008). We also performed analysis in 26 of 36 patients who received sequential therapy. Higher serum HBV DNA plus RNA titer following 3 months of NA treatment was significantly associated with HBV DNA rebound (P=0.035, OR=3.064) and the following factors, higher levels of serum HBV DNA plus RNA (more than 4.8 Log copies/ml) following 3 months of treatment and

the existence of HBeAg at the end of NA therapy, were significantly associated with ALT rebound (P=0.042; OR=1 8214, P=0.035; OR=15.370, respectively). Conclusions: HBV markers were see more closely associated with rebound of HBV DNA and ALT after discontinuation of NA therapy. Measurement of serum HBV DNA plus RNA levels might be useful for predicting re-activation of chronic hepatitis B after discontinuation of NA therapy. Disclosures: Kazuaki Chayama – Consulting: Abbvie; Grant/Research Support:

Dainippon Sumitomo, Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, Toray, BMS, MSD; Speaking and Teaching: Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, KYORIN, Nihon Medi-Physics, BMS, Dainippon Sumitomo, MSD, ASKA, Astellas, AstraZeneca, Eisai, Olympus, GlaxoSmithKline, ZERIA, Bayer, Minophagen, JANSSEN, JIMRO, TSUMURA, Otsuka, Taiho, Nippon Kayaku, Nippon Shinyaku, Takeda, AJINOMOTO, Meiji Seika, selleck inhibitor Toray The following people have nothing to disclose: Masataka Tsuge, Eisuke Murakami, Michio Imamura, Hiromi Abe, Daiki Miki, Nobuhiko Hiraga, Hidenori Ochi, C. Nelson Hayes, Hiroyuki Ginba, Kazuhiro Matsuyama, Hiroiku Kawakami Background and aims: Entecavir (ETV) induces biochemical and histologic improvement of the liver in patients with chronic

hepatitis B. This study aimed to verify whether ETV improves liver function and fibrosis in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC) during 2 years treatment. Methods: A total 145 naïve patients with HBV associated LC was treated by ETV for at least 2 years, between March 2007 and December 2012. All patients had HBV DNA level over than 4 log10 copies/mL and ALT level over than 40 IU/mL, because of regulation of Korea national health insurance. Exclusion criteria were the patients MCE公司 who 1) skipped the ETV more than 3 months and 2) developed hepatocelullar carcinoma within 2 years after ETV treatment. For the evaluation of liver function, laboratory findings, model for end stage liver disease (MELD) score, Child-Pugh (CP) score and class were compared between the baseline and 2 years after ETV treatment. For the evaluation of fibrosis, AST platelet ratio index (APRI) score, FIB-4 index, and fibrosis index (FI) were compared between the baseline and 2 years after ETV treatment. Results: The final 1 1 1 patients were enrolled. The mean age was 53±9 years old and 62.2% of patients was male. The baseline mean AST and ALT were 110±83 IU/L and 110±87 IU/L, respectively. The mean HBV DNA level was 6.8±1.2 log10 copies/mL. At 2 years after ETV treatment, the rate of ALT normalization was 77.

Using this RGT, subjects with HCV RNA < 1.2 log IU/mL or undetectable after 4 weeks' treatment, and undetectable after 12 weeks, were administered Peg-IFNα-2a + RBV for 12 weeks (total treatment duration 24 weeks), and all other subjects for 36 weeks (total treatment duration 48 weeks). As a result, 99% of subjects met the response-guided criteria, and underwent

