In this review,

In this review, selleck products we summarized studies on the molecular epidemiology and nationwide surveillance of norovirus in South Korea. This review will provide information for vaccine development and prediction of new emerging variants of norovirus in South Korea.”
“Alginic acid (Alg) is a natural anionic polysaccharide, which consists of alpha-L-guluronic acid (G) and

beta-D-mannuronic acid (M). G-G sequence-rich chain regions, known as G-blocks (GB), are important regions for gelation of Alg using divalent cations. In this study, calcium-induced GB gel beads were prepared, and drug release profiles and degradation properties of the GB gel beads were investigated in aqueous media. The GB gel beads swelled slightly in JP XVI 1st fluid (pH 1.2), and only slight release of sodium diclofenac (DF) from the GB gel beads was observed. Disintegration of the GB gel beads was not observed in the 1st

fluid. On the other hand, the GB gel beads disintegrated in JP XVI 2nd fluid (pH 6.8), and the rate of disintegration depended on the concentration of calcium chloride used to prepare the GB gel beads. The DF release profiles of the GB gel beads in the 2nd fluid could be controlled by the concentration of CaCl2 used to prepare the GB gel beads. The initial release profile of DF from GB gel beads was not consistent with the profile of disintegration. According to the Higuchi-plot of the percentage of drug content released against the square root of time, gel disintegration did not affect LY2835219 the release of DF from GB gel beads. It appears that a diffusion-type mechanism was responsible for DF release. We propose that the GB gel bead gel matrix is an effective medium by which to control the release of drug within the gastrointestinal tract.”
“The present study reports a facile approach for sulfite biosensing, based on enhanced direct electron transfer of a human sulfite oxidase (hSO) immobilized KU-57788 concentration on a gold nanoparticles modified electrode. The spherical core shell AuNPs were prepared via a new

method by reduction of HAuCl4 with branched poly(ethyleneimine) in an ionic liquids resulting particles with a diameter less than 10 nm. These nanoparticles were covalently attached to a mercaptoundecanoic acid modified Au-electrode where then hSO was adsorbed and an enhanced interfacial electron transfer and electrocatalysis was achieved. UV/Vis and resonance Raman spectroscopy, in combination with direct protein voltammetry, are employed for the characterization of the system and reveal no perturbation of the structural integrity of the redox protein. The proposed biosensor exhibited a quick steady-state current response, within 2 s, a linear detection range between 0.5 and 5.4 mu M with a high sensitivity (1.85 nA mu M-1). The investigated system provides remarkable advantages in the possibility to work at low applied potential and at very high ionic strength.

The groups of birth defects with the highest proportion of second

The groups of birth defects with the highest proportion of second-trimester terminations were defects of the nervous system (347/740; 48%) and abdominal wall (58/149; 39%). For many types of birth defects, however, find more that proportion was less than 10%. Conclusion: The proportion of terminated pregnancies carrying birth defects is considerably greater than the corresponding

proportion for pregnancies that end as live births or stillbirths. The proportion of birth defects unobserved at birth due to second-trimester terminations depends on type of defect and lethality.”
“Natural components endogenous to plant material extracts often interfere with traditional PD-1/PD-L1 Inhibitor 3 cost peroxidase assays by reducing the oxidized product generated as a result of the peroxidase-catalyzed reaction. This leads to

an underestimation of peroxidase activity when the oxidized product provides the signal for enzyme activity quantification. This article describes a relatively simple way to alleviate complications arising due to the presence of such confounding compounds. The method is based on using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) as the reducing substrate. The oxidized product of the reaction is ABTS’, the accumulation of which can be followed spectrophotometrically. It is shown here that one can selectively inactivate the endogenous compounds that confound the peroxidase assay by treating

the enzyme preparation with the oxidized product itself, ABTS(+), prior to initiating the quantification assay. This approach is selective for those compounds likely to interfere with peroxidase quantification. The presented method is shown to alleviate the complications associated with lag phases typical of plant extract peroxidase assays and, thus, to more accurately reflect total peroxidase activity. The presented assay is expected to be applicable to the wide range of biological systems for which the determination of peroxidase activity is desired. (C) 2015 Elsevier Inc. All rights reserved.”
“The motor control of the eight highly flexible arms of the common octopus (Octopus vulgaris) has been the focus of several recent studies. Our study is the first to manage PD-1/PD-L1 Inhibitor 3 to introduce a physical constraint to an octopus arm and investigate the adaptability of stereotypical bend propagation in reaching movements and the pseudo-limb articulation during fetching. Subjects (N=6) were placed inside a transparent Perspex box with a hole at the center that allowed the insertion of a single arm. Animals had to reach out through the hole toward a target, to retrieve a food reward and fetch it. All subjects successfully adjusted their movements to the constraint without an adaptation phase.

