2 chain, hypersecrete T helper 1 (Th1) and Th2 cytokines and chem

2 chain, hypersecrete T helper 1 (Th1) and Th2 cytokines and chemokines upon stimulation with an appropriate ligand, such as alpha-galactosylceramide (α-GalCer). In doing so, these iNKT cells exert considerable and promiscuous immune function, including altering immune regulation by activating dendritic cells (DCs), macrophages, NK cells, T cells, B cells, and driving the development of adaptive immunity.12, 13 iNKT cells appear to play a critical role in the regulation of several other autoimmune diseases, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.13-17 Previously, our laboratory has proposed

that activation of iNKT cells is a critical factor in accelerating disease.18-20 To explore this issue buy RAD001 in depth, we immunized C57BL/6 mice with 2-OA-BSA (bovine serum albumin) and activated their iNKT cells with

α-GalCer. We report herein that iNKT cell activation by α-GalCer leads to a profound exacerbation of portal disease in 2-OA-BSA-immunized mice, including increased AMA production, increased CD8+ T cell biliary infiltration, portal inflammation, granuloma formation, bile duct damage, and fibrosis. These results are critical and emphasize the role of innate immunity in the natural history of PBC and they further suggest mechanisms by which biliary disease becomes perpetuated in humans as well as explaining the recurrence of Olaparib nmr PBC following liver transplantation in the absence of major histocompatability complex (MHC) compatibility. These data also emphasize the appearance of fibrosis, a feature thus far lacking in the other murine models of autoimmune cholangitis. 2-OA, 2-octynoic acid; α-GalCer, alpha-galactosylceramide; α-SMA, alpha-smooth muscle actin; AMAs, antimitochondrial antibodies; BSA, bovine serum albumin; CFA, complete Freund’s adjuvant; DC, dendritic cells; dnTGF-βRII, TGF-β receptor II dominant-negative; HSCs, hepatic stellate cells; iNKT, invariant natural killer T; PBC, primary biliary cirrhosis; click here PDC-E2, E2 subunits of the pyruvate dehydrogenase complex; TGF-β,

transforming growth factor beta. The protocol for induction of autoimmune cholangitis is similar to our previous reports.7 Briefly, female C57BL/6 mice aged 8-10 weeks were obtained from the National Laboratory Animal Center and maintained in the Animal Center of the College of Medicine, National Taiwan University. Mice were intraperitoneally immunized with 2-OA-BSA (100 μg) in the presence of complete Freund’s adjuvant (CFA, Sigma-Aldrich, St. Louis, MO) and subsequently boosted at weeks 2, 4, 6, 8, and 10 with 2-OA-BSA and incomplete Freund’s adjuvant (IFA, Sigma-Aldrich). Two μg of α-GalCer (Alexis, San Diego, CA) was diluted in phosphate-buffered saline (PBS) and injected intravenously 1 day before first, second, and third 2-OA-BSA immunizations (group name: α-GC/CFA/2-OA).

The expression of CD80 was limited in some APCs and not found in

The expression of CD80 was limited in some APCs and not found in cholangiocarcinoma cells. Consequently, cholangiocarcinoma cells expressing HLA-DR, but lacking costimulatory molecules (CD80 and CD86) were found in 54% of cases. These cancer cells could act as nonprofessional APCs, possibly generating IL-10–producing Treg cells (anergy T cells), and then an IL-10–predominant cytokine milieu could cause the induction of IgG4-positive cells.5, 6 In these phenotypic cases, the number of IgG4-positive cells find more infiltrating carcinoma tissue was higher than in HLA-DR–negative cases and both HLA-DR– and CD86-positive

cases, confirming this speculation. Cells positive for both HLA-DR and CD86 are suggested to play the role of professional APCs, as it was reported that MHC-II–positive thyroid epithelial cells could present antigens to T cells and activate autoreactive T cells.25, 26 Although further study is needed to clarify the functional mechanism of these cholangiocarcinoma cells as APCs, this study demonstrated that HLA-DR– and CD86-positive cancer cells were not associated with IgG4 reactions in cholangiocarcinoma tissue. As to pathogenesis of IgG4 reactions in IgG4-related diseases,

