Microbiology 1996,142(Pt 3):601–10.CrossRefPubMed 22. Tiwari RP, Reeve WG, Dilworth MJ, Glenn AR: Acid tolerance in Rhizobium meliloti strain WSM419 involves a two-component sensor-regulator system. Microbiology 1996,142(Pt 7):1693–704.CrossRefPubMed 23. Fenner BJ, Tiwari RP, Reeve WG, Dilworth MJ, Glenn AR:Sinorhizobium medicae genes whose regulation involves the ActS and/or ActR signal transduction proteins. FEMS Microbiol Lett 2004, 236:21–31.CrossRefPubMed 24. Dilworth MJ, Howieson JG, Reeve WG, Tiwari RP, Glenn AR: Acid tolerance in legume root

TH-302 clinical trial nodule bacteria and selecting for it. Australian Journal of Experimental Agriculture 2001, 41:435–446.CrossRef 25. Vinuesa P, Neumann-Silkow F, Pacios-Bras C, Spaink HP, Martinez-Romero E, Werner D: Genetic analysis of a pH-regulated operon from Rhizobium tropici CIAT899 involved in acid

tolerance and nodulation competitiveness. Mol Plant Microbe Interact 2003, 16:159–168.CrossRefPubMed 26. Dondrup M, Goesmann A, Bartels D, Kalinowski J, Krause L, Linke Ilomastat chemical structure B, et al.: EMMA: a platform for consistent storage and efficient analysis of microarray data. J Biotechnol 2003, 106:135–46.CrossRefPubMed 27. Reeve WG, Tiwari RP, Guerreiro N, Stubbs J, Dilworth MJ, Glenn AR, et al.: Probing for pH-regulated proteins in Sinorhizobium medicae using proteomic analysis. J Mol Microbiol Biotechnol 2004, 7:140–7.CrossRefPubMed 28. Reeve WG, Bräu L, Castelli J, Garau G, Sohlenkamp C, Geiger O, et al.: The Sinorhizobium medicae WSM419 lpiA gene is transcriptionally activated by FsrR and required to enhance survival in lethal acid conditions. Microbiology 2006, 152:3049–3059.CrossRefPubMed 29. Sohlenkamp 17-DMAG (Alvespimycin) HCl C, Galindo-Lagunas KA, Guan ZQ, Vinuesa P, Robinson S, Thomas-Oates J, et al.: The lipid lysyl-phosphatidylglycerol is present in membranes of Rhizobium tropici CIAT899 and confers increased resistance to polymyxin B under acidic growth conditions. Molecular Plant-Microbe Interactions 2007, 20:1421–1430.CrossRefPubMed

30. Merlin C, Masters M, McAteer S, Coulson A: Why is carbonic anhydrase essential to Escherichia coli ? Journal of Bacteriology 2003, 185:6415–6424.CrossRefPubMed 31. Sauviac L, Philippe H, Phok K, Bruand C: An extracytoplasmic function sigma factor acts as a general stress response regulator in Sinorhizobium meliloti. Journal of Bacteriology 2007, 189:4204–4216.CrossRefPubMed 32. Bittner AN, Foltz A, Oke V: Only one of five groEL genes is required for viability and successful symbiosis in Sinorhizobium meliloti. J Bacteriol 2007, 189:1884–1889.CrossRefPubMed 33. Oke V, Long SR: Bacterial genes induced within the nodule during the Rhizobium -legume symbiosis. Mol Microbiol 1999, 32:837–849.CrossRefPubMed 34. Davey ME, de Bruijn FJ: A homologue of the tryptophan-rich sensory protein TspO and FixL regulate a novel nutrient deprivation-induced Sinorhizobium meliloti locus. Appl Environ Microbiol 2000, 66:5353–5359.

