8A) When the biofilms were maintained in contact with


8A). When the biofilms were maintained in contact with

the Cur for 5 and 20 min of incubation, brighter fluorescence was observed after 20 min of incubation ( Fig. 7B, D and F), suggesting that Cur penetration into the cells of the biofilm after 20 min might have achieved greater amounts than after 5 min. The drugs need to effectively penetrate the extracellular matrix to ensure the occurrence of intimate contact with the microorganisms. For these reasons, in all the P+L+ groups, 20 min of PIT promoted the highest PF-01367338 supplier reductions in cell viability. C. albicans seemed to be the only species whose cell viabilities were clearly dependent on PIT after 4 and 8 min of irradiation. The C. albicans biofilms submitted to PDT showed higher reduction in cell viability after 20 min of PIT (p < 0.01). When PIT was reduced, cell viability was also reduced proportionally. Cell viability of C. dubliniensis biofilms after 8 min of irradiation was PIT-dependent. However, C. dubliniensis biofilms after 4 min Rigosertib datasheet of irradiation, and C. glabrata biofilms (after 4 and 8 min of irradiation) showed no clear tendency to be PIT-dependent, although 1 and 20 min of

PIT, respectively, resulted in the worst and best results. The morphology of the microorganisms seems to have great importance in PDT. A survey by Jackson et al. 26 evaluated whether the hyphae and yeasts forms of C. albicans could be killed by PDT. The results demonstrated that both forms are susceptible to photosensitisation. However, hyphal forms presented Ureohydrolase higher susceptibility to PDT than the yeasts. In the present study, the biofilms were grown in RPMI 1640, which induces hyphae formation. 19C. albicans and C dubliniensis are dimorphic fungi (ovoid yeasts and/or filaments). 12, 18 and 52 On the other hand, C. glabrata presents itself as a single

morphological species and does not transform itself into hyphae. 53 Therefore, considering the possibility that within each PIT, Cur is able to reach the same depth in the biofilms of the three species, fungi that were transformed into hyphae and were sensitised with Cur might have been more susceptible to the phototoxic effects of PDT. This might justify the fact that C. glabrata was the only species that did not present a clear tendency to be PIT-dependent under any of the evaluated conditions. Due to structural and biological differences, different behaviours are expected from distinct Candida strains. C. glabrata produces adhesins capable of promoting adhesion to buccal epithelial cells. 18 It also has high hydrophobicity values and efficient co-adhesion mechanisms, which allows cells to bind to other cells. 54 In addition, the C. glabrata biofilm matrix has higher amounts of both proteins and carbohydrates. 53 Thus, it is possible that drug penetration through the C.

JC-1 fluorescence was quantitated using a fluorescence plate read

JC-1 fluorescence was quantitated using a fluorescence plate reader (BioTek, KC-4) at 37 °C. The fluorescence of the JC-1 monomer was measured at 485 nm (excitation) and 590 nm (emission). For each experiment, the ratios of J-1 aggregate to JC-1 monomer were normalized to untreated controls; values reported, therefore, represent a percentage of mitochondrial function in untreated cells. HepG2 cells were grown in 24 well plates until 70% confluence. Further cells were treated with

BPA with or without ADW extract along with experimental controls. Twenty-four hours later, cell culture medium and cell scrapings were harvested and kept at -80 °C for following quantification of several parameters. Cell scrapings were harvested in lysis buffer (25 mM KH2PO4, 2 mM MgCl2, 5 mM KCl, 1 mM EDTA, 1 mM EGTA, 100 μM PMSF, pH 7.5) after rinsing the cells with PBS, (pH 7.4). The extent Tenofovir price of lipid peroxidation was estimated by the levels of malondialdehyde measured using the thiobarbituric acid reactive substances (TBARS) assay at 535 nm [25]. The results are expressed as nmol/mg of protein using a molar extinction coefficient of 1.56 × 105 MCm−1. Cells were homogenized in trichloroacetic acid (5% w/v), and deproteinized supernatant was used for GSH assay. The glutathione content in the

