a framework for isolating the particular components that differ significantly between the groups. Simulation studies reveal that discouragingly large experiments are necessary to obtain acceptable power for comparing genetic covariance component matrices. For example, even in cases of a single trait measured on 900 individuals in a nested design of 100 sires and three dams per sire in each population, the power was only about 0.5 when additive genetic variance differed by a factor of 2.5. Nevertheless, this flexible method makes valid comparison of covariance component matrices possible. 相似文献
58.
Jerry L. Ruth 《Molecular biotechnology》1996,6(2):163-178
The simple use of nonisotopic hybridization probes to detect complementary sequences provides valuable information in a large
number of research and commercial applications. In hybridization assays, the four ‘S’s (speed, simplicity, sensitivity, and
specificity) are important criteria for determining the choice of probe and label. The direct chemical combination of synthetic
oligonucleotide probes and enzyme labels offer advantages unmatched by other approaches, with the oligonucleotide providing
rapid hybridization and high specificity, and the direct enzyme label providing simple and sensitive detection. Such oligonucleotide-enzyme
conjugates (“oligozymes”) can be used in a variety of hybridization and detection formats, including dot blots, Southern/northern
blots,in situ, and solution hybridization/capture schemes. The practical synthesis and use of such oligozymes are summarized. 相似文献
59.
Berit M. Mortensen Hanne W. Lund Greg Jablonski Ruth H. Paulssen Jan O. Gordeladze 《Bioscience reports》1995,15(3):135-150
In normal rats treated with 1,25(OH)2D3 or 24,25(OH)2D3, serum Ca2+, ALP, PRL and GH are significantly altered. In order to study the primary effect of vitamin D3 analogues on target organ function, rat UMR 106 osteosarcoma and GH3 pituitary adenoma cells in monolayer culture were exposed accordingly.Surprisingly, prolonged exposure of these cell lines to physiological levels of either 1,25(OH)2D3 or 24,25(OH)2D3 did not significantly affect the secretory parameters (ALP, PRL or GH) tested. However, 1,25(OH)2D3 exposure significantly reduced PTH- and Gpp(NH)p-elicited AC as well as Gpp(NH)p-stimulated PLC activities in the UMR 106 cells. These changes were accompanied by an increase and decrease in the membrane contents of the G-protein subunits G36 and Gq/11, respectively. In contrast, 24,25(OH)2D3 remained without significant biological effect on these signalling systems despite concomitantly augmented levels of G36. TRH- and Gpp(NH)p-elicited PLC activities in the GH3 cells were significantly reduced by 1,25(OH)2D3 with a concurrent reduction in cellular amounts of Gq/11, however, 24,25(OH)2D3 did not significantly alter any signalling systems nor G-proteins analyzed.It is concluded that the osteoblastic and pituitary cell secretion of ALP, PRL and GH remain unaffected by the presence of 1,25(OH)2D3 and 24,25(OH)2D3, despite distinct alterations in components of G-protein mediated signalling pathways. Hence, other factors like ambient Ca2+ may be responsible for the perturbed secretory patterns of ALP and PRL seen in vitamin D3 treated rats.Abbreviations AC
adenylate cyclase
- ALP
alkaline phosphatase
- BGP
osteocalcin
- BSA
bovine serum albumin
- DA
dopamine
- DAG
diacylglycerol
- GH
growth hormone
- GHRH
growth hormone releasing hormone
- Gpp(NH)p
guanosine 5-[-imido]triphosphate
- G-protein
guanine nucleotide-binding regulatory protein
- Gs etc.
Gs protein -subunit
- IP3
inositol 1,4,5 trisphosphate
- OAF
osteoclast activating factor
- PGE2
prostaglandin E2
- PKA & PKC
protein kinase A & C
- PLC
phospholipase C
- PRL
prolactin
- PTH
parathyroid hormone
- SRIF
somatostatin
- TRH
thyrotropin releasing hormone
- VIP
vasoactive intestinal peptide
- 25(OH)D3
25 hydroxy vitamin D3
- 1,25(OH)2D3
1·25 dihydroxy vitamin D3
- 24,25(OH)2D3
24,25 dihydroxy vitamin D3 相似文献
60.
Henri Wintz Hsu-Ching Chen Claudia A. Sutton Catharine A. Conley Angela Cobb David Ruth Maureen R. Hanson 《Plant molecular biology》1995,28(1):83-92
The expression of a 25 kDa protein, encoded by the fused mitochondrial pcf gene, is associated with cytoplasmic male sterility (CMS) in petunia. To investigate the role of the 25 kDa protein in CMS we have transformed petunia and tobacco plants with constructs expressing a portion of the urfS sequence of the pcf cDNA which encodes the 25 kDa protein. The urfS sequence was fused with two different mitochondrial targeting sequences. The chimeric gene coding region was placed under the control of the CaMV 35S promoter or a tapetum-specific promoter. Expression of the PCF protein was obtained in mitochondria of transgenic petunia and tobacco plants, yet fertility of the plants was not affected. Analysis of the location of the urfS-encoded protein revealed that it fractionates primarily into the soluble fraction in the transgenic plants whereas the genuine 25 kDa protein is found primarily in the soluble fraction but also in the membrane portion of immature buds from CMS petunia plants. Fertile transgenic plants were obtained which expressed the 25 kDa protein in the tapetal layer of post-meiotic anthers, while CMS plants express the endogenous 25 kDa protein in both the tapetal layer and sporogenous tissue of pre-meiotic anthers. 相似文献