Several pathways could be involved in these mechanisms including activation of anti-apoptotic factors, inactivation of pro-apoptotic effectors, and/or reinforcement of survival signals [122]. Based on an understanding of their characteristics, the refractory response of CSCs to drugs and radiation treatments may be attributed to: drug effluxion glutathione (GSH) system apoptosis; enrichment of CSCs during disease progression tumor dormancy and CSC quiescence Drug effluxion It can be caused by an altered uptake or efflux of drug in the target

cell. Platinum compounds enter the cell, primarily by passive diffusion, however several different ways have been described such as copper transporter proteins (CTR), organic cation transporters (OCTs) from de SLC22 family, ATP-binding cassette (ABC) multidrug transporters, copper-transporting ATPases, and multidrug and toxin extrusion from the SLC47 subfamily members that might this website facilitate the active efflux of anticancer platinum agents. Some of most frequently studied drug transporters associated with acquisition of resistance in normal SCs as well as in CSCs are multifunctional efflux transporters from the ABC gene family [123]. These contribute to tumor resistance by actively transporting drugs across cell membranes

through ATP hydrolysis [83, 124–127]. Efflux transporters in the ABC family such as ABCG2 are cell surface drug-resistance markers involved in the transport of substances and cellular products [128–133]. The resistance gene BCRP/MXR/ABCP has been studied for its involvement in development of chemoresistance. ABCG2/BCRP plays a key role in cellular homeostasis and selleck chemicals llc tissue integrity. It has been observed that ovarian CSCs exposed to chemotherapy overexpress this ABC family of transporters. Consequently, ABCG2/BCRP acts as a xenobiotic drug transported

by promoting expulsion through an ejection system. Glutathione (GSH) system Also inflammatory processes can contribute to multiple CSC capabilities by supplying bioactive molecules to the tumor microenvironment and, additionally, inflammatory cells can release reactive oxygen species that are actively mutagenic for nearby cancer cells and accelerate their genetic evolution toward states of heightened malignancy [134]. GSH system protects cells against the effect of external Org 27569 cytotoxic agents, including platinum [135, 136]. The GSH system can suppress oxidative stress and maintain cellular redox homeostasis [137]. The contribution of GSH and GSH-related enzymes to chemoresistance has been demonstrated in different types of tumor, including ovarian cancer and brain tumor [138]. GSH is also involved in the detoxification of various xenobiotics [139]. Upon metabolism of chemotherapeutic agents, the enzymes of glutathione-S-transferase (GST) family could prompt the formation of GSH-drug conjugates. Many chemotherapeutic agents have been shown to conjugate with GSH, including chloroethylnitrosoureas, platinum compounds, and other alkylating agents.

Figure 19 Methods used to fabricate a flexible mold for R2R and R2P NIL compiled from various studies. Figure 20 Roller mold fabrication using imprint lithography technique by Hwang and the team [26] . Most of the other studies, however, use a simpler approach for Autophagy inhibitor fabrication of flexible molds for the R2R and R2P NIL processes, where a replica of a master mold is used as the flexible mold for the roller imprint process. In general, the desired structures are first patterned onto a silicon or quartz substrate using conventional nanolithography techniques

such as EBL and followed by the RIE process, similar to its P2P variant. The replication of the master mold can then be conducted using several methods. One of the common techniques involves deposition of an anti-stick layer onto the master mold, followed by a layer OICR-9429 price of metal such as nickel directly onto the master mold, where it will then be peeled off to be used as a flexible mold in the roller

nanoimprint process as observed in [32, 43, 46]. In some cases such as in [30], an imprint replica of the master mold is first obtained using nanoimprint lithography (step-and-repeat technique) onto a resist-coated wafer, where a nickel layer is then deposited onto the imprint and peeled off to be used as the flexible mold in the imprint process published in [42]. Alternatively, the imprint replica of the master mold may also be produced via the polymer cast molding technique using non-sticking polymers such as PDMS or ETFE to be used as the flexible soft mold for the imprint process as observed Oxymatrine in the work of a few research groups [7, 15, 35]. It is highlighted in the work of Ye et al. [59] that polymer cast molds (typically made of PDMS) are usually more preferable in the UV-based roller imprinting process due to their advantages of being low cost, low surface energy (fewer sticking issues), chemically inert, elastic, and simpler to produce as compared to metal molds. One of the important challenges of producing roller molds is the surface planarity of the attached flexible mold