the participation of CD4+CD25+Foxp3+ Treg cells, Atezolizumab purchase which are capable of producing IL-10, has been speculated.27 Foxp3 is thought to be the master transcription factor of Treg cells and, until recently, Foxp3 expression was thought to be restricted to the T cell lineage. However, immunohistochemistry and flow cytometric analysis demonstrated that some carcinoma tissues and cultured cancer cell lines expressed Foxp3.7-10 Immunohistochemistry using the antibody recognizing the N

terminus, but not the C terminus, of Foxp3-highlighted cholangiocarcinoma tissue in 39% of cases as well as selleck chemicals llc Treg cell morphology, suggesting the presence of the splicing variant of Foxp3 in cholangiocarcinoma cells. Molecular analysis using a cholangiocarcinoma cell line demonstrated that the cells expressed mRNA of Foxp3, but lack Exon 3. This type of splicing variant has already been reported in a melanoma cell line and created a novel amino acid caused by a frame shift at the C terminus.9 This is why the antibody recognizing the C terminus of Foxp3 could not detect the variant of Foxp3 found in cholangiocarcinoma tissue. Although a functional analysis of this variant as a transcription factor is necessary, it has already been reported that Foxp3 expression is closely correlated with the expression of IL-10 in all Foxp3-positive cell lines.10 The present study, using a cholangiocarcinoma cell line, also demonstrated that cells express mRNA of IL-10 as well as Foxp3. Moreover, the IL-10 protein was detected in the culture medium by ELISA at a concentration of 7.8-15.

The expression of CD80 was limited in some APCs and not found in

The expression of CD80 was limited in some APCs and not found in cholangiocarcinoma cells. Consequently, cholangiocarcinoma cells expressing HLA-DR, but lacking costimulatory molecules (CD80 and CD86) were found in 54% of cases. These cancer cells could act as nonprofessional APCs, possibly generating IL-10–producing Treg cells (anergy T cells), and then an IL-10–predominant cytokine milieu could cause the induction of IgG4-positive cells.5, 6 In these phenotypic cases, the number of IgG4-positive cells check details infiltrating carcinoma tissue was higher than in HLA-DR–negative cases and both HLA-DR– and CD86-positive

cases, confirming this speculation. Cells positive for both HLA-DR and CD86 are suggested to play the role of professional APCs, as it was reported that MHC-II–positive thyroid epithelial cells could present antigens to T cells and activate autoreactive T cells.25, 26 Although further study is needed to clarify the functional mechanism of these cholangiocarcinoma cells as APCs, this study demonstrated that HLA-DR– and CD86-positive cancer cells were not associated with IgG4 reactions in cholangiocarcinoma tissue. As to pathogenesis of IgG4 reactions in IgG4-related diseases,

the participation of CD4+CD25+Foxp3+ Treg cells, BAY 80-6946 which are capable of producing IL-10, has been speculated.27 Foxp3 is thought to be the master transcription factor of Treg cells and, until recently, Foxp3 expression was thought to be restricted to the T cell lineage. However, immunohistochemistry and flow cytometric analysis demonstrated that some carcinoma tissues and cultured cancer cell lines expressed Foxp3.7-10 Immunohistochemistry using the antibody recognizing the N

terminus, but not the C terminus, of Foxp3-highlighted cholangiocarcinoma tissue in 39% of cases as well as selleck screening library Treg cell morphology, suggesting the presence of the splicing variant of Foxp3 in cholangiocarcinoma cells. Molecular analysis using a cholangiocarcinoma cell line demonstrated that the cells expressed mRNA of Foxp3, but lack Exon 3. This type of splicing variant has already been reported in a melanoma cell line and created a novel amino acid caused by a frame shift at the C terminus.9 This is why the antibody recognizing the C terminus of Foxp3 could not detect the variant of Foxp3 found in cholangiocarcinoma tissue. Although a functional analysis of this variant as a transcription factor is necessary, it has already been reported that Foxp3 expression is closely correlated with the expression of IL-10 in all Foxp3-positive cell lines.10 The present study, using a cholangiocarcinoma cell line, also demonstrated that cells express mRNA of IL-10 as well as Foxp3. Moreover, the IL-10 protein was detected in the culture medium by ELISA at a concentration of 7.8-15.

The expression of CD80 was limited in some APCs and not found in

The expression of CD80 was limited in some APCs and not found in cholangiocarcinoma cells. Consequently, cholangiocarcinoma cells expressing HLA-DR, but lacking costimulatory molecules (CD80 and CD86) were found in 54% of cases. These cancer cells could act as nonprofessional APCs, possibly generating IL-10–producing Treg cells (anergy T cells), and then an IL-10–predominant cytokine milieu could cause the induction of IgG4-positive cells.5, 6 In these phenotypic cases, the number of IgG4-positive cells Antifection chemical infiltrating carcinoma tissue was higher than in HLA-DR–negative cases and both HLA-DR– and CD86-positive

cases, confirming this speculation. Cells positive for both HLA-DR and CD86 are suggested to play the role of professional APCs, as it was reported that MHC-II–positive thyroid epithelial cells could present antigens to T cells and activate autoreactive T cells.25, 26 Although further study is needed to clarify the functional mechanism of these cholangiocarcinoma cells as APCs, this study demonstrated that HLA-DR– and CD86-positive cancer cells were not associated with IgG4 reactions in cholangiocarcinoma tissue. As to pathogenesis of IgG4 reactions in IgG4-related diseases,

the participation of CD4+CD25+Foxp3+ Treg cells, click here which are capable of producing IL-10, has been speculated.27 Foxp3 is thought to be the master transcription factor of Treg cells and, until recently, Foxp3 expression was thought to be restricted to the T cell lineage. However, immunohistochemistry and flow cytometric analysis demonstrated that some carcinoma tissues and cultured cancer cell lines expressed Foxp3.7-10 Immunohistochemistry using the antibody recognizing the N

terminus, but not the C terminus, of Foxp3-highlighted cholangiocarcinoma tissue in 39% of cases as well as see more Treg cell morphology, suggesting the presence of the splicing variant of Foxp3 in cholangiocarcinoma cells. Molecular analysis using a cholangiocarcinoma cell line demonstrated that the cells expressed mRNA of Foxp3, but lack Exon 3. This type of splicing variant has already been reported in a melanoma cell line and created a novel amino acid caused by a frame shift at the C terminus.9 This is why the antibody recognizing the C terminus of Foxp3 could not detect the variant of Foxp3 found in cholangiocarcinoma tissue. Although a functional analysis of this variant as a transcription factor is necessary, it has already been reported that Foxp3 expression is closely correlated with the expression of IL-10 in all Foxp3-positive cell lines.10 The present study, using a cholangiocarcinoma cell line, also demonstrated that cells express mRNA of IL-10 as well as Foxp3. Moreover, the IL-10 protein was detected in the culture medium by ELISA at a concentration of 7.8-15.

04 x 10-12, odds ratio [OR] = 075) In the second replication st

04 x 10-12, odds ratio [OR] = 0.75). In the second replication study, we again confirmed the association and finally observed a highly significant association (Pcombined = 3.59 x 10-16, OR = 0.79, 95% confidence interval [CI] 0.75–0.84) and we observed no heterogeneity among the three studies (heterogeneity test P = 0.1 13). After adjusting for gender and age using multiple logistic regression analysis, the SNP remained highly significant with an OR = 0.79 (95% CI 0.70–0.89). Conclusions: Our findings suggest that a common variation in HLA-DQ locus affects

