These rhythms are synchronized to the diurnal day/night cycle by

These rhythms are synchronized to the diurnal day/night cycle by environmental cues such as light and temperature. Output pathways check details link the clock to particular biological processes, ensuring that they peak in activity at the appropriate times of day or night. Recently, significant progress was

made in defining the mechanisms by which output pathways are activated at specific times. Here these issues are emphasized by describing how the clock regulates growth and development throughout the life cycle of Arabidopsis thaliana, including seed germination, seedling growth, stress responses and the transition to flowering. This wide impact of the clock on growth and development appears to provide an advantage by enhancing growth and seed production in different environments.”
“Purpose: Recent comparisons of the impact of the surgical approach on pediatric pyeloplasty outcomes have generally incorporated a form of internal ureteral drainage. We hypothesized that the surgical approach does not affect outcomes in children who undergo unstented pyeloplasty and stenting offers no long-term benefit in those with pediatric pyeloplasty.

Materials and Methods: After receiving institutional review board approval we examined the records of all children who underwent initial pyeloplasty from December

2001 find more to December 2009. We compared unstented and stented pyeloplasties, and each surgical approach in the unstented group.

Results: During the study period 367 pyeloplasties were performed, including 231 unstented and 136 stented procedures. When comparing unstented many to stented pyeloplasties, there was no difference in the complication or failure rate. Of unstented pyeloplasties 71, 67 and 93 were done using a transperitoneal laparoscopic approach, a flank approach and dorsal lumbotomy, respectively. There were 5 failures, of which 2 were laparoscopic,

2 used a flank approach and 1 used dorsal lumbotomy (p = 0.51). A total of 31 patients, including 10 treated with a laparoscopic approach, 3 with a flank approach and 18 with dorsal lumbotomy (p = 0.02), required second procedures, of which 24 were temporary drainage for a urine leak. Univariate analysis of factors associated with secondary procedures in the unstented pyeloplasty group showed that only surgical approach was significant (p = 0.05).

Conclusions: In pediatric pyeloplasty there is no significant difference in outcome between stented and unstented repairs. In unstented repairs complications may vary by surgical approach. Regardless of the approach unstented pyeloplasty is safe and effective in the pediatric population.”
“The vagus nerves supply the major cholinergic tone to airway smooth muscles physiologically and play critical roles in the genesis of airway hyperreactivity under some pathological conditions.

Resveratrol supplementation did not improve mitochondrial content

Resveratrol supplementation did not improve mitochondrial content, the subcellular localization of cytochrome c protein content, or PGC1 https://www.selleckchem.com/products/SB-431542.html protein content. Resveratrol increased manganese superoxide dismutase (MnSOD), reduced hydrogen peroxide, and lipid peroxidation levels in muscle samples, but

it was unable to significantly reduce protein carbonyl levels. The data suggest that resveratrol has a protective effect against aging-induced oxidative stress in skeletal muscle, likely through the upregulation of MnSOD activity, but sarcopenia was not attenuated by resveratrol.”
“There is converging evidence for genetic, biochemical, and neuropsychological factors to increase the risk for anxiety and anxiety disorders. The pathogenesis of anxiety disorders is assumed to be influenced by a complex interaction of these individual risk factors on several levels,

affecting intermediate phenotypes of anxiety such as the startle reflex. Thus, in the present double-blind, placebo-controlled study we attempted to paradigmatically investigate a multi-level pathogenetic model of Obeticholic anxiety by testing the effect of 300 mg caffeine citrate as an antagonist at the adenosine A2A receptor vs placebo on the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) startle reflex in 110 healthy individuals (male = 56, female = 54) stratified for the adenosine A2A receptor (ADORA2A) 1976T>C MEK162 ic50 polymorphism (rs5751876). In addition to the expected main effect of picture category (highest

startle amplitude for unpleasant, lowest for pleasant pictures) groups across all ADORA2A 1976T>C genotype and intervention (caffeine vs placebo) groups, an interaction effect of genotype, intervention, and picture category was discerned: In ADORA2A 1976TT risk genotype carriers, highest startle magnitudes were observed after caffeine administration in response to unpleasant pictures, with this effect arising particularly from the female subgroup. Our data point to a complex, multi-level, and potentially gender-specific pathogenetic model of anxiety, with genetic and biochemical factors interactively increasing the risk of maladaptive emotional processing and thereby possibly also anxiety disorders. The present findings may eventually aid in improving primary and secondary prevention by sharpening the risk profiles of anxiety-prone individuals. Neuropsychopharmacology (2012) 37, 759-769; doi: 10.1038/npp.2011.253; published online 19 October 2011″
“HIV infection, once established, is never cleared. Rare individuals do, however, control viral replication to low levels. These successful immune responses are primarily linked to certain class I MHC alleles (MHC-I). Because of this association, many AIDS vaccines in development are designed to generate virus-specific CD8+ T cells.

