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51.
52.
Suppressive subtractive hybridization as a tool for identifying genetic diversity in an environmental metagenome: the rumen as a model 总被引:10,自引:0,他引:10
Molecular techniques previously used for genome comparisons of closely related bacterial species could prove extremely valuable for comparisons of complex microbial communities, or metagenomes. Our study aimed to determine the breadth and value of suppressive subtractive hybridization (SSH) in a pilot-scale analysis of metagenomic DNA from communities of microorganisms in the rumen. Suppressive subtractive hybridization was performed using total genomic DNA isolated from rumen fluid samples of two hay-fed steers, arbitrarily designated as tester or driver. Ninety-six subtraction DNA fragments from the tester metagenome were amplified, cloned and the DNA sequences were determined. Verification of the isolation of DNA fragments unique to the tester metagenome was accomplished through dot blot and Southern blot hybridizations. Tester-specific SSH fragments were found in 95 of 96 randomly selected clones. DNA sequences of subtraction fragments were analysed by computer assisted DNA and amino acid comparisons. Putative translations of 26 (32.1%) subtractive hybridization fragments exhibited significant similarity to Bacterial proteins, whereas 15 (18.5%) distinctive subtracted fragments had significant similarity to proteins from Archaea. The remainder of the subtractive hybridization fragments displayed no similarity to GenBank sequences. This metagenomic approach has exposed an unexpectedly large difference in Archaeal community structure between the rumen microbial populations of two steers fed identical diets and housed together. 16S rRNA dot blot hybridizations revealed similar proportions of Bacteria and Archaea in both rumen samples and suggest that the differences uncovered by SSH are the result of varying community structural composition. Our study demonstrates a novel approach to comparative analyses of environmental microbial communities through the use of SSH. 相似文献
53.
K. A. Miller T. M. Gunn M. M. Carrasquillo M. L. Lamoreux D. B. Galbraith G. S. Barsh 《Genetics》1997,146(4):1407-1415
The mouse mutations mahogany (mg) and mahoganoid (md) are negative modifiers of the Agouti coat color gene, which encodes a paracrine signaling molecule that induces a switch in melanin synthesis from eumelanin to pheomelanin. Animals mutant for md or mg synthesize very little or no pheomelanin depending on Agouti gene background. The Agouti protein is normally expressed in the skin and acts as an antagonist of the melanocyte receptor for α-MSH (Mc1r); however, ectopic expression of Agouti causes obesity, possibly by antagonizing melanocortin receptors expressed in the brain. To investigate where md and mg lie in a genetic pathway with regard to Agouti and Mc1r signaling, we determined the effects of these mutations in animals that carried either a loss-of-function Mc1r mutation (recessive yellow, Mc1r(e)) or a gain-of-function Agouti mutation (lethal yellow, A(y)). We found that the Mc1r(e) mutation suppressed the effects of md and mg, but that md and mg suppressed the effects of A(y) on both coat color and obesity. Plasma levels of α-MSH and of ACTH were unaffected by md or mg. These results suggest that md and mg interfere directly with Agouti signaling, possibly at the level of protein production or receptor regulation. 相似文献
54.
55.
Current status of antisense DNA methods in behavioral studies 总被引:4,自引:0,他引:4
The antisense DNA method has been used successfully to block the expression
of specific genes in vivo in neuronal systems. An increasing number of
studies in the last few years have shown that antisense DNA administered
directly into the brain can modify various kinds of behaviors. These
findings strongly suggest that the antisense DNA method can be used as a
powerful tool to study causal relationships between molecular processes in
the brain and behavior. In this article we review the current status of the
antisense method in behavioral studies and discuss its potentials and
problems by focusing on the following four aspects; (i) optimal application
paradigms of antisense DNA methods in behavioral studies; (ii) efficiencies
of different administration methods of antisense DNA used in behavioral
studies; (iii) determination of specificity of behavioral effects of
antisense DNA; and (iv) discrepancies between antisense DNA effects on
behaviors and those on protein levels of the targeted gene.
相似文献
56.
We report the characterization of a higher-plant C-24 sterol methyltransferase by yeast complementation. A Zea mays endosperm expressed sequence tag (EST) was identified which, upon complete sequencing, showed 46% identity to the yeast C-24 methyltransferase gene (ERG6) and 75% and 37% amino acid identity to recently isolated higher-plant sterol methyltransferases from soybean and Arabidopsis, respectively. When placed under GAL4 regulation, the Z. mays cDNA functionally complemented the erg6 mutation, restoring ergosterol production and conferring resistance to cycloheximide. Complementation was both plasmid-dependent and galactose-inducible. The Z. mays cDNA clone contains an open reading frame encoding a 40 kDa protein containing motifs common to a large number of S-adenosyl-L-methionine methyltransferases (SMTs). Sequence comparisons and functional studies of the maize, soybean and Arabidopsis cDNAs indicates two types of C-24 SMTs exist in higher plants. 相似文献
57.
