Owing to the ecological overlap of many species, it makes sense t

Owing to the ecological overlap of many species, it makes sense that such heterospecific social learning is common, and in some cases, information from another species may be more profitable than that provided by members of the same species. Here, we review the existing literature about learning from individuals of different species. We discuss the cognitive mechanisms underlying this form of information gathering and highlight the importance of past experience and

innate predispositions in the formation Epigenetics inhibitor of interspecific learning events. In many cases, seemingly complex forms of ‘copying’ from members of other species can be explained by relatively simple forms of conditioning. I saw several humble-bees … visiting these flowers … cutting with their mandibles holes through the under side of R788 cost the calyx and thus sucking the nectar … and the humble-bees were thus saved much trouble in sucking. The very next day I found all the hive-bees, without exception, sucking through the holes which had been made by the humblebees … I must think that the hive-bees either saw the humble-bees

cutting the holes and understood what they were doing and immediately profited by their labour; or that they merely imitated the humble-bees after they cut the holes …’ Charles Darwin quoted in Romanes (1883, pp. 220–221) should this be verified, it will … be a very instructive case of acquired knowledge in insects. We should be astonished did one genus

of monkeys adopt from another a particular manner of opening hard-shelled fruit; how much more so ought we to be in a tribe of insects … so pre-eminent for their instinctive faculties, which are generally supposed to be in inverse ratio to the intellectual!’ Charles Darwin (1841, p. 301) Animals are surrounded by a variable and complex environment in which they have to exhibit the appropriate behaviour to succeed in getting food, finding the best habitat Megestrol Acetate or avoiding predation. Animals often share the same needs and problems with other individuals. Thus, in addition to gathering information personally by costly trial-and-error strategies, an individual can rely on information previously sampled by conspecifics regarding the quality of alternatives when deciding from what and where to feed, where to live or from whom to escape (Danchin et al., 2004; Galef & Laland, 2005; Grüter, Leadbeater & Ratnieks, 2010). Such social learning is widespread in the animal kingdom, from insects to mammals (Freeberg, 2000; Galef & Giraldeau, 2001; Brown & Laland, 2003; Leadbeater & Chittka, 2007). It can be defined as the use of social cues, often inadvertently left by other animals engaged in making choices between various options (Heyes, 1994; Danchin et al., 2004; Dall et al., 2005; Leadbeater & Chittka, 2007). However, the use of socially acquired information should be regulated by adaptive strategies concerning when to copy and from whom (Laland, 2004).

Owing to the ecological overlap of many species, it makes sense t

Owing to the ecological overlap of many species, it makes sense that such heterospecific social learning is common, and in some cases, information from another species may be more profitable than that provided by members of the same species. Here, we review the existing literature about learning from individuals of different species. We discuss the cognitive mechanisms underlying this form of information gathering and highlight the importance of past experience and

innate predispositions in the formation Proteases inhibitor of interspecific learning events. In many cases, seemingly complex forms of ‘copying’ from members of other species can be explained by relatively simple forms of conditioning. I saw several humble-bees … visiting these flowers … cutting with their mandibles holes through the under side of selleck compound the calyx and thus sucking the nectar … and the humble-bees were thus saved much trouble in sucking. The very next day I found all the hive-bees, without exception, sucking through the holes which had been made by the humblebees … I must think that the hive-bees either saw the humble-bees

cutting the holes and understood what they were doing and immediately profited by their labour; or that they merely imitated the humble-bees after they cut the holes …’ Charles Darwin quoted in Romanes (1883, pp. 220–221) should this be verified, it will … be a very instructive case of acquired knowledge in insects. We should be astonished did one genus

