Belt, Laura Wilson, Cynthia D. Guy, Matthew M. Yeh Background: FibroTest(FT), a non-invasive serum marker of liver fibrosis, has a significant prognostic value for the 5-years survival without CRC in T2D patients(1). However, no studies have evaluated the association between liver fibrosis progression and onset of

new CRC. Aim: To evaluate the relationship between liver fibrosis progression and cardiovascular-related complications in T2D patients followed during 7 years with repeated evaluation of liver this website fibrosis by FibroTest. Methods: 627 T2D-patients with minimal fibrosis(FT<0.48 -F0F1 METAVIR) were prospectively foIIowed[2004-2013] for CRC[myocardiaI infarction, unstable angina, coronary-bypass, ischemic stroke]. Liver fibrosis

progression was evaluated by repeated FT during follow-up. Progression to advanced fibrosis(AF-F2F3F4) wasdefined by FT≥0.48 at the end of follow-up. Framingham risk score(FRS) was calculated at baseline to predict CRC risk. Results: During the follow-up 46(7%) patients died. Among 581 alive T2D-patients with minimal INCB024360 fibrosis at baseline, 133(23%) had a re-evaluation of liver fibrosis and were included [56% males, age 57 yrs, BMI(range) 28.7(20.2-50.8)Kg/m2]. During a median follow-up of 6.8 yrs 16(12%) patients progressed to AF and 17(13%) patients developed CRC(26 coronary diseases; 1 stroke). The survival without CRC(Kaplan-Meier mean 95%CI) was 69%(41-86) in patients who progressed to AF vs 91%(84-95) in those who did not progress(Logrank p<0.01). Progression to AF increased the risk of cRc[RR=3.8(95%CI 1.3-10.7); p<0.01). In a multivariate Cox model progression to AF remained significant after adjustment on FRS for the prediction of CRC[HR=3.8(1.3-11.1); p=0.013]. Conclusion: In type-2 diabetics, progression from minimal to advanced fibrosis, estimated by FibroTest, was independently

associated to higher incidence of cardiovascular-related complications. References: Loperamide 1 Perazzo H et al. Hepatology 2012; 56(Sup S1): 40A-40A Disclosures: Yen Ngo – Employment: BioPredictive Mona Munteanu – Employment: Biopredictive Vlad Ratziu – Advisory Committees or Review Panels: GalMed, Abbott, Genfit, Enterome, Gilead; Consulting: Astellas, Axcan, Pfizer, Sanofi-Synthelabo, Genentech, Nycomed Agnes Hartemann-Heurtier – Consulting: Sanofi-Aventis, Pfizer; Grant/Research Support: Lilly Thierry Poynard – Advisory Committees or Review Panels: MSD; Speaking and Teaching: BMS; Stock Shareholder: BioPredictive The following people have nothing to disclose: Hugo Perazzo, Noemi Seurat, Fanny Rutka, Marion Couteau, Sophie Jacqueminet, Denis Monneret, Francoise Imbert-Bismut Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associates with development of metabolic disease including cardiovascular disease. Purpose: to examine the association of NAFLD with prevalent clinical and subclinical cardiovascular disease (CVD) outcomes in a large communitybased sample, the Framingham Heart Study (FHS).

Belt, Laura Wilson, Cynthia D. Guy, Matthew M. Yeh Background: FibroTest(FT), a non-invasive serum marker of liver fibrosis, has a significant prognostic value for the 5-years survival without CRC in T2D patients(1). However, no studies have evaluated the association between liver fibrosis progression and onset of

new CRC. Aim: To evaluate the relationship between liver fibrosis progression and cardiovascular-related complications in T2D patients followed during 7 years with repeated evaluation of liver high throughput screening assay fibrosis by FibroTest. Methods: 627 T2D-patients with minimal fibrosis(FT<0.48 -F0F1 METAVIR) were prospectively foIIowed[2004-2013] for CRC[myocardiaI infarction, unstable angina, coronary-bypass, ischemic stroke]. Liver fibrosis

