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Results for “Pathway modelling”

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At least 1,081 records · Page 60Linked to original sources
PubMed1993

Kinetic study on the effects of intracellular K+ and Na+ on Na+, K+, Cl- cotransport of HeLa cells by Rb+ influx determination.

The effects of intracellular K+ and Na+ (K+c, Na+c) on the Na+, K+, Cl- cotransport pathway of HeLa cells were studied by measuring ouabain-insensitive, furosemide-sensitive Rb+ influx (JRb) at various intracellular concentrations of K+ and Na+ ([K+]c, [Na+]c). When [K+]c was increased and [Na+]c was decreased, keeping the sums of their concentrations almost constant, JRb as a function of the extracellular Rb+ or Na+ concentration ([Rb+]e, [Na+]e) was stimulated. However, the apparent K0.5 for Rb+e or Na+e remained unchanged and the ratio of the apparent K0.5 for K+c and the apparent Ki for Na+c was larger than 1. When JRb was increased by hypertonicity by addition of 200 mM mannitol, the apparent maximum JRb increased without change in the apparent K0.5 for Rb+e. These results show that K+c stimulates and Na+c inhibits JRb, without change in the affinities of the pathway for Rb+e and Na+e. The affinity for K+c is slightly lower than that for Na+c. Hypertonicity enhances JRb without any change in the affinity for Rb+e. We derived a kinetic equation for JRb with respect to K+c and Na+c and proposed a general and a special model of the pathway. The special model suggests that, in HeLa cells, JRb takes place when Rb+e binds to the external K+ binding site of the pathway after the binding of K+c to the internal regulatory site.

Biological Transport↗
PubMed2005

Parental illness, family functioning, and adolescent well-being: a family ecology framework to guide research.

A family ecology model for understanding adolescents' reactions to parental illness is presented and used to (a) critically evaluate existing research that examines direct effects of parental illness on family functioning and youth well-being and (b) provide a blueprint for future research in the area. Theoretical, clinical, and empirical literature is reviewed for each mediational and moderational pathway in the model, and limitations of the existing research are discussed. The blueprint for future research emphasizes a greater understanding of the mediational pathways in the model, which is essential for developing effective interventions for families experiencing parental illness. In addition, greater elucidation of moderator variables, such as the youth's developmental stage, social support, and cultural norms will provide critical information on contextual factors that enhance or impede adolescents' adaptation to serious parental illness.

Adaptation, Psychological↗
PubMed2004

A dynamic model of keratinocyte stem cell renewal and differentiation: role of the p21WAF1/Cip1 and Notch1 signaling pathways.

We present here a dynamic model of functional equilibrium between keratinocyte stem cells, transit amplifying populations and cells that are reversibly versus irreversibly committed to differentiation. According to this model, the size of keratinocyte stem cell populations can be controlled at multiple levels, including relative late steps in the sequence of events leading to terminal differentiation and by the influences of a heterogeneous extra-cellular environment. We discuss how work in our laboratory, on the interconnection between the cyclin/CDK inhibitor p21WAF1/Cip1 and the Notch1 signaling pathways, provides strong support to this dynamic model of stem cell versus committed and/or differentiated keratinocyte populations.

Animals↗
PubMed2006

Biosynthesis of novel carotenoid families based on unnatural carbon backbones: a model for diversification of natural product pathways.

We show that the C40 carotenoid desaturase CrtI from Pantoea ananatis (Erwinia uredovora) is capable of desaturating unnaturally long C45 and C50 carotenoid backbones in recombinant E. coli. Desaturation step number in these pathways is not very specific, and at least ten new C45 and C50 carotenoids were synthesized. We also present evidence for a novel asymmetric C40 backbone formed by the condensation of farnesyl diphosphate (C15PP) with farnesylgeranyl diphosphate (C25PP), and the subsequent desaturation of this backbone by CrtI in an atypical manner. Under some conditions, the C40, C45, and C50 carotenoid backbones synthesized in E. coli were monohydroxylated; their desaturation by CrtI in vitro led to yet more novel carotenoids. Challenging CrtI with larger-than-natural substrates in vivo has allowed us to show that this enzyme regulates desaturation step number by sensing the end groups of its substrate. Analysis of the mechanisms by which chemical diversity is generated and propagated through the nascent pathways provides insight into how natural product diversification occurs in nature.

Biological Products↗
PubMed2006

The control of flowering in time and space.