[51]. A similar uniformity is needed to achieve imprint rollers in order to prevent transmission of low-frequency and long-range surface waviness onto the replicated pattern. Conclusions Since its introduction back in 1995, the rapid development of the nanoimprint lithography process has resulted in a number of variants in the process, which can be categorized based on its two main operation features: resist curing and type of imprint contact. To date, in terms of resist curing, there are two fundamental types of processes: thermal NIL and ultraviolet (UV) NIL. As for the types of imprint contact, the process can be categorized into three common types: plate-to-plate (P2P) NIL, roll-to-plate (R2P) NIL, and roll-to-roll (R2R) NIL.

In order to achieve high-quality InN film, effort has been made by researchers with different methods such as optimizing GSK3235025 nmr growth temperature, controlling V/III ratio, introducing buffer layer, or employing pulsed atomic layer epitaxy technique [15, 16]. However, the crystalline quality of InN film is still far below a satisfactory level due to the existence of huge quantity of defects [16]. To elucidate the original difficulty in In film deposition, the formation kinetics of InN with N and In atoms on the In polar GaN surface has been systematically

studied by first-principles calculations [17], it was found that the pre-deposition of In bilayer on the surface could improve the In migration on the surface and the smoothness of In film. In this work, the epitaxy method of In bilayer controlling and penetrated nitridation

selleck chemical was employed for the InN film growth on GaN template. In order to determine critical trimethylindium (TMI) flow required for forming In bilayer, the pulse time of TMI supply was optimized. The results revealed that the film quality became better as the thickness of the top indium atomic layers was close to bilayer. Based on the In bilayer deposition, a moderate, stable, and slow nitridation process by NH3 flow also played the key role in growing better-quality InN film. X-ray diffraction (XRD) measurements confirmed the gradual relaxation of biaxial strain in InN epilayers during increment of the Carbohydrate smoothness. Methods Growth of samples InN films were grown on a 3-μm-thick GaN template with(0001) sapphire substrate by using metalorganic chemical vapor deposition (MOCVD) system with a Thomas Swan closely coupled showerhead (CCS) reactor. The trimethylgallium (TMG), trimethylindium (TMI), and ammonia (NH3) were used as the precursors for Ga, In, and N, respectively, and H2 and N2

were used as the carrier gasses. Prior to the GaN/AlGaN superlattice growth, thermal cleaning of the (0001)-oriented sapphire substrate was carried out under hydrogen ambient at 1,050°C for 10 min to remove native oxide from the surface. Then, an approximately 30-nm low-temperature GaN buffer layer (approximately 570°C) was grown followed by a approximately 3-μm high-quality GaN underlaying layer (approximately 1,090°C). During the stage of InN growth, the pressure was set to 450 torr at 550°C [18]. In order to accurately control the deposition of indium atomic multilayers and the following nitridation process, the pulse growth method was employed through switching and adjusting the pulsed supply time of TMI and ammonia flows, as shown in Figure 1. For samples A, B, C, and D, a constant TMI flow of 2.0 × 10−5 mol/min was used whereas a series of duration time of the pulsed TMI flow, 16, 8, 4, and 3 s, was applied, respectively. Then, they were followed by a 33-s pulse of NH3 flow for the nitridation process. The mole flow of ammonia was set to be 0.5 mol/min.