All four types of responses involve the genetic machineries that

All four types of responses involve the genetic machineries that underlie a number of complex human diseases such as cancer and neurodegenerative diseases, including Alzheimer’s and Parkinson’s. We highlight the types of stress response experiments required to detect the genes and pathways underlying human disease and suggest that studying stress biology in worms can be translated to understanding human disease and provide potential targets for drug discovery.”
“Background: In endothelial dysfunction, vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression (collectively termed cell adhesion

molecules; CAMs) EPZ-6438 chemical structure increase at sites of atherosclerosis and are stimulated by proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). Methods: We evaluated the effect of alpha-tocopherol (AT; 10-150 mu M) and BAY 11-7082 (BAY; 0.1 or 1 mu m) on CAMs mRNA expression as well as their protein in soluble release form (sCAMs) in human aortic

endothelial cells (HAECs) activated by TNF-alpha (1 or 10 ng/ml). Also, we determined the extent of lymphocyte adhesion to activated HAECs. Results: BAY reduced VCAM-1, E-selectin and ICAM-1 mRNA expression by 30, 30 and AMN-107 clinical trial 10%, respectively. Furthermore, protein reduction of sVCAM-1 by 70%, sE-selectin by 51% and sICAM-1 by 25% compared to HAECs stimulated by TNF-alpha was observed (p < 0.05). AT (50, 75 and 150 mu M) decreased VCAM-1 mRNA expression by 30% and sVCAM-1 protein by 33% compared to HAECs stimulated by TNF-alpha (p < 0.05). TNF-alpha-activated HAEC adhesion to human Jurkat T lymphocytes was higher compared

to nonactivated HAECs (p < 0.05). BAY (2 and 5 mu m) reduced this lymphocyte adhesion (p < 0.05). https://www.selleck.cn/products/GDC-0449.html Conclusion: BAY reduces all the CAMs studied as well as cell adhesion, while AT selectively inhibits VCAM-1; both induce endothelial dysfunction improvement. Copyright (C) 2012 S. Karger AG, Basel”
“BACKGROUND: The evidence of or against the presence of a “”July phenomenon”" in resident teaching hospitals has been inconsistent. Moreover, there are limited data on the “”July phenomenon”" in the field of neurosurgery.

OBJECTIVE: To determine whether a “”July phenomenon”" exists for neurosurgical mortality or complications.

METHODS: A search of the National Inpatient Sample database from 1998 to 2008 was performed for all admissions for International Classification of Diseases, 9th Revision codes corresponding to nontraumatic hemorrhage, central nervous system (CNS) trauma, CNS tumor, and hydrocephalus. Generalized linear mixed-model analysis was performed, adjusted for patient demographics and hospital characteristics, for the outcomes of mortality and complications for the month of July compared with all other months in teaching hospitals.

5 g, 2 g, 2 g plus HIF inhibitor U0126 (10(-5)M), 17-[2-(dimethyl

5 g, 2 g, 2 g plus HIF inhibitor U0126 (10(-5)M), 17-[2-(dimethylamino)ethyl] amino-17-desmethoxygeldanamycin (17-DMAG, 10(-5)M), or echinomycin (10(-6)M), or 2 g plus dimethyloxallyl glycine (DMOG; 10(-4)M), a prolyl-hydroxylase inhibitor that stabilizes HIF. The fold-change in PHE and KCl contraction was compared with the control contraction at 0.5-g tension for 1 hour. Vein tissue homogenates were analyzed for HIF-1 alpha, HIF-2 alpha, MMF-2, and MMP-9 messenger RNA (mRNA) and protein amount using real-time reverse transcription

polymerase chain reaction and Western blots.