24 weeks of treatment. The SVR24 rate was 89% (109/123) for the triple therapy group, significantly higher than that of 57% (34/60) in the control group (Fig. 1). Peg-IFNα-2b was used in the CONCERTO-4 trial,[11] conducted with IFN-naïve subjects, the same response-guided criteria were set, all subjects met the criteria and underwent 24 weeks of treatment, yielding an SVR24 rate of 92% (22/24) (Fig. 2). Sorafenib datasheet In the overseas QUEST-1 study,[12] subjects were administered SMV 150 mg once daily + Peg-IFNα-2a + RBV Rapamycin concentration triple therapy for the first 12 weeks, then response-guided criteria were set as

for the CONCERTO-1 trial, with 85% of subjects meeting the criteria and undergoing 24 weeks of treatment. The overall SVR12 rate was 80%; 71% (105/147) in genotype 1a and 90% (105/117) in genotype 1b. The QUEST-2 study[13] set two groups, with either Peg-IFNα-2a or Peg-IFNα-2b, otherwise following the same protocol as the QUEST-1 study for treatment durations. As a result, 91% of subjects met the criteria and underwent 24 weeks of treatment. The overall SVR12 rate was 81%; 80% (86/107) and 82% (123/150) in genotype 1a and 1b, respectively. The SVR12 rate for Peg-IFNα-2a and Peg-IFNα-2b was 88% and 78%, respectively. In both these studies, triple therapy including SMV yielded significantly higher SVR rates than for 48 weeks of Peg-IFN + RBV dual therapy. In this

way, clinical trials of SMV-based triple therapy regimens were conducted using a response-guided protocol that set a treatment duration of 24 or 48 weeks, with almost all subjects meeting the criteria for the shorter duration. The SVR rate for IFN-naïve subjects in the Japanese studies was 89–92%, and in MCE the overseas studies it was 82–90% for genotype 1b, significantly higher than the SVR rate in the control groups administered 48 weeks of Peg-IFN + RBV dual therapy. The Japanese CONCERTO-3 trial,[10] conducted with subjects who relapsed following previous IFN therapy, was conducted using a similar protocol to the CONCERTO-1 trial.[9] All subjects met the response-guided criteria and underwent 24 weeks of treatment, yielding an SVR24 rate of 90% (44/49) (Fig. 3). Similarly, the CONCERTO-4 trial,[11] conducted with relapsers, followed a similar therapeutic protocol to the CONCERTO-3 trial,[10] using Peg-IFNα-2b. All subjects met the response-guided criteria and underwent 24 weeks of treatment, yielding an SVR24 rate of 97% (28/29) (Fig. 2).

Using this RGT, subjects with HCV RNA < 1.2 log IU/mL or undetectable after 4 weeks' treatment, and undetectable after 12 weeks, were administered Peg-IFNα-2a + RBV for 12 weeks (total treatment duration 24 weeks), and all other subjects for 36 weeks (total treatment duration 48 weeks). As a result, 99% of subjects met the response-guided criteria, and underwent

24 weeks of treatment. The SVR24 rate was 89% (109/123) for the triple therapy group, significantly higher than that of 57% (34/60) in the control group (Fig. 1). Peg-IFNα-2b was used in the CONCERTO-4 trial,[11] conducted with IFN-naïve subjects, the same response-guided criteria were set, all subjects met the criteria and underwent 24 weeks of treatment, yielding an SVR24 rate of 92% (22/24) (Fig. 2). Deforolimus in vitro In the overseas QUEST-1 study,[12] subjects were administered SMV 150 mg once daily + Peg-IFNα-2a + RBV Talazoparib concentration triple therapy for the first 12 weeks, then response-guided criteria were set as

for the CONCERTO-1 trial, with 85% of subjects meeting the criteria and undergoing 24 weeks of treatment. The overall SVR12 rate was 80%; 71% (105/147) in genotype 1a and 90% (105/117) in genotype 1b. The QUEST-2 study[13] set two groups, with either Peg-IFNα-2a or Peg-IFNα-2b, otherwise following the same protocol as the QUEST-1 study for treatment durations. As a result, 91% of subjects met the criteria and underwent 24 weeks of treatment. The overall SVR12 rate was 81%; 80% (86/107) and 82% (123/150) in genotype 1a and 1b, respectively. The SVR12 rate for Peg-IFNα-2a and Peg-IFNα-2b was 88% and 78%, respectively. In both these studies, triple therapy including SMV yielded significantly higher SVR rates than for 48 weeks of Peg-IFN + RBV dual therapy. In this

