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At least 793 records · Page 44Linked to original sources
PubMed2006

Assessment of axonal degeneration along the human visual pathway using diffusion trace analysis.

PURPOSE: The effectiveness of diffusion trace value analysis for non-invasive assessment of retinal ganglion cell (RGC) axonal degeneration at multiple anatomic levels along the human visual pathway under clinical setting was evaluated. DESIGN: Imaging study. METHODS: Ten patients with unilateral chronic optic neuropathy of varying cause and 16 age-matched normal subjects were studied. Trace, a tensor invariant that is considered to be a sensitive index for pathologic changes in axons, was analyzed at nine anatomic sites in each subject, namely, bilaterally at the level of the optic nerves, uncrossed chiasmal fibers, optic tracts and optic radiations, and crossed chiasmal fibers, using a 3.0 Tesla magnetic resonance imaging system. RESULTS: Trace values of the optic nerve and uncrossed chiasmal fibers ipsilateral to the affected eye, the crossed chiasmal fibers, and optic tracts bilaterally were significantly higher than those of the corresponding anatomic sites in normal subjects. The optic nerve and uncrossed chiasmal fibers ipsilateral to the unaffected side and optic radiations, bilaterally, had trace values which were not significantly different from the values of the corresponding anatomic levels in normal subjects. The increase in trace value in the optic nerve and uncrossed chiasmal fibers ipsilateral to the affected side was greater than those of the crossed chiasmal fibers and optic tracts. CONCLUSIONS: Findings are highly consistent with a degenerative process of RGC axons and trace values are quantitatively well correlated to predicted pathology at the given anatomical sites. Trace value measurement at multiple sites along fiber pathways appears to be a powerful addition to clinical assessment of the functionality of components of the visual pathways during various stages of a pathologic process.

Adult↗
PubMed2006

PUMA2--grid-based high-throughput analysis of genomes and metabolic pathways.

The PUMA2 system (available at http://compbio.mcs.anl.gov/puma2) is an interactive, integrated bioinformatics environment for high-throughput genetic sequence analysis and metabolic reconstructions from sequence data. PUMA2 provides a framework for comparative and evolutionary analysis of genomic data and metabolic networks in the context of taxonomic and phenotypic information. Grid infrastructure is used to perform computationally intensive tasks. PUMA2 currently contains precomputed analysis of 213 prokaryotic, 22 eukaryotic, 650 mitochondrial and 1493 viral genomes and automated metabolic reconstructions for >200 organisms. Genomic data is annotated with information integrated from >20 sequence, structural and metabolic databases and ontologies. PUMA2 supports both automated and interactive expert-driven annotation of genomes, using a variety of publicly available bioinformatics tools. It also contains a suite of unique PUMA2 tools for automated assignment of gene function, evolutionary analysis of protein families and comparative analysis of metabolic pathways. PUMA2 allows users to submit batch sequence data for automated functional analysis and construction of metabolic models. The results of these analyses are made available to the users in the PUMA2 environment for further interactive sequence analysis and annotation.

Computational Biology↗
PubMed1999

Morphological and biochemical analysis of the secretory pathway in melanoma cells with distinct metastatic potential.

In this report, we have investigated whether alterations of the morphological and functional aspects of the biosecretory membrane system are associated with the metastatic potential of tumor cells. To this end, we have analyzed the morphology of the Golgi complex, the cytoskeleton organization and membrane trafficking steps of the secretory pathway in two human melanoma A375 cell line variants with low (A375-P) and high metastatic (A375-MM) potential. Immunofluorescence analysis showed that in A375-P cells, the Golgi complex showed a collapsed morphology. Conversely, in A375-MM cells, the Golgi complex presented a reticular and extended morphology. At the ultrastructural level, the Golgi complex of A375-P cells was fragmented and cisternae were swollen. When the cytoskeleton was analyzed, the microtubular network appeared normal in both cell variants, whereas actin stress fibers were largely absent in A375-P, but not in A375-MM cells. In addition, the F-actin content in A375-P cells was significantly lower than in A375-MM cells. These morphological differences in A375-P cells were accompanied by acceleration and an increase in the endoplasmic reticulum to Golgi and the trans-Golgi network to cell surface membrane transport, respectively. Our results indicate that in human A375 melanoma cells, metastatic potential correlates with a well-structured morphofunctional organization of the Golgi complex and actin cytoskeleton.