progression was evaluated by repeated FT during follow-up. Progression to advanced fibrosis(AF-F2F3F4) wasdefined by FT≥0.48 at the end of follow-up. Framingham risk score(FRS) was calculated at baseline to predict CRC risk. Results: During the follow-up 46(7%) patients died. Among 581 alive T2D-patients with minimal BTK inhibitor fibrosis at baseline, 133(23%) had a re-evaluation of liver fibrosis and were included [56% males, age 57 yrs, BMI(range) 28.7(20.2-50.8)Kg/m2]. During a median follow-up of 6.8 yrs 16(12%) patients progressed to AF and 17(13%) patients developed CRC(26 coronary diseases; 1 stroke). The survival without CRC(Kaplan-Meier mean 95%CI) was 69%(41-86) in patients who progressed to AF vs 91%(84-95) in those who did not progress(Logrank p<0.01). Progression to AF increased the risk of cRc[RR=3.8(95%CI 1.3-10.7); p<0.01). In a multivariate Cox model progression to AF remained significant after adjustment on FRS for the prediction of CRC[HR=3.8(1.3-11.1); p=0.013]. Conclusion: In type-2 diabetics, progression from minimal to advanced fibrosis, estimated by FibroTest, was independently

associated to higher incidence of cardiovascular-related complications. References: Telomerase 1 Perazzo H et al. Hepatology 2012; 56(Sup S1): 40A-40A Disclosures: Yen Ngo – Employment: BioPredictive Mona Munteanu – Employment: Biopredictive Vlad Ratziu – Advisory Committees or Review Panels: GalMed, Abbott, Genfit, Enterome, Gilead; Consulting: Astellas, Axcan, Pfizer, Sanofi-Synthelabo, Genentech, Nycomed Agnes Hartemann-Heurtier – Consulting: Sanofi-Aventis, Pfizer; Grant/Research Support: Lilly Thierry Poynard – Advisory Committees or Review Panels: MSD; Speaking and Teaching: BMS; Stock Shareholder: BioPredictive The following people have nothing to disclose: Hugo Perazzo, Noemi Seurat, Fanny Rutka, Marion Couteau, Sophie Jacqueminet, Denis Monneret, Francoise Imbert-Bismut Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associates with development of metabolic disease including cardiovascular disease. Purpose: to examine the association of NAFLD with prevalent clinical and subclinical cardiovascular disease (CVD) outcomes in a large communitybased sample, the Framingham Heart Study (FHS).

Thus, there is a significant unmet need in terms of effective available treatments and this unmet need may be overcome by adopting alternate therapeutic strategies such as (1) employing different agents to improve insulin resistance (e.g., GLP-1 agonists) and oxidative stress (betaine, SAMe); (2) exploring agents affecting different targets such as apoptosis (e.g., GS 9450) and FXR (e.g., obeticholic acid), or stellate cell activation (losartan); or (3) investigating a combination NVP-LDE225 mouse of agents affecting different targets/pathways. In this issue of HEPATOLOGY, Harrison’s

group6 report the results of their randomized controlled trial that investigated two different combination therapies to treat NASH. Angiotensin II receptors have been identified on hepatic stellate cells (HSC) and their activation leads PF-02341066 mw to HSC proliferation. Angiotensin II receptor knockout

mice when challenged with carbon-tetrachloride had significantly reduced hepatic fibrosis when compared to wildtype mice, suggesting angiotensin receptor II is a novel target to improve hepatic fibrosis.7 Losartan, an angiotensin II receptor blocker (ARB), has been shown in mice models to have beneficial effects on liver fibrosis,8, 9 and in a small study consisting of seven patients with NASH, Yokohama et al.10 suggested that losartan may improve necroinflammation and fibrosis. Torres et al.6 randomized 137 subjects with biopsy-proven NASH to a 48-week course of rosiglitazone

4 mg twice daily alone, or in combination with either metformin 500 mg twice daily or losartan 50 mg daily. The primary endpoint was change in hepatic histology as evidenced by at least one point improvement in steatosis, inflammation, and fibrosis. Steatosis, inflammation, and Dipeptidyl peptidase fibrosis improved between baseline and the end of treatment within each treatment arm, but the changes in liver histology were statistically not different between the three treatment groups.6 Randomized controlled trials of NASH with histological endpoints are expensive and difficult to conduct, and thus Harrison’s group must be applauded for undertaking this study and for their other important contributions to the field. However, we suggest caution in interpreting the results of this study because of some of its limitations. This study was prematurely stopped due to severe restrictions imposed by the Food and Drug Administration on rosiglitazone use in the United States, leading to an underpowered sample size. The presence of fibrosis was not a prerequisite at baseline and yet its improvement was required to achieve the primary outcome.