way, clinical trials of SMV-based triple therapy regimens were conducted using a response-guided protocol that set a treatment duration of 24 or 48 weeks, with almost all subjects meeting the criteria for the shorter duration. The SVR rate for IFN-naïve subjects in the Japanese studies was 89–92%, and in medchemexpress the overseas studies it was 82–90% for genotype 1b, significantly higher than the SVR rate in the control groups administered 48 weeks of Peg-IFN + RBV dual therapy. The Japanese CONCERTO-3 trial,[10] conducted with subjects who relapsed following previous IFN therapy, was conducted using a similar protocol to the CONCERTO-1 trial.[9] All subjects met the response-guided criteria and underwent 24 weeks of treatment, yielding an SVR24 rate of 90% (44/49) (Fig. 3). Similarly, the CONCERTO-4 trial,[11] conducted with relapsers, followed a similar therapeutic protocol to the CONCERTO-3 trial,[10] using Peg-IFNα-2b. All subjects met the response-guided criteria and underwent 24 weeks of treatment, yielding an SVR24 rate of 97% (28/29) (Fig. 2).

However, other parameters measured were not influenced by the range of CO2(aq) treatments. This included growth rates, chlorophyll a concentration and photosynthetic yield (FV/FM). Different light treatments had a large effect on nutrient uptake. High light conditions DNA Damage inhibitor caused an increased nutrient uptake rate compared to cells grown in low light conditions. Light and CO2 conditions co-determined in various ways the response of P. alata to changing environmental conditions. Overall P. alata appeared to be well adapted to the natural variability in light availability and CO2(aq) concentration of the modern Southern Ocean. Nevertheless, our results showed that P. alata is susceptible to future changes in inorganic

carbon concentrations in the Southern Ocean. “
“In this study, we present the first comprehensive analyses of the diversity and distribution of marine protist (micro-, nano-, and picoeukaryotes) in the Western Fram Strait, using 454-pyrosequencing and high-pressure liquid chromatography (HPLC) at five stations in summer 2010. Three stations (T1; T5; T7) were influenced by Polar Water, characterized by cold water with lower salinity (<33) and different extents of ice concentrations. Atlantic Water influenced the other two stations (T6; T9). While T6 was located in the mixed water zone characterized by cold water with intermediate salinity (~33) and high ice concentrations, T9 was

located in warm water with high salinity (~35) and no ice-coverage at all. General trends in community structure according to prevailing environmental settings, observed with both methods, coincided well. At two stations, T1 and T7, characterized by Selleck PLX4032 lower ice concentrations, diatoms (Fragilariopsis sp., Porosira sp., Thalassiosira spp.) dominated the protist community. The third station (T5) was ice-covered, but has been ice-free for ~4 weeks prior to sampling. At this station, dinoflagellates

(Dinophyceae 1, Woloszynskia sp. and Gyrodinium sp.) were dominant, reflecting a post-bloom situation. At station T6 and T9, the protist communities consisted mainly of picoeukaryotes, e.g., Micromonas spp. Based on our results, 454-pyrosequencing has proven to be an adequate tool to provide comprehensive information on the composition of protist communities. MCE公司 Furthermore, this study suggests that a snap-shot of a few, but well-chosen samples can provide an overview of community structure patterns and succession in a dynamic marine environment. “
“Phototrophic”Dinophysis Ehrenberg species are well known to have chloroplasts of a cryptophyte origin, more specifically of the cryptophyte genus complex Teleaulax/Geminigera. Nonetheless, whether chloroplasts of “phototrophic”Dinophysis are permanent plastids or periodically derived kleptoplastids (stolen chloroplasts) has not been confirmed. Indeed, molecular sequence data and ultrastructural data lead to contradictory interpretations about the status of Dinophysis plastids.

