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1.
2.
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
3.
Francesc Gòdia Carles Casas Bernardo Castellano Carles Solà 《Applied microbiology and biotechnology》1987,26(4):342-346
Summary Data of cell concentration, viability and microscopic observation of cell distribution inside carrageenan immobilized yeast beads are reported. Results were obtained from a continuous packed-bed reactor performing alcoholic fermentation and the main observations made on cell activity are in agreement with the fermentation profiles inside the fermenter. 相似文献
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F Villarroya A Felipe T Mampel 《Comparative biochemistry and physiology. A, Comparative physiology》1987,86(3):481-483
Brown adipose tissue properties as well as noradrenaline turnover in the tissue were determined in 15-day lactating rats and virgin controls. Brown adipose tissue thermogenic activity was reduced in lactating rats as shown by a decrease in weight, cytochrome oxidase activity and mitochondrial GDP-binding. The noradrenaline turnover rate was lower in brown adipose tissue from lactating rats. It is suggested that diminished sympathetic activity in brown adipose tissue may be a major cause of the reduced tissue thermogenic activity during lactation. 相似文献
6.
Evidence for a differential physiological modulation of brown fat iodothyronine 5'-deiodinase activity in the perinatal period 总被引:1,自引:0,他引:1
M Giralt I Martin T Mampel F Villarroya R Iglesias O Vi?as 《Biochemical and biophysical research communications》1988,156(1):493-499
Brown adipose tissue iodothyronine 5'-deiodinase increases progressively in fetuses from the day 17 of pregnancy on, it reaches peak values on the 20th day of gestation and declines in the last days of fetal life as well as during the first day of life. Birth of premature fetuses causes a sudden drop in the enzyme activity. Postmaturity is associated to a decrease in brown fat 5'-deiodinase similar to that found after birth in fetuses born at term. In the first hours of life brown fat iodothyronine 5'-deiodinase is essentially insensitive to the cold-stimulus. Present data indicates that, differently from adult rats, brown fat iodothyronine 5'-deiodinase activity during the perinatal period is dissociated from the thermogenic activity of the tissue. It is suggested that factors different from the action of the sympathetic nervous system may play a main role in brown fat iodothyronine 5'-deiodinase activity modulation in the fetal and neonatal life. 相似文献
7.
Immaculada Martin Josep A. Villena Marta Giralt Roser Iglesias Teresa Mampel Octavi Vińas Francesc Villarroya 《Molecular and cellular biochemistry》1996,154(2):107-111
The action of thyroid hormones on the expression of the mitochondrial ATP synthase -subunit gene (ATPsyn) is controversial. We detected a binding site for the thyroid hormone receptor between-366 and-380 in the human ATPsyn gene by DNase I footprint analysis and band-shift assays. However, expression vectors in which the chloramphenicol acetyl transferase (CAT) reporter gene is driven by the 5 upstream region of ATPsyn gene were unresponsive to T3 when transiently transfected to HepG2 or GH4C1 cells. CAT constructs driven by the rat phosphoenolpyruvate carboxykinase (PEPCK) or the growth hormone (GH) promoters were stimulated several fold by T3 in parallel experiments. It is proposed that the biological effects of thyroid hormones on the ATPsyn expression occur through indirect mechanisms. 相似文献
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Carles Campmajó Jordi Joan Cairó Anna Sanfeliu Esteve Martínez Salvador Alegret Francesc Gòdia 《Cytotechnology》1994,14(3):177-182
A flow injection anlytical system based on a gas diffusion membrane module for ammonia and an ammonium flow-through potentiometric detector has been set up for measurement of L-glutamine and ammonium ions in hybridoma cell cultures. The main feature of the system is that the same basic analytical concept and equipment is used in both measurements, the only difference being for the determination of L-glutamine, in which the sample flows through an immobilized glutaminase cartridge. The conditions to enable the performance of both analysis consecutively, avoiding potential interferences by unwanted deamination of other compounds in the samples, have been determined. Finally, the proposed system has been compared with reference analytical methods for batch hybridoma cell culture experiments. 相似文献
10.
Longitudinal patterns of dissolved organic carbon concentration and suspended bacterial density along a blackwater river 总被引:2,自引:0,他引:2
Dissolved organic carbon (DOC) is the dominant form of carbon in transport in blackwater rivers, and bacteria are the major
biological agents of its utilization. This study describes longitudinal patterns in DOC concentration and relates them to
suspended bacterial populations in the channel. Concentrations of total DOC, three molecular weight fractions, and bacterial
numbers were determined at 12 sites along the Ogeechee River in 1985–1986 and 1989 during periods of low and high discharge.
Suspended bacterial populations were compared with DOC concentrations to determine if differences in bacterial abundance were
related to longitudinal patterns of DOC concentration. Three distinct longitudinal patterns were observed: (1) The longitudinal
pattern followed by both total and intermediate molecular weight DOC concentrations was a linear function of the geographic
distance along the river. (2) During low flow conditions, there was a high degree of correspondence between patterns of bacterial
numbers and low MW DOC (< 1000 apparent MW). (3) During periods of high discharge, the proportion of high (> 10,000) and intermediate
(1000–10,000) MW fractions increased, and there was no longer a clear relationship between bacterial cells and low MW DOC. 相似文献