Biological Transport↗
PubMed2003

Kinetic modelling of Amadori N-(1-deoxy-D-fructos-1-yl)-glycine degradation pathways. Part II--kinetic analysis.

A kinetic model for N-(1-deoxy-D-fructos-1-yl)-glycine (DFG) thermal decomposition was proposed. Two temperatures (100 and 120 degrees C) and two pHs (5.5 and 6.8) were studied. The measured responses were DFG, 3-deoxyosone, 1-deoxyosone, methylglyoxal, acetic acid, formic acid, glucose, fructose, mannose and melanoidins. For each system the model parameters, the rate constants, were estimated by non-linear regression, via multiresponse modelling. The determinant criterion was used as the statistical fit criterion. Model discrimination was performed by both chemical insight and statistical tests (Posterior Probability and Akaike criterion). Kinetic analysis showed that at lower pH DFG 1,2-enolization is favoured whereas with increasing pH 2,3-enolization becomes a more relevant degradation pathway. The lower amount observed of 1-DG is related with its high reactivity. It was shown that acetic acid, a main degradation product from DFG, was mainly formed through 1-DG degradation. Also from the estimated parameters 3-DG was found to be the main precursor in carbohydrate fragments formation, responsible for colour formation. Some indication was given that as the reaction proceeded other compounds besides DFG become reactants themselves with the formation among others of methylglyoxal. The multiresponse kinetic analysis was shown to be both helpful in deriving relevant kinetic parameters as well as in obtaining insight into the reaction mechanism.

Acetic Acid↗
PubMed1990

Integration of temporal analysis and control analysis of metabolic systems.

A theory is developed that integrates approaches to the analysis of pathway transient response and metabolic control analysis. A Temporal Control Coefficient is defined that is a measure of the system's transient response to modulation of enzyme activity or concentration. The approach allows for the analysis of the establishment of a steady state from rest, of the system's 'agility' of response to minor perturbations of a pre-existing steady state and of the macroscopic transition between steady states. In the last-mentioned case it is shown that, like the transient time itself, the control of transient response retains the property of independence from the mechanism of the transition. In consequence, the Temporal Control Coefficient can be defined in terms of the control properties of the initial and final states alone without reference to the mechanism of transition. A summation property is shown to apply to the Temporal Control Coefficients in each case. Connectivity relationships between elasticities and Temporal Control Coefficients are also established.

Enzymes↗
PubMed2003

The role of cryptochrome 2 in flowering in Arabidopsis.

We have investigated the genetic interactions between cry2 and the various flowering pathways in relation to the regulation of flowering by photoperiod and vernalization. For this, we combined three alleles of CRY2, the wild-type CRY2-Landsberg erecta (Ler), a cry2 loss-of-function null allele, and the gain-of-function CRY2-Cape Verde Islands (Cvi), with mutants representing the various photoreceptors and flowering pathways. The analysis of CRY2 alleles combined with photoreceptor mutants showed that CRY2-Cvi could compensate the loss of phyA and cry1, also indicating that cry2 does not require functional phyA or cry1. The analysis of mutants of the photoperiod pathway showed epistasis of co and gi to the CRY2 alleles, indicating that cry2 needs the product of CO and GI genes to promote flowering. All double mutants of this pathway showed a photoperiod response very much reduced compared with Ler. In contrast, mutations in the autonomous pathway genes were additive to the CRY2 alleles, partially overcoming the effects of CRY2-Cvi and restoring day length responsiveness. The three CRY2 alleles were day length sensitive when combined with FRI-Sf2 and/or FLC-Sf2 genes, which could be reverted when the delay of flowering caused by FRI-Sf2 and FLC-Sf2 alleles was removed by vernalization. In addition, we looked at the expression of FLC and CRY2 genes and showed that CRY2 is negatively regulated by FLC. These results indicate an interaction between the photoperiod and the FLC-dependent pathways upstream to the common downstream targets of both pathways, SOC1 and FT.

Arabidopsis↗
PubMed1994

Characterization of human peripheral blood monocyte thromboxane A2 receptors.

