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PubMed2006

Text mining and its potential applications in systems biology.

With biomedical literature increasing at a rate of several thousand papers per week, it is impossible to keep abreast of all developments; therefore, automated means to manage the information overload are required. Text mining techniques, which involve the processes of information retrieval, information extraction and data mining, provide a means of solving this. By adding meaning to text, these techniques produce a more structured analysis of textual knowledge than simple word searches, and can provide powerful tools for the production and analysis of systems biology models.

Artificial Intelligence↗
PubMed2003

Inhibition of the plant cytokinin transduction pathway by bacterial histidine kinase inhibitors in Catharanthus roseus cell cultures.

We describe the isolation of two Catharanthus roseus cDNAs encoding proteins putatively involved in the final steps of a 'histidine-to-aspartate' phosphorelay in cytokinin (CK) signaling. The expression of one of these genes, CrRR1, was specifically up-regulated by CKs in C. roseus cell suspensions. We used this system as a biological model to test the activity of bacterial histidine kinase inhibitors. Our data demonstrate that these inhibitors are active on the CK transduction pathway and represent powerful chemical tools to study hormone signal transduction in plants. Moreover, these data suggest a strong conservation of functional features between prokaryotic and plant signaling pathways utilizing histidine kinases.

Amino Acid Sequence↗
PubMed1992

Optimal selection of metabolic fluxes for in vivo measurement. II. Application to Escherichia coli and hybridoma cell metabolism.

A method of analysis was presented in part I of this series for determining the fluxes in a biochemical network that are the optimal choices for experimental measurement. This algorithm is applied to two important biological models: Escherichia coli and a hybridoma cell line (167.4G5.3). Our results show that potentially poor choices for in vivo measurement of metabolic fluxes exist for both model systems. For the subset of reactions in E. coli that was studied, the condition number of the augmented stoichiometric matrix reveals that a 60-fold amplification of experimental error during computations is possible. The biochemical network of the hybridoma cell is more complex than the E. coli system, and thus results in much larger possible error amplification--up to 100,000-fold. The physiological situations appear to have sensitivities that are less than 1/4 to 1/10 of those estimated by the condition number, and the maximum sensitivities are proportional to the condition number. These maximum sensitivities calculated using estimates of the fluxes and the worst possible error vector are upper bounds on the system's actual sensitivity. By examining the effect of measurement error on the sensitivity, the most probable sensitivity is calculated. These results indicate that an approximate two-fold increase in sensitivity of the E. coli system is likely when the worst set of fluxes are measured rather than the best set. The most likely sensitivity of the hybridoma system can range three orders of magnitude, depending on the set of fluxes that are measured. The propagation of experimental error during computations can be diminished for both systems by increasing the number of flux measurements over and above the minimum number of experimental measurements. The findings from these two model systems indicate that the calculation of the condition number can be a useful method for efficient experimental design, and that the usefulness of this method increases as the order of the system increases.

Animals↗
PubMed2006

Analysis of Ras transformation of human thyroid epithelial cells.

Activation of Ras oncogene by point mutations is an early frequent event in thyroid tumorigenesis. In this chapter, we describe the use of human primary thyroid follicular epithelial cells expressing oncogenic mutant Ras by means of retroviral transduction as a biological model of human cancer initiation that provides powerful insights into thyroid tumorigenesis. We describe protocols for manipulating primary epithelial cells and describe the use of this model to dissect the signaling pathways required for Ras-induced proliferation in these cells. We also highlight the importance of studying Ras signaling in an appropriate cell context, summarizing some of the key differences identified between more widespread experimental models based on fibroblasts or rodent cell lines and primary epithelial cells.