[28] These observations were accredited the elevated basal level of NRF2 in the lesser sensitive cell line, as an elevated level of NRF2 also results in and increase in

GSH level rendering the cells more resistant to PEITC. Important features of cancerous cells are the elevated level of ROS,[27] and the ability to promote NRF2-dependent ROS detoxification,[29] which again points to the importance of the basal GSH level which presumably may vary with cell types. Thus, the reduced sensitivity in MKN74 cells might be explained through an elevated basal level of GSH content in consistency with no elevation of ROS levels yet a weak but significant reduction in GSH content following PEITC Selleck BIBW2992 treatment. In conclusion, the present study demonstrated PEITC as a potential inhibitor of human gastric cancer cell Galunisertib nmr growth, and further

suggests the disintegration of microtubules as an important contributory factor in this process leading to accumulation of cells in G2/M phase and ultimately apoptosis. The present findings contribute to an increased understanding of the cellular effects of PEITC in gastric cancer cells, and further suggest PEITC as a potential gastric chemopreventive agent. We would like to thank Kristin Grendstad Sæterbø (Department of Physics, NTNU, Norway) for help with flow cytometric analyses, and Timothy Wang (Columbia University, USA) for kindly providing MKN74 cell line. This study was supported by The Norwegian Research Council project 184146 “a systems biology approach for modelling of plant signalling and host defence,” the Joint Programme of the Medical Faculty and St. Olavs’ University Hospital, the Liaison Committee between the Central Norway Regional Health Authority, and a PhD grant from The Norwegian University of Science and Technology to Anders Øverby. “
“Secretion of cholesterol into bile Casein kinase 1 is important for the elimination of cholesterol from the

body. Thyroid hormone (TH) increases biliary cholesterol secretion and hepatic gene expression of adenosine triphosphate (ATP)-binding cassette, subfamily G (WHITE), member 5 (ABCG5) and ATP-binding cassette, subfamily G (WHITE), member 8 (ABCG8), two half-transporters that act as a heterodimeric complex promoting sterol secretion. In addition, nuclear liver x receptor-alpha (LXRa), also regulated by TH, induces gene expression of ABCG5/G8. We here investigated if the TH-induced stimulation of biliary cholesterol secretion is mediated by the ABCG5/G8 complex in vivo, and if so, whether LXRa is involved. Mice homozygous for disruption of Abcg5 (Abcg5−/−) or Lxra (Lxra−/−) and their wild-type counterparts were treated with triiodothyronine (T3) for 14 days and compared to untreated mice of corresponding genetic backgrounds.

Conclusion: Age per se does not potentiate liver fibrosis development. By contrast, previous exposure to a pro-fibrotic stimulus enhances the fibrotic response to a given stimuli later in life. Disclosures: Yves J. Horsmans – Consulting: helssinn, johnson&johnson, roche, merck, ipsen, helssinn, johnson&johnson, roche, merck, ipsen, helssinn, johnson&johnson, roche, merck, ipsen, helssinn, johnson&johnson, roche, merck, ipsen; Grant/Research Support: gsk, astra-zeneca, gsk, astra-zeneca, gsk, astra-zeneca, gsk, astra-zeneca; Speaking and Teaching: bms, bms, bms, bms The following people have nothing to disclose:

Charlotte Selvais, Valérie Lebrun, Isabelle A. Leclercq Background & Aims: Oxidative stress STI571 research buy is considered to play a key role in the progression of chronic Pembrolizumab mouse liver diseases such as hepatitis C and non-alcoholic steatohepatitis. However, since both the production of oxidative stress and liver fibrosis may merely represent the consequences of cell damage caused by the primary disease, it is virtually unknown whether oxidative stress is linked directly to fibrogenesis. Here we examined the direct effects of oxidative stress on hepatic fibrogenesis by using “Tet-mev-1 mouse”, in which mitochondrial reactive oxygen species can be induced by doxycycline (Dox)-regulable expression of mutant succinate dehydrogenase.

Methods: Hepatocytes obtained from wild type or Tet-mev-1 mice were treated with different Dox concentrations. Production of reactive oxygen species and decreased membrane potential of mitochondria were examined by using dichlorofluoresceine diacetate (DCFDA) and tetramethyl rhodamine methyl ester (TMRM), respectively. Both wild type and Tet-mev-1 mice oxyclozanide were administered 0.4 mg/mL of Dox for 1 year, and subsequently fed either normal diet chow or high fat/high sucrose

(HFHS) diet. Liver tissues obtained from these mice were subjected to histopatho-logical examination and microarray gene expression analyses. Hepatocytes isolated from the same mice were co-cultured with hepatic stellate cells (HSC) prepared from transgenic col1a2 luciferase reporter mice (COL/LUC). Results: DCFDA fluorescent intensities were significantly increased after 1 and 1 0 μg/mL of Dox treatment of hepatocytes from Tet-mev-1 mice, but not control animals. Mitochondrial membrane potential was decreased in Dox-treated Tet-mev-1 hepatocytes as compared with untreated cells. Histopathological examination revealed considerable infiltration of inflammatory cells around the portal tracts, but no apparent cell damage, in Dox-treated Tet-mev-1 mouse liver. Microarray analyses indicated that c-JUN/c-fos expression was markedly elevated in liver tissues from Dox-treated Tet-mev-1 mice as compared with control animals.

Cultural methods essentially provide qualitative data even though quantitative information can also be obtained, for example the number of colonies in relation to a certain quantity of samples. One rather obvious advantage of culturing methods is that successful isolation yields objective proof of the presence of the pathogen and a culture that is available for further characterization. Another quite common technique for the isolation Trichostatin A order of some soil- and waterborne pathogens is their baiting with selective hosts. This method can also provide generic information on the quantity of the pathogen

and is effective for the detection of oomycetes such as Pythium and Phytophthora species, because their zoospores can move in a liquid media and easily reach baiting tissues (Erwin and Ribeiro 1996). Baiting has also been proposed as a useful method to detect some true fungi, but it may be not sensitive enough to detect the pathogen in naturally infested soils (Ruano-Rosa et al. 2007). However, most of the above-mentioned methods are time-consuming, and results are not always conclusive, for instance when closely related organisms need to be discriminated. Moreover, traditional http://www.selleckchem.com/products/rxdx-106-cep-40783.html methods may not be sensitive enough to detect the pathogen in presymptomatic infections, and they could not detect several soilborne seasonally active pathogens (Cooke

et al. 2007). The invention of PCR in 1984 by Kary Mullis has revolutionized basic and applied studies in all biological fields, including plant pathology. In particular, the potential of conventional PCR (cPCR) was greatly increased in the early 1990s with the development of real-time quantitative amplification technologies (qPCR). This technique is now widely utilized for a number of different applications, and several

reviews have been published on its use in plant pathology (Schena et al. 2004; Okubara et al. 2005; Mumford et al. 2006; Cooke et al. 2007; Vincelli and Tisserat 2008; O’Brien et al. 2009; Bilodeau 2011). Furthermore, a comprehensive review focusing on critical steps and practical difficulties that can be encountered developing a qPCR is available Fludarabine cell line (Schena et al. 2013). The present review focuses on qPCR as an automated routine technical support in plant pathology by providing an updated report on its most important applications for the detection and quantification of filamentous fungi and oomycetes (Fig. 1; Table S1). Indeed, they include the most important plant pathogens, whose extreme similarity in both appearance and lifestyle has been related to the multiple horizontal gene transfers that have occurred from filamentous ascomycete fungi to the distantly related oomycetes (Richards et al. 2006). Thus, they also share several common aspects related to their detection and quantification within host tissues and in soil, air and water.

Cultural methods essentially provide qualitative data even though quantitative information can also be obtained, for example the number of colonies in relation to a certain quantity of samples. One rather obvious advantage of culturing methods is that successful isolation yields objective proof of the presence of the pathogen and a culture that is available for further characterization. Another quite common technique for the isolation Metformin of some soil- and waterborne pathogens is their baiting with selective hosts. This method can also provide generic information on the quantity of the pathogen

and is effective for the detection of oomycetes such as Pythium and Phytophthora species, because their zoospores can move in a liquid media and easily reach baiting tissues (Erwin and Ribeiro 1996). Baiting has also been proposed as a useful method to detect some true fungi, but it may be not sensitive enough to detect the pathogen in naturally infested soils (Ruano-Rosa et al. 2007). However, most of the above-mentioned methods are time-consuming, and results are not always conclusive, for instance when closely related organisms need to be discriminated. Moreover, traditional Natural Product Library methods may not be sensitive enough to detect the pathogen in presymptomatic infections, and they could not detect several soilborne seasonally active pathogens (Cooke

et al. 2007). The invention of PCR in 1984 by Kary Mullis has revolutionized basic and applied studies in all biological fields, including plant pathology. In particular, the potential of conventional PCR (cPCR) was greatly increased in the early 1990s with the development of real-time quantitative amplification technologies (qPCR). This technique is now widely utilized for a number of different applications, and several