Thromboxane A2 (TxA2) is the predominant eicosanoid metabolite produced by activated human blood-borne monocytes. This study was designed to characterize TxA2 receptors on human peripheral blood monocytes via identification of radioligand binding characteristics using the stable TxA2 mimetic [125I]-BOP ([1S,(1 alpha,2 beta(5Z),3 alpha(1E,3S*),4 alpha]-7-[3-hydroxy-4-(4'- iodophenoxy-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-he ptenoic acid) and via analysis of second messenger signal transduction pathways. Scatchard analysis of the binding of [125I]-BOP in human monocyte membranes revealed a single class of binding sites, Kd = 1.49 +/- 0.14 nM and Bmax = 696 +/- 113 fmol/mg membrane protein (n = 8). [125I]-BOP interacted specifically with a TxA2 receptor, as shown by competition binding studies with a range of TxA2 receptor agonists and antagonists that gave a rank order of potency of (-)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid > I-BOP = I-SAP > ONO11113 > SQ29548 > U46619 > (+)-9-chlorobenzyl-6-fluoro-1,2,3,4- tetrahydrocarbazol-1-yl acetic acid. I-BOP caused a dose-dependent increase in intracellular free calcium (EC50 = 7.14 +/- 1.1 nM, n = 4), which was attenuated by preincubation with the TxA2 receptor antagonists SQ29548 (1 microM) and (-)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid (100 nM). This study provides further evidence for a TxA2 receptor in monocytes and supports the potential for future characterization of TxA2 receptor subtypes using molecular techniques.

Bridged Bicyclo Compounds↗
PubMed2004

The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX.

The ataxia-telangiectasia mutated (ATM) protein kinase is activated in response to ionizing radiation (IR) and activates downstream DNA-damage signaling pathways. Although the role of ATM in the cellular response to ionizing radiation has been well characterized, its role in response to other DNA-damaging agents is less well defined. We previously showed that genistein, a naturally occurring isoflavonoid, induced increased ATM protein kinase activity, ATM-dependent phosphorylation of p53 on serine 15 and activation of the DNA-binding properties of p53. Here, we show that genistein also induces phosphorylation of p53 at serines 6, 9, 20, 46, and 392, and that genistein-induced accumulation and phosphorylation of p53 is reduced in two ATM-deficient human cell lines. Also, we show that genistein induces phosphorylation of ATM on serine 1981 and phosphorylation of histone H2AX on serine 139. The related bioflavonoids, daidzein and biochanin A, did not induce either phosphorylation of p53 or ATM at these sites. Like genistein, quercetin induced phosphorylation of ATM on serine 1981, and ATM-dependent phosphorylation of histone H2AX on serine 139; however, p53 accumulation and phosphorylation on serines 6, 9, 15, 20, 46, and 392 occurred in ATM-deficient cells, indicating that ATM is not required for quercetin-induced phosphorylation of p53. Our data suggest that genistein and quercetin induce different DNA-damage induced signaling pathways that, in the case of genistein, are highly ATM-dependent but, in the case of quercetin, may be ATM-dependent only for some downstream targets.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1986

The effect of feedback on pathway transient response.

The effect of variation of the rate of input of material on the transient behaviour of metabolic pathways is examined. This reveals the existence of three transient times which make up the overall pathway transient. Two of these have been described previously and represent the times required for the accumulation of the free intermediate pool and the pool of enzyme-bound intermediate. They are state functions and as such are independent of the way in which the steady state was reached. The third is attributable to the variation in the rate of input of material to the pathway. It is dependent on three further factors. These are (a) the time required for the initial enzyme to reach its own steady state, (b) substrate depletion and (c) feedback. The description of the transient is: (Formula: see text) where V0 represents the rate of input and Vss represents the steady-state flux. The transient time associated with the transition between steady-states is shown to be a simple function of the transients for the establishment of each steady state from rest and may be expressed as: tau = tau b-Va/Vb . tau a where Va and Vb refer to the fluxes in the two steady states and tau a and tau b represent the transient times for the establishment of each of the steady-states from rest. The total pathway transient may now be completely defined as: (formula: see text) where summation over all intermediates, I, is implied. The significance of this to the analysis of pathway behaviour is discussed with more general examples of pathway transient analysis.