Cell Transformation, Neoplastic↗
PubMed1996

Comparative treatment planning between proton and X-ray therapy in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: Conformal treatment planning with megavoltage X-rays and protons for medically inoperable patients with a large rectal cancer has been studied in an attempt to determine if there are advantages of using protons instead of X-rays. MATERIAL AND METHODS: Three dose plans were made for each of the six patients: one proton plan, including three beams covering the primary tumour and adjacent lymph nodes and three boost beams covering the primary tumour: one X-ray plan, eight beams including a boost with four beams and one mixed plan with four X-ray beams and a boost with three proton beams. A three dimensional treatment-planning systems, TMS, was used. The evaluation of the different plans was made by applying the biological models TCP and NTCP on the dose distributions in terms of dose-volume histograms. RESULTS: The comparison shows advantages of using protons instead of X-rays for all six patients, but in three of them, the advantage is only marginal. The dose-limiting organ at risk is the small bowel, but the proton plan and the mixed plan also spare the bladder and the femoral heads better. At 5% NTCP in any risk organ, the calculated mean TCP value for the six patients is increased by 14%-units with the proton plan and 8%-units with the mixed plan compared to X-rays only. CONCLUSIONS: Proton beam therapy has potential advantages when treating medically inoperable patients with a large rectal cancer over conventional X-ray therapy. Since the benefits are comparatively small, although clinically worthwhile, large randomised studies are needed.

Aged↗
PubMed1998

Monitoring brain activity of human subjects during delayed matching to sample tasks comparing verbal and pictorial stimuli with modal and cross-modal presentation: an event related potential study employing a source reconstruction method.

The time course of the event related potentials evoked within a delayed matching to sample task employing verbal and pictorial stimuli was analyzed with a source reconstruction method (minimum norm method). During signal stimulus presentation pictorial stimuli evoked more activity than verbal stimuli. Activity was particularly prominent in left frontal areas for the match of verbal-verbal stimulus pairs and over right posterior regions for the match of verbal-pictorial stimuli. Anticipation of the to-be-matched stimulus produced more pronounced activity for pictorial stimuli and generally stronger left and frontal activity. Results are discussed referring to a biological model of language processing.

Adult↗
PubMed1998

Precautions in warming light therapy as an adjuvant to postoperative flap care.

Warming lights, circulating-water blankets, space heaters, and the Bair Hugger are used by surgeons in the perioperative period to maintain a patients core body temperature. Warming lights in particular are often used by plastic surgeons to augment the postoperative vasodilatation of reconstructive flaps by increasing the ambient temperature of the area around the flap. A review of the literature fails to elucidate even anecdotal experience regarding the actual intensity of thermal energy directly imparted to tissues from these modalities with respect to distance. The purpose of our study was to quantify actual tissue temperatures generated, as a function of distance, with the Emerson warming light. Our interest in this is a result of a full-thickness burn which occurred to a portion of a pedicled TRAM flap used for breast reconstruction when a warming light was inadvertently positioned, during the course of the first postoperative night, at a distance less than that recommended by the manufacturer. A biological model was created simulating a sympathectomized flap and the temperature curves generated by Emerson warming lights were recorded by calibrated glass bulb thermometers at 15 min intervals for distances of 32 and 71 cm using both focused and defocused light beams. The distance of 32 cm was used as a parameter as it was the distance noted between the patient and the warming light when the TRAM flap burn occurred. Temperatures obtained at a distance of 32 cm rose to 120 degrees F (48.8 degrees C) within 30 min for the focused beam and 118 degrees F (48 degrees C) after 1 h for the defocused beam. This exceeds the temperature at which tissue necrosis is known to occur (111.2 degrees F/44 degrees C). However, temperatures obtained at 71 cm for the focused and defocused beams plateaued at 93.2 and 96.8 degrees F (34 and 36 degrees C) respectively, which is well within physiologic limits and below the temperature resulting in tissue necrosis. Our conclusion is that warming lights can be successfully used as a safe adjuvant in order to optimize flap vasodilatation without compromising the thermal threshold of tissue damage if maintained at the manufacturer's minimum recommended distance of 71 cm. If this source of thermal energy is used, however, strict precautions and nursing guidelines must be instituted to maintain this minimum distance parameter and prevent patient morbidity.