To study

the spatiotemporal characteristics of this molec

To study

the spatiotemporal characteristics of this molecular process we carried out Brownian dynamics simulations of the interactions of the MDM2 SB203580 chemical structure protein with a p53 peptide in its wild type state and when phosphorylated at Thr18 (pThr18) and Ser20 (pSer20). We found that p53 phosphorylation results in concerted changes in the topology of the interaction landscape in the diffusively bound encounter complex domain. These changes hinder phosphorylated p53 peptides from binding to MDM2 well before reaching the binding site. The underlying mechanism appears to involve shift of the peptide away from the vicinity of the MDM2 protein, peptide reorientation, and reduction in peptide residence time relative to wild-type p53 peptide. pThr18 and pSr20 p53 peptides experience reduction in residence times by factors of 13.6 and 37.5 respectively relative to the wild-type p53

peptide, indicating a greater role for Ser20 phosphorylation in abrogating p53 MDM2 interactions. These detailed insights into the effect of phosphorylation on molecular interactions are not available from conventional experimental and theoretical approaches and open up new avenues that incorporate molecular interaction dynamics, for stabilizing p53 against MDM2, which is a major focus of anticancer drug lead development.”
“Epidemiological, preclinical and cellular studies in the last 5 years have shown that metformin exerts anti-tumoral properties, but its mode of action in cancer remains unclear. Here, we investigated the effects of metformin on a mouse Ferroptosis assay hepatocellular carcinoma (HCC) model and tumor-associated T cell immune responses. Oral metformin administration led to a significant reduction of tumor growth, which was accompanied by decreased interleukin-22 (IL-22). Meanwhile, Transmembrane Transporters inhibitor IL-22-induced STAT3 phosphorylation

and upregulation of downstream genes Bcl-2 and cyclin D1 were inhibited by metformin. At the cellular level, metformin attenuated Th1- and Th17-derived IL-22 production. Furthermore, metformin inhibited de novo generation of Th1 and Th17 cells from naive CD4(+) cells. These observations were further supported by the fact that metformin treatment inhibited CD3/CD28-induced IFN- and IL-17A expression along with the transcription factors that drive their expression (T-bet [Th1] and ROR-t [Th17], respectively). The effects of metformin on T cell differentiation were mediated by downregulated STAT3 and STAT4 phosphorylation via the AMP-activated kinase-mammalian target of rapamycin complex 1 pathway. Notably, metformin led to a reduction in glucose transporter Glut1 expression, resulting in less glucose uptake, which is critical to regulate CD4(+) T cell fate. Taken together, these findings provide evidence for the growth-inhibitory and immune-modulatory effects of metformin in HCC and thus, broaden our understanding about the action of metformin in liver cancer treatment.

However, additional research is required to determine both treatm

However, additional research is required to determine both treatment efficacy and safety.”
“Membranes based on

sulfonated polyarylethersulfone with cardo (SPES-C) were prepared and characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and contact angle metering. The results show that both the hydrophilicity and amorphous region of the membranes increased with increasing sulfonation degree (SD). Sulfonic acid groups exist as a form of ion clusters and homogeneously distribute in the membranes leading to a depression in their crystallinity and an increase in the interaction between methanol and the membranes. The effects Selleck LDK378 of SD on the swelling and separation performance of the membranes were studied. The SPES-C membrane with excellent thermal stability is found to have improved performance when the SD is 0.64. A flux of 4.06 kg mu m m(-2) h(-1) and separation factor of 1300 at 40 degrees C are achieved in pervaporation of 15 wt% methanol/methyl tert-butyl ether mixture. (C) 2012 Elsevier B.V. All rights reserved.”
“A GW4869 mouse coated circular inclusion embedded in an infinite matrix is analyzed in the framework of two-dimensional isotropic linear elasticity. A closed-form solution is obtained for