cell homogenate was determined by the DTNB-GSSG reductase recycling assay as previously described [26]. The results are expressed as nmol GSH/mg CDK inhibitor of protein. The antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase, (GPx) activities were analyzed using cytosolic fraction. Total SOD activity was determined by monitoring the inhibition

of the reduction of ferricytochrome C at 550 nm, using the xanthine – xanthine oxidase system as the source of superoxide. One unit of the SOD is defined as the amount of the enzyme required to inhibit 50% of the rate of cytochrome C reduction [27]. Catalase activity was measured by following the rate of H2O2 consumption spectrophotometrically at 240 nm and expressed as μmol H2O2 oxidized/min/mg protein [28]. Glutathione peroxidase Aprepitant activity was determined by following the enzymatic NADPH oxidation at 340 nm [29]. Statistical analysis was carried out using Graph Pad Prism statistical software (Graph Pad Prism, San Diego, CA, USA). Results are analyzed by one-way analysis of variance (ANOVA) and the significance was calculated using the Tukey-Kramer multiple comparison test and results are considered as significant at P < 0.05. Cytotoxicity of BPA and ADW in HepG2 cells was evaluated using MTT assay (Fig. 2 and Fig. 3). ADW did not present any cytotoxic effect at concentration ranging from 0-100 μg/mL (when tested for 0-72 h. On the other hand BPA was tested for its cytotoxicity with wide range of concentration for 0-72 h and the results are given in Fig. 2. The results showed that BPA at (10-200 nM) caused cytotoxicity to HepG2 cells. The CTC50 of BPA was determined to be 100 nM at 72 h.

All of these processes interact in a complex way Nonetheless, in

All of these processes interact in a complex way. Nonetheless, in experimentally well controlled tasks, some of these variables can be varied, whereas others can be kept constant. The experimental

variation of attentional processes is a typical characteristic of tasks that are used to investigate the P1. Spatial cuing paradigms are a good example. According to our hypotheses, two different processes, T and S are of primary importance in this type of tasks. In type 1 tasks, T is experimentally manipulated by instructing subjects to attend to the left or right hemifield. In type 2 tasks, T is varied by the cue and its validity. T establishes a top–down control process that operates to increase SNR in task relevant networks. In contrast, S is a process that blocks information this website processing in interfering networks. Thus, attentional benefits – associated with the influence of T – and attentional costs – associated with the influence of S – are both due to an increase in inhibition which leads to an increase in P1 amplitude. The difference between T and S is seen in different inhibitory processes that operate in task relevant vs. interfering networks (cf. Fig. 5A). Attentional processes are not the only class of cognitive processes that affect the P1 component. Processing complexity (C) during early stimulus selleck screening library categorization is another important

cognitive process that shapes the P1. As an example, orthographic neighborhood size (N), and word length may be considered variables that directly affect C. A pop-out color target search may be considered an example affecting D, the focused Celastrol search for a complex target lacking pop-out features may be considered an example affecting primarily T, whereas the processing of a distractor item may be considered an example for S. In this section we apply the proposed theory particularly to those findings which are difficult to interpret in terms of stimulus evoked activity

or on the basis of an enhancement hypothesis. An overview over the findings reviewed in Section 2 and their interpretation on the basis of the P1 inhibition timing hypothesis are presented in Fig. 5B. The central prediction of the proposed theory rests on inhibition and on the idea that suppression of task irrelevant and potentially competing information and or neural structures leads to a particularly large increase in the P1 amplitude. Under controlled conditions this suppression related increase will be at least as large or larger than for task relevant processes where inhibition is used to increase the SNR. As a first example let us consider the finding of a large ipsilateral P1 amplitude. We assume that the increased ipsilateral P1 reflects inhibition of task irrelevant and potentially competing processes.