Animals↗
PubMed2000

Biochemical and ultrastructural alterations caused by newly synthesized 1,2,4-triazole[1,5a]pyrimidine derivatives against Phytomonas staheli (Trypanosomatidae).

Six compounds, all newly synthesized triazole-pyrimidine derivatives that proved inhibitory of in in vitro growth of epimastigotes in Trypanosoma cruzi and of promastigotes of Leishmania donovani and Phytomonas staheli, were studied to investigate their toxic effects. As a biological model, the plant trypanosome P. staheli, which causes sudden wilt in the oil palm and Hartrot in the coconut palm, was used. The six compounds markedly inhibited macromolecule synthesis (nucleic acids and proteins) by the parasite. The cells treated with these compounds present severe damage in their ultrastructure-intense 'vacuolization, and appearance of lysosomes as well as other residual bodies. The mitochondrial section appeared larger in size. with a swollen matrix. In addition, these compounds changed the excretion of end metabolites, primarily affecting ethanol and acetate excretion, possibly by directly influencing certain enzymes (alcohol dehydrogenase and acetate synthetase) or their synthesis. 2000 Elsevier Science Ltd.

Animals↗
PubMed1992

The Drosophila nuclear receptors: new insight into the actions of nuclear receptors in development.

In Drosophila melanogaster, an increasing number of members of the steroid hormone receptor superfamily are being identified and characterized. Molecular and genetic analysis of receptor function provides evidence for a set of functions underlying the determination of pattern formation, metamorphosis, eye development, and reproduction. Many of the Drosophila receptor genes show striking homologies to mammalian receptor genes. This suggests that genetic analysis in flies could facilitate the generation of biological models that pertain to complex hormonal responses in development and which are relevant to both vertebrate and invertebrate systems.

Animals↗
PubMed2000

Temperament and personality: origins and outcomes.

This article reviews how a temperament approach emphasizing biological and developmental processes can integrate constructs from subdisciplines of psychology to further the study of personality. Basic measurement strategies and findings in the investigation of temperament in infancy and childhood are reviewed. These include linkage of temperament dimensions with basic affective-motivational and attentional systems, including positive affect/approach, fear, frustration/anger, and effortful control. Contributions of biological models that may support these processes are then reviewed. Research indicating how a temperament approach can lead researchers of social and personality development to investigate important person-environment interactions is also discussed. Lastly, adult research suggesting links between temperament dispositions and the Big Five personality factors is described.

Adult↗
PubMed1984

Role of the liver in normal iron metabolism.

An integrated approach to normal hepatic iron metabolism requires an understanding of the complex interactions between the dynamic processes of iron uptake, utilization, storage, and release. Lack of knowledge of the specific chemical and physical properties of certain critical compartments of hepatic iron (such as the transit pool and hemosiderin) and of their relative turnover rates has made it extremely difficult to assign precise parameters to their dynamic interactions. With refinement in biochemical and biophysical techniques and with their application to valid biologic models, it should be possible to obtain insights into these areas, which are currently obscure.

Ferritins↗
PubMed2001

Overcompensation stimulation: a mechanism for hormetic effects.

Whether hormetic responses result from a direct or an overcompensation type of stimulatory response has been an unresolved and contentious issue in both radiation and chemical toxicology. The goal of the present article is to identify numerous examples of overcompensation stimulation in the biological/biomedical literature and to evaluate their descriptive and quantitative features. The findings provide support for the hypothesis that hormetic dose-response relationships from a broad array of biological models can occur after an initial disruption in homeostasis. The finding also demonstrates the significant role of temporal factors in the assessment of dose response relationships.

Adaptation, Physiological↗
PubMed2001

Adrenergic receptors: biphasic dose responses.