Results: Compared with control IVC contraction at 0.5-g tension for 1 hour, the PHE and KCl contraction after prolonged 0.5-g tension was 2.0 +/- 0.35 and 1.1 +/- 0.06, respectively. Vein contraction to PHE and KCl after PRN1371 prolonged 2-g tension was significantly reduced (0.87 +/- 0.13 and 0.72 +/- 0.05, respectively). PHE-induced contraction was restored in IVC exposed to prolonged 2-g tension plus the HIF inhibitor SBI-0206965 chemical structure U0126 (1.38 +/- 0.15) or echinomycin (1.99 +/- 0.40). U0126 and echinomycin also restored KCl-induced contraction in NC exposed to prolonged 2-g tension (1.14 +/- 0.05 and 1.11 +/- 0.15, respectively). Treatment with DMOG further reduced PHE- and KCl-induced contraction in veins subjected to prolonged 2-g tension (0.47 +/- 0.06 and 0.57 +/- 0.01, respectively). HIF-1 alpha and HIF-2 alpha

inRNA were overexpressed in NC exposed to prolonged 2-g tension, and the overexpression was reversed by U0126. The overexpression of HIF-1 alpha and HIF-2 alpha in stretched NC was associated with increased MMP-2 and MMP-9 mRNA. The protein amount of HIf-1 alpha,

HIF-2 alpha, MMP-2, and MMP-9 was also increased in NC exposed to prolonged 2-g wall tension.

Conclusions:Prolonged increases in vein wall tension are associated with Selleck Fosbretabulin overexpression of HIF-1 alpha and HIF-2 alpha, increased MMP-2 and MMP-9 expression, and reduced venous contraction in rat IVC. Together with our report that MMP-2 and MMP-9 inhibit NC contraction, the data suggest that increased vein wall tension induces HIF overexpression and causes an increase in MMP expression and reduction of venous contraction, leading to progressive venous dilation and varicose vein formation. (J Vase Surg 2011;53:764-73.)”
“Midkine (MK), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is upregulated in different brain areas after administration of different drugs of abuse suggesting MK could modulate drugs of abuse-induced pharmacological or neuroadaptative effects. To test this hypothesis, we have studied the effects of amphetamine administration in MK genetically deficient (MK-/-) and wild-type (MK+/+) mice. In conditioning studies, we found that amphetamine induces conditioned place preference (CPP) similarly in both MK-/- and MK+/+ mice.

Moreover, the unique genome carries a nonbleaching protein A (Nbl

Moreover, the unique genome carries a nonbleaching protein A (NblA) gene (open reading frame [ORF] 022L), which is present in all phycobilisome-containing organisms and mediates phycobilisome

degradation. Western blot detection confirmed that 022L was expressed after PaV-LD infection in the host filamentous cyanobacterium. In addition, its appearance was companied by Buparlisib concentration a significant decline of phycocyanobilin content and a color change of the cyanobacterial cells from blue-green to yellow-green. The biological function of PaV-LD nblA was further confirmed by expression in a model cyanobacterium via an integration platform, by spectroscopic analysis and electron microscopy observation. The data indicate that PaV-LD is an exceptional cyanophage of filamentous cyanobacteria, and this novel cyanophage will also provide us with a new vision of the cyanophage-host interactions.”
“The mitochondrial inhibitor 1-methyl-4-phenylpyridinium (MPP+) is the toxicologically relevant metabolite of 1-methyl-4-phenyltetrahydropyridine (MPTP), which causes relatively selective degeneration of dopaminergic neurons in the substantia nigra. Dopaminergic LUHMES PS-341 mw cells were used

to investigate whether ATP-depletion can be uncoupled from cell death as a downstream event in these fully post-mitotic human neurons. Biochemical assays indicated that in the homogeneously differentiated cell cultures, MPP+ was taken up by the dopamine transporter (DAT). MPP+ then triggered oxidative stress and caspase activation, as well as ATP-depletion followed by cell death. Enhanced survival of the neurons in the presence of agents interfering with mitochondrial pathology, such as the fission inhibitor Mdivi-1 or a Bax channel click here blocker suggested a pivotal role of mitochondria in this model. However, these compounds did not prevent cellular ATP-depletion. To further investigate whether cells could be rescued despite respiratory chain inhibition by MPP+, we have chosen a diverse set of

pharmacological inhibitors well-known to interfere with MPP+ toxicity. The antioxidant ascorbate, the iron chelator desferoxamine, the stress kinase inhibitor CEP1347, and different caspase inhibitors reduced cell death, but allowed ATP-depletion in protected cells. None of these compounds interfered with MPP+ accumulation in the cells. These findings suggest that ATP-depletion, as the initial mitochondrial effect of MPP+, requires further downstream processes to result in neuronal death. These processes may form self-enhancing signaling loops, that aggravate an initial energetic impairment and eventually determine cell fate. (C) 2011 Elsevier Inc. All rights reserved.”
“Increased conversion of glucose to lactate is a key feature of many cancer cells that promotes rapid growth. Pyruvate kinase M2 (PKM2) expression is increased and facilitates lactate production in cancer cells.