369 (1.279–4.368) (P < 0.05), 1.504 (0.819–2.713) (P > 0.05), and 2.332 (0.823–2.550) (P > 0.05) in Y-27632 ic50 men. In women, the OR were 2.541 (1.118–5.771), 3.578 (1.464–8.748), and 3.215 (1.387–7.455) (P < 0.05). Our data suggest that HGB combined with TG and ferritin may serve as the indicator of predicting NAFLD. "
“A high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present study a novel metastasis-related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized

for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger

RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) of metastatic tumors. Functional studies found that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion in vitro and tumor metastasis in vivo in an experimental mouse model. Moreover, inhibition of EIF5A by small interfering RNA (siRNA) or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 was able to induce epithelial-mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized Talazoparib molecular weight by down-regulation of epithelial markers (E-cadherin and β-catenin) and up-regulation of mesenchymal markers (fibronectin, N-cadherin, α-SMA, and vimentin). In addition, EIF5A2

could also activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia. Conclusion: EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1. (HEPATOLOGY 2010.) A worldwide increase in mortality associated with hepatocellular MCE carcinoma (HCC) has recently been reported.1, 2 Clinical treatment of HCC remains challenging due to a high incidence of tumor recurrence. The main cause of death in HCC patients is intrahepatic metastasis but the underlying mechanisms are still not fully understood. It is generally believed that to give rise to a metastatic tumor, cancer cells from a primary site must complete all of the following steps: invasion, intravasation, survival and arrest in the blood stream, extravasation, and colonization at a new site. The motility of cancer cells, driven by the actin cytoskeleton network, has been well documented to play crucial roles at multiple steps during the metastasis process.

1 In this article, we report that TNFα sensitizes primary mouse hepatocytes to FasL-induced apoptosis in a Bid-dependent and Bim-dependent manner. We further show that this crosstalk involves JNK activation and most likely Bim phosphorylation, cleavage of Bid, and, consequently, activation of

the type II mitochondrial pathway and results in cytochrome c release and effector caspase-3/caspase-7 activation. Controversial results have so far been reported concerning the crosstalk of TNFα and FasL in apoptosis induction. On the one hand, TNFα has been shown to confer resistance to Fas-induced cell death in eosinophilic acute myeloid leukemia cells because of its NF-κB–mediated antiapoptotic functions.25

In this respect, we analyzed some typical antiapoptotic NF-κB target genes such as cellular inhibitor of apoptosis DAPT datasheet 2 (cIAP2), c-FLIP, and XIAP, but we found that they were only moderately up-regulated (if ever) in response to TNFα (see Supporting Fig. 16). cIAP1 protein was not at all detected in hepatocytes (see also Walter et al.12; data not shown). On the other hand, several studies have indicated that TNFα positively this website regulates Fas-mediated apoptosis. In one case, TNFα could even overcome the Fas resistance of human lung fibroblasts26 by allowing more FADD adaptor to bind to Fas and therefore increase DISC formation and FasL-mediated apoptotic signaling. In contrast to human lung fibroblasts, primary mouse hepatocytes do not seem to have impaired DISC formation because they are quite sensitive to FasL-induced apoptosis.

To obtain evidence for the physiological relevance of TNFα/FasL crosstalk, Costelli et al.27 used gene targeting to show that a loss of TNFR1 and TNFR2 protects mice from anti-Fas antibody–induced liver injury. Our results confirm these findings and demonstrate that TNFα is necessary for efficient FasL-mediated hepatocyte apoptosis. However, the exact mechanism of the interplay medchemexpress of the two pathways was not unraveled in the previous study. It was shown that liver tissue levels of Fas and FasL as well as Fas expression on the hepatocyte surface were unchanged, but Bcl2 was up-regulated upon TNFR1 and TNFR2 depletion; this indicates that TNFα may regulate Bcl2 family members.27 This again is consistent with our finding that neither Fas up-regulation nor endogenous FasL is critical for the TNFα sensitizing effect, and changes in members of the Bcl2 protein family could be the underlying mechanisms for the involvement of the type II mitochondrial pathway in the sensitization process. On the other hand, it is widely accepted that TNFα fails to induce apoptosis in hepatocytes under normal conditions because of activation of the NF-κB survival pathway. Inhibition of this pathway restores apoptosis, and one mechanism involves the inducement of sustained activation of JNK.