To have a representative set of the

liver contigs of B m

To have a representative set of the

liver contigs of B. microlepidotus, reads of each individual were mapped back to the assembled transcriptome using the alignment program TMAP (http://github.com/iontorrent/TMAP/tarball/tmap.0.3.7) (for more details see Supplementary methods) and contigs showing expression in the three individuals were chosen. In total 13,724 contigs (Supplementary information 1) with an average length of 836.8 bp were retained for the functional annotation ( Table 1; Fig. 1A). The raw sequence data is accessioned in the NCBI Sequence Read Archive (SRA accession SRP046041). The Blastx function was performed with a minimum E-value score of 1.0E− 06 and the gene ontology (GO) terms of molecular function, cellular component, and biological process were selleck assigned to the 13,724 retained contigs using the Blast2GO software (Conesa et al., 2005). A total of 2803 sequences presented Blast results and 7938 (57.8%) sequences were successfully annotated (Fig. S1, Supplementary information 2). As expected, the species distribution of the Blast hits showed that most hits correspond to fish species (Fig. S2, Supplementary information 2). A total of 40,814 annotations (Supplementary information 3) for the 13,724 contigs were obtained; the biological processes class was the most highly represented (44.2%), followed

by molecular function (35%) and cellular component (20.8%) (Fig. 1B). These proportions were similar to these described for Oncorchynchus mykiss ( Fox et al.,

2014). For B. microlepidotus, the biological buy GDC-0941 processes involved mainly the diversity of gene expression, with Clomifene predominance of cellular, metabolic and single-organism processes ( Fig. 2A), while the GO annotations for molecular functions were mostly represented by binding and catalytic activity ( Fig. 2B). The cellular component class was mainly composed of cell, organelle, membrane and macromolecular complex components ( Fig. 2C). See Supplementary methods for details regarding functional annotation. The following are the supplementary data related to this article. Supplementary methods We thank C Quezada-Romegialli, JP Oyanedel and P Muñoz-Rojas for support during field work and Dr. Arne Nolte for support during the analyses. The authors thank R Espejo and Omics-Solutions Chile for sequencing. DV thanks Basal Grant PFB 023, ICM P05-002 and Nucleo Milenio NC120030; CVR thanks Conicyt Doctoral Fellowship 21090188 and doctoral thesis fellowship 24121005. All analyses were conducted in Chile and complied with its existing laws (Resolución Exenta No. 3329 Subsecretaria de Pesca). “
“Brine shrimp (Artemia franciscana) are small crustaceans found worldwide, mainly in hypersaline environments. This zooplanktonic organism has been extensively used in fish aquaculture as larval feed for over 85% of cultured species ( Kayim et al., 2010). Besides this role in aquaculture, Artemias spp.

Levy Videos of hemostasis of an actively

Levy Videos of hemostasis of an actively check details bleeding gastric Dieulafoy lesion, hemostasis of an actively bleeding duodenal ulcer, carbon dioxide–based cryotherapy of diffuse gastric antral vascular ectasia, radiofrequency ablation of gastric antral vascular ectasia, animation of the OverStitch endoscopic suturing device, and OverStitch suture closure of endoscopic submucosal dissection defect accompany this article Several new devices and innovative adaptations of existing modalities have emerged as primary, adjunctive, or rescue therapy in endoscopic hemostasis of gastrointestinal hemorrhage. These techniques include over-the-scope clip devices, hemostatic sprays, cryotherapy, radiofrequency ablation, endoscopic suturing, and endoscopic

ultrasound–guided angiotherapy. This review highlights the technical aspects and clinical applications of these devices in the context of nonvariceal upper gastrointestinal bleeding. Sujal M. Nanavati Since the 1960s, interventional radiology has played a role in the management of gastrointestinal