susceptibility to chronic infection with HCV in the Japanese population. Disclosures: Norio Akuta – Patent Held/Filed: SRL. Idasanutlin purchase Inc. Kenji Ikeda – Speaking and Teaching: Dainippon Sumitomo Pharmaceutical Company Hiromitsu Kumada – Speaking and Teaching: Bristol-Myers Squibb,Pharma International Joji Toyota – Speaking and Teaching: MSD 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, find protocol Olympus, GlaxoSmithKline, ZERIA, Bayer, Minophagen, JANSSEN, JIMRO, TSUMURA, Otsuka, Taiho, Nippon Kayaku, Nippon Shinyaku, Takeda, AJINOMOTO, Meiji Seika, Toray The following people have nothing to disclose: Daiki Miki, Hidenori Ochi, C. Nelson Hayes, Hiromi Abe, Tomokazu Kawaoka, Masataka Tsuge, Nobuhiko Hiraga, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Shoichi Takahashi, Fumitaka Suzuki, Yoshiyasu Karino Whether HCV plays a direct role in hepatocarcinogenesis is still unknown. In particular, there are limited data on the HCV load and expression within the tumor. We analyzed up to 17 liver samples collected from each of 1 0 livers with HCV-related HCC undergoing liver transplantation (LT) or resection, including 5 samples from the tumor (1 from the center; 4 from the check details periphery), and 12 from outside the tumor (4 at 1 cm, 4 at 3 cm and 4 from the liver edge). As

controls, we studied up to 4 liver samples (2 from the right and 2 from the left lobe) from each of 6 non-HCC HCV cirrhotic explants. Serum samples were available from all patients at the time of LT. Gene expression profiling (GEP) identified 2,035 differentially expressed genes among the different liver areas, with a sharp separation between tumor and non-tumor tissue at the perilesional border. Strikingly, the tumors showed significantly less HCV RNA (1–3 logs) than the perilesional non-tumor areas, mirroring the sharp separation seen by GEP. The degree of HCV RNA decrease within the tumor correlated with the degree of malignancy. No differences in HCV RNA were seen in various areas of non-HCC cirrhotic livers.

04 x 10-12, odds ratio [OR] = 075) In the second replication st

04 x 10-12, odds ratio [OR] = 0.75). In the second replication study, we again confirmed the association and finally observed a highly significant association (Pcombined = 3.59 x 10-16, OR = 0.79, 95% confidence interval [CI] 0.75–0.84) and we observed no heterogeneity among the three studies (heterogeneity test P = 0.1 13). After adjusting for gender and age using multiple logistic regression analysis, the SNP remained highly significant with an OR = 0.79 (95% CI 0.70–0.89). Conclusions: Our findings suggest that a common variation in HLA-DQ locus affects

susceptibility to chronic infection with HCV in the Japanese population. Disclosures: Norio Akuta – Patent Held/Filed: SRL. Akt inhibitor Inc. Kenji Ikeda – Speaking and Teaching: Dainippon Sumitomo Pharmaceutical Company Hiromitsu Kumada – Speaking and Teaching: Bristol-Myers Squibb,Pharma International Joji Toyota – Speaking and Teaching: MSD 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, NVP-BGJ398 in vivo Olympus, GlaxoSmithKline, ZERIA, Bayer, Minophagen, JANSSEN, JIMRO, TSUMURA, Otsuka, Taiho, Nippon Kayaku, Nippon Shinyaku, Takeda, AJINOMOTO, Meiji Seika, Toray The following people have nothing to disclose: Daiki Miki, Hidenori Ochi, C. Nelson Hayes, Hiromi Abe, Tomokazu Kawaoka, Masataka Tsuge, Nobuhiko Hiraga, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Shoichi Takahashi, Fumitaka Suzuki, Yoshiyasu Karino Whether HCV plays a direct role in hepatocarcinogenesis is still unknown. In particular, there are limited data on the HCV load and expression within the tumor. We analyzed up to 17 liver samples collected from each of 1 0 livers with HCV-related HCC undergoing liver transplantation (LT) or resection, including 5 samples from the tumor (1 from the center; 4 from the this website periphery), and 12 from outside the tumor (4 at 1 cm, 4 at 3 cm and 4 from the liver edge). As

controls, we studied up to 4 liver samples (2 from the right and 2 from the left lobe) from each of 6 non-HCC HCV cirrhotic explants. Serum samples were available from all patients at the time of LT. Gene expression profiling (GEP) identified 2,035 differentially expressed genes among the different liver areas, with a sharp separation between tumor and non-tumor tissue at the perilesional border. Strikingly, the tumors showed significantly less HCV RNA (1–3 logs) than the perilesional non-tumor areas, mirroring the sharp separation seen by GEP. The degree of HCV RNA decrease within the tumor correlated with the degree of malignancy. No differences in HCV RNA were seen in various areas of non-HCC cirrhotic livers.