1 In this article, we report that TNFα sensitizes primary mouse hepatocytes to FasL-induced apoptosis in a Bid-dependent and Bim-dependent manner. We further show that this crosstalk involves JNK activation and most likely Bim phosphorylation, cleavage of Bid, and, consequently, activation of

the type II mitochondrial pathway and results in cytochrome c release and effector caspase-3/caspase-7 activation. Controversial results have so far been reported concerning the crosstalk of TNFα and FasL in apoptosis induction. On the one hand, TNFα has been shown to confer resistance to Fas-induced cell death in eosinophilic acute myeloid leukemia cells because of its NF-κB–mediated antiapoptotic functions.25

In this respect, we analyzed some typical antiapoptotic NF-κB target genes such as cellular inhibitor of apoptosis FK866 manufacturer 2 (cIAP2), c-FLIP, and XIAP, but we found that they were only moderately up-regulated (if ever) in response to TNFα (see Supporting Fig. 16). cIAP1 protein was not at all detected in hepatocytes (see also Walter et al.12; data not shown). On the other hand, several studies have indicated that TNFα positively VX-809 mouse regulates Fas-mediated apoptosis. In one case, TNFα could even overcome the Fas resistance of human lung fibroblasts26 by allowing more FADD adaptor to bind to Fas and therefore increase DISC formation and FasL-mediated apoptotic signaling. In contrast to human lung fibroblasts, primary mouse hepatocytes do not seem to have impaired DISC formation because they are quite sensitive to FasL-induced apoptosis.

To obtain evidence for the physiological relevance of TNFα/FasL crosstalk, Costelli et al.27 used gene targeting to show that a loss of TNFR1 and TNFR2 protects mice from anti-Fas antibody–induced liver injury. Our results confirm these findings and demonstrate that TNFα is necessary for efficient FasL-mediated hepatocyte apoptosis. However, the exact mechanism of the interplay medchemexpress of the two pathways was not unraveled in the previous study. It was shown that liver tissue levels of Fas and FasL as well as Fas expression on the hepatocyte surface were unchanged, but Bcl2 was up-regulated upon TNFR1 and TNFR2 depletion; this indicates that TNFα may regulate Bcl2 family members.27 This again is consistent with our finding that neither Fas up-regulation nor endogenous FasL is critical for the TNFα sensitizing effect, and changes in members of the Bcl2 protein family could be the underlying mechanisms for the involvement of the type II mitochondrial pathway in the sensitization process. On the other hand, it is widely accepted that TNFα fails to induce apoptosis in hepatocytes under normal conditions because of activation of the NF-κB survival pathway. Inhibition of this pathway restores apoptosis, and one mechanism involves the inducement of sustained activation of JNK.

1 In this article, we report that TNFα sensitizes primary mouse hepatocytes to FasL-induced apoptosis in a Bid-dependent and Bim-dependent manner. We further show that this crosstalk involves JNK activation and most likely Bim phosphorylation, cleavage of Bid, and, consequently, activation of

the type II mitochondrial pathway and results in cytochrome c release and effector caspase-3/caspase-7 activation. Controversial results have so far been reported concerning the crosstalk of TNFα and FasL in apoptosis induction. On the one hand, TNFα has been shown to confer resistance to Fas-induced cell death in eosinophilic acute myeloid leukemia cells because of its NF-κB–mediated antiapoptotic functions.25