of monkeys adopt from another a particular manner of opening hard-shelled fruit; how much more so ought we to be in a tribe of insects … so pre-eminent for their instinctive faculties, which are generally supposed to be in inverse ratio to the intellectual!’ Charles Darwin (1841, p. 301) Animals are surrounded by a variable and complex environment in which they have to exhibit the appropriate behaviour to succeed in getting food, finding the best habitat Farnesyltransferase or avoiding predation. Animals often share the same needs and problems with other individuals. Thus, in addition to gathering information personally by costly trial-and-error strategies, an individual can rely on information previously sampled by conspecifics regarding the quality of alternatives when deciding from what and where to feed, where to live or from whom to escape (Danchin et al., 2004; Galef & Laland, 2005; Grüter, Leadbeater & Ratnieks, 2010). Such social learning is widespread in the animal kingdom, from insects to mammals (Freeberg, 2000; Galef & Giraldeau, 2001; Brown & Laland, 2003; Leadbeater & Chittka, 2007). It can be defined as the use of social cues, often inadvertently left by other animals engaged in making choices between various options (Heyes, 1994; Danchin et al., 2004; Dall et al., 2005; Leadbeater & Chittka, 2007). However, the use of socially acquired information should be regulated by adaptive strategies concerning when to copy and from whom (Laland, 2004).

Owing to the ecological overlap of many species, it makes sense t

Owing to the ecological overlap of many species, it makes sense that such heterospecific social learning is common, and in some cases, information from another species may be more profitable than that provided by members of the same species. Here, we review the existing literature about learning from individuals of different species. We discuss the cognitive mechanisms underlying this form of information gathering and highlight the importance of past experience and

innate predispositions in the formation CAL-101 molecular weight of interspecific learning events. In many cases, seemingly complex forms of ‘copying’ from members of other species can be explained by relatively simple forms of conditioning. I saw several humble-bees … visiting these flowers … cutting with their mandibles holes through the under side of Temsirolimus the calyx and thus sucking the nectar … and the humble-bees were thus saved much trouble in sucking. The very next day I found all the hive-bees, without exception, sucking through the holes which had been made by the humblebees … I must think that the hive-bees either saw the humble-bees

cutting the holes and understood what they were doing and immediately profited by their labour; or that they merely imitated the humble-bees after they cut the holes …’ Charles Darwin quoted in Romanes (1883, pp. 220–221) should this be verified, it will … be a very instructive case of acquired knowledge in insects. We should be astonished did one genus

of monkeys adopt from another a particular manner of opening hard-shelled fruit; how much more so ought we to be in a tribe of insects … so pre-eminent for their instinctive faculties, which are generally supposed to be in inverse ratio to the intellectual!’ Charles Darwin (1841, p. 301) Animals are surrounded by a variable and complex environment in which they have to exhibit the appropriate behaviour to succeed in getting food, finding the best habitat not or avoiding predation. Animals often share the same needs and problems with other individuals. Thus, in addition to gathering information personally by costly trial-and-error strategies, an individual can rely on information previously sampled by conspecifics regarding the quality of alternatives when deciding from what and where to feed, where to live or from whom to escape (Danchin et al., 2004; Galef & Laland, 2005; Grüter, Leadbeater & Ratnieks, 2010). Such social learning is widespread in the animal kingdom, from insects to mammals (Freeberg, 2000; Galef & Giraldeau, 2001; Brown & Laland, 2003; Leadbeater & Chittka, 2007). It can be defined as the use of social cues, often inadvertently left by other animals engaged in making choices between various options (Heyes, 1994; Danchin et al., 2004; Dall et al., 2005; Leadbeater & Chittka, 2007). However, the use of socially acquired information should be regulated by adaptive strategies concerning when to copy and from whom (Laland, 2004).