Fetal bovine serum (FBS), penicillin G, streptomycin, and amphotericin B were purchased from Chemicon (Billerica, MA, USA). Heparin, dimethylsulfoxide (DMSO), and in vitro toxicology assay kit (XTT based) were purchased from Sigma (St. Louis, MO, USA). Vero (African green monkey

kidney cells, ATCC CCL-81), HEL (human embryonic lung fibroblast, ATCC CCL-137), and A549 (human lung carcinoma, ATCC CCL-185) cells were obtained from the American Type Culture Collection (ATCC; Rockville, MD, USA) and cultured in DMEM supplemented with 10% FBS, 200 U/ml penicillin G, 200 μg/ml streptomycin, and 0.5 μg/ml amphotericin B. MK-4827 mw Huh-7.5 (human hepatocarcinoma Huh-7 cell derivative; provided by Dr. Charles M. Rice, The Rockefeller University, New York, NY, USA) and HEp-2 (human epithelial cells derived from a larynx carcinoma; provided by R. Anderson) cells were cultured

in the same medium condition as just described. CHO-SLAM or Chinese hamster ovary cells expressing human signaling lymphocyte activation molecule, the receptor for wild-type measles, were generated as previously reported and cultured in AMEM supplemented with 10% FBS and 800 μg/ml of G418 [37, 38]. HCMV (AD169 strain; provided CUDC-907 ic50 by Dr. Karen L. Mossman, McMaster University, Hamilton, ON, Canada), wild-type human adenovirus type-5 (ADV-5), and VSV-GFP (vesicular stomatitis virus with green fluorescent protein tag) have been described elsewhere and viral

titers and antiviral assays were determined by standard plaque assay using methanol fixation followed by crystal violet (Sigma) [33, 39, 40]. Cell-culture derived HCV particles were produced by electroporation of Huh-7.5 cells using the Jc1FLAG2(p7-nsGluc2A) construct (genotype 2a; kindly provided by Dr. Charles M. Rice), new which harbors a Gaussia luciferase reporter that allows detection of virus infectivity, as previously described [41]. HCV viral titer and antiviral assays were determined by immunofluorescence staining of TCID50 using anti-NS5A 9E10 antibody (gift from Dr. Charles M. Rice) and luciferase assays. DENV-2 (dengue virus type 2; strain 16681) and RSV (serogroup A, Long strain; ATCC VR-26) were propagated in Vero and HEp-2 cells, respectively [42, 43].

This should improve its effectiveness both as a probiotic and as a treatment for diarrhea. Acknowledgments Our laboratory is supported by the following grants awarded to N. Austriaco: NIGMS R15 GM094712, NSF MRI-R2 0959354, NIH Grant 8 P20 GM103430-12 to the Rhode Island INBRE Program for student training, and a CAFR faculty research grant from Providence College. The funders had no role in study design, data collection C188-9 in vivo and analysis, decision to publish, or preparation of the manuscript. Non nisi te, Domine. Electronic supplementary material Additional file 1: Differentially Regulated Genes

in S. boulardii Cells Cultured in an Acidic Environment. S. boulardii genes showing 4-fold or greater increase (up-regulated) or decrease (down-regulated) expression in response to an acidic environment. This data has been submitted to the Gene Expression Omnibus (GEO) at the NCBI with accession number, GSE43271. (XLS 286 kb) (XLS 286 KB) References 1. FAO/WHO: Guidelines for the Evaluation of Probitics in Food. Food and Agriculture Organization

of the United Nations: In. London Ontario, Canada: World Health Organization; 2002. 2. Gismondo MR, Drago L, Lombardi A: Review of probiotics available to modify gastrointestinal flora. Int J Antimicrob Agents 1999,12(4):287–292.PubMedCrossRef 3. McCullough MJ, Clemons KV, McCusker JH, Stevens DA: Species identification and virulence attributes of Saccharomyces boulardii (nom. inval.). J Clin Microbiol 1998,36(9):2613–2617.PubMed 4. Htwe K, Yee KS, Tin M, Vandenplas Y: Effect of Saccharomyces boulardii Uroporphyrinogen III synthase in the treatment Pitavastatin mw of acute watery diarrhea in Myanmar children: a randomized controlled study. Am J Trop Med Hyg 2008,78(2):214–216.PubMed 5. McFarland LV: Meta-analysis of probiotics for the prevention