The transition to flowering is one of the most important developmental decisions made by plants. Classical studies have highlighted the importance of photoperiod in controlling flowering time. More recently, the identification of mutants specifically affected in the photoperiod pathway in the model system Arabidopsis thaliana has enabled the flowering time pathways to be placed in a molecular context. This review highlights recent advances in understanding how photoperiod signals (perceived in the leaves) act at the apex of the plant where the floral stimulus is perceived. The photoperiod pathway acts predominantly through the gene CONSTANS to activate the small signalling molecule FT. While FT transcription is induced in the leaves, it is essential that FT protein is present at the apex of the plant. FT at the apex interacts with the transcription factor FD to induce flowering.

Arabidopsis↗
PubMed2004

An informatics search for the low-molecular weight chromium-binding peptide.

BACKGROUND: The amino acid composition of a low molecular weight chromium binding peptide (LMWCr), isolated from bovine liver, is reportedly E:G:C:D::4:2:2:2, though its sequence has not been discovered. There is some controversy surrounding the exact biochemical forms and the action of Cr(III) in biological systems; the topic has been the subject of many experimental reports and continues to be investigated. Clarification of Cr-protein interactions will further understanding Cr(III) biochemistry and provide a basis for novel therapies based on metallocomplexes or small molecules. RESULTS: A genomic search of the non-redundant database for all possible decapeptides of the reported composition yields three exact matches, EDGEECDCGE, DGEECDCGEE and CEGGCEEDDE. The first two sequences are found in ADAM 19 (A Disintegrin and Metalloproteinase domain 19) proteins in man and mouse; the last is found in a protein kinase in rice (Oryza sativa). A broader search for pentameric sequences (and assuming a disulfide dimer) corresponding to the stoichiometric ratio E:D:G:C::2:1:1:1, within the set of human proteins and the set of proteins in, or related to, the insulin signaling pathway, yields a match at an acidic region in the alpha-subunit of the insulin receptor (-EECGD-, residues 175-184). A synthetic peptide derived from this sequence binds chromium(III) and forms a metal-peptide complex that has properties matching those reported for isolated LMWCr and Cr(III)-containing peptide fractions. CONCLUSION: The search for an acidic decameric sequence indicates that LMWCr may not be a contiguous sequence. The identification of a distinct pentameric sequence in a significant insulin-signaling pathway protein suggests a possible identity for the LMWCr peptide. This identification clarifies directions for further investigation of LMWCr peptide fractions, chromium bio-coordination chemistry and a possible role in the insulin signaling pathway. Implications for models of chromium action in the insulin-signaling pathway are discussed.

Journal Article↗
PubMed2004

A model of perceived risk for colorectal cancer among Japanese Americans.

BACKGROUND: Despite the higher rate of colorectal cancer (CRC) among Japanese Americans, little is known about their risk perceptions. The objective of this study was to test an exploratory model explaining psychosocial pathways to perceived risk of CRC. METHODS: The postulated model was tested using path analysis with data from a random sample of 306 Japanese Americans aged 30 and older. RESULTS: The model fit the data very well: chi(2)(10) = 10.22, P = .42; goodness-of-fit index = .993; comparative fit index = .999; and root mean square are of approximation = .008. Cancer fear exerted the strongest effect on perceived risk followed by family history. CONCLUSIONS: Risk communication for Japanese Americans should be tailored to individual emotional patterns associated with cancer to alleviate fear that may impede accurate risk self-assessment.

Acculturation↗
PubMed2007

Explanatory models and help-seeking behavior: Pathways to psychiatric care among patients admitted for depression in Mulago hospital, Kampala, Uganda.

In this article, the authors present findings from a qualitative study exploring how people diagnosed with depression conceptualize their condition and how their conceptualization shaped their efforts to seek help. They used an interview guide based on an explanatory model framework for data collection. Four major themes emerged from the analysis: (a) somatization, social meaning of illness, and help seeking; (b) meaning and perceived consequences of illness; (c) How did I get here? Making sense of psychiatric admission; and (d) variations in the causal attribution and the role of significant others in help seeking. Somatization of emotional problems, variations in causal attribution between patients and their significant others, the nature of the available health care system, and burden of infectious disease complicate access to care. These findings suggest the need to raise the awareness of primary care providers on how to recognize and help people with depression appropriately in this setting.

Adolescent↗
PubMedDate not supplied

The probability of the least likely non-length-controlled bigram affects lexical decision reaction times.

The frequency effect, by which high frequency words are recognized with more ease than low frequency words, is one of the most robust effects in cognitive psychology. Frequency interacts with many word-level variables, to the extent that most effects reported in word recognition literature have an impact only on low frequency words. This has been taken as evidence that high frequency words are accessed in a special way, via either an addressed pathway as in the dual-route model or an assembled pathway as in a PDP model. Under either model, sublexical effects should have no bearing on the ease with which representations for high frequency words are accessed. In this article, however, we describe a series of studies that examine a sublexical effect (namely nonlength controlled minimal bigram frequency) that is only found for high frequency words, suggesting that sublexical processing must play a role in the recognition of even high frequency words.