Methods: Primary rat hepatocytes and 3T3 fibroblasts were co-enca

Methods: Primary rat hepatocytes and 3T3 fibroblasts were co-encapsulated into collage hydrogel and combined with HGF to establish a novel hepatocyte 3D co-culture system and morphology, phenotype and www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html functions of glycogen and albumin synthesis were analyzed by histological examinations. Then five different hepatocyte to fibroblast (H : F) seeding ratio (1 : 0.5, 1 : 1, 1 : 2, 1 : 4, 1 : 8), four various cell inoculum concentration (2 × 104/mL, 2 × 105/mL, 2 × 106/mL and 2 × 107/ml) and three ways of cultivation (single-culture, insert-culture, co-culture) were

compared in order to establish optimum condition of culture. Cell viability was analyzed by LIVE/DEAD staining and liver-cell-specific functions (LDL uptake, albumin secretion, urea synthesis) were evaluated. In addition, the expression levels of hepatocyte-specific genes were tested by Real-time PCR. Results: We successfully established the hepatocyte 3D co-culture system. Histological examinations revealed liver-specific morphology, phenotype and well-preserved glycogen storage and albumin synthesis. In this system, H : F of 2 : 1, seeding density of 2 × 106/ml and co-culture group yielded maximal albumin and urea production. Compared with single culture, our 3D co-culture system exhibited high viability (52.25 ± 4.62% vs. 32.92 ± 5.32 %, P < 0.01, day 20) and stronger LDL uptake (day 7). Albumin secretion and urea synthesis were

also highly preserved at least for 20 days in co-culture group, whereas the single cultured hepatocytes exhibited a markedly reduced time course of secretion. In addition, Real-time PCR revealed CH5424802 clinical trial higher hepatocyte-specific gene expression (Albumin, HNF-4α, CK18, Claudin-3,

CYP1A1, CYP3A1 Cell Penetrating Peptide and G6P) in 3D co-culture than single culture model (P < 0.05). Conclusion: The novel 3D co-culture system provides a valuable way to prolong the viability and function of the encapsulated hepatocytes, which would have great application potentials in hepatocyte-based therapies. Key Word(s): 1. hepatocyte; 2. 3D culture; 3. collagen hydrogel; 4. tissue engineering; Presenting Author: JIANPING QIN Additional Authors: MINGDE JIANG Corresponding Author: JIANPING QIN Affiliations: Chengdu Military General Hospital Objective: To observe the clinical effects and complications of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension due to cirrhosis. Methods: Two hundred and eighty patients with portal hypertension due to cirrhosis underwent TIPS. Portal trunk pressure of was checked before and after operation. The changes of hemodynamics and the condition of the stent were detected by ultrasound and the esophageal and fundic veins observed endoscopically. Results: The success rate of TIPS was 99.3%. The portal trunk pressure was 26.8 ± 3.6 cmH2O after operation and 46.5 ± 3.4 cmH2O before operation (P < 0.01). The velocity of blood flow in the portal vein increased.

PAI-1 was produced by hepatocyte, and PAI-1 was increased in any

PAI-1 was produced by hepatocyte, and PAI-1 was increased in any portion of liver after hepatectomy. PAI-1 upregulation in the liver was also noted in intestinal adhesion model. This molecular

mechanism also regulates adhesion formation in patients following hepatectomy. These results indicate that the IFN-۷ and PAI-1 are possible therapeutic targets and HGF could prevent postoperative adhesion formation after hepatectomy. Disclosures: The following people have nothing to disclose: Koichiro Ohashi, Tomohiro Yoshimoto, Hisashi Kosaka, Tadamichi Hirano, Yuji Iimuro, Shuhei Nishiguchi, Kenji Nakanishi, Jiro Fujimoto Aims: Human mesenchymal stem cells (hMSCs) have regenerative potential by producing trophic factors as well as hepatic differentiation capacity, and cell-based selleck inhibitor therapies utilizing hMSCs are expected to be an

alternative treatment for liver transplantation. For future clinical applications, we focused on Wnt/beta-catenin signal inhibitors since suppression of Wnt/beta-catenin signaling by siRNA enhances hepatic differentiation of hMSCs. In this study, we screened 10 small compounds inhibiting Wnt/beta-catenin signal as candidate compounds driving hMSCs to transdifferentiate into functional hepatocytes, and examined whether cell sheets made from hMSCs by Wnt/beta -catenin signal inhibitors can ameliorate acute liver failure in mice. Methods: First, the effects of Wnt/beta-catenin signal-inhibiting small compounds on TCF4/beta-catenin transcriptional activities were screened by reporter assay in UE7T-13 hMSC cells. Differentiation capacities were assessed by RT-PCR analysis and functional Palbociclib cell line assays. Cell sheets were fabricated by differentiation procedure on temperature-responsive polymer-grafted culture dishes and then transplanted into NOD/SCID mice. One, two, and three layered cell sheets