bleeding. What began primarily as a diagnostic modality has evolved into much more of a therapeutic tool. And although the frequency find more of gastrointestinal bleeding has diminished thanks to management by pharmacologic and endoscopic methods, the need for additional invasive interventions still exists. Transcatheter angiography and intervention is a fundamental step in the algorithm for the treatment of gastrointestinal bleeding. Philip Wai Yan Chiu and James Yun Wong Lau Management of bleeding peptic ulcers is increasingly challenging in an aging population. Endoscopic therapy reduces the need for emergency surgery in bleeding peptic ulcers. Initial endoscopic control offers an opportunity for selecting high-risk ulcers for potential early preemptive surgery. However, such an approach has not been supported by evidence Lepirudin in the literature. Endoscopic retreatment can be an option to control ulcer rebleeding and reduce complications. The success of endoscopic retreatment largely depends on the severity of rebleeding and ulcer characteristics. Large chronic ulcers with urgent bleeding are less likely to respond to endoscopic

retreatment. Expeditious surgery is advised. Sumit Kumar, Sumeet K. Asrani, and Patrick S. Kamath Acute variceal bleeding (AVB) is a potentially life-threatening complication of cirrhosis and portal hypertension. Combination therapy with vasoactive drugs and endoscopic variceal ligation is the first-line treatment in the management of AVB after adequate hemodynamic resuscitation. Short-term antibiotic prophylaxis, early resuscitation, early use of lactulose for prevention of hepatic encephalopathy, targeting of conservative goals for blood transfusion, and application of early transjugular intrahepatic portosystemic shunts in patients with AVB have further improved the prognosis of AVB. This article discusses the epidemiology, diagnosis, and nonendoscopic management of AVB. Jawad A.

The high NOELs for DHC indicate that the contribution of sensory

The high NOELs for DHC indicate that the contribution of sensory irritation and airflow limitation are insignificant in our previous animal set-up with reaction products of limonene (Clausen et al., 2001); similarly, the relatively high RFs suggest that the impact of DHC would be minor or insignificant in offices. The derived RFs for 4-AMCH showed Selleckchem BIBW2992 that airflow limitation was the critical effect. Its concentration in our previous ozone-limonene set-up was 0.1–0.12 ppm (Clausen et al., 2001); thus, its contribution to effects in the conducting airways is considered negligible in this mouse bioassay

experiment. To our knowledge measurements of 4-AMCH in offices have not been reported. The derived RFs for 6-MHO showed that both sensory irritation and airflow limitation may be critical effects. 6-MHO has been measured in office air from 0.8 ppb (Salonen et al., 2009) to 2.3 ppb

in a simulated office (28.5 m3, air exchange rate: 1 h−1) with two subjects and an initial ozone concentration of 33 ppb (Wisthaler and Weschler, 2010), and in an occupied and simulated aircraft cabin exposed to ozone (60–70 ppb; air exchange rate: 4.4–8.8 h−1) to 3–6 ppb (Weschler et al., 2007). For sensory irritation, the hazard index is ≤0.02; thus, indicating that 6-MHO can be ruled out as a significant sensory irritant or bronchoconstrictor at indoor buy Ulixertinib air concentrations. Effects in Carnitine palmitoyltransferase II the conducting airways of mice were reported in previous studies about the ozone-limonene system (Rohr et al., 2002 and Wolkoff et al., 2008). However, the concentration of 4-OPA was less than 0.02 ppb in these studies (unpublished) and thus, would not be expected

to affect the lower airways in view of its NOEL value (Table 3). Downstream 4-OPA concentration of 10 ppb has been measured from used ozone exposed ventilation filters (Destaillats et al., 2011) and concentrations from 2 to 6 ppb have been measured in aircraft cabin and office air (Weschler et al., 2007 and Wisthaler and Weschler, 2010); slightly lower concentrations have been measured in forest environments (Matsunaga et al., 2004). These levels at their maximum still provide a hazard index ≤0.3; thus, indicating that lower airway effects would not be expected. High limonene (and other precursors) concentrations would be prerequisite together with an ozone concentration ≥0.1 ppm, if lung effects should be developed, in agreement with human exposure studies, cf. (Wolkoff et al., 2012). In view of its low RF value, conditions that promote the production of 4-OPA should be considered precautionary. Further precautionary actions would be cleaning, that removes human and animal skin debris, and to avoid crowded spaces with low ventilation. The airflow limitation of 4-OPA could be caused by inflammatory reactions.