of traveler’s diarrhea. Travel Med Infect Dis 2007,5(2):97–105.PubMedCrossRef 6. Brassart DSE: The use of probiotics to reinforce mucosal defense mechanisms. Trends Food Sci Technol 1997, 8:321–326.CrossRef 7. Surawicz CM, McFarland LV, Greenberg RN, Rubin M, Fekety R, Mulligan ME, Garcia RJ, Brandmarker S, Bowen K, Borjal D: The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 2000,31(4):1012–1017.PubMedCrossRef 8. Tung JM, Dolovich LR, Lee CH: Prevention of Clostridium difficile infection with Saccharomyces boulardii: a systematic review. Can J Gastroenterol 2009,23(12):817–821.PubMed 9. Dinleyici EC, Eren M, Ozen M, Yargic ZA, Vandenplas Y: Effectiveness and safety of Saccharomyces boulardii for acute infectious diarrhea. Expert Opin Biol Ther 2012,12(4):395–410.PubMedCrossRef 10. Sudha MR, Bhonagiri S, Kumar MA: Oral consumption of potential probiotic Saccharomyces boulardii strain Unique 28 in patients with acute diarrhoea: a clinical report. Benef Microbes 2012,3(2):145–150.PubMedCrossRef 11.

Arthritis Rheum 48:1041–1046PubMedCrossRef 21. Birrell F, Croft P, Cooper C, Hosie G, Macfarlane GJ, Silman A (2000) Radiographic change is common in new presenters in primary care with hip pain. PCR Hip Study Group. Rheumatol (Oxf) 39:772–775CrossRef 22. Naganathan V, Zochling J, March L, Sambrook PN (2002) Peak bone mass is increased in the hip indaughters of women with osteoarthritis. Bone 30:287–292PubMedCrossRef 23. Stewart A, Black AJ (2000) Bone mineral density in osteoarthritis. Curr Opin Rheumatol 12:464–467PubMedCrossRef 24. Meta M, Lu Y, Keyak JH, Lang T (2006) Young-elderly

differences in bone density, geometry and strength indices depend on proximal femur sub-region: a cross sectional study in Caucasian-American women. Bone 39:152–158PubMedCrossRef selleck chemicals 25. Lyles KW, Colon-Emeric GDC-0994 mw CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809PubMedCrossRef”
“Introduction Osteoporosis is a devastating disease resulting in substantial health care costs and increased mortality. In Europe, osteoporotic

fractures affect one in two women and one in five men aged 50 years and older [1]. In Europe, total health care costs associated with these fractures have been estimated to be around €30 billion [1]. In 2000, an estimated 5.8 million disability-adjusted life years were caused by osteoporotic fractures worldwide [2]. Among patients who have sustained

a hip fracture, one in five will die within the first year after the fracture, whilst one in three of those surviving needs assistance with walking [3, 4]. Because of this huge burden, assessment of an individual’s risk of fracture is important so that a prophylactic intervention can be effectively targeted. As of July 1, 2010, the FRAX® tool has been calibrated to the total Dutch population (http://​www.​sheffield.​ac.​uk/​FRAX). FRAX uses easily obtainable clinical risk factors, with or without femoral neck bone mineral density (BMD), to estimate 10-year fracture probability [5]. It has been constructed using primary data from nine population-based cohorts around the world. The gradients of fracture risk have been validated externally in 11 independent cohorts with a similar geographic distribution [6]. FRAX is a platform MycoClean Mycoplasma Removal Kit technology using Poisson models that integrate risk variables, fracture risk, and death risk over a 10-year interval. Using the incidence rates of hip and osteoporotic fractures and mortality rates, FRAX can be calibrated to create a country-specific model [7]. With the introduction of the online Dutch FRAX tool, it is important to understand the origin of the data for further validation if needed. Furthermore, the possibilities of the Dutch FRAX tool and its strengths/limitations compared to other Dutch models need to be discussed.

