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排序方式: 共有475条查询结果,搜索用时 15 毫秒
1.
Daniel Rivas-Barragan Sarah Mubeen Francesc Guim Bernat Martin Hofmann-Apitius Daniel Domingo-Fernndez 《PLoS computational biology》2020,16(12)
Elucidating the causal mechanisms responsible for disease can reveal potential therapeutic targets for pharmacological intervention and, accordingly, guide drug repositioning and discovery. In essence, the topology of a network can reveal the impact a drug candidate may have on a given biological state, leading the way for enhanced disease characterization and the design of advanced therapies. Network-based approaches, in particular, are highly suited for these purposes as they hold the capacity to identify the molecular mechanisms underlying disease. Here, we present drug2ways, a novel methodology that leverages multimodal causal networks for predicting drug candidates. Drug2ways implements an efficient algorithm which reasons over causal paths in large-scale biological networks to propose drug candidates for a given disease. We validate our approach using clinical trial information and demonstrate how drug2ways can be used for multiple applications to identify: i) single-target drug candidates, ii) candidates with polypharmacological properties that can optimize multiple targets, and iii) candidates for combination therapy. Finally, we make drug2ways available to the scientific community as a Python package that enables conducting these applications on multiple standard network formats. 相似文献
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Tumor necrosis factor induces acute phase proteins in rats 总被引:2,自引:0,他引:2
I Gresser F Delers N Tran Quangs S Marion R Engler C Maury C Soria J Soria W Fiers J Tavernier 《Journal of biological regulators and homeostatic agents》1987,1(4):173-176
Inoculation of WAG rats with recombinant mouse tumor necrosis factor results in a rapid and marked increase in several acute phase proteins in the serum (haptoglobin, alpha 1 acid glycoprotein, alpha 2 macroglobulin) and in the plasma (fibrinogen). We conclude that TNF may play an important role in the inflammatory response in vivo and possibly in the pathogenesis of inflammatory disorders. 相似文献
4.
R Lorenzetti A Sidoli R Palomba L Monaco D Martineau D A Lappi M Soria 《FEBS letters》1986,200(2):343-346
To determine whether phospholipid is required for the activity of mammalian signal peptidase, the enzyme was partially purified from porcine pancreas and then extensively freed of phospholipid by SP-Sephadex C-50 chromatography. The delipidated enzyme showed signal peptidase activity, with a low concentration of detergent. Phospholipid was found to release the enzyme from the inhibition due to excess detergent. 相似文献
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Injection of purified autoantibodies against human centromeric proteins into HeLa cells during interphase disrupts the organization of the kinetochore and interferes with chromosomal movements during the subsequent mitosis even though the chromosomes retain the ability to bind microtubules. We have investigated the hypothesis that this phenotype arises from effects on cytoplasmic dynein, the microtubule motor protein. In previous experiments we found that introduction of anticentromere antibodies into cell nuclei during the G1- or S-phases causes a prometaphase-like arrest, while injections during G2-phase cause a metaphase arrest. We show here that, in both cases, the level of detectable cytoplasmic dynein at kinetochores is significantly decreased. In contrast, when injected cells were permitted to enter mitosis in the absence of microtubules (conditions where trilaminar kinetochores could be detected by electron microscopy), the intensity of dynein labeling on the kinetochores was identical to that seen in uninjected control cells exposed to colcemid. Therefore, the loss of dynein label on mitotic kinetochores was correlated both with the injection of anticentromere antibodies and with the presence of intact spindle microtubules. We suggest that the injection of anticentromere antibodies somehow weakens the association of dynein with the kinetochore, so that when microtubules are present, these motor molecules are pulled away from the kinetochores as they generate force. This model offers an explanation for the failure of chromosomes of injected cells to move normally in mitosis even though they have attached microtubules. 相似文献
7.
Arsenio Fernández-López Carlos Soria Victoria Revilla Tomás Gómez Pedro Calvo 《Neurochemical research》1994,19(4):445-449
At 4 days after the implantation of two subcutaneous 75 mg morphine pellets in the back skin, rats were morphine-dependent. In the three layers studied in the occipital cortex we found that the values of the 2-adrenergic agonist [3H]bromoxidine binding increased with respect to animals implanted with placebo pellets. Typical behavioral and physiological symptoms of the abstinence syndrome appeared 30 minutes after administration of naloxone, [3H]bromoxidine binding values being similar to those obtained in animals implanted with placebo pellets. The pattern of response of the [3H]bromoxidine binding was similar in the hippocampus and the superficial gray layer of the superior colliculus of the mesencephalon, but the differences were not statistically significant in these areas. This paper concludes that exist brain regional differences in the 2-adrenoreceptors response under morphine-treatment and possibly under naloxone-induced morphine abstinence syndrome. 相似文献
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The life-history parameters reproduction rate, developmental time and age specific survival of the western flower thrips,Frankliniella occidentalis (Pergande) [Thysanoptera: Thripidae], were determined on susceptible and resistant cucumber (Cucumis sativus L.) genotypes. Both newly emerged andF. occidentalis females of mixed ages showed a substantial reduction (36 to 50%) of the reproduction rate on all resistant genotypes, in
particular after the second day. On the resistant genotypes 9127 and 9140,F. occidentalis had a prolonged developmental period. This was primarily due to a prolongation of the second larval stage. On all resistant
genotypes,F. occidentalis suffered from high (82 to 97%) preadult mortality, predominantly at the second larval stage. It is conclude that the resistant
genotypes do not cause an immediate intoxication of adult nor preadult thrips stages. 相似文献
10.
The ammonification rates in surficial sediments of the Marica lagoon (Rio de Janeiro, Brazil) were estimated using two methods:
The sedimentation rate, evaluated by means of the 210Pb method, differed in various areas of the lagoon. It was 0.35 cm y–1 in the open area of the lagoon (at 1.6 m in water depth), near the mouth of the Mombuca river (site M2); and 0.27 to 0.28 cm y–1 at 1.6 to 1.7 m at a greater distance of the river mouth (site M4). In a confined part of the lagoon (Z1), surrounded by reeds (Typha dominguensis), the rate is lower: 1 to 1.4 mm y–1 in the upper level (from 0 to 4 cm) where the organic matter amount reaches 60 to 80% (dry w.), and 1.1 to 1.2 mm y–1 deeper (below 5 cm) where organic matter corresponds to less than 40% of the sediment. 相似文献
(1) | A direct evaluation of the ammonia productivity in sediments by means of an incubation procedure: the ammonia production rate is deduced from the difference in the ammonia concentrations in interstitial waters which were extracted directly after sampling and after incubation from two samples collected at the same point. |
(2) | Since ammonia results essentially from the destruction of organic nitrogen, the ammonia productivity will be obtained by evaluating the nitrogen destruction rate: the amount of organic N mineralized is assumed to correspond to NH inf4 sup+ produced. The organic N destruction rate can be calculated by means of the matter balance equation provided the organic nitrogen profile and the sediment accumulation rate are known. |