Enzymes↗
PubMed1994

Network analysis of cortical visual pathways mapped with PET.

Brain metabolic mapping techniques, such as positron emission tomography (PET), can provide information about the functional interactions within entire neural systems. With the large quantity of data that can accumulate from a mapping study, a network analysis, which makes sense of the complex interactions among neural elements, is necessary. A network analysis was performed on data obtained from a PET study that examined both the changes in regional cerebral blood flow (rCBF) and interregional correlations among human cortical areas during performance of an object vision (face matching) and spatial vision (dot-location matching) task. Brain areas for the network were selected based on regions showing significant rCBF or interregional correlations between tasks. Anterior temporal and frontal lobe regions were added to the network using a principal components analysis. Interactions among selected regions were quantified with structural equation modeling. In the structural equation models, connections between brain areas were based on known neuroanatomy and the interregional correlations were used to calculate path coefficients representing the magnitude of the influence of each directional path. The combination of the anatomical network and interregional correlations created a functional network for each task. The functional network for the right hemisphere showed that in the object vision task, dominant path influences were among occipitotemporal areas, while in the spatial vision task, occipitoparietal interactions were stronger. The network for the spatial vision task also had a strong feedback path from area 46 to occipital cortex, an effect that was absent in the object vision task. There were strong interactions between dorsal and ventral pathways in both networks. Functional networks for the left hemisphere did not differ between tasks. Networks for the interhemispheric interactions showed that the dominant pathway in the right hemisphere also had stronger effects on homologous left hemisphere areas and are consistent with a hypothesis that intrahemispheric interactions were greater in the right hemisphere in both tasks, and that these influences were transmitted callosally to the left hemisphere.

Adult↗
PubMed2026

ACE2 and Parkinsonism‑related bone metabolic alterations: signaling pathways and hub gene analysis.

Clinical co-occurrence of Parkinson's disease (PD) and age-related bone loss in elderly patients has garnered increasing attention, yet its molecular mechanisms remain incompletely elucidated. This study used an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in Ace2-/y mice to investigate the regulatory mechanisms of bone-brain axis-related genes and signaling pathways. Behavioral tests assessed motor and non-motor symptoms. Immunohistochemistry, Western blot, and histopathological staining analyzed dopaminergic neuron activity, microglial activation, and bone metabolic abnormalities. GEO dataset transcriptomics and weighted gene co-expression network analysis (WGCNA) identified key hub genes, with receiver operating characteristic (ROC) curves evaluating their diagnostic value in public single-disease transcriptome data. MPTP significantly exacerbated motor dysfunction and depression-like behaviors; Ace2 deletion lowered total Wnt, β-catenin, BMP and IGF-1 protein abundance alongside reduced phosphorylation ratios of their downstream kinases in brain and bone, while upregulating RANKL/RANK/OPG-associated inflammatory mediators, accompanied by elevated total α-synuclein, Casp3 and Bax protein levels. The parallel reduction of these signaling proteins only suggests potential perturbation of related cascades; WGCNA identified 10 hub genes (e.g., DNM1, OCRL, OPA1), whose dysregulation was linked to synaptic dysfunction and inflammation. ROC analysis based on single-disease datasets showed high diagnostic accuracy for PD and `osteoporosis (OP) (AUC: 0.683-0.981), with core genes influencing synaptic, MAPK, Rap1, and Ras pathways. These preclinical findings indicate that Ace2 deficiency is associated with concurrent pathological abnormalities in the brain and transient bone metabolic disturbance under short-term MPTP treatment in growing young male mice; coordinated dysregulation of shared signaling pathways was observed in the two tissues, consistent with a potential bone-brain axis pathological phenotype, though causal bidirectional tissue cross-talk cannot be confirmed in the current experimental design, providing candidate targets that warrant further validation.

Animals↗
PubMed2004

Functional topology in a network of protein interactions.