One assumption was that TiO2 translocated from compartment 1 to t

One assumption was that TiO2 translocated from compartment 1 to the thoracic lymph nodes (Eq. (7)) BTK inhibitor library and the other assumption was that TiO2 translocated from compartment 2 to the thoracic lymph nodes (Eq. (8)). equation(7) dBLymdt=kLung→LymB1   (t=0, BLym=0) equation(8) dBLymdt=kLung→LymB2   (t=0, BLym=0)Where, BLym was the total TiO2 burden in the right and left posterior mediastinal lymph nodes, and the parathymic lymph nodes (μg); B1 was the TiO2 lung burden in compartment 1 (μg); B2 was the TiO2 lung burden in compartment 2 (μg); and kLung→Lym was the translocation rate constant from lung to thoracic lymph nodes (/day). The least squares

method was used for the estimation (Eq. (9)). equation(9) Sum of square  difference=∑(LnBLym_measured−LnBLym_estimated)2  Sum of square  difference=∑(LnBLym_measured−LnBLym_estimated)2  Where BLym_measured was the measured thoracic lymph node TiO2 burden and BLym_estimated was the estimated thoracic lymph node TiO2 burden. The differences in tissue Ti or TiO2 concentrations between the study

groups were statistically analyzed by Student’s t test or one-way ANOVA (Welch’s test) after F-testing using SPSS 20.0. The Z-average particle sizes were 143–148 nm in the administered suspensions, with ζ potentials of −44 mV. Fig. 3 shows the TiO2 nanoparticle size distribution Stem Cell Compound Library purchase and a scanning electron micrograph of the nanoparticle in the stock suspension. The specific surface area of TiO2 nanoparticles in the administered suspension was 59 m2/g, which was very similar to that of the primary particles (50 ± 15 m2/g, catalog value). The TiO2 concentrations in the diluted suspensions, determined by ICP-AES, were >95% of the concentration estimated by weight measurement and accounting for the dilution factor. Thus, the concentration of the stock solution was confirmed. The concentrations of Ti in drinking water and feed, determined by ICP-SFMS, were <0.10 ng/mL and 2700 ng/g,

respectively. MYO10 This corresponded to TiO2-equivalent concentrations of <0.17 ng/mL and 4500 ng/g, respectively. TiO2 burdens in lung after BALF sampling, BALF, and trachea between 1 day and 26 weeks after administration of TiO2 nanoparticles were significantly higher (P < 0.01) than those of the control group ( Fig. 4). The rat TiO2 burden depended on the dose administered. TiO2 burdens in lung after BALF sampling and BALF decreased over time. One day after administration, 58% ± 16%, 70% ± 15%, 78% ± 13%, 64% ± 15%, and 77% ± 15% of the TiO2 administered was present in the lungs after BALF sampling of rats dosed with 0.375, 0.75, 1.5, 3.0, and 6.0 mg/kg, respectively, while 6.1% ± 1.7%, 6.5% ± 0.75%, 8.6% ± 1.7%, 13% ± 3.4%, and 31% ± 4.9% of administered TiO2 was present in the lungs after BALF sampling 26 weeks after administration of 0.375, 0.75, 1.5, 3.0, and 6.0 mg/kg, respectively.