L-Lactate dehydrogenase (L-LDH, E.C. 1.1.1.27) is encoded by two or three
loci in all vertebrates examined, with the exception of lampreys, which
have a single LDH locus. Biochemical characterizations of LDH proteins have
suggested that a gene duplication early in vertebrate evolution gave rise
to Ldh-A and Ldh-B and that an additional locus, Ldh-C arose in a number of
lineages more recently. Although some phylogenetic studies of LDH protein
sequences have supported this pattern of gene duplication, others have
contradicted it. In particular, a number of studies have suggested that
Ldh-C represents the earliest divergence among vertebrate LDHs and that it
may have diverged from the other loci well before the origin of
vertebrates. Such hypotheses make explicit statements about the
relationship of vertebrate and invertebrate LDHs, but to date, no closely
related invertebrate LDH sequences have been available for comparison. We
have attempted to provide further data on the timing of gene duplications
leading to multiple vertebrate LDHs by determining the cDNA sequence of the
LDH of the tunicate Styela plicata. Phylogenetic analyses of this and other
LDH sequences provide strong support for the duplications giving rise to
multiple vertebrate LDHs having occurred after vertebrates diverged from
tunicates. The timing of these LDH duplications is consistent with data
from a number of other gene families suggesting widespread gene duplication
near the origin of vertebrates. With respect to the relationships among
vertebrate LDHs, our data are not consistent with previous claims that
Ldh-C represented the earliest divergence. However, the precise
relationships among some of the main lineages of vertebrate LDHs were not
resolved in our analyses.
相似文献
58.
G Teasdale S Galbraith L Murray P Ward D Gentleman M McKean 《BMJ (Clinical research ed.)》1982,285(6356):1695-1697
Deciding which head-injured patients should be transferred to a neurosurgical unit can be difficult. Traditional criteria emphasise the development of deteriorating responsiveness but lead to delayed diagnosis and to avoidable mortality and morbidity. To discover if a more liberal admission policy improved results a study was conducted analysing data collected prospectively from 683 patients who had a traumatic intracranial haematoma evacuated in the Glasgow neurosurgical unit between 1974 and 1980. In the first four years, before the change in policy, mortality was 38% but decreased to 29% afterwards. This reflected a reduction in the proportion of patients who talked after injury but who deteriorated into coma before operation--that is, 31% before the change in policy, 16% afterwards. If the potential benefits of CT scanning in the management of head injuries are to be realised patients must be scanned sooner than in the past. This will usually mean that more patients should go to a neurosurgical unit and that simple criteria for transfer should be established. 相似文献
59.
60.
The regulation of exogenous NAD(P)H oxidation in spinach (Spinacia oleracea) leaf mitochondria by pH and cations. 总被引:3,自引:0,他引:3 下载免费PDF全文
P J Goldschmidt-Clermont R M Galbraith D L Emerson F Marsot A E Nel P Arnaud 《The Biochemical journal》1985,232(2):471-477
Essentially chlorophyll-free mitochondria were isolated from green leaves of spinach (Spinacia oleracea L. cv. Viking II). Uncoupled oxidation of exogenous NADPH (1 mM) to oxygen had an optimum at pH 6.0, and activity was relatively low at pH 7.0, even in the presence of 1 mM-CaCl2. There was a proportional increase in the apparent Km for NADPH with decreasing H+ concentrations, suggesting that NADPH protonated on the 2'-phosphate group was the true substrate. Exogenous NADH was oxidized by oxygen with an optimum at pH 6.9. Under low-cation conditions, EGTA or EDTA (both 1 mM) had no effect on the Vmax. of NADH oxidation, although the removal of bivalent cations from the membrane surface by the chelators could be observed by use of 9-aminoacridine fluorescence. In contrast, under high-cation conditions, chelators lowered the Vmax. by about 50%, probably due to a better approach of the negatively charged chelators to the negative membrane surface than under low-cation conditions. In a low-cation medium, the Vmax. of NADH oxidation was increased by about 50% by the addition of cations. This was caused by a lowering of the size of the negative surface potential through charge screening. In contrast with other cations, La3+ inhibited NADH oxidation, possibly through binding to lipids essential for NADH oxidation. The apparent Km for NADH varied 6-fold in response to changes in the size of the surface potential, suggesting that the approach of the negatively charged NADH to the active site is hampered by the negative surface potential. The results demonstrate that the spinach leaf cell can regulate the mitochondrial NAD(P)H oxidation through several mechanisms: the pH; the cation concentration in general; and the concentration of Ca2+ in particular. The results also emphasize the importance of electrostatic considerations when investigating the kinetic behaviour of membrane-bound enzymes. 相似文献