Agonists and antagonists of the adrenergic receptor system were assessed for their capacity to affect dose-response relationships across biological model, tissue and endpoint. U shaped dose responses were commonly reported, affecting multiple endpoints such as smooth muscle contraction/relaxation, memory, blood pressure, sexual behavior, platelet aggregation, and others. In six of the endpoints studied, mechanistic foundations of the biphasic nature of the dose response were established. The quantitative features of the dose-response relationships indicated that the maximum stimulatory responses, with but one exception, were less than twofold greater than the controls. The range of stimulatory responses was generally within 10- to 1000-fold, except for the platelet aggregation endpoint where the range was 10(3) to 10(5).

Adrenergic Agonists↗
PubMed2005

Testing simple indices of habitat proximity.

Simple measures of habitat proximity made primarily on the basis of land cover are widely used in the ecological literature to infer habitat connectivity, or the potential for animal movement among resource patches. However, such indices rarely have been tested against observations of animal movement or against more detailed biological models. We developed a priori expectations as to the types of study systems and organisms for which various habitat proximity indices would be best suited. We then used data from three study systems and four species to test which, if any, of the indices were good predictors of population-level responses. Our a priori expectations about index performance were not upheld. The indices that consider both habitat area and distance from the focal patch were highly correlated with each other, suggesting that they do index similar quantities. However, none of the indices performed well in predicting population response variables. The results suggest that the pattern of habitat cover alone may be insufficient to predict the process of animal movement.

Animal Migration↗
PubMed1979

Familial aggregation of blood pressure and weight in adoptive families. II. Estimation of the relative contributions of genetic and common environmental factors to blood pressure correlations between family members.

An analysis of the familial aggregation of blood pressure (BP) was conducted to provide estimates of the role of genes and household environment in determining the phenotypic resemblance between biologically related family members. The biological model used for this analysis parameterizes the correlations between family members into the contributions of genetic and environmental variability shared within and across generations. Hypothesis testing about different parameters in the model suggests that shared environment explains larger fractions of the parent-natural child and the full sib correlations for diastolic BP than for systolic BP. For diastolic BP, children in a household share the effects of common environment in addition to the effects which they share with their parents. Dependence of the degree of resemblance between household members on the effects of environmental factors shared within and a-ross generations is not explained by the variability of length of cohabitation among individuals.

Adolescent↗
PubMed1983

Familial aggregation of blood pressure and weight in adoptive families. III. Analysis of the role of shared genes and shared household environment in explaining family resemblance for height, weight and selected weight/height indices.

This study presents an analysis of the role of genetic and household environment in explaining the familial aggregation of height (HT), weight (WT), and body mass indices (WT/HT1.2 and WT/HT2.0). The biologic model used for the analysis partitions the covariances between family members into the contributions of genetic and environmental variability shared within and across generations, including a variance component shared only by a mother and her natural children. Tests of hypotheses suggest that shared genes and shared household environmental factors make significant contributions to the familial aggregation of WT (adjusted for age and sex) and of HT (adjusted for age and sex), whereas family resemblance of WT adjusted for age and HT can be attributed mostly to the effects of shared genes. The familial aggregation of selected WT/HT indices is attributed to the effects of shared household environment only, suggesting that these variables measure a characteristic of stature that is independent of height and weight.

Adolescent↗
PubMed2002

Color constancy: the role of low-level mechanisms.

Color constancy (CC) is an important psychophysical phenomenon, which has been studied extensively. However, it is not clearly understood. This study presents a novel biological model for the contribution of low level mechanisms to CC. The model is based on two chromatic adaptation mechanisms in the color-coded retinal ganglion cells, 'local' and 'remote', which cause a 'curve-shifting' effect at each receptive field subregion. Simulations are employed for calculating the perceived image and measuring the degree of CC using both 'human-perception' and 'machine-vision' indices. The results indicate that the contribution of adaptations to CC is significant, robust and in agreement with experimental findings. The model is successful in performing CC under multiple chromatic illumination sources, a condition which mimics common natural environments.

Adaptation, Physiological↗