In this respect, we analyzed some typical antiapoptotic NF-κB target genes such as cellular inhibitor of apoptosis BMN 673 2 (cIAP2), c-FLIP, and XIAP, but we found that they were only moderately up-regulated (if ever) in response to TNFα (see Supporting Fig. 16). cIAP1 protein was not at all detected in hepatocytes (see also Walter et al.12; data not shown). On the other hand, several studies have indicated that TNFα positively Doxorubicin cell line regulates Fas-mediated apoptosis. In one case, TNFα could even overcome the Fas resistance of human lung fibroblasts26 by allowing more FADD adaptor to bind to Fas and therefore increase DISC formation and FasL-mediated apoptotic signaling. In contrast to human lung fibroblasts, primary mouse hepatocytes do not seem to have impaired DISC formation because they are quite sensitive to FasL-induced apoptosis.

To obtain evidence for the physiological relevance of TNFα/FasL crosstalk, Costelli et al.27 used gene targeting to show that a loss of TNFR1 and TNFR2 protects mice from anti-Fas antibody–induced liver injury. Our results confirm these findings and demonstrate that TNFα is necessary for efficient FasL-mediated hepatocyte apoptosis. However, the exact mechanism of the interplay medchemexpress of the two pathways was not unraveled in the previous study. It was shown that liver tissue levels of Fas and FasL as well as Fas expression on the hepatocyte surface were unchanged, but Bcl2 was up-regulated upon TNFR1 and TNFR2 depletion; this indicates that TNFα may regulate Bcl2 family members.27 This again is consistent with our finding that neither Fas up-regulation nor endogenous FasL is critical for the TNFα sensitizing effect, and changes in members of the Bcl2 protein family could be the underlying mechanisms for the involvement of the type II mitochondrial pathway in the sensitization process. On the other hand, it is widely accepted that TNFα fails to induce apoptosis in hepatocytes under normal conditions because of activation of the NF-κB survival pathway. Inhibition of this pathway restores apoptosis, and one mechanism involves the inducement of sustained activation of JNK.

Lymphopenia was not associated with longer remission of UC/CD. Conclusion: Conclusion: Lymphopenia during purine treatment does not predict the rate of IBD relapses. This may be limited by our small sample size or possibly the main pathway Carfilzomib manufacturer of IBD inflammation is not mediated mainly through lymphocytes. Key Word(s): 1. IBD; 2. Lymphopenia; 3. purine use; 4. IBD relapse; Presenting Author: QINFAN YANG Additional Authors: QINGSEN ZHANG, BAILI CHEN, YAO HE, MINHU CHEN, ZHIRONG ZENG Corresponding Author: ZHIRONG ZENG Affiliations: Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University;

Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University Objective: Glucocorticoids NVP-LDE225 research buy (GCs) play a pivotal role in inducing remission of inflammatory bowel disease (IBD), however, the sensitivity to GCs vary from person to person. Genes such as Multidrug resistance 1 (MDR1), NACHT leucine-rich-repeat protein 1 (NALP1), Glucocorticoid receptor (GR/NR3C1) and

its co-chaperone FK506-binding protein FKBP5 participate in modulating the metabolism of GCs. Variations of these genes were reported influencing on GCs response and MDR1 polymorphisms also associated with the susceptibility to IBD. This article aims to evaluate whether the polymorphisms of these genes influence the response to GCs in Chinese IBD patients as well as investigate the relationships between MDR1 and IBD susceptibility. Methods: Eight single nucleotide polymorphisms were genotyped in 156 IBD patients (including 117 CD and 39 UC cases) and 223 healthy controls by MALDI-TOF