04) increased cellular GPAM levels (Fig 5B) To determine if miR

04) increased cellular GPAM levels (Fig. 5B). To determine if miR-27b modulates PPARG transcriptional activity, we performed PPARG

binding assays with nuclear extracts from transfected Huh7 cells (Supporting Methods). Inhibition of endogenous miR-27b resulted in a significant (P = 0.01) increase in PPARG binding to immobilized response elements (Supporting Fig. S2). It should be noted that, whereas overexpression of miR-27b significantly reduced (39% loss, P = 0.002) secreted ANGPTL3 levels (Fig. 5A) after 48 hours, Acalabrutinib cellular GPAM protein levels and PPARG transcriptional activity were not affected (Fig. 5B; Supporting Fig. S2). These observations are likely explained at least in part by the stability and temporal dynamics of each protein. Next we searched for canonical 3′ UTR seed-based miR-27b target sites within each of the six genes (Materials and Methods). As expected, SREBF1, which did not change (mRNA level) in response to overexpression of either miR-27b mimic or its antagomiR, did not harbor any canonical miR-27b seed sites (Fig. 4F). Three out of the five genes that were repressed by miR-27b (PPARG, NDST1, and GPAM) contained one or more seed sites within their 3′ UTRs (Fig. 4A-E). GPAM harbors two highly conserved and one moderately conserved miR-27b target site within its 3′

UTR (Fig. 4). To determine if miR-27b directly targets GPAM through one of these predicted sites, we performed reporter gene (luciferase) assays. A portion of the GPAM 3′ UTR, containing one putative miR-27b site, was http://www.selleckchem.com/products/R788(Fostamatinib-disodium).html cloned downstream of firefly luciferase (Materials and Methods). Dual transfection with miR-27b in HEK293 cells significantly (P = 0.001) reduced firefly luciferase activity (Supporting Fig. S3). After site-directed mutagenesis to eliminate

the putative miR-27b site (Materials and Methods), miR-27b failed to knock-down firefly luciferase activity, indicating that the site is directly involved in miR-27b mediated regulation of GPAM (Supporting Fig. S3). ANGPTL3 was the only down-regulated gene that did not harbor any miR-27b seed sites in its 3′ UTR. To further investigate the observed strong miR-27b-mediated regulation of ANGPTL3 (Fig. 4C, 5A), we expanded the search to two recently discovered classes of target selleck chemicals sites: (1) 3′ UTR centered sites and (2) open reading frame (ORF) sites (Materials and Methods). As its name implies, 3′ UTR centered sites base pair to the center of the miRNA sequence,37 as opposed to the 5′-end seed region. Functional ORF sites are typically preceded by a stretch of rare codons,38 which can cause ribosomal pausing,39 thereby allowing miRNA silencing complexes to form stable interactions with the target site without ribosomal interference. We developed and implemented computational strategies to predict 3′ UTR centered sites based on the strength of base pairing to the center of a miRNA, and ORF seed sites based on a metric that evaluates codon rarity in the preceding sequence (Materials and Methods).

04) increased cellular GPAM levels (Fig 5B) To determine if miR

04) increased cellular GPAM levels (Fig. 5B). To determine if miR-27b modulates PPARG transcriptional activity, we performed PPARG

binding assays with nuclear extracts from transfected Huh7 cells (Supporting Methods). Inhibition of endogenous miR-27b resulted in a significant (P = 0.01) increase in PPARG binding to immobilized response elements (Supporting Fig. S2). It should be noted that, whereas overexpression of miR-27b significantly reduced (39% loss, P = 0.002) secreted ANGPTL3 levels (Fig. 5A) after 48 hours, this website cellular GPAM protein levels and PPARG transcriptional activity were not affected (Fig. 5B; Supporting Fig. S2). These observations are likely explained at least in part by the stability and temporal dynamics of each protein. Next we searched for canonical 3′ UTR seed-based miR-27b target sites within each of the six genes (Materials and Methods). As expected, SREBF1, which did not change (mRNA level) in response to overexpression of either miR-27b mimic or its antagomiR, did not harbor any canonical miR-27b seed sites (Fig. 4F). Three out of the five genes that were repressed by miR-27b (PPARG, NDST1, and GPAM) contained one or more seed sites within their 3′ UTRs (Fig. 4A-E). GPAM harbors two highly conserved and one moderately conserved miR-27b target site within its 3′

UTR (Fig. 4). To determine if miR-27b directly targets GPAM through one of these predicted sites, we performed reporter gene (luciferase) assays. A portion of the GPAM 3′ UTR, containing one putative miR-27b site, was LBH589 cloned downstream of firefly luciferase (Materials and Methods). Dual transfection with miR-27b in HEK293 cells significantly (P = 0.001) reduced firefly luciferase activity (Supporting Fig. S3). After site-directed mutagenesis to eliminate

the putative miR-27b site (Materials and Methods), miR-27b failed to knock-down firefly luciferase activity, indicating that the site is directly involved in miR-27b mediated regulation of GPAM (Supporting Fig. S3). ANGPTL3 was the only down-regulated gene that did not harbor any miR-27b seed sites in its 3′ UTR. To further investigate the observed strong miR-27b-mediated regulation of ANGPTL3 (Fig. 4C, 5A), we expanded the search to two recently discovered classes of target see more sites: (1) 3′ UTR centered sites and (2) open reading frame (ORF) sites (Materials and Methods). As its name implies, 3′ UTR centered sites base pair to the center of the miRNA sequence,37 as opposed to the 5′-end seed region. Functional ORF sites are typically preceded by a stretch of rare codons,38 which can cause ribosomal pausing,39 thereby allowing miRNA silencing complexes to form stable interactions with the target site without ribosomal interference. We developed and implemented computational strategies to predict 3′ UTR centered sites based on the strength of base pairing to the center of a miRNA, and ORF seed sites based on a metric that evaluates codon rarity in the preceding sequence (Materials and Methods).

We find that claw marks are an important source of data on intera

We find that claw marks are an important source of data on interactions between lions and giraffes. The lion Panthera leo is the most important http://www.selleckchem.com/products/DAPT-GSI-IX.html predator of the giraffe Giraffa camelopardalis (Berry, 1973; Dagg & Foster, 1982), yet the relationship between these species has been rarely studied. Lions may be the primary cause of death for giraffe calves (Dagg & Foster, 1982), which suffer an estimated 58–73% mortality in the first of year of life (Foster & Dagg, 1972; Leuthold & Leuthold, 1978; Pellew, 1983a). Although giraffe mortality drops off substantially after 1 year of age (Pellew, 1983a), lion predation remains a significant mortality factor for subadults and even

for adults (e.g. Hirst, 1969; Pienaar, 1969), which weigh 800–1200 kg (Owen-Smith, 1988) and reach heights of up to 4.5–5.5 m for females and males, respectively (Dagg & Foster, 1982; Pellew, 1983a). Direct observations of lion attacks on giraffes are rare. GSK3235025 concentration In a 3-year study of Serengeti lions, Schaller (1972) observed only 10 such attacks, none of which led to a kill. Consequently, little is known about the effects of lions on giraffe

mortality and behavior. What is known is largely anecdotal or inferred from short-term studies of giraffe demography or from carcass records. If the majority of attacks are occurring in conditions not conducive to direct observation, such as at night or in dense vegetation, then alternative sources of data will be required. In this paper, we examine lion predation on giraffes by applying a novel methodology that has been used primarily in marine biology: predation marks on live animals. Underwater predation is difficult to observe directly (Bertilsson-Friedman, 2006); thus, predation marks visible on surfacing animals are an important