For instance, in 2011, Thompson et al (2014) reported resistant,

For instance, in 2011, Thompson et al. (2014) reported resistant, intermediate, and susceptible wheat cultivars treated with Quilt or Stratego producing yields 4.09%, −0.46%,

and 1.41% greater than the respective untreated plots.1 In 2012, Enzalutamide research buy these yield increases were 19.86%, 19.76%, and 15.67% respectively. Although our finding in 2012 could be attributed to differences in uncontrollable factors between the treated and untreated groups, it is possible that the disease severity in the untreated plots could have increased since the day it was last measured (i.e., an undetected late disease infection in the untreated plots). On the other hand, Zhang et al. (2010) and Hunger and Edwards (2012) explain that EGFR signaling pathway fungicides protect the yield potential by increasing the activity of the plant antioxidants and by slowing

chlorophyll and leaf protein degradation, which allows plants to keep their leaves longer and use more nutrients during late developmental stages (Morris et al., 1989 and Dimmock and Gooding, 2002). Several results, although expected, were also important to confirm. For example, similar to Orum et al. (2006), there were statistical differences in yields (Table 5) and net returns (Table 6) among locations during each year. Statistical differences in locations are usually attributed to agronomic practices such as crop rotation, soil quality, and disease severity (Orum et al., 2006), or attributed to different fungicides and temperature conditions (Tadesse et al., 2010). Statistical differences among locations in this study may be attributed to small differences in the two soil types, rainfall, elevations over the sea level, and/or several other uncontrollable factors such as temperature and wind (Table 2). There were also statistical differences in yield (Table 7) and net returns (Table 8) among the cultivars during each year. Thompson et al., 2014, Edwards et al., 2012 and Ransom and McMullen, 2008,

and Mercer and Ruddock (2005) explain that wheat cultivars that are susceptible to common foliar diseases are more likely to generate positive returns when treated with fungicide. Among the four cultivars considered in this study, Coker 9553 was the most susceptible cultivar to common foliar diseases, followed Metalloexopeptidase by Magnolia (Table 1). Among the untreated plots, Coker 9553 had the highest yield and it was statistically different from Magnolia and Pioneer 25R47 in 2011; and statistically different from the other three cultivars in 2012 (Table 7). Among the treated plots, Coker 9553 also had the highest yield and it was statistically different from the other three cultivars in both 2011 and 2012 (Table 7). Although Coker 9553 provided the highest average yield in each of the two years (Table 7), it did not necessarily provide the highest average net return from treatment in both years (Table 8).

, 2007), thereby contributing to the development of these tumors

, 2007), thereby contributing to the development of these tumors. There are few studies investigating the influence of stress hormones on HNSCC. Recently, the presence of β-adrenergic receptors (β-AR) for NE and E has been identified in oral (Shang et al., 2009) and esophagus cancer (Liu et al., 2008) cell lines. These investigations also showed that the proliferation of these cell lines is Selleckchem 3-deazaneplanocin A stimulated

by NE and E, respectively. Nevertheless, there is no evidence that IL-6 expression in oral cancer can be influenced by stress hormones. In this study, we have evaluated the effects of stress-related hormones on IL-6 expression and proliferation of OSCC cells, and evidence that OSCC biopsies express β-ARs is provided. The OSCC-derived

cell lines SCC9, SCC15, and SCC25 Duvelisib in vitro were used in the evaluation of the effects of stress hormones. The cell lines were kindly provided by Dr. Ricardo Della Coletta (School of Dentistry, State University of Campinas, Piracicaba, São Paulo, Brazil). These cells were maintained and propagated in a 1:1 mixture of Dulbecco’s modified Eagle’s medium (DMEM) and Ham’s F12 medium (DMEM/F12; Invitrogen, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (FBS), 100 μg/mL penicillin, 100 μg/mL streptomycin, and 0.1% gentamicin, at 37 °C, in 5% CO2 humidified atmosphere. Experiments were carried out with 80% confluent cultures. SCC9, SCC15, and SCC25 cells were seeded in 24-well plates (1.0 × 105 cells per well) Celecoxib and cultured