OBJECTIVE: We studied the expression and phosphorylation of diffe

OBJECTIVE: We studied the expression and phosphorylation of different intracellular signaling molecules in the IA wall compared with IA morphological features to understand better the

cellular pathways involved in IA development and wall degeneration.

METHODS: Nine ruptured and 17 unruptured human IA samples were collected intra-operatively. The expression levels and phosphorylation state of 3 mitogen-activated protein kinases (c-Jun N-terminal kinase [JNK], p38, extracellular signal-regulated kinase [ERK]), Bcl-2 antagonist of cell death (Bad), mammalian target of rapamycin (mTOR), cyclic AMP response element binding protein (CREB), and Akt were determined by Western blotting. AZD1480 The localization of signaling proteins was determined by immunofluorescence. From 3-dimensional segmentation of computed tomography angiographic data, size and shape indexes were calculated.

RESULTS:

We found a 5-fold difference in phospho-Bad levels between ruptured and unruptured IAs. Phospho-mTOR was downregulated 2.5-fold in ruptured IAs. Phospho-p54 JNK, phospho-p38, and phospho-Akt levels correlated Selleckchem CH5183284 positively with IA size. Phospho-CREB levels were significantly associated with nonsphericity and ellipticity indexes. Phospho-Akt and phospho-p38 correlated negatively with undulation index.

CONCLUSION: The signaling pathway profile (apoptosis, cell proliferation, stress signaling) differs between ruptured and unruptured IAs and is associated with IA geometry. Our results increase the knowledge of IA development and wall degeneration.”
“In this study, we examined HPA axis responses to acute psychosocial stress in retation to effort-reward-imbalance (ERI) and overcommitment (OC) to test whether chronic stress at work is accompanied by attered HPA axis stress responses in teachers. According to Siegrist’s work stress model, ERI reflects stress due to a tack of reciprocity between personal costs and gains at work, whereas CC is conceptualized as a personality trait mainly characterized by the inability to withdraw below from work obligations. Fifty-three

medication-free, non-smoking, healthy teachers (33 women, 20 men, 29-63 years, mean age 49.9 +/- 8.58 years) were confronted with the Trier Social Stress Test (TSST), a widely used standardized stress protocol to induce acute psychosociat stress in the laboratory. ACTH (five samples), total plasma (six samples) and free salivary cortisol (eight samples) were repeatedly measured before and after challenge. In the total group, ERI and OC were only marginally associated with HPA axis responses to acute stress. However, in the subgroup of responders (N = 30) high levels of OC were significantly associated with lower ACTH (p = 0.03) as well as plasma (p = 0.02) and salivary cortisol (p < 0.001) responses and results remained significant controlling for depressive symptoms.

g , prior learning experience, memory expression prior to deficit

g., prior learning experience, memory expression prior to deficit). The following experiments examined the size and persistence of these deficits after matching both the amount of experience with MDV3100 in vivo a context and the levels of performance in that context prior to delivery of the protein synthesis inhibitor anisomycin. We found that systemic or intrahippocampal administration of anisomycin caused a deficit in groups receiving context conditioning (consolidation groups) or reactivation (reconsolidation groups) immediately prior to the injections. With systemic injections, the deficit was larger and more persistent in consolidation groups;

with intrahippocampal injections, the initial deficit was statistically identical, yet was more persistent in the consolidation group. These experiments showed that when experiences and performance are matched prior to anisomycin injections, consolidation deficits are generally larger and more persistent compared to reconsolidation deficits.”
“Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of retinal ganglion cells (RGCs)