source of data on predator–prey interactions. While predation marks cannot be used alone to estimate predation rates, they can be used to identify predatory species (e.g. Corkeron, Morris & Bryden, 1987; Cockcroft, Cliff & Ross, 1989), to elucidate attack behavior, to infer which age–sex classes of prey are better able to evade predation (e.g. Corkeron et al., 1987; Heithaus, learn more 2001) and to examine variation in predation risk over space and time (Heithaus, 2001; Bertilsson-Friedman, 2006). Similarly, the predation-mark method can increase the sample size of lion predation events on giraffes. Only a portion of lion attacks are fatal (Schaller, 1972; Funston, Mills & Biggs, 2001) and surviving prey may incur bite wounds or claw marks. Lion claw marks are distinctive and can be differentiated from marks inflicted by other predators (Figs 1 and 2). Claw marks are observed on giraffe carcasses (Schaller, 1972) and on live giraffes (Fig. 2). Interpretation of claw marks, however, requires caution. For example, an absence of claw marks in an age–sex class could indicate that all attacked individuals die, that no individuals are attacked or that too few individuals were sampled.

We find that claw marks are an important source of data on intera

We find that claw marks are an important source of data on interactions between lions and giraffes. The lion Panthera leo is the most important TAM Receptor inhibitor predator of the giraffe Giraffa camelopardalis (Berry, 1973; Dagg & Foster, 1982), yet the relationship between these species has been rarely studied. Lions may be the primary cause of death for giraffe calves (Dagg & Foster, 1982), which suffer an estimated 58–73% mortality in the first of year of life (Foster & Dagg, 1972; Leuthold & Leuthold, 1978; Pellew, 1983a). Although giraffe mortality drops off substantially after 1 year of age (Pellew, 1983a), lion predation remains a significant mortality factor for subadults and even

for adults (e.g. Hirst, 1969; Pienaar, 1969), which weigh 800–1200 kg (Owen-Smith, 1988) and reach heights of up to 4.5–5.5 m for females and males, respectively (Dagg & Foster, 1982; Pellew, 1983a). Direct observations of lion attacks on giraffes are rare. click here In a 3-year study of Serengeti lions, Schaller (1972) observed only 10 such attacks, none of which led to a kill. Consequently, little is known about the effects of lions on giraffe

mortality and behavior. What is known is largely anecdotal or inferred from short-term studies of giraffe demography or from carcass records. If the majority of attacks are occurring in conditions not conducive to direct observation, such as at night or in dense vegetation, then alternative sources of data will be required. In this paper, we examine lion predation on giraffes by applying a novel methodology that has been used primarily in marine biology: predation marks on live animals. Underwater predation is difficult to observe directly (Bertilsson-Friedman, 2006); thus, predation marks visible on surfacing animals are an important

source of data on predator–prey interactions. While predation marks cannot be used alone to estimate predation rates, they can be used to identify predatory species (e.g. Corkeron, Morris & Bryden, 1987; Cockcroft, Cliff & Ross, 1989), to elucidate attack behavior, to infer which age–sex classes of prey are better able to evade predation (e.g. Corkeron et al., 1987; Heithaus, selleck chemicals 2001) and to examine variation in predation risk over space and time (Heithaus, 2001; Bertilsson-Friedman, 2006). Similarly, the predation-mark method can increase the sample size of lion predation events on giraffes. Only a portion of lion attacks are fatal (Schaller, 1972; Funston, Mills & Biggs, 2001) and surviving prey may incur bite wounds or claw marks. Lion claw marks are distinctive and can be differentiated from marks inflicted by other predators (Figs 1 and 2). Claw marks are observed on giraffe carcasses (Schaller, 1972) and on live giraffes (Fig. 2). Interpretation of claw marks, however, requires caution. For example, an absence of claw marks in an age–sex class could indicate that all attacked individuals die, that no individuals are attacked or that too few individuals were sampled.