the case of far-field uniaxial tension using Muskelishvilis complex potential method. The solutions for the stress and strain distributions for all three regions, that is, matrix, coating, and inclusion, NVP-AUY922 were obtained for various coating-to-matrix shear modulus ratios, while keeping the fiber and matrix shear moduli the same. Test cases for an inclusion without the coating

and hollow inclusion were also studied. The energy release rate was evaluated using the path-independent M-integral, which is used to calculate the energy release rate for the self-similar expansion of defects surrounded by the closed contour of the integral. The results for the stress and strain concentrations along with the energy release rate due to this material inhomogeneity were analyzed to yield a better understanding of the mechanics of materials with circular inclusions. This can be helpful in designing intelligent composite structures with embedded optical fiber sensors.”
“Purpose: When planning implant therapy, knowledge of the bone volume in the implant area is needed to plan and place implants in the most appropriate locations from the prosthetic and surgical perspectives. Commercial software for digital planning of implants in the craniofacial region is not yet available. This article describes a method that enables digital planning of extraoral implants in the mastoid region utilizing commercially available computer-aided design (CAD) software and rapid-prototyping techniques to manufacture a corresponding surgical guide.

cruzi positive guinea pig were independent correlates of T cruzi

cruzi positive guinea pig were independent correlates of T. cruzi infection. Only one species of triatomine was found, Panstrongylus lignarius, formerly P. herreri. Approximately forty percent (39.9%, 95% CI: 33.2 – 46.9%) of surveyed households were infested with this vector and 14.9% (95% CI: 10.4 – 20.5%) had at least one triatomine positive for T. cruzi. The cardiac

abnormality of right AG-881 bundle branch block was rare, but only identified in seropositive individuals. Conclusions Our research documents a substantial prevalence of T. cruzi infection in Cutervo and highlights a need for greater attention and vector control efforts in northern Peru.”
“The associations between intake of or circulating fatty acids and risk of colorectal cancer (CRC) are unclear. We examined prospectively the associations between dietary or biomarker fatty acids and CRC. For 41,514 men and women, aged 40-69

years, baseline (1990-94) dietary intakes of fatty acids were estimated using a food frequency questionnaire and plasma phospholipid (PPL) fatty acids were measured for 4,205 participants including 395 CRC cases, according to a case-cohort design. Hazard ratios were computed using Cox regression adjusting for education, alcohol intake, smoking status, physical activity and total energy intake; and stratified for gender, ethnicity and family history of cancer, with age as the time scale. We assessed the OICR-9429 in vitro heterogeneity of associations with colon and rectal cancers. PPL saturated fatty acids (SFAs) were positively associated with CRC risk, while total n-3 polyunsaturated fatty acids (PUFA) and long chain marine n-3 PUFAs showed inverse associations, significant only for 22:5 n-3. No significant MK2206 associations were observed for dietary fatty acid intakes but positive associations with CRC of borderline significance were seen for both dietary and PPL linoleic acid. Positive associations with dietary palmitic acid (16:0), MUFAs and n-6 PUFAs were seen for rectal but not colon cancers. PPL 22:6 n-3 was inversely associated

with rectal cancer. Limiting intakes of SFAs and MUFAs could be assisted by following existing guidelines to limit red and processed meats which are important sources in the Australian diet. Our observations regarding linoleic acid should be examined further. What’s new? While there is considerable evidence that diet is associated with colorectal cancer (CRC) risk, the associations for specific fatty acids remain unclear. Here, the authors prospectively examine associations between dietary intake estimates or plasma phospholipids (PPL) estimates of fatty acids and incident CRC. PPL saturated fat (SF) is positively associated with incident CRC and dietary SF with rectal cancer, while long chain n-3 fats are inversely associated with both.

It has been found that the effects of degenerate pressure and num

It has been found that the effects of degenerate pressure and number density of electron and inertial positively as well as negatively charged light ion fluids, and various charging state of positively charged static heavy ions significantly modify the basic features of mIA shock structures. The implications of our results to dense plasmas in astrophysical compact objects (e.g., non-rotating white dwarfs, neutron stars, etc.) are briefly discussed.”
“IFN gamma is a potent activator and IL-10 a powerful inhibitor of macrophage functions. However, AC220 concentration neither all cellular functions are enhanced

by IFN gamma nor IL-10 inhibits all cellular responses. Thus. Fc gamma Rs-mediated phagocytosis in monocyte-derived macrophages (MDM) increases after IL-10 treatment, and decreases after treatment with IFN gamma, although both IL-10 and IFN gamma up

regulate Fc gamma RI expression. In this work we investigated the effect of IFN gamma and IL-10 on phagocytic signaling by Fc gamma Rs in MDM. Treatment with IFN gamma diminished phagocytosis of IgG-opsonized SRBC (IgG-SRBC) while treatment with IL-10 increased it. These opposite effects cannot be attributed to changes in Fc gamma R expression induced by each cytokine. Early biochemical responses mediated by Fc gamma Rs were distinctly affected by cytokine treatment. Syk phosphorylation and the rise in [Ca2+](i) were higher after GSK1838705A solubility dmso IL-10 treatment, whereas IFN gamma treatment also increased Syk phosphorylation but had no effect on the rise in [Ca2+](i). IFN gamma treatment led to increased basal levels of F-actin and this effect correlated with the decrease in phagocytosis of both IgG-SRBC GDC-0941 in vitro and non-opsonized Escherichia coli. IL-10 did not alter F-actin basal levels, and enhanced the phagocytosis of

E. coli and IgG-SRBC. The level of F-actin reached after IFN gamma treatment was not further increased after stimulation with IgG-SRBC or CCL5, whereas MDM treated with IL-10 showed a slightly higher response than control cells to CCL5. IFN gamma increased Rac1-GTP levels. Inhibition of PI3K with LY294002 prevented IFN gamma-mediated actin polymerization. Our data suggest that IFN gamma induces a higher basal level of F-actin and activation of Rac1, affecting the response to stimuli that induce cytoskeleton rearrangement such as phagocytic or chemotactic stimuli. (C) 2011 Elsevier Ltd. All rights reserved.”
“The gene networks that comprise the circadian clock modulate biological function across a range of scales, from gene expression to performance and adaptive behaviour. The clock functions by generating endogenous rhythms that can be entrained to the external 24-h day-night cycle, enabling organisms to optimally time biochemical processes relative to dawn and dusk.

4 mm) We evaluated the findings with thin-section CT for each pe

4 mm). We evaluated the findings with thin-section CT for each peripheral tumor; emphasis was laid on the predominant internal characteristics (whether the mass is solid), tumor-lung interface characteristics (whether the mass is well-defined with a smooth surface or with lobulation

or spiculation), and surrounding structures (the presence or absence of perivascular thickening adjacent to the tumor). In all patients, most portions of the tumor consisted of a non-calcified solid mass. Contrast enhancement in selleck chemicals llc varying degrees was observed in the tumors of all 8 patients, who were evaluated with enhanced CT. The tumor-lung interface characteristics observed on the CT images included a well-defined mass with a smooth surface (n = 5), a well-defined mass with lobulation (n = 3), and a mass with spiculation (n = 4). An irregular perivascular thickening adjacent to the tumor was observed in 4 patients. We conclude that peripheral SCLC without associated lymphadenopathy manifests as a non-calcified solid mass and is occasionally characterized by BAY 57-1293 supplier perivascular thickening.”
“The incidence of esophageal cancer

has grown over the recent decades and 30 % of esophageal cancer patients are now 75 years or older at the time of diagnosis. The aim of this study was to evaluate trends in management and survival of patients aged 75 years or older with esophageal cancer.\n\nIn the Netherlands cancer registry, we identified all patients aged 75 years or older who were diagnosed

with esophageal cancer between 1989 and 2008. Trends in management and survival were analyzed by time period (1989-2001 vs. 2002-2008), TNM stage, and age (75-79, 80-84, and 85+ years). chi(2) testing was used to analyze time trends in treatment, Kaplan-Meier analysis and log-rank testing to estimate survival, and Cox regression model to calculate hazard ratios for death.\n\nSome 7,253 patients were included in the study. The surgical resection rate increased over the 1989-2008 period from 8.9 to 12.6 % (p = 0.028), especially among patients aged 75-79 years Selleck AZD6094 (44.6 vs. 55.4 %, p < 0.001) and patients with TNM stage I disease (12.7 vs. 22.0 %, p < 0.001). The use of definitive chemoradiotherapy (CRT) also increased (0.19 vs. 2.20 %, p < 0.001). Whereas the use of chemotherapy as a single-modality treatment more than doubled (0.64 vs. 1.54 %, p = 0.004), that of radiotherapy alone decreased (38.1 vs. 31.6 %, p < 0.001). Although median survival time was marginally higher in the 2002-2008 period than in 1989-2001, overall 5 year survival rates remained low at 6 and 5 %, respectively (p < 0.001). Five-year survival rate after surgery increased from 16 to 30 % (p < 0.001).\n\nIn patients of 75 years or older, surgical treatment and use of definitive CRT have increased between 1989 and 2008. Also, an increase in the use of chemotherapy as a single modality was noted.

In conclusion, C-13-MBT correlates with clinical scoring systems,

In conclusion, C-13-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.”
“The mineralization of organic matter in anoxic environments

relies on the cooperative activities of hydrogen producers and consumers obligately linked by interspecies metabolite exchange in syntrophic consortia that may include sulfate reducing species such as Desulfovibrio. To evaluate the metabolic flexibility of syntrophic Desulfovibrio to adapt to naturally fluctuating methanogenic environments, DAPT nmr we studied Desulfovibrio alaskensis strain G20 grown learn more in chemostats under respiratory and syntrophic conditions with alternative methanogenic partners, Methanococcus maripaludis and Methanospirillum hungatei, at different growth rates. Comparative whole-genome transcriptional analyses, complemented by G20 mutant strain growth experiments and physiological data, revealed a significant influence of both energy source availability (as controlled by dilution rate) and methanogen on the electron transfer systems, ratios of interspecies electron carriers, energy generating systems, and interspecies physical associations.

A total of 68 genes were commonly differentially expressed under syntrophic versus respiratory lifestyle. Under low-energy (low-growth-rate) conditions, strain G20 further had the capacity to adapt to the metabolism of its methanogenic partners, as shown by its differing gene expression of enzymes involved in the

direct metabolic interactions (e. g., periplasmic hydrogenases) and the ratio shift in electron carriers used for interspecies metabolite exchange (hydrogen/formate). A putative monomeric [Fe-Fe] hydrogenase and Hmc (high-molecular-weight-cytochrome c(3)) complex-linked reverse menaquinone (MQ) redox loop become increasingly important for the reoxidation Adriamycin datasheet of the lactate-/pyruvate oxidation-derived redox pair, DsrC(red) and Fd(red), relative to the Qmo-MQ-Qrc (quinone-interacting membrane-bound oxidoreductase; quinone-reducing complex) loop. Together, these data underscore the high enzymatic and metabolic adaptive flexibility that likely sustains Desulfovibrio in naturally fluctuating methanogenic environments.”
“Inner hair cell ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles per s) are unknown. We found that an aspartate to glycine substitution in the C2F domain of the synaptic vesicle protein otoferlin impaired hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. In vitro estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca2+ signaling and vesicle fusion were normal.

“Several bacterial pathogens inject virulence proteins int

“Several bacterial pathogens inject virulence proteins into host target cells that are substrates of eukaryotic tyrosine kinases. One of the key examples is the Helicobacter pylori CagA effector protein which is translocated by a type-IV secretion system. Injected CagA becomes tyrosine-phosphorylated on EPIYA sequence motifs by Src and Abl family kinases. CagA then binds to and activates/inactivates multiple signaling proteins in a phosphorylation-dependent and phosphorylation-independent manner. A recent proteomic screen systematically identified eukaryotic binding

partners of the EPIYA phosphorylation sites of CagA and similar sites in other bacterial effectors by high-resolution mass spectrometry. Individual phosphorylation sites recruited a surprisingly high number of interaction partners suggesting that each phosphorylation site can interfere with many downstream pathways. We now count 20 reported cellular binding partners of CagA, which represents the highest Apoptosis inhibitor quantitiy among all yet known virulence-associated effector proteins in the microbial world. This complexity generates a highly remarkable and puzzling scenario. In addition, the first crystal structure of CagA provided us with new information on the function of this important virulence determinant. Here we review the recent advances in characterizing the multiple