Cognition↗
PubMed1988

Transition state of the glycolytic pathway under FDP saturating conditions: experimental studies and a theoretical model.

1. The transition state of the glycolytic pathway, under FDP saturating conditions, from no ADP to ADP-saturating levels, is studied in a metabolic model in vitro obtained from rat skeletal muscle. 2. When ADP is absent from the reaction mixture a steady state for NADH concentration is observed. After ADP addition, a new steady state is reached. The transition state from the first steady state to the second one shows a pulse of NADH. Both the profile and the size of this pulse depend on the enzyme concentration. 3. A kinetic model of the lower part of glycolysis (after PFK reaction) is proposed, and this is described by a set of first order coupled nonlinear differential equations. The results obtained through stability analysis and numerical integration of these equations agree with the experimental ones. 4. The possible role of the above mentioned transition state on the transmitter mechanism of glycolytic oscillations from PFK to the lower part of the glycolysis is discussed.

Adenosine Diphosphate↗
PubMed1978

Pharmacokinetic analysis of percutaneous absorption: evidence of parallel penetration pathways for methotrexate.

Compartmental models were developed to describe the penetration of a drug from a topically applied vehicle through the skin. Data for in vitro penetration of methotrexate through hairless mouse skin from vehicles varying in pH from 3.5 to 6.5 were computer-fitted to estimate model parameters. Comparison of lag time and the exponential coefficient suggested that parallel penetration pathways exist. The fraction of drug penetrating through the shunt pathway increased as vehicle pH and ionization increased. Penetration curves were quantitatively partitioned into bulk tissue and shunt contributions. At pH 6.5, flux through the shunt pathway predominated.

Animals↗
PubMed2006

Comparative study of parameter sensitivity analyses of the TCR-activated Erk-MAPK signalling pathway.

Parameter estimation is a major challenge for mathematical modelling of biological systems. Given the uncertainties associated with model parameters, it is important to understand how sensitive the model output is to variations in parameter values. A local sensitivity analysis determines the model sensitivity to parameter variations over a localised region around the nominal parameter values, whereas a global sensitivity analysis (GSA) investigates the sensitivity over the entire parameter space. Using a T-cell receptor-activated Erk-MAPK signalling pathway model as an example, the authors present a comparative study of a variety of different sensitivity analysis techniques. These techniques include: local sensitivity analysis, existing GSA methods of partial rank correlation coefficient, Sobol's, extended Fourier amplitude sensitivity test, as well as a weighted average of local sensitivities and a new GSA method to extract global parameter sensitivities from a parameter identification routine. Results of this study revealed critical reactions in the signalling pathway and their impact on the signalling dynamics and provided insights into embedded regulatory mechanisms such as feedback loops in the pathway. From this study, a recommendation emerges for a general sensitivity analysis strategy to efficiently and reliably infer quantitative, dynamic as well as topological properties from systems biology models.

Algorithms↗
PubMed2004

Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis.

In multiple sclerosis (MS), long-term disability is primarily caused by axonal and neuronal damage. We demonstrated in a previous study that neuronal apoptosis occurs early during experimental autoimmune encephalomyelitis, a common animal model of MS. In the present study, we show that, in rats suffering from myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis, systemic application of erythropoietin (Epo) significantly increased survival and function of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve. We identified three independent intracellular signaling pathways involved in Epo-induced neuroprotection in vivo: Protein levels of phospho-Akt, phospho-MAPK 1 and 2, and Bcl-2 were increased under Epo application. Using a combined treatment of Epo together with a selective inhibitor of phosphatidylinositol 3-kinase (PI3-K) prevented upregulation of phospho-Akt and consecutive RGC rescue. We conclude that in MOG-EAE the PI3-K/Akt pathway has an important influence on RGC survival under systemic treatment with Epo.

Animals↗
PubMed2003

Neuronal network modelling of the effects of anaesthetic agents on somatosensory pathways.

The whole question of consciousness, awareness and depth of anaesthesia is both timely, little understood and deeply challenging. Models of the underlying neural pathway mechanisms/dynamics are necessary for understanding the interactions involved and their structure and function. A neuronal network of the somatosensory pathways is proposed in this paper based on experimental information and physiological investigation into anaesthesia. Existing mathematical neuronal models from the literature have been modified and then employed to describe the dynamics of the proposed pathway network. Effects of anaesthetic agents on the cortex were simulated in the model which describes the evoked cortical responses. By comparison with responses from anaesthetised rats, the model's responses are able to describe the dynamics of typical responses. Thus, the proposed model promises to be valuable for investigating the mechanisms of anaesthesia on the cortex and the effects of brain lesions.

Anesthetics↗