Furthermore, it is very interesting to note that the fluorescent signals of PTX-PLA NPs were much stronger than those of PTX-MPEG-PLA NPs. The results were speculated to be associated with these important reasons. Firstly, a great deal of hydrophilic PEG on the surface of MPEG-PLA

NPs could prevent the PLA core from transporting across the lipid-rich cell membranes and entering the internal environment of the cells. Secondly, the lipophilicity of PLA facilitated the delivery of NPs to the interior of the cells across the phospholipid bilayer of cellular membranes. Lastly, there is also some contribution of the large particle size of PTX-PLA NPs, which was in favor of entrapping more rhodamine B. In consequence, powerful red fluorescent signals could Autophagy Compound Library cell line be seen in the cell. However, there is another possibility that the large particle size of PTX-PLA NPs resulted in the aggregation of NPs. Then the aggregates became too large to enter the cell, so the strong red dot signals were from the PTX-PLA NPs absorbed on the cell surface. In this case, both PTX-PLA NPs and PTX-MPEG-PLA NPs Epigenetics had similar cellular uptake. Figure 6 CLSM images of cells incubated with PTX-loaded NPs which were labeled by rhodamine B. For each panel, the images from left to right showed rhodamine B fluorescence in cells (red), cell nuclei stained by Hochest 33258

(blue), and overlays of the two images. (A) PTX-PLA NPs, (B) PTX-MPEG-PLA NPs. In vitro cell viability assays As shown in Figure  7, the survival rate of A549 cells was basically suppressed in a drug dose-dependent manner by free PTX, PTX-PLA NPs, and PTX-MPEG-PLA NPs. Interestingly, the lowest concentration group (loaded with an equivalent amount of PTX) of the PTX-MPEG-PLA NPs observably presented lower cell viability than that of free PTX with the concentration of 2.5 μg/mL (P < 0.05), indicating that the PTX-MPEG-PLA NPs presented

a more effective bioavailability compared with the free PTX solution. On the contrary, the other groups with the concentration of 10, 20, and 40 μg/mL of PTX-MPEG-PLA NPs presented a significantly low level of inhibition effect compared to free PTX. This different phenomenon could be explained by the cell penetration STK38 rate of drug depending on NP advantage and drug concentration differences between the internal and external environment of the cell membrane. It should be emphasized that, in the case of the lowest concentration (2.5 μg/mL) of PTX, the NP advantage played a rather important role in the cell penetration rate of drug; their particle size can easily and virtually increase the cellular uptake of drug and the accumulation in the cell through endocytosis mechanism. However, in the case of other high concentrations of PTX (10, 20, and 40 μg/mL), the drug concentration differences played a main role.

Proc Natl Acad Sci USA 101:4712–4717PubMedCrossRef Stitt M (1991) Rising carbon dioxide levels and their potential significance for carbon flow in photosynthetic cells. Plant Cell Environ 14:741–762CrossRef Stitt M, Hurry V (2002) A plant for all seasons: alterations in photosynthetic carbon metabolism during cold acclimation in Arabidopsis. Curr Opin Plant Biol 5:199–206PubMedCrossRef

Strand A, Hurry V, Gustafsson P, Gardestrom P (1997) Development of Arabidopsis thaliana leaves at low temperatures releases the suppression of photosynthesis and photosynthetic gene expression despite the accumulation of soluble carbohydrates. Plant J 12:605–614PubMedCrossRef Terashima I, Hanba YT, Tholen D, Niinemets U (2011) Leaf functional anatomy in relation to photosynthesis. Plant Physiol 155:108–116PubMedCrossRef Tessadori F et al (2009) Phytochrome B and histone deacetylase 6 control light-induced chromatin WZB117 clinical trial compaction in Arabidopsis thaliana. PLoS Genet 5:e000638CrossRef Tholen D, Boom C, Noguchi K, Ueda S, Katase T, Terashima I (2008) The chloroplast avoidance response decreases internal conductance to CO2 diffusion in Arabidopsis thaliana leaves. Plant Cell Environ 31:1688–1700PubMedCrossRef

