Myristoylation is catalyzed by N-myristoyltransferase (NMT) and i

Myristoylation is catalyzed by N-myristoyltransferase (NMT) and is recognized to be a widespread and functionally important

modification of proteins. The main objective of this review is to focus on the potential role of NMT and CaN in epileptic brain and its involvement in neuronal apoptosis. The findings on the interaction of NMT and CaN with various Combretastatin A4 molecular weight signaling molecules in epileptic chickens adds to our understanding of the mechanism of CaN signaling in neuronal apoptosis. Understanding the regulation of NMT by specific inhibitors may help us to control the action of this enzyme on its specific substrates and may lead to improvements in the management of various neurological disorders like Alzheimer’s disease, ischemia and epilepsy. (C) 2007 Elsevier Ltd. All rights reserved.”
“Airway mucus is a hallmark of respiratory syncytial virus (RSV) lower respiratory tract illness. Laboratory RSV strains differentially induce airway mucus production in mice. Here, we tested the hypothesis that RSV strains differ in pathogenesis by screening six low-passage RSV clinical isolates for mucogenicity and virulence in BALB/cJ mice. The RSV clinical isolates induced variable disease severity, lung ARN-509 supplier interleukin-13 (IL-13) levels, and gob-5 levels in BALB/cJ mice. We chose two of these

clinical isolates for further study. Infection of BALB/cJ mice with RSV A2001/2-20 (2-20) resulted in greater disease severity, Benzatropine higher lung IL-13 levels, and higher lung gob-5 levels than infection with RSV strains A2, line 19, Long, and A2001/3-12 (3-12). Like the line 19 RSV strain, the 2-20 clinical isolate induced airway mucin expression in BALB/cJ mice. The 2-20 and 3-12 RSV clinical isolates had higher lung viral loads than laboratory RSV strains at 1 day postinfection (p.i.). This increased viral load correlated with higher viral antigen levels in the bronchiolar epithelium

and greater histopathologic changes at 1 day p.i. The A2 RSV strain had the highest peak viral load at day 4 p.i. RSV 2-20 infection caused epithelial desquamation, bronchiolitis, airway hyperresponsiveness, and increased breathing effort in BALB/cJ mice. We found that RSV clinical isolates induce variable pathogenesis in mice, and we established a mouse model of clinical isolate strain-dependent RSV pathogenesis that recapitulates key features of RSV disease.”
“Emotional disorders such as depression, panic attacks, generalized anxiety, phobias and post-traumatic stress have been associated to decreased serotonin (5-HT) function, based on the positive effects of treatments that enhance 5-HT neurotransmission. However, it has been difficult to establish a primary role for 5-HT deficiency in these diseases, making preclinical models particularly useful. Over the last ten years a variety of genetic mouse models of 5-HT depletion have been produced, complementing previous pharmacologically-based models.

The receiver-operating characteristic (ROC) curve was calculated

The receiver-operating characteristic (ROC) curve was calculated to assess the optimal cut-off value of hsCRP. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Multiple logistic regression analysis was used CP673451 to identify the predictors of the primary outcome. The primary outcome was a composite of periprocedural myocardial damage, defined as cardiac troponin I (cTn-I) elevation above the decision limit of 0.15 mu g/L, death, acute coronary syndrome, stroke, acute heart failure, or intrastent thrombosis within 30 days of

surgery.

Results: On ROC analysis, the optimal cut-off value of hsCRP was 3.2 g/L. The primary outcome occurred in 48 patients (20.1%). On univariate analysis, smoking (P = .009), known hypercholesterolemia (P = .01), previous ischemic heart disease (P = .0003), open surgery (P = .03), and hsCRP levels (P < .0001) were associated with the primary outcome. On multiple logistic regression analysis, only hsCRP was independently associated with the primary outcome. The unadjusted and adjusted selleck chemicals llc ORs for the primary outcome among

patients with hsCRP levels >3.2 mg/L were 7.5 (CI, 3.7-15.2; P < .0001) and 4.6 (CI, 2.1-9.9; P = .0001), respectively.

Conclusion: Our data suggest that higher levels of hsCRP are independently associated with an increased risk of perioperative myocardial damage and early adverse cardiovascular events in patients undergoing elective vascular surgery. This may have implications for risk stratification and therapeutic approach. (J Vase Surg 2011;54:474-9.)”
“It is well documented that schizophrenia patients exhibit dysfunction in various cognitive domains, including attention/vigilance, as demonstrated by impaired performance in the myriad of Continuous Performance Tests (CPTs). NMDA receptor

antagonists provide a pharmacological model in animals of the cognitive disruption presented in the disorder. We therefore examined the effects of a sub-chronic PCP treatment regimen (5.0 mg/kg 7-days bi-daily) in the recently developed rodent test of vigilance, the 5-Choice Continuous Performance Test LY294002 (5C-CPT). We assessed the effects of this regimen after at least a 7-day washout period on both baseline performance and when the attentional load was increased. Sub-chronic PCP treatment impaired 5C-CPT performance in a manner consistent with impaired vigilance in patients with schizophrenia, with reduced hit rate and impaired signal sensitivity. These effects were only evident when performance was challenged following parameter manipulations. These data demonstrate that attention/vigilance is sensitive to disruption following sub-chronic PCP treatment in a pre-clinical task that may demonstrate increased analogy to human vigilance tasks.


“Background: Effective strategies are urgently needed to r


“Background: Effective strategies are urgently needed to reduce mother-to-child selleck chemicals transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings.

Methods: Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine)

or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth.

Results: Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection AZD1480 (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two

extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug.

Conclusions: Extended prophylaxis with nevirapine or with nevirapine

and Florfenicol zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.).”
“Objective: This report elucidates the long-term safety and effectiveness of extended aortic arch replacement with an open stent-grafting technique from our 12 years of experience.

Methods: From 1994 to 2004, 126 patients (mean age 67.8 years) with different pathologic conditions of the aortic arch with extension to the descending aorta (57 dissections [acute/chronic = 31/26] and 69 aneurysms) were operated on with an open stent-grafting technique. During deep hypothermic circulatory arrest with selective cerebral perfusion, the stent graft was delivered through the transected proximal aortic arch, and arch replacement with a 4-branched prosthesis was performed.

Results: Operative mortality within 30 days was 3.2%. Perioperative morbidity included 7 (5.6%) strokes and 8 (6.3%) spinal injuries (paraplegia in 3, transient paraparesis in 5). Sixty-three percent of the patients were extubated within 24 hours. In long-term follow-up (mean 60.4 +/- 36.5 months, maximum 153 months), survival was 81.1%, 63.3%, and 53.7% at 1, 5, and 8 years. Five (3.

Herein, we report the crystal structure of SLEV E in the posfusio

Herein, we report the crystal structure of SLEV E in the posfusion trimer conformation. The structure revealed specific features that differentiate SLEV E from trimers of related flavi-and alphaviruses. SLEV E fusion loops have distinct intermediate spacing such that they are positioned further apart than previously observed in flaviviruses but closer together than Semliki Forest virus, an alphavirus. Domains II and III (DII and DIII) of SLEV E also adopt different angles relative to DI, which suggests that the DI-DII joint may accommodate spheroidal motions.

However, trimer interfaces are well conserved among flaviviruses, so it is likely the differences observed represent structural features specific to SLEV CYT387 datasheet function. Analysis of surface potentials revealed a basic platform underneath flavivirus fusion loops that may interact with the anionic lipid head groups found in membranes. Taken together, these results highlight variations in E structure and assembly that may direct virus-specific interactions with host determinants to influence pathogenesis.”
“The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders,

studying the effect of genetic variation in the BDNF Selleck Copanlisib gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional

magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing. Forty healthy participants performed an implicit fear task during scanning, where subjects made gender judgments from facial images with neutral or fearful emotion. Subjects were tested for facial emotion recognition post-scan. Functional connectivity was investigated using psycho-physiological interactions. Subjects were genotyped for the BDNF Val66Met polymorphism and the measures L-NAME HCl compared between genotype groups. Met carriers showed overactivation in the anterior cingulate cortex (ACC), brainstem and insula bilaterally for fear processing, along with reduced functional connectivity from the ACC to the left hippocampus, and impaired fear recognition ability. The results show that during fear processing, Met allele carriers show an increased neural response in regions previously implicated in mediating autonomic arousal. Further, the Met carriers show decreased functional connectivity with the hippocampus, which may reflect differential retrieval of emotional associations. Together, these effects show significant differences in the neural substrate for fear processing with genetic variation in BDNF. (C) 2010 Elsevier Ireland Ltd.

Further experiments found that VCR increased levels of the p-Auro

Further experiments found that VCR increased levels of the p-Aurora B through the activation of c-Jun N-terminal kinase, which was blocked in SHP099 nmr the presence of AZD1152-HQPA. Laboratory Investigation (2009) 89, 1364-1373; doi:10.1038/labinvest.2009.106; published online 12 October 2009″
“The human myelin proteolipid protein 1 gene (hPLP1), which encodes the major structural myelin proteins of the central nervous system (CNS), is classically described as expressed in the oligodendrocytes, the CNS myelinating cells. We identified

two new exons in the intron 1 of the hPLP1 gene that lead to the expression of additional mRNA and protein isoforms mainly expressed in neurons instead of oligodendrocytes. Those novel neuronal PLP isoforms are detected as soon as human fetal development and their concomitant expression

is specific of the human species. As classical PLP proteins, the novel protein isoforms seem to be addressed to the plasma membrane. These results suggest for the first time that PLP may have functions in humans not only in oligodendrocytes but also in neurons and could be implicated in axono-glial communication. Moreover, this neuronal expression of the hPLP1 gene might explain the neuronal dysfunctions in patients carrying hPLP1 gene mutations. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The rodent visual cortex retains significant ocular dominance plasticity beyond the traditional postnatal critical EPZ5676 cost period. However, the intracellular

mechanisms that underlie the cortical response to monocular deprivation are predicted to be different in juveniles and adults. Here we show monocular deprivation in adult, but not juvenile rats, induced an increase in the phosphorylation of the prominent presynaptic effecter protein synapsin at two key sites known to regulate synapsin function. Monocular deprivation in adults induced an increase in synapsin phosphorylation at the enough PKA consensus site (site 1) and the CaMKII consensus site (site 3) in the visual cortex ipsilateral to the deprived eye, which is dominated by non-deprived eye input. The increase in synapsin phosphorylation was observed in total cortical homogenate, but not synaptoneurosomes, suggesting that the pool of synapsin targeted by monocular deprivation in adults does not co-fractionate with excitatory synapses. Phosphorylation of sites 1 and 3 stimulates the release of synaptic vesicles from a reserve pool and increases in the probability of evoked neurotransmitter release, which may contribute to the strengthening of the non-deprived input characteristic of ocular dominance plasticity in adults. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The peribiliary inflammation of cholangiopathy affects the physiological properties of biliary epithelial cells (cholangiocyte), including bicarbonate-rich ductular secretion.

Results: Each animal in the 12- and 24-week groups developed a co

Results: Each animal in the 12- and 24-week groups developed a constant, alternating esotropic strabismus and a nasotemporal asymmetry of pursuit when viewing with either eye. Spatial vision MM-102 was normal (no amblyopia). The 3-week duration monkeys were indistinguishable from control animals; they had normal eye alignment and symmetric pursuit. In the 12-

and 24-week monkeys, the longer the duration of binocular decorrelation, the greater the pursuit asymmetry: for 15 degrees/s target motion, the NBI in the 12-week and 24-week animals was 16x and 22x greater respectively, than that in the 3-week animals (ANOVA, P=0.03).

Conclusions: Binocular decorrelation in primates during an early period of fusion development causes permanent smooth pursuit asymmetries when the duration exceeds the equivalent of 3 months in human. These findings support the conclusion that early correction of infantile strabismus promotes normal development of cerebral gaze pathways. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“A new adeno-associated

virus (AAV), referred to as AAV(VR-942), selleck products has been isolated as a contaminant of adenovirus strain simian virus 17. The sequence of the rep gene places it in the AAV serotype 2 (AAV2) complementation group, while the capsid is only 88% identical to that of AAV2. High-level AAV(VR-942) transduction activity requires cell surface heparan sulfate proteoglycans, although AAV(VR-942) lacks residues equivalent to the AAV2 R585 and R588 amino acid residues essential for mediating the interaction of AAV2 with the heparan sulfate proteoglycan receptor. Instead, AAV(VR-942) uses a distinct transduction region. This finding shows that distinct domains on different AAV isolates can be responsible for the same activities.”
“Background

CC chemokine receptor 5 antagonists are a new class of antiretroviral agents.

Methods We conducted two double- blind, placebo- controlled, phase 3 studies – Maraviroc versus Optimized Therapy Amobarbital in Viremic Antiretroviral Treatment- Experienced Patients ( MOTIVATE) 1 and MOTIVATE 2 – with patients who had R5 human immunodeficiency virus type 1 ( HIV- 1) only. They had been treated with or had resistance to three antiretroviral- drug classes and had HIV- 1 RNA levels of more than 5000 copies per milliliter. The patients were randomly assigned to one of three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice daily, or placebo, each of which included optimized background therapy ( OBT) based on treatment history and drug- resistance testing. Safety and efficacy were assessed after 48 weeks.

Results A total of 1049 patients received the randomly assigned study drug; the mean baseline HIV- 1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter.

Right ventricular decompression was done in all patients

Right ventricular decompression was done in all patients.

Results: After ligation, coronary flow converted from moderately or largely retrograde to antegrade pefusion. Ligation produced no visual myocardial consequences or immediate local wall motion abnormalities. For 3 patients, however, apical-septal wall motion abnormalities appeared from 2 hours to 3 days postoperatively. Serial studies were done to assess the later effects in the

16 of 19 30-day survivors. No evidence for myocardial injury was found, and all continued on a 2-ventricle repair course.

Conclusion: Epigenetic Reader Domain inhibitor The location and ligation of right ventricle to coronary artery connections can be reliably accomplished off bypass. Coronary flow became antegrade, improving myocardial oxygenation. No myocardial damage was observed. Inapparent right ventricle to coronary artery connections occasionally enlarge secondarily after right ventricular decompression, making early follow-up evaluation necessary after ligation. Despite the initial presence of significant right ventricle to coronary artery connections, 2-ventricle repairs are possible with long-term benefits.”
“PACAP is a neurotransmitter involved in the signal transduction of light stimulation in the suprachiasmatic nucleus (SCN).

Light stimulation affects autonomic nerve activity via the SCN, and here we tested whether PACAP participates in light-induced regulation of sympatho-adrenal activity by using PACAP-deficient (Adcyap1(-/-)) mice. CFTRinh-172 in vivo Light stimulation (100 lux, 30 min) significantly elevated both renal sympathetic nerve activity (RSNA), which was monitored on a digital oscilloscope, and plasma corticosterone levels in wildtype mice, but both responses were almost abolished in Adcyap1(-/-) mice. Although light-induced c-Fos expression in the SCN was observed in both genotypes, the numbers of c-Fos positive cells were significantly decreased in Adcyap1(-/-) mice. These Methocarbamol data suggest that PACAP signaling pathway is involved in light-induced stimulation of RSNA and plasma corticosterone release through SCN of brain. (C) 2008 Elsevier

Ireland Ltd. All rights reserved.”
“Objective: The purposes of this study were to identify the occurrence of fibrillin-1 gene polymorphisms or mutations in exons 24 to 28 and to identify the relationship between “”DNA sequence variants” and aortic dilatation in the presence of abnormal aortic histopathology and other variables in patients undergoing intracardiac repair of tetralogy of Fallot.

Methods: Operatively excised full-thickness aortic wall tissue and 5 to 10-mL venous blood samples from 74 consecutive patients undergoing intracardiac repair of tetralogy of Fallot were studied. Histopathologic evaluation was done by light microscopy. Polymerase chain reaction amplification of fibrillin-1 gene was carried out for 5 exons (24-28), and amplified products were subjected to single-strand conformation polymorphism analysis to identify sequence alterations, if any.

Mass spectrometry analysis demonstrated that UL97 can phosphoryla

Mass spectrometry analysis demonstrated that UL97 can phosphorylate Cdh1 in vitro, and the majority of the sites identified correlated with previously characterized cyclin-dependent kinase (Cdk) consensus sites. Analysis of the APC core complex during Delta UL97 virus infection showed APC dissociation occurring at the same time as during infection with wild-type virus, suggesting that the UL97-mediated phosphorylation of Cdh1 is not required for this to occur. Further investigation of the APC subunits click here showed a proteasome-dependent loss of the APC5 and APC4 subunits that was temporally associated with

the disassembly of the APC. Immediate early viral gene expression was not sufficient for the degradation of APC4 and APC5, indicating that a viral early gene product(s), possibly in association with a de novo-synthesized cellular protein(s), is involved.”
“We characterized the distribution of AMPA receptor (AMPAR) subunits and the transmembrane AMPA receptor

regulatory proteins (TARPs) gamma-2 and gamma-4 in adult rat nucleus accumbens (NAc) using a method that separates plasma membranes into synaptic membrane-enriched and extrasynaptic membrane-enriched fractions. We also measured GluA1 phosphorylated at serine 845 (pS845 GluA1) and serine 831 (pS831 GluA1). GluA1-3 protein levels and pS831 GluA1/total GluA1 were higher in synaptic membranes. However, pS845 QNZ GluA1/total GluA1 was higher in extrasynaptic membranes, consistent with a role for 5845 phosphorylation in GluA 1 insertion at extrasynaptic sites. Homeric GluA1 receptors were

detected in extrasynaptic membranes, consistent with evidence for extrasynaptic Ca2+-permeable AMPARs in other systems. The TARP gamma-2 was enriched in synaptic membranes, whereas gamma-4 was mainly found in extrasynaptic membranes, suggesting distinct roles for these proteins in the NAc. These experiments provide fundamental information that will aid in the interpretation of studies on AMPAR-related plasticity in the NAc. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The gC1qR/p32 protein is a multiple receptor for several proteins and pathogens. We cloned a gC1qR homologue in a crustacean, Pacifastacus leniusculus, and analyzed the expression of P. leniusculus C1qR (PlgC1qR) in various tissues. The gC1qR/p32 transcript almost was significantly enhanced by white spot syndrome virus (WSSV) infection 6 h after viral infection both in vitro in a hematopoietic tissue cell culture (Hpt) and in vivo compared to appropriate controls. Moreover, PlgC1qR silencing in both the Hpt cell culture and live crayfish enhanced the WSSV replication. In addition, by making a recombinant PlgC1qR protein we could show that if this recombinant protein was injected in a crayfish, Pacifastacus leniusculus, followed by injection of WSSV, this significantly reduced viral replication in vivo.

(J Vasc Surg 2012;56:291-7 )”
“One major limitation in prote

(J Vasc Surg 2012;56:291-7.)”
“One major limitation in proteomics is the detection and analysis of low-abundant proteins, i.e. in plasma. Several years ago, a technique to selectively enrich the relative concentration of low-abundant EPZ015666 proteins was introduced by Boschetti and co-workers. It is based on a specific and saturable interaction of proteins to a high diversity of binding sites, realized by a hexapeptide library coupled to beads. This technology was commercialized as Equalizer beads or ProteoMiner. However, during application of ProteoMiner beads to plasma samples unexpected results questioned the proposed mode of action. Therefore, ProteoMiner beads were compared with chromatographic

beads exhibiting completely different surface chemistry. Sepabeads FP-OD400 octadecyl, FP-DA400 diethylamine, FP-BU400 butyl, FP-HG400 hydroxyl and EXE056 epoxy were used. The results show that ProteoMiner or the different Sepabeads behave surprisingly similarly in the separation of complex protein mixtures. ProteoMiner beads interact with protein mixtures according to a general hydrophobic binding mechanism, where diversity in surface ligands plays only a negligible role.”
“Objective: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) that also involve the common iliac artery (CIA) typically

is accomplished by endograft limb extension into the external iliac Elafibranor ic50 artery (EIA). In order to prevent endoleak, the internal iliac artery (IIA) is usually embolized, or alternatively a branched limb is deployed. However, IIA embolization is associated with longer operative time and increased use of contrast and radiation. It has been our practice not to routinely coil embolize the IIA. The purpose of this study was to

present the midterm outcomes of this approach.

Methods: Between April 1997 and June 2010, 137 patients (130 men; mean age, 70.9 years; range, 45-92 years) underwent EVAR of their AAA and had IIA coverage without coil embolization in 112 patients (no embolization [NE] group) and after coil embolization in 25 patients (coil embolization [CE] group). Anatomic indications for coverage of the IIA without coil embolization included presence of adequate sealing Teicoplanin in the distal 5 mm of the CIA, or sealing ring at the origin of the CIA, or IIA diameter <5 mm. Preoperative mean AAA size was 60 +/- 14 mm, and mean CIA diameter was 38 +/- 13 mm. Postoperative computed tomography (CT) scanning was performed at 1, 6, and 12 months, and yearly thereafter.

Results: Thirty-day mortality was 0.7% (1 of 137 patients). A patient presented with gluteal skin necrosis (0.7%). The incidence of postoperative buttock claudication was not different between the two groups (NE: 15 of 112 patients; CE: 3 of 25 patients; P = .852). Procedure and fluoroscopy time, contrast use, and hospital stay were significantly reduced in the NE group. Patients were followed up for 33 +/- 30 months.

These various markers are involved in a host of cellular function

These various markers are involved in a host of cellular functions, including

cell-cycle progression, cell proliferation, AC220 apoptosis, cell adhesion, and tumor vascularity. In this companion article to our first review of Ki-67 as a marker of pituitary adenomas, we present and analyze the literature regarding matrix metalloproteinases and their inhibitors (tissue inhibitor metalloproteinases), vascular endothelial growth factor, fibroblast growth factor and its receptor, apoptotic markers and p53, as well as cyclooxygenase-2, galectin-3, and pituitary tumor transforming gene. Some of these markers, such as fibroblast growth factor and fibroblast growth factor receptor and matrix metalloproteinases, show particular promise in their ability to identify pituitary tumors that behave in an aggressive PRT062607 manner. We suggest the need for uniform design and application of methods and standardized criteria for the interpretation of results. A uniform approach

will establish clinicopathological utility of emerging markers.”
“The Arabidopsis thaliana flower organ specification gene regulatory network (FOS-GRN) has been modeled previously as a discrete dynamical system, recovering as steady states configurations that match the genetic profiles described in primordial cells of inflorescence, sepals, petals, stamens and carpels during early flower development. In this study, we first update the FOS-GRN by adding interactions and modifying some rules according Vitamin B12 to new experimental data. A discrete model of this updated version of the network has a dynamical behavior identical to previous versions, under both wild type and mutant conditions, thus confirming its robustness. Then, we develop a continuous version of the FOS-GRN using a new methodology

that builds upon previous proposals. The fixed point attractors of the discrete system are all observed in the continuous model, but the latter also contains new steady states that might correspond to genetic activation states present briefly during the early phases of flower development. We show that both the discrete and the continuous models recover the observed stable gene configurations observed in the inflorescence meristem, as well as the primordial cells of sepals, petals, stamens and carpels. Additionally, both models are subjected to perturbations in order to establish the nature of additional signals that may suffice to determine the experimentally observed order of appearance of floral organs. Our results thus describe a possible mechanism by which the network canalizes molecular signals and/or noise, thus conferring robustness to the differentiation process. (C) 2010 Elsevier Ltd. All rights reserved.