for 24 h in serum-reduced medium (0.1% FBS). The following hormones were tested: NE (Calbiochemical Co, La Jolla, CA), cortisol (Sigma–Aldrich, St. Louis, MO) and isoproterenol (Sigma–Aldrich, St. Louis, MO), a β-adrenergic agonist. The cells SCC9 and SCC25 were then treated with NE or isoproterenol at 0, 0.1, 1, and 10 μM, or cortisol at 0, 1, 10, 100, and 1000 nM. These concentrations were used in the subsequent experiments. The cells SCC15 were treated with NE and cortisol. For blocking experiments, 1 μM propranolol was added to the cell cultures 1 h before addition of 10 μM NE. Cell-free supernatants and cells were collected at 1, 6, and 24 h, and kept at − 80 °C until the assays were performed. The hormone concentrations employed were defined by taking the physiological levels that usually reaching in the tumor microenvironment. NE basal circulating levels range between 10 pM and 1 nM (Sood et al., 2006), and studies have suggested that stress increases these levels to approximately 100 nM, and they may reach 10 μM in the microenvironment of some types of tumors (Antoni et al., 2006 and Sood et al., 2006). The concentrations of 10 and 100 nM cortisol reflect similar levels to those found in stress conditions, and higher concentrations (1000 nM) simulate pharmacological doses of glucocorticoids (Miller and O’Callaghan, 2002).

There, the observed chlorophyll concentration, as well as the one

There, the observed chlorophyll concentration, as well as the one simulated in CM5_piCtrl, is lower than 0.05 mg/m3 (e.g. Séférian et al., 2012). As

a result, less heat is trapped in the surface layer in these areas in CM5_piCtrl as compared to CM5_piCtrl_noBio, explaining the cold surface anomalies seen on Fig. 4. Coastal upwellings in equatorial regions, on the other hand, are relatively rich in chlorophyll, and one would expect a net surface warming in CM5_piCtrl as compared to CM5_piCtrl_noBio. This is what is found by Lengaigne et al. (2006) and Patara et al. (2012), two independent studies using similar twin experiments with another coupled climate model and the same oceanic component as ours, namely NEMO. Yet, in our case, the warming effect is very weak or absent (Fig. 4). At mid to high latitudes, previous studies (e.g. Lengaigne et al., 2009 and Manizza, 2005) Sorafenib have suggested that bio-physical feedbacks would result in an intensification of the seasonal cycle: in summer, the presence of phytoplankton MLN0128 increases the surface warming, as more heat is trapped at the ocean surface, while in fall and winter, the deepening of the mixed layer acts to bring

the underlying anomalously cold layers to the surface. This is indeed the case in our simulations for the Southern Ocean and the subpolar North Atlantic and North Pacific that are marked by a warming in local summer in CM5_piCtrl (Fig. 4, right panel), and a moderate to strong cooling in winter (Fig. 4, middle panel). Consistently, the seasonal cycle of SST at mid to high latitudes is slightly enhanced in CM5_piCtrl as compared to CM5_piCtrl_noBio (Fig. 5). Note however that the physical parameterization changes Alanine-glyoxylate transaminase described in Table 1 induce much stronger changes to the seasonal cycle amplitude in CM5_piStart compared to CM5_RETRO than to CM5_piCtrl_noBio (Fig. 5).

Such effect can hardly be seen in forced mode (Fig. 3) and might thus be due to air-sea interactions. In annual mean (Fig. 4, left), ice-free areas at northern high latitudes experience a cooling in CM5_piCtrl as compared to CM5_piCtrl_noBio, which again differs from earlier studies, in particular Lengaigne et al. (2009). These authors have argued that warming associated to phytoplankton blooms occurs concomitantly with the ice retreat along the Arctic coastal shelves in spring and this mechanism is then amplified in summer due to a larger reduction of sea-ice thickness and concentration. In our model, such biologically-induced warming occurs indeed in summer but its global effect is largely counteracted by the winter cooling. Fig. 6 shows the adjustment of the model to the biogeochemical component, helping to understand differences with previous model versions: during the first decade (left panel), the anomalous vertical temperature profile is close to what is expected from the one-dimensional adjustment described above, and broadly agrees with results from Lengaigne et al., 2006 and Lengaigne et al.