MS assay. Patients included were all treated with GCs and defined as GCs responders, dependants or resisters after one year follow 上海皓元 up. The influences of these variations on GCs response or MDR1 effect on IBD susceptibility and clinical phenotypes were analyzed. Results: The CC genotypes of rs1128503 (C1236T) (OR 6.583, 95%CI 1.760–24.628, P = 0.019) and rs1045642 (C3435T) (OR 3.873, 95%CI 1.578–9.506, P = 0.009) in MDR1 gene were more frequent in GC dependants compared with the respond patients of CD, while the other seven SNPs have no association with GCs response. In addition, the G allele of MDR1 rs2032582 (G2677A/T) was more frequent among CD cases in comparison to controls (OR 0.668, 95%CI 0.484–0.921, P = 0.014); Patients who carried G allele of MDR1 rs2032582 (G2677A/T) had reduced risk for developing non-stricturing and non-penetrating CD (OR 0.661, 95% CI 0.462–0. 946, P = 0.023) or ileocolonic CD (OR 0.669, 95%CI 0.472–0.948, P = 0.024). There was no significant finding in UC. Conclusion: Our results revealed polymorphisms of MDR1 have an effect on GCs response and the predisposition to CD in Chinese population. More studies are needed to further confirm our results and elucidate the function of MDR1 polymorphisms on the pathogenesis of IBD and their role as genetic markers for GCs response.

Lions are a clear threat to giraffes.

Observational studies indicate that giraffes alter their behavior in the presence of lions. A typical vigilance posture is shown in Supporting Information Fig. S1. When lions are nearby, giraffes avoid waterholes (Valeix et al., 2009a), where they are particularly vulnerable (Dagg & Foster, 1982; Périquet et al., 2010), and favor open grasslands over denser vegetation (Valeix et al., 2009b). Females with young calves spend a disproportionate amount of time in open habitats, sacrificing browse availability for improved ability to detect and evade predators (Young ICG-001 solubility dmso & Isbell, 1991). Calves often remain in open areas in crèche groups, while mothers travel to feed (Langman, 1977; Leuthold, 1979; Mejia, in Moss, 1982). Carcass records from southern Africa reveal that lions kill more male than female giraffes (Hirst, 1969; Pienaar, 1969; Owen-Smith, 2008) and that predation on giraffes is highest in the mid- to late dry season (Hirst, 1969; Owen-Smith, 2008). However, it can take years to acquire a reasonably sized carcass sample and these records suffer from the underrepresentation of rapidly consumed calves (Hirst, 1969; Dagg & Foster, 1982; Owen-Smith & Mills, 2008). The mechanics and frequency of lion attacks and the circumstances in which giraffes are

able to evade attacks remain unclear. Easily collected claw-mark data reduce these gaps in knowledge. We used lion claw marks on Masai giraffes Giraffa camelopardalis tippelskirchi living in Serengeti National Park,

Tanzania to elucidate lion attack behavior HSP inhibitor and predation patterns. Specifically, we studied relationships between claw marks and giraffe 上海皓元 age, sex, herd size, height and study area, and we used supplemental carcass data from the Serengeti Lion Project to examine seasonal effects. We integrate our findings with results from prior studies on lion–giraffe interactions. Serengeti National Park forms part of the 25 000-km2 Serengeti ecosystem, a region of northern Tanzania and southern Kenya that supports large numbers of resident and migratory ungulates and, consequently, high numbers of predators, including lions (Sinclair & Norton-Griffiths, 1979). Giraffes were sampled in 3 non-neighboring areas of Serengeti during each dry season between August 2008 and November 2010 (study areas first described by Pellew, 1983a): (1) Seronera (240 km2); (2) Kirawira (210 km2); (3) Bologonja (175 km2, sampled only in 2010). Study area comparisons focus on the well-sampled areas of Seronera and Kirawira. While giraffe density is similar in these areas (Strauss, unpubl. data), Kirawira has a lower lion density than Seronera (Packer, 1990; Mosser et al., 2009; A. Kittle, pers. comm., 2012) and high year-round densities of preferred lion prey such as wildebeest Connochaetes taurinus and topi Damaliscus lunatus.