binding signaling activities of CagA. Injected CagA can act as a ‘master key’ that evolved the ability to highjack multiple host Navitoclax inhibitor cell signalling cascades, SHP099 which include the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as

proliferative, pro-inflammatory and anti-apoptotic nuclear responses. The discovery that different pathogens use this common strategy to subvert host cell functions suggests that more examples will emerge soon.”
“Objective: To evaluate the capacity of fetal echocardiography for predicting the more likely surgical approach in new-borns with coarctation of the aorta (CoAo) (left thoracotomy vs. median sternotomy). Material and Methods: We selected all cases of suspected CoAo prenatally diagnosed in 2003-2012 (n = 95). 49/95 were considered at high-risk and 46/95 at low-risk of CoAo, and 38/49 and 7/46 were postnatally confirmed, respectively. We firstly evaluated in 40 cases of CoAo surgically repaired (24 thoracotomy, 16 sternotomy) whether there were differences in fetal echocardiographic parameters between both groups. Secondly, we assessed the performance of these parameters for predicting the surgical approach in fetuses at high risk of CoAo. Results: Sternotomy approach was associated with higher rate of postoperative complications and longer hospital stay compared with thoracotomy (81.3 vs. 41.7%, p = 0.014; 30.5 vs. 15.4 days, p = 0.0004, respectively). The Z-score of the aortic isthmus, measured in the sagittal plane, was significantly smaller in the sternotomy group.

There are several studies supporting this idea, but in all studie

There are several studies supporting this idea, but in all studies, we used dicoumarol, an inhibitor of DT-diaphorase. We have designed and developed two siRNA to silence the expression of DT-diaphorase to study its role in aminochrome metabolism. We transduced RCSN-3 cells with retroviral particles containing

a pRetroSuper plasmid coding a siRNA for DT-diaphorase. The cells selected in the presence of puromycin generated a stable cell line RCSN-3Nq6 and RCSN-3Nq7 with low expression of DT-diaphorase Dinaciclib (27% and 33% of wild type. respectively). A significant cell death was observed in RCSN-3 cells expressing siRNA Ny6 and Ny7 for DT-diaphorase when were incubated with 100 mu M aminochrome during 48 (4- and 3.5-fold, respectively; P < 0.01). These results support the protective

role of DT-diaphorase against aminochrome neurotoxicity in dopaminergic neurons containing neuromelanin and show that Ny6 and Ny7 siRNA are very useful tools to study the role of DT-diaphorase in aminochrome metabolism.”
“Bioactivity-directed fractionation of extracts from the seeds of Trichosanthes kirilowii led to the isolation of (-)-1-O-feruloylsecoisolariciresinol (2), named hanultarin, In addition, four known lignans were also isolated, including (-)-secoisolariciresinol (1), 1,4-O-diferuloylsecoisolariciresinol (3), (-)-pinoresinol (4), and 4-ketopinoresinol (5). Their structures were elucidated on the basis of spectroscopic data. Compounds 2 and 3 exhibited strong cytotoxic effects against human lung carcinoma A549 cells, click here melanoma SK-Mel-2 cells, and mouse skin melanoma B16F1 cells with IC(50) ranges of 3 -13 mu g/mL. Compound 2 showed an inhibitory effect on the polymerization of the actin cytoskeleton in normal epidermal keratinocyte (HaCaT cells), suggesting unique biological properties of compound 2 compared to those of the other isolates. (C) 2008 Elsevier Ltd. GW3965 cost All rights reserved.”

can constitute a metastable intermediate between normal diploidy and oncogenic aneuploidy. Here, we show that the absence of p53 is not only permissive for the survival but also for multipolar asymmetric divisions of tetraploid cells, which lead to the generation of aneuploid cells with a near-to-diploid chromosome content. Multipolar mitoses (which reduce the tetraploid genome to a sub-tetraploid state) are more frequent when p53 is down-regulated and the product of the Mos oncogene is upregulated. Mos inhibits the coalescence of supernumerary centrosomes that allow for normal bipolar mitoses of tetraploid cells. In the absence of p53, Mos knockdown prevents multipolar mitoses and exerts genome-stabilizing effects. These results elucidate the mechanisms through which asymmetric cell division drives chromosomal instability in tetraploid cells. The EMBO Journal (2010) 29, 1272-1284. doi:10.1038/emboj.2010.