were transplanted onto two sites of liver surface in group 1, 2 and 3, respectively and sham operated mice in group 4 were compared as controls. All mice were administrated carbon tetrachloride on day 1. Liver function tests were performed on day 2, 4 and 8, and mice were followed up to day 8. Results: Hexachlorophene potently inhibited TCF4/betacatenin transcriptional activity and enhanced hepatocyte-specific gene expressions, Galactosylceramidase such as albumin, C3, C4, and APOE. Glycogen storage and urea synthesis were also induced by hexachlorophene. Transplantation of hexachlorophene-induced hepatic cell sheets resulted in significant reduction of serum aminotransferases in group 3, 2, 1 in this order, compared to group 4 on day 4 (P<0. 01, each). Total bilirubin on day 2 was also decreased in group 3, 2 and 1 in this order (P<0. 01, each). Furthermore, survival rate was remarkably improved in group 2 and 3 (P<0. 05). Mitotic and Ki 67-labelled hepatocytes were significantly increased in cell sheets-transplanted mice. RT-PCR analysis showed several human-specific humoral factors such as SCF, HGF, APOE, and C3 were expressed in the graft tissues.

Our aim was to evaluate the efficacy and safety of infliximab and

Our aim was to evaluate the efficacy and safety of infliximab and cyclosporine in this clinical scenario. Methods: A retrospective review of inpatients with severe, steroid-refractory UC, who were admitted to The Royal Melbourne Hospital between January 2003 and December 2013, was conducted. The primary end-point was time to colectomy at 12 months. Secondary end-points were C-Reactive protein (CRP) levels and number of stools/day for the first 7 days of

rescue therapy, time to discharge from initiation of rescue therapy, hospitalization for UC up to 12 months following discharge PF-01367338 cell line and documented adverse events. Results: 28 cases of severe, steroid-refractory UC requiring rescue therapy were analyzed, with 15 cases in the cyclosporine group and 13 cases in the infliximab group. By 12 months, the colectomy

rate was 33% (5/15) for those receiving cyclosporine and 31% (4/13) for those on infliximab (p = 0.871). There was no difference in the number of stools/day and CRP levels between cyclosporine and infliximab over the first 7 days of treatment. Patients receiving infliximab stayed in hospital a median of 4 days less than those on cyclosporine (p = 0.006). 30% (3/10) of cyclosporine-treated patients and 10% (1/10) of infliximab-treated patients were re-hospitalized for UC after successful rescue therapy initially. There were more adverse events associated see more with cyclosporine but this was non-significant (p = 0.136). Conclusion: Infliximab is as safe and effective as cyclosporine in treating severe, steroid-refractory UC. Infliximab leads to a shorter duration of hospital stay after initiation of treatment. Colectomy rates were the same for both drugs at 12 months. 1. Laharie D, Bourreille A, Branche J, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomized controlled trial. Lancet. 2012; 380: 1909–1915. MCS CHOY,1 AC MURPHY,1 AE BLOCH,1 AJ THOMPSON,1 M LUST,1 SJ BROWN,1 EK WRIGHT,1 MA Cyclic nucleotide phosphodiesterase KAMM,1 G ALEX,2 WR CONNELL,1 SJ BELL1 1Department of Gastroenterology,

St Vincent’s Hospital, Melbourne, Australia, 2Department of Gastroenterology, Royal Children’s Hospital, Melbourne, Australia Introduction and Aims: Natural history studies have shown that pediatric-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid disease progression. However, there is little data describing disease activity and clinical outcomes as individuals transition to adult care, a process that can be challenging as patients adopt responsibility for their own care as well as accept changes in care and service provision. We therefore evaluated our experience with transition patients referred to a large tertiary adult IBD clinic over the period 2004–2014.