MOTIVATION: The building blocks of biological networks are individual protein-protein interactions (PPIs). The cumulative PPI data set in Saccharomyces cerevisiae now exceeds 78 000. Studying the network of these interactions will provide valuable insight into the inner workings of cells. RESULTS: We performed a systematic graph theory-based analysis of this PPI network to construct computational models for describing and predicting the properties of lethal mutations and proteins participating in genetic interactions, functional groups, protein complexes and signaling pathways. Our analysis suggests that lethal mutations are not only highly connected within the network, but they also satisfy an additional property: their removal causes a disruption in network structure. We also provide evidence for the existence of alternate paths that bypass viable proteins in PPI networks, while such paths do not exist for lethal mutations. In addition, we show that distinct functional classes of proteins have differing network properties. We also demonstrate a way to extract and iteratively predict protein complexes and signaling pathways. We evaluate the power of predictions by comparing them with a random model, and assess accuracy of predictions by analyzing their overlap with MIPS database. CONCLUSIONS: Our models provide a means for understanding the complex wiring underlying cellular function, and enable us to predict essentiality, genetic interaction, function, protein complexes and cellular pathways. This analysis uncovers structure-function relationships observable in a large PPI network.

Algorithms↗
PubMed1994

Analysis of the mitogenic pathway of the FLT3 receptor and characterization in its C terminal region of a specific binding site for the PI3' kinase.

The FLT3 receptor tyrosine kinase (RTK) belongs to the class III subfamily which includes PDGF, CSF1 and SLF receptors. The recent cloning of the FLT3 ligand suggesting its important role in the differentiation and proliferation of the hematopoietic stem cells, has confirmed the initial expression analysis showing restricted pattern of receptor expression within the primitive hematopoietic population. To better understand the function of the FLT3 receptor and its relationship with the other hematopoietic RTKs, we analyzed the mitogenic pathway and substrate specificity of this receptor. The construction of a chimeric receptor called FF3, between the extracellular region of the CSF1 receptor fused with the transmembrane and the cytoplasmic regions of FLT3, has allowed an analysis in the absence of FLT3 ligand. We have shown in previous studies that FF3 is able to transduce the signal induced by CSF1, to induce tyrosine phosphorylation and/or association of several cytoplasmic proteins. We show here that this new receptor is fully functional in Ba/F3 hematopoietic cells, inducing a CSF1 dependence when expressed at the surface of this IL3 dependent cell line. The PI3' Kinase interacts with the FF3 receptor through SH2 domains and its binding site is localized on the tyrosine residue 958 in the C terminal part of the receptor.

Animals↗
PubMed2003

Diagnostic pathway of syncope and analysis of the impact of guidelines in a district general hospital. The ECSIT study (epidemiology and costs of syncope in Trento).

BACKGROUND: The ECSIT study was aimed at evaluating the hospital management of syncope patients, at comparing the appropriateness and costs of the hospital diagnostic pathway before (phase 1) and after (phase 2) the introduction of new guidelines and at analyzing the physicians' compliance to the guidelines. METHODS: All syncope patients admitted to the emergency room between August 1 and October 31, 1999 (phase 1) and between March 1 and May 31, 2000 (phase 2) were enrolled and their clinical records were analyzed in a blind fashion. RESULTS: During the study 538 consecutive patients came to the emergency room for syncope with a hospitalization rate of 53% in phase 1 (n = 151) and of 42% in phase 2 (n = 107). The in-hospital stay increased from 9 days in phase 1 to 11.3 days in phase 2 and diagnostic tests from 2.6 per patient (phase 1) to 2.9 per patient (phase 2) with total costs that rose from [symbol: see text] 3,474 to [symbol: see text] 3,647. Patients with no diagnosis decreased from 51 to 45.8% and the principal causes were identified as vascular brain disease (36.1 vs 33.7%) and neurally-mediated mechanisms (35.3 vs 42.2%). CONCLUSIONS: Despite the high costs of syncope management, the appropriateness and efficacy of the hospital diagnostic pathway remains far from ideal and simply introducing new guidelines seems unable to modify clinical practice.

Adolescent↗
PubMed2006

Professional delay in head and neck cancer patients: analysis of the diagnostic pathway.