Von Caemmerer S (2000) Biochemical models of leaf photosynthesis. CSIRO publishing, Collingwood Walters RG (2005) Towards an understanding of photosynthetic acclimation. J Exp Bot 56:435–447PubMedCrossRef Walters RG, Horton P (1994) Acclimation of Arabidopsis thaliana to the light environment: changes in composition of the photosynthetic apparatus. Planta 195:248–256CrossRef Walters RG, Rogers JJM, Shephard F, Horton P (1999) Acclimation of Arabidopsis thaliana SHP099 clinical trial to

the light environment: the role of photoreceptors. Planta 209:517–527PubMedCrossRef Westbeek MHM, Pons TL, Cambridge ML, Atkin OK (1999) Analysis of differences in photosynthetic nitrogen use efficiency of alpine and lowland Poa species. Oecologia 120:19–26CrossRef Wullschleger many SD (1993) Biochemical limitations to carbon assimilation in C3 plants—a retrospective analysis of the A/Ci curves from 109 species. J Exp Bot 44:907–920CrossRef Yamori W, Noguchi K, Terashima I (2005) Temperature acclimation of photosynthesis in spinach leaves: analyses of photosynthetic components and temperature dependencies of photosynthetic partial reactions. Plant Cell Environ 28:536–547CrossRef Yamori W, Suzuki K, Noguchi K, Nakai M, Terashima I (2006) Effects of Rubisco kinetics and Rubisco activation state on the temperature dependence of the photosynthetic rate in spinach leaves from contrasting growth temperatures. Plant Cell Environ 29:1659–1670PubMedCrossRef Yamori W, Noguchi K, Hikosaka K, Terashima I (2009) Cold-tolerant crop species have greater temperature homeostasis of leaf respiration and photosynthesis than cold-sensitive species. Plant Cell Physiol 50:203–215PubMedCrossRef”
“Erratum to: Photosynth Res (2011) 108:157–170 DOI 10.

Lwoff-CNRS, Villejuif, France The phosphoinositide 3-kinase related kinases (PIKKs) family mainly comprised the ATR ATM and DNA-PK proteins. These large

proteins initiate cellular stress responses when genome integrity is compromised. Emerging evidence suggest that hypoxia led to activation of these stress kinases in severe hypoxic conditions. For example, stalled replication forks contribute to ATR activation. ATM is also activated in severe hypoxia (less than 0.1% O2) through alternate mechanisms that do not involve DNA breaks. However, the role of this DDR –like response on hypoxia AZD5363 tolerance remains unknown. We first demonstrated here that the third member of the PI3KK family, DNA-PK (that comprises a DNA binding sub-unit Ku and a catalytic

sub-unit DNA-PKcs) is activated by mild hypoxia conditions (0.1 to 1% O2). This was shown by Ku/DNA-PK mobilization from a soluble nucleoplasmic compartment to a less extractable nuclear fraction and its autophosphorylation on serine 2056. This activation was independent Selleck AZD6244 Sirolimus of DNA double strand breaks (DSBs) and probably relies on the chromatin modification observed in hypoxic cells according to our preliminary results. Importantly, DNA-PK nuclear activation positively regulates

HIF-1α accumulation and its subsequent target gene expression as shown using DNA-PK deficient cells. This effect is dependent of the kinase activity of the whole DNA-PK complex since a strong decrease in HIF-1α expression was observed in cells deficient in its regulatory sub-unit Ku and in presence of a selective inhibitor of the kinase activity of DNA-PK, Nu7026. Finally, the reduced half-life of HIF-1α in DNA-PK deficient cells upon hypoxia provided a mechanistic explanation for the observed effects. In conclusion, our results demonstrate that a new nuclear and DNA dependent stress response pathway contributes to the adaptative response of hypoxic tumours cells and shed a new light on the interest of DNA-PK inhibitors to down-regulate HIF-1α expression in human tumours. Poster No.