Because of the danger of developing additional HCC, liver transpl

Because of the danger of developing additional HCC, liver transplantation was proposed, taking into consideration that immunosuppression would increase the risk of other malignancies. By using part of the liver of the find more sister, who already acted as bone marrow donor 13 years earlier, immunosuppression could be avoided. Liver transplantation was performed in 2007 without complication. Five years

after liver transplantation the patient is doing well. This case is twofold special being the first case reporting FA co-occurring with Marfan syndrome and being the first reported case of FA treated for HCC by liver transplantation from a HLA-identical sibling donor without the use of immunosuppression. “
“The human gastrointestinal tract harbors trillions of bacteria, most of which are commensal and have adapted over time to the milieu of the human colon. Their many metabolic interactions

with each other, and with the human host, influence human nutrition and metabolism in diverse ways. Our understanding of these influences has come Small molecule library mw through breakthroughs in the molecular profiling of the phylogeny and the metabolic capacities of the microbiota. The gut microbiota produce a variety of nutrients including short-chain fatty acids, B vitamins, and vitamin K. Because of their ability to interact with receptors on epithelial cells and subepithelial cells, the microbiota also release a number of cellular factors that influence human metabolism. Thus, they have potential

roles in the pathogenesis of metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and cognition, which extend well beyond their traditional contribution to nutrition. This review explores the roles of the gut microbiota in human nutrition and metabolism, and the putative mechanisms underlying these effects. The lumen of the human gastrointestinal tract contains trillions of commensal bacteria that are estimated to outnumber the cells of the human host by a factor of 10. These microbes are, for the most part, obligate or facultative anaerobes that are difficult to cultivate. Our 17-DMAG (Alvespimycin) HCl understanding of the importance of the gut luminal microbiota and their role in human nutrition has greatly expanded in recent years because of the availability of molecular methods to study the gut microbiota.[1] The gene pool of the microbial habitants of the gut is very diverse and considerably larger than the gene pool of the host, and determines a number of metabolic capacities that are necessary for the survival of these organisms in the gut.[1-3] The microbial communities residing in the gut have adapted over time to the milieu of the human intestine and colon, and expectedly, their enzymatic capacities complement each other and that of the human host. Traditionally, the role of the gut bacteria in human metabolism and nutrition was investigated using biochemical tests.

[Conclusions] Patients with

GSD type I showed a growth sp

[Conclusions] Patients with

GSD type I showed a growth spurt after LT or PCS and caught up growth Doxorubicin 2 years later. Although they did not reach at level of Z-score=0, they overcame the general growth pattern of non-operation group in GSD type I. And we are waiting the result about their final height after following a growth period. The annual m-delta Z-score for height before & after PCS or LT in GSD type I Disclosures: The following people have nothing to disclose: YoungRok Choi, Nam-Joon Yi, Jae Sung Ko, Jin Soo Moon, Tae Yoo, Sukwon Suh, Jeong-moo Lee, Kwang-Woong Lee, Kyung-Suk Suh Background: Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5, and graded its severity based on required clinical management. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients. Methods: ISGLS definition of PHLF was retrospectively assessed with 210 consecutive HCC patients who underwent curative hepatectomy at our facility from January 2005 to December 2010. The median follow-up period after

hepatectomy was 35.2 months. Results: Thirty-nine (18.6%) patients fulfilled the ISGLS definition of PHLF. Mortality, hospital stay, and morbidity excluding PHLF increased with higher grades of PHLF (P < .001). Overall survival (OS) rates at 1, 3, and 5 years in patients with/without Bay 11-7085 Idasanutlin datasheet PHLF were 69.1/93.5, 45.1/72.5, 45.1/57.8%, respectively (P = .002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, 15.7/20.3%, respectively (P = .003). Multivariate analysis revealed that PHLF was significantly associated with both OS