and optic nerves. Although glaucoma is often associated with elevated intraocular pressure, recent studies have shown a relatively high prevalence of normal tension glaucoma (NTG) in glaucoma patient GSK1120212 cost eltoprazine populations In the mammalian retina, glutamate/aspartate transporter (GLAST) is localized to Muller glial cells. whereas excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Since the loss of GLAST or EAAC1 leads to retinal degeneration similar to that seen in NTG, we examined the effects of interleukin-1 (IL-1) on RGC death in GLAST- and EAAC1-deficient mice. IL-1 promoted increased glutamate uptake in Muller

cells by suppressing intracellular Na(+) accumulation, which is necessary to counteract Na(+)-glutamate cotransport The observed trends for the glutamate uptake increase in the wild-type (WT), GLAST- and EAAC1-deficient mice were similar: however, the baseline glutamate uptake and intracellular Na(+) concentration in the GLAST-deficient mice were significantly lower than those in the wild-type mice. Consistently, pretreatment with IL-1 exhibited no beneficial effects on glutamate-induced RGC degeneration in the GLAST-deficient mice. In contrast, IL-1 significantly increased glutamate uptake by Muller cells and the number of surviving RGCs in the wild-type and EAAC1-deficient mice. Our findings suggest that the use of IL-1 for enhancing the function of glutamate transporters may be useful for neuroprotection in retinal degenerative disorders including NTG. (c) 2009 Elsevier Ireland Ltd All rights reserved.

The most effective interventions are probably

The most effective interventions are probably buy SHP099 structural changes to improve access to education and employment for young people and to reduce the risk of transport-related injury.”
“BACKGROUND AND IMPORTANCE: Purely intraorbital arteriovenous fistulas (AVFs), which are rare vascular malformations that clinically mimic carotid-cavernous fistulas (CCFs), involve a fistula from the ophthalmic artery to 1 of the draining ophthalmic veins. We describe a case of an intraorbital AVF treated with transvenous endovascular coil embolization via the inferior petrosal sinus (IPS) route

and review the literature on this rare entity.

CLINICAL PRESENTATION: An 81-year-old woman sought treatment after check details 7 days of progressive left-sided visual acuity loss, chemosis, and lateral rectus palsy. Magnetic resonance imaging demonstrated dilated vascularity in the left orbit raising suspicions for a CCF. Cerebral angiography showed a purely intraorbital AVF with a fistula between the left ophthalmic artery and superior ophthalmic vein (SOV). Transvenous selective catheterization of the fistula was performed by successfully

navigating the ipsilateral IPS to the cavernous sinus and SOV. The fistula was then embolized using detachable coils. The patient was discharged the next day. Three weeks after embolization, her ocular symptoms and findings had resolved.

CONCLUSION: Intraorbital AVFs are a rare type of AVF that can be treated by direct surgical ligation, transarterial embolization, or transvenous embolization. We successfully navigated the IPS, which is frequently stenotic or occluded secondary to chronically increased fistulous drainage, and utilized this route to embolize the fistula with detachable coils.”
“Background. The role of

the brain-derived neurotrophic factor (BDNF) in the pathogenesis of affective disorders such as depression has been controversial. Mounting evidence comes from structural imaging, that the functional BDNF Val66Met polymorphism influences the hippocampal volume with Amylase carriers of the 66Met allele (Val/Met and Met/Met group) having smaller hippocampi. Given that stress-induced atrophy of the hippocampus is associated with the pathogenesis of affective disorders, the functional BDNF Val66Met polymorphism could be an incremental risk factor.

Method. Eighty-seven healthy Caucasian participants underwent structural imaging and were genotyped for the BDNF Val66Met polymorphism. Data were analysed by means of voxel-based morphometry (VBM).

Results. Region of interest (ROI) analyses revealed an association between the 66Met allele and smaller parahippocampal volumes and a smaller right amygdala. In addition, the whole-brain analysis showed that the thalamus, fusiformus gyrus and several parts of the frontal gyrus were smaller in 66Met allele carriers.

Conclusions.