The aim of this study was to identify which factors are related to specialist delay and to determine the length of the diagnostic pathway in head and neck cancer patients. Three hundred and six patients with a carcinoma of the larynx, pharynx or oral cavity were included in the study. Logistic regression analysis was used to identify risk factors for specialist delay. Large (T3-T4) tumors showed significantly less specialist delay than small (T1-T2) tumors (p=0.045, odds ratio [OR]=0.6). Pharyngeal (p=0.00, OR=0.2) and oral carcinomas (p=0.00, OR=0.2) had less specialist delay than glottic carcinomas. Hoarseness was associated with prolonged specialist delay (p=0.00, OR=5.9). Heavy drinking in combination with smoking (p=0.005, OR=0.3), a sore throat (p=0.02, OR=0.4) or having a lesion (p=0.03, OR=0.2) showed a shorter diagnostic period. The duration of the diagnostic process in a general hospital ranged from 0 to 570 days, with a median of 14 days. Only a small group of patients met the ideal management standards in our head and neck clinic. Although prolonged delay was associated with small (glottic) tumors, the diagnostic process takes a fairly long time. The results indicate that continued educational programs for professionals are warranted.

Adolescent↗
PubMed1994

Molecular analysis of the biosynthesis pathway of the alpha-2,8 polysialic acid capsule by Neisseria meningitidis serogroup B.

The genes encoding all enzymes necessary for capsular polysaccharide biosynthesis in Neisseria meningitidis B are located on a 5 kb DNA fragment within the chromosomal cps gene cluster. Nucleotide sequence analysis revealed four open reading frames (ORFs), which can encode proteins with molecular masses of 41.4 kDa, 24.9 kDa, 38.3 kDa, and 54.4 kDa, respectively. These ORFs constitute a transcriptional unit as demonstrated by Northern blots. Primer extension analysis revealed that the transcriptional start site is preceded by a nucleotide sequence with homologies to the sigma 70 consensus promoter sequence of Escherichia coli. Functional analysis of the proteins encoded by the ORFs indicated that ORF2 encodes the CMP-NeuNAc synthetase, ORF3 encodes the NeuNAc condensing enzyme, and ORF4 encodes the alpha-2,8 polysialyltransferase. ORF1 encodes an enzyme, which provides a precursor molecule for synthesis of monomeric NeuNAc. In E. coli the subcloned ORFs 2-4 were able to synthesize a high-molecular-weight alpha-2,8 polysialic acid. In contrast, inactivation of ORF1 in the meningococcal genome resulted in a complete loss of capsule production. A regulatory enzyme, the CMP-NeuNAc hydrolase, which cleaves CMP-NeuNAc to CMP and NeuNAc, was not found as a part of the capsular polysaccharide biosynthesis gene operon or within the cps gene cluster.

Amino Acid Sequence↗
PubMed2003

The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway.

Wnt signaling plays an important role in both oncogenesis and development. Activation of the Wnt pathway results in stabilization of the transcriptional coactivator beta-catenin. Recent studies have demonstrated that axin, which coordinates beta-catenin degradation, is itself degraded. Although the key molecules required for transducing a Wnt signal have been identified, a quantitative understanding of this pathway has been lacking. We have developed a mathematical model for the canonical Wnt pathway that describes the interactions among the core components: Wnt, Frizzled, Dishevelled, GSK3beta, APC, axin, beta-catenin, and TCF. Using a system of differential equations, the model incorporates the kinetics of protein-protein interactions, protein synthesis/degradation, and phosphorylation/dephosphorylation. We initially defined a reference state of kinetic, thermodynamic, and flux data from experiments using Xenopus extracts. Predictions based on the analysis of the reference state were used iteratively to develop a more refined model from which we analyzed the effects of prolonged and transient Wnt stimulation on beta-catenin and axin turnover. We predict several unusual features of the Wnt pathway, some of which we tested experimentally. An insight from our model, which we confirmed experimentally, is that the two scaffold proteins axin and APC promote the formation of degradation complexes in very different ways. We can also explain the importance of axin degradation in amplifying and sharpening the Wnt signal, and we show that the dependence of axin degradation on APC is an essential part of an unappreciated regulatory loop that prevents the accumulation of beta-catenin at decreased APC concentrations. By applying control analysis to our mathematical model, we demonstrate the modular design, sensitivity, and robustness of the Wnt pathway and derive an explicit expression for tumor suppression and oncogenicity.

Adenomatous Polyposis Coli Protein↗