(P = .047) and RFS (P = .019). Extent of resection (P < .001), intraoperative blood loss (P = .002), and fibrosis stage (P = .040) were identified as independent risk factors for developing PHLF. Conclusion: The ISGLS definition of PHLF was associated with OS and RFS in HCC patients, and long-term survival will be improved by reducing the incidence of PHLF. Disclosures: The following people have nothing to disclose: Kenji Fukushima, Takumi Fukumoto, Kaori Kuramitsu, Masahiro Kido, Atsushi Takebe, Motofumi Tanaka, Tomoo Itoh, Yonson Ku Adult to adult live donor liver transplantation (LDLT) offers excellent post-LT outcomes and reduces wait-list mortality. However, only a proportion of LT candidates have a potential LD. We hypothesize that potentially modifiable differences exist between LT candidates for whom at least one potential LD steps forward and those for whom not.

[Conclusions] Patients with

GSD type I showed a growth sp

[Conclusions] Patients with

GSD type I showed a growth spurt after LT or PCS and caught up growth selleck products 2 years later. Although they did not reach at level of Z-score=0, they overcame the general growth pattern of non-operation group in GSD type I. And we are waiting the result about their final height after following a growth period. The annual m-delta Z-score for height before & after PCS or LT in GSD type I Disclosures: The following people have nothing to disclose: YoungRok Choi, Nam-Joon Yi, Jae Sung Ko, Jin Soo Moon, Tae Yoo, Sukwon Suh, Jeong-moo Lee, Kwang-Woong Lee, Kyung-Suk Suh Background: Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5, and graded its severity based on required clinical management. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients. Methods: ISGLS definition of PHLF was retrospectively assessed with 210 consecutive HCC patients who underwent curative hepatectomy at our facility from January 2005 to December 2010. The median follow-up period after

hepatectomy was 35.2 months. Results: Thirty-nine (18.6%) patients fulfilled the ISGLS definition of PHLF. Mortality, hospital stay, and morbidity excluding PHLF increased with higher grades of PHLF (P < .001). Overall survival (OS) rates at 1, 3, and 5 years in patients with/without Dichloromethane dehalogenase Selleck RG-7204 PHLF were 69.1/93.5, 45.1/72.5, 45.1/57.8%, respectively (P = .002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, 15.7/20.3%, respectively (P = .003). Multivariate analysis revealed that PHLF was significantly associated with both OS

(P = .047) and RFS (P = .019). Extent of resection (P < .001), intraoperative blood loss (P = .002), and fibrosis stage (P = .040) were identified as independent risk factors for developing PHLF. Conclusion: The ISGLS definition of PHLF was associated with OS and RFS in HCC patients, and long-term survival will be improved by reducing the incidence of PHLF. Disclosures: The following people have nothing to disclose: Kenji Fukushima, Takumi Fukumoto, Kaori Kuramitsu, Masahiro Kido, Atsushi Takebe, Motofumi Tanaka, Tomoo Itoh, Yonson Ku Adult to adult live donor liver transplantation (LDLT) offers excellent post-LT outcomes and reduces wait-list mortality. However, only a proportion of LT candidates have a potential LD. We hypothesize that potentially modifiable differences exist between LT candidates for whom at least one potential LD steps forward and those for whom not.

5 ± 13 days; P = 02696) Surgical liver biopsies were obtained

5 ± 1.3 days; P = 0.2696). Surgical liver biopsies were obtained from morbidly obese patients (n = 13, Table 1) at the time of bariatric surgery and

histological scoring of steatosis evaluated as previously described.[19] Patients were divided into two groups according to steatosis grades, S0 (<5%) and S2 (30%-60%). Animal procedures were conducted in accordance with French government policies (Comité d'éthique COMETH, Authorization Nos. 10-0048 and 11-0068). Female C57BL6/J and BALB/c mice were fed for 17 days with a liquid diet adapted from Lieber-De Carli as described.[14] Female C57BL6/J mice were given a single dose of ethanol (5 g/kg body weight, 20% ethanol) or isocