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1.
How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncover the fitness landscape defined by gene expression levels. We found strong antagonism and sign epistasis between these beneficial mutations. Mutations with the largest individual benefit interacted the most antagonistically with other mutations, a trend we also uncovered through analyses of datasets from other model systems. However, these beneficial mutations interacted multiplicatively (i.e., no epistasis) at the level of enzyme expression. By generating a model that predicts fitness from enzyme levels we could explain the observed sign epistasis as a result of overshooting the optimum defined by a balance between enzyme catalysis benefits and fitness costs. Knowledge of the phenotypic landscape also illuminated that, although the fitness peak was phenotypically far from the ancestral state, it was not genetically distant. Single beneficial mutations jumped straight toward the global optimum rather than being constrained to change the expression phenotypes in the correlated fashion expected by the genetic architecture. Given that adaptation in nature often results from optimizing gene expression, these conclusions can be widely applicable to other organisms and selective conditions. Poor interactions between individually beneficial alleles affecting gene expression may thus compromise the benefit of sex during adaptation and promote genetic differentiation. 相似文献
2.
The cellular and network effects of acetylcholine (ACh) on the control system for feeding in Limax maximus were measured by intracellular recordings from feeding command-like interneurons and whole nerve recordings from buccal ganglion motor nerve roots that normally innervate the ingestive feeding muscles. The buccal ganglion motor nerve root discharge pattern that causes rhythmic feeding movements, termed the feeding motor program (FMP), was elicited either by attractive taste solutions applied to the lip chemoreceptors or by ACh applied to the cerebral ganglia. The ability of exogenous ACh applied to the cerebral ganglia to trigger FMP was blocked by the cholinergic antagonists curare and atropine. If the strength of the lip-applied taste stimulus was in the range of 1-2 times threshold, cerebral application of the cholinergic antagonists blocked or greatly decreased the ability of lip-applied taste solutions to trigger FMP (5 of 8 trials). The cerebral feeding interneurons, some of which activate FMP when stimulated intracellularly, are excited by small pulses of ACh applied directly to the cell body from an ACh-filled micropipette. A pulse of ACh that activates several of the feeding interneurons simultaneously triggers FMP. The data suggest that under certain stimulus conditions an obligatory set of cholinergic synapses onto the feedininterneurons must be activated for taste inputs to trigger ingestion. The determination of ACh's action within the feeding control system is necessary for understanding how enhanced cholinergic transmission leads to prolonged associative memory retention (Sahley, et al., 1986). 相似文献
3.
Fifty bronchial washing specimens from 36 patients with acquired immune deficiency syndrome (AIDS) were retrospectively reviewed to assess the sensitivity of the various special stains used to diagnose Pneumocystis carinii. In 76% of the cases, the Diff-Quik stain was positive; it was the easiest and most rapid of the special stains used. The sensitivity was increased to 92%, 96% and 100%, respectively, by also doing cresyl echt violet, Grocott's Gomori methenamine silver and both the cresyl violet and Grocott stains in addition to the Diff-Quik stain. We conclude that the Diff-Quik stain is a fairly reliable and rapid screening procedure for making the diagnosis of Pneumocystis infection in bronchial washings from AIDS patients. The routine Papanicolaou stain gave less sensitive results in the smears of the washing specimens, but does give a markedly improved yield in bronchoalveolar lavage specimens. 相似文献
4.
K. Delaney A. Gelperin 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1986,159(3):281-295
Summary An agar-based artificial diet containing carbohydrates, fats and twenty amino acids was constructed (Fig. 1). This diet is highly palatable and nutritionally complete forLimax maximus as demonstrated by significant ingestion on first encounter, consistent ingestion on subsequent days and good growth of young slugs fed this diet. Removing methionine, an essential amino acid, from the complete diet produces a food which is initially as palatable as the complete diet, but after one day's intake the amount of this deficient diet eaten is greatly reduced (Fig. 2). Removing alanine, a nonessential amino acid, does not produce any decrement in feeding relative to the complete diet (Fig. 5).A single meal can be sufficient for establishing the aversion to the deficient diet (Fig. 5). Following seven days of feeding on the deficient diet the aversion is retained with little or no attenuation for at least 30 days (Fig. 3) and does not generalize to either a known safe food (Fig. 3) or a novel food (Fig. 4). Evidence of a mild neophobia towards the artificial diet which attenuated after one or two meals was seen (Fig. 5).The learned aversion to the deficient diet is reversible if slugs are repeatedly fed the complete diet following feeding on the deficient diet. Also, slugs initially fed the complete diet will develop an aversion to the methionine-deficient diet after sampling it (Fig. 7).Slugs readily ate the artificial diets when these were offered 7 days post-hatch. The methionine-deficient diet however was not eaten in large amounts after the first meals and did not support growth (Fig. 9). Baby slugs fed the methionine-deficient diet for 10 days and then maintained on rat chow ate only small amounts when the deficient diet was presented again 126 days later, while baby slugs fed the complete diet or an alanine deficient diet for 10 days ate large amounts when these diets were presented 126 days later (Fig. 11 b).Supplementing the methionine-deficient diet with an injection of methionine into the haemocoel one hour after the completion of a meal completely blocks the development of a learned aversion while injection ofLimax saline does not (Fig. 8).These results are best explained by the hypothesis that the slugs acquire, post-ingestively, an aversion to the taste and probably the odor of the diet as the result of associative learning. The results of the experiments reported here indicate that there are substantial parallels at the behavioral level between mollusc and mammal with respect to post-ingestive feedback learning. 相似文献
5.
6.
R Fathi Q Huang G Coppola W Delaney R Teasdale A M Krieg A F Cook 《Nucleic acids research》1994,22(24):5416-5424
Oligonucleotide (2-aminoethyl)phosphonates in which the backbone consisted of isomerically pure, alternating (2-aminoethyl)-phosphonate and phosphodiester linkages have been prepared and characterized. One of these single isomer oligonucleotides (Rp) formed a more stable duplex with DNA or RNA than its corresponding natural counterpart. Hybrid stability was more pH-dependent, but less salt-dependent than a natural duplex. The specificity of hybridization was examined by hybridization of an oligonucleotide containing one (2-aminoethyl)phosphonate to oligonucleotides possessing mismatches in the region opposite to the aminoethyl group. In contrast to oligonucleotides containing (aminomethyl)-phosphonate linkages, oligonucleotide (2-aminoethyl)phosphonates were completely stable to hydrolysis in aqueous solution. These oligonucleotides were resistant to nuclease activity but did not induce RNase H mediated cleavage of a complementary RNA strand. Incubation in a serum-containing medium resulted in minimal degradation over 24 hours. Studies of cell uptake by flow cytometry and confocal microscopy demonstrated temperature dependent uptake and intracellular localization. (2-Aminoethyl)phosphonates represent a novel approach to the introduction of positive charges into the backbone of oligonucleotides. 相似文献
7.
8.
Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway 总被引:18,自引:6,他引:12
Kay A. Lawton Leslie Friedrich Michelle Hunt Kris Weymann Terrance Delaney Helmut Kessmann Theodor Staub John Ryals 《The Plant journal : for cell and molecular biology》1996,10(1):71-82
Benzothiadiazole (BTH) is a novel chemical activator of disease resistance in tobacco, wheat and other important agricultural plants. In this report, it is shown that BTH works by activating SAR in Arabidopsis thaliana. BTH-treated plants were resistant to infection by turnip crinkle virus, Pseudomonas syringae pv ‘tomato’ DC3000 and Peronospora parasitica. Chemical treatment induced accumulation of mRNAs from the SAR-associated genes, PR-1, PR-2 and PR-5. BTH treatment induced both PR-1 mRNA accumulation and resistance against P. parasitica in the ethylene response mutants, etr1 and ein2, and in the methyl jasmonate-insensitive mutant, jar1, suggesting that BTH action is independent of these plant hormones. BTH treatment also induced both PR-1 mRNA accumulation and P. parasitica resistance in transgenic Arabidopsis plants expressing the nahG gene, suggesting that BTH action does not require salicylic acid accumulation. However, because BTH-treatment failed to induce either PR-1 mRNA accumulation or P. parasitica resistance in the non-inducible immunity mutant, nim1, it appears that BTH activates the SAR signal transduction pathway. 相似文献
9.
Relationship of lipoamide dehydrogenases from Pseudomonas putida to other FAD-linked dehydrogenases 总被引:5,自引:0,他引:5
Pseudomonas putida produces two lipoamide dehydrogenases, LPD-glc and LPD-val. LPD-val is specifically required as the lipoamide dehydrogenase of branched-chain keto acid dehydrogenase and LPD-glc fulfills all other requirements for lipoamide dehydrogenase. Both proteins are dimers with one FAD per subunit. LPD-glc has an absorption maximum at 455 nm, but LPD-val has a maximum at 460 nm. Comparison of amino acid compositions revealed that LPD-glc was more closely related to Escherichia coli and pig heart lipoamide dehydrogenase than to LPD-val. LPD-val did not appear to be closely related to any of the proteins compared with the possible exception of mercuric reductase. 相似文献
10.
Summary We have developed a miniature silver-silver chloride electrode. The outer diameter of the electrodes averaged 22 m and the input resistance 8.8 k. Since the core of the electrode is a glass fiber, the problem of the extreme malleability of a small diameter silver fiber is circumvented. The properties of the electrode permit us to insert it into short (600 m) fragments of the amphibian collecting duct while they are being perfusedin vitro. The passage of currents in the range of 0 to 6×10–8 amperes allowed us to voltage clamp the nephron fragment between +20 and –20 mV. The current-voltage plots are linear over this range. Two lines of evidence suggest that the voltage clamp is homogeneous. First, the voltage measured at the perfusion end during a voltage-clamp experiment of the tubule is not significantly different from that measured at the collecting end. Secondly, the specific resistance of collecting ducts estimated from the core conductor analysis is 3.3±0.8×104 cm, a value not significantly different from that computed from the current-voltage plots as determined with the Ag–AgCl electrode, 3.0±0.5×104 cm. This method permits precise control of both the ionic and electrical gradients across fragments of the amphibian collecting duct. 相似文献