reviews have been published on its use in plant pathology (Schena et al. 2004; Okubara et al. 2005; Mumford et al. 2006; Cooke et al. 2007; Vincelli and Tisserat 2008; O’Brien et al. 2009; Bilodeau 2011). Furthermore, a comprehensive review focusing on critical steps and practical difficulties that can be encountered developing a qPCR is available Carbachol (Schena et al. 2013). The present review focuses on qPCR as an automated routine technical support in plant pathology by providing an updated report on its most important applications for the detection and quantification of filamentous fungi and oomycetes (Fig. 1; Table S1). Indeed, they include the most important plant pathogens, whose extreme similarity in both appearance and lifestyle has been related to the multiple horizontal gene transfers that have occurred from filamentous ascomycete fungi to the distantly related oomycetes (Richards et al. 2006). Thus, they also share several common aspects related to their detection and quantification within host tissues and in soil, air and water.

8 Moreover, important questions arise not only to the class of angiogenic inhibitors that can be used successfully, but also with respect to the safety, especially considering potential application in patients with critically ill portal hypertension and cirrhosis. Many of the currently available multitargeted therapeutic strategies are associated with toxicities, thereby limiting their use in critically ill patients. Recent preclinical studies suggest that therapies targeting placental growth factor (PlGF) activity may possess such a safety profile.9, 10 PlGF is a member of the VEGF

family and a specific ligand for VEGFR1 that was originally discovered and isolated from the human placenta. The human transcript for PlGF generates four isoforms (PlGF-1 to −4), PlGF-2 being the only one present Obeticholic Acid mw in mice.11 Unlike SCH727965 mouse VEGF, PlGF plays a negligible role in physiological angiogenesis and is not required as a survival signal for the maintenance of quiescent vessels in healthy tissues. Furthermore, studies in transgenic mice revealed that the angiogenic activity of PlGF is restricted to pathological conditions.12, 13 In contrast to VEGF inhibitors, a monoclonal anti-PlGF antibody (αPlGF) has been shown to reduce pathological angiogenesis

in various spontaneous cancers and other disease models without affecting healthy blood vessels, resulting in no major side effects in mice and humans.9, 10, 14, 15 Based on the aforementioned considerations, PlGF might be an attractive therapeutic target for cirrhosis, but nearly nothing is known about its pathogenetic role in this disorder, nor its therapeutic potential. Here, we demonstrate that anti-PlGF antibody treatment might be considered as a novel potential therapy for cirrhosis due to its multiple mechanisms of action against angiogenesis, inflammation, and hepatic fibrosis. We also provide mechanistic insight into the fibrogenic role of PlGF by demonstrating its biological effect on HSCs. Importantly, all these results were obtained in the

absence of the adverse effects that are usually associated with antiangiogenic therapies based on VEGF blockade. αPlGF, Casein kinase 1 anti-PlGF antibody; αSMA, α-smooth muscle actin; αVEGFR, anti-VEGFR antibody; BrdU, bromodeoxyuridine; ERK, extracellular signal-regulated kinase; HSC, hepatic stellate cell; IgG1, immunoglobulin G1; mRNA, messenger RNA; PAS, periodic acid-Schiff; PDGFRA, platelet-derived growth factor receptor-α; PlGF, placental growth factor; RTK, tyrosine kinase receptor; RT-PCR, reverse-transcription polymerase chain reaction; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor. All experiments were performed in 8-week-old male PlGF wild-type (PlGF+/+) mice (50% Sv129/50% Swiss), matched PlGF-knockout mice (PlGF−/−) of the same genetic background (Vesalius Research Center Leuven, Belgium), and male Wistar rats (Charles River, Saint Aubin les Elseuf, France).

Mice were depleted exclusively

of plasmacytoid DC using 120G8 before APAP challenge. However, plasmacytoid DC depletion Raf inhibitor drugs did not exacerbate APAP liver toxicity (Supporting Fig. 4). Similarly, we tested whether activation of the aryl hydrocarbon receptor on DC, which inhibits liver DC maturation in vivo and mitigates their ability to induce adaptive Th2 responses27, 30 (Supporting Fig. 5A,B), would also lead in exacerbated injury when administered to APAP-challenged mice. However, VAG539 did not modulate APAP toxicity (Supporting Fig. 5C-E). Because the absence of DC results in exacerbated APAP-mediated injury, we interrogated the immune-phenotype of DC in animals challenged with APAP. Both the absolute number and fraction of liver DC among hepatic leukocytes did not change after APAP challenge (Fig.

3A,B); however, DC underwent an increase in maturation and alteration in subset composition in acute APAP hepatotoxicity (Fig. 3C). In particular, DC harvested from APAP-injured liver had elevated expression of MHC II and CD86, exhibited Depsipeptide mouse a lower B220+ plasmacytoid fraction, and underwent a “myeloid shift” expressing higher CD11b and lower CD8 (Fig. 3C). Conversely, spleen DC phenotype was unchanged after APAP challenge (Fig. 3C). Liver DC also increased their expression of Toll-like receptor (TLR)2, TLR4, TLR7, and TLR9 after APAP challenge (Supporting Fig. 6A). However, there was no measurable increase in selected byproducts of sterile inflammation in APAP-DC liver compared with APAP alone (Supporting Fig. 6B,C). In addition to an altered surface phenotype, the

immunogenicity of DC harvested from the APAP injured liver was altered as DC from APAP liver produced higher IL-6, MCP-1, and TNF-α (Fig. 3D) compared with liver DC from saline-treated mice. Furthermore, consistent with their increased TLR expression, liver DC had an exaggerated cytokine response to TLR ligation after APAP toxicity (Fig. 3E). Spleen DC did not produce altered levels of cytokines after APAP challenge (not shown). Despite changes in hepatic DC surface phenotype and cytokine production after APAP challenge, their capacity to stimulate antigen-restricted CD4+ and CD8+ T cells was not Carnitine palmitoyltransferase II enhanced (Fig. 3F). Because DC depletion exacerbates APAP-mediated hepatotoxicity, we postulated that expansion of DC populations would mitigate liver injury. To test this, we employed Flt3L, which we have previously shown expands DC populations in vivo more than 10-fold.31, 32 Mice were treated with Flt3L for 10 days before APAP challenge followed by sacrifice at 12 hours. Notably, the maturation level of liver DC in Flt3L-treated mice was similar to controls except for a greater fraction of B220+ plasmacytoid DC in the Flt3L-treated group (Supporting Fig. 7A,B). However, after APAP treatment the fractions of plasmacytoid DCs were similar in both the Flt3L + APAP and in the APAP-only group (Supporting Fig. 7B).

3; Martínez et al., 2007, 2011), which hatch after about 38 days of incubation. In contrast, the common buzzard is a sedentary raptor and the study area represents the southernmost

part of the distribution range (del Hoyo, Elliot & Sargatal, 1994; Zuberogoitia et al., 2006). Buzzard females lay one to www.selleckchem.com/GSK-3.html three eggs and their breeding phenology is similar to that of booted eagles. Data were collected during intensive monitoring in the study area of 69 territories and 154 nests between 1998 and 2012. During the breeding seasons, from the end of March to the beginning of May, all territories were visited to detect occupancy, as were other suitable but previously unoccupied areas in the search for newly established territories (for more details see Martínez et al., 2006a). Occupancy was determined

when signs of territorial or mating behaviour were observed, including courtship and territorial flights and responses (e.g. elicited vocalizations, approaches), copulations, nest material transfers, the presence of at least one freshly refurbished nest or direct evidence of reproduction (details in Martínez et al., 2006a,b). When a territory was considered to be occupied, at least three visits were made to record breeding success (the fledging of one or more young) and productivity (number of fledglings per monitored pair; Martínez et al., 2006a), considering those which survived to Selleck PF-6463922 about 45 days old (Steenhof, 1987). We were able to differentiate new establishments and reoccupancy events in both

species because the locations of all breeding sites were known during the study period, and no substantial habitat changes were observed in any of the raptors’ territories as a result of wood exploitation. We define a new establishment as the occupancy of breeding territories that were uncreated, unoccupied or occupied by another species during the previous year. We define reoccupancy as the settlement in an old territory that was occupied by the species during the previous year and assume that this event occurs because at selleck chemicals least one member of the couple, and often both, are returning to the same territory due to previous breeding success (Jiménez-Franco et al., 2013). We recorded the following parameters for each species: new establishment in new territory/new establishment in old territory/reoccupancy, nest building/nest reuse, breeding success/failure and productivity. A generalized linear mixed model (GLMM; McCulloch & Searle, 2000) was used to examine differences in the probabilities of settlement in new territories between newly established pairs of the two studied species (booted eagle/common buzzard). We also used GLMMs to compare, for each species, the probability of nest building and nest reuse in relation to different patterns of territorial settlement (new establishments in old territories and reoccupations).