Patients exhibited a significantly greater response slope (i e ,

Patients exhibited a significantly greater response slope (i.e., patients’ perception changed more rapidly) and greater shift point (i.e., patients still perceived mild expressions of anger as happy faces)

with increasing emotion signal compared with healthy controls when the facial expression morphed from happy to angry. Furthermore, patients with schizophrenia still perceived mild expressions of fear as angry faces(a greater shift point) and were less discriminative from angry to fearful emotion(a flatter response slope). They were sensitive to sadness (a smaller shift point) and the perception changed rapidly (a sharper response slope) as compared https://www.selleckchem.com/products/pf-03084014-pf-3084014.html with healthy controls in the emotion continuum of happy to sad. In conclusion, patients with schizophrenia demonstrated impaired categorical perception of facial expressions, with generally ‘rapid’ but ‘late’ discrimination

towards social Selleckchem SB202190 threat-related stimuli such as angry facial expression. Compared with healthy controls, these patients have a sharper discrimination perception pattern in the emotion continua from positive valence to negative valence. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Hepatitis C virus (HCV)-mediated liver disease progression may reflect distinct molecular mechanisms for increased hepatocyte growth and hepatic stellate cell activation. In this

study, we have observed that primary human hepatocytes, when infected in vitro with FAD cell culture-grown HCV genotype 1a or 2a, display viral RNA and protein expression. Infected hepatocytes displayed a fibroblast-like shape and an extended life span. To understand the changes at the molecular level, we examined epithelial-mesenchymal transition (EMT) markers. Increased mRNA and protein expression levels of vimentin, snail, slug, and twist and a loss of the epithelial cell marker E-cadherin were observed. Snail and twist, when examined separately, were upregulated in chronically HCV-infected liver biopsy specimens, indicating an onset of an active EMT state in the infected liver. An increased expression level of fibroblast-specific protein 1 (FSP-1) in the infected hepatocytes was also evident, indicating a type 2 EMT state. Infected hepatocytes had significantly increased levels of phosphorylated beta-catenin (Ser(552)) as an EMT mediator, which translocated into the nucleus and activated Akt. The phosphorylation level of beta-catenin at Thr(41)/Ser(45) moieties was specifically higher in control than in HCV-infected hepatocytes, implicating an inactivation of beta-catenin. Together, these results suggested that primary human hepatocytes infected with cell culture-grown HCV display EMT via the activation of the Akt/beta-catenin signaling pathway.

In this study we aimed to determine the precise location of DRN n

In this study we aimed to determine the precise location of DRN neurons projecting to mPFC and the extent to which they contain serotonin (5-hydroxytryptamine); we have also assessed whether Hcrt1/OxA neurons innervate DRN neurons that could sustain behavioral wakefulness through their projections to mPFC. The retrograde tracer

Fluorogold was injected into mPFC and DRN sections were processed for double immunolabeling of anti-Fluorogold and either anti-5-hydroxytryptamine or anti-Hcrt1/OxA antisera. Most DRN neurons projecting to mPFC were located in the ventral sector CX-6258 of the rostral and intermediate DRN, and around half of them were serotonergic. Hcrt1/OxA-immunoreactivity in DRN was observed in unmyelinated axons and axon boutons (varicosities or axon terminals). Hcrt1/OxA immunoreactivity was observed within the cytoplasm and in dense-cored vesicles of these axons. Hcrt1/OxA-labeled boutons established both asymmetric synapses (n=30) and appositional contacts selleck screening library (n=102) with Fluorogold-labeled dendrites belonging to DRN neurons projecting to mPFC. Our results show that Hcrt1/OxA neurons may exert a direct synaptic influence on DRN neurons that could facilitate wakefulness, although other non-synaptic

actions through volume transmission are also suggested. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Under the cancer stem cell (CSC) hypothesis, sustained metastatic growth requires the dissemination of a CSC from the primary tumour followed by its re-establishment in a secondary site. The epithelial-mesenchymal transition (EMT), a differentiation process crucial to normal development, has been implicated in conferring metastatic ability on carcinomas.

Balancing these two concepts has led researchers to investigate a possible link between EMT and the CSC phenotype-indeed, recent evidence indicates that, following induction of EMT in human breast cancer and related cell lines, stem cell activity increased, as judged by the presence of cells displaying ALOX15 the CD44(high)/CD24(low) phenotype and an increase in the ability of cells to form mammospheres. We mathematically investigate the nature of this increase in stem cell activity. A stochastic model is used when small number of cells are under consideration, namely in simulating the mammosphere assay, while a related continuous model is used to probe the dynamics of larger cell populations. Two scenarios of EMT-mediated CSC enrichment are considered. In the first, differentiated cells re-acquire a CSC phenotype this model implicates fully mature cells as key subjects of de-differentiation and entails a delay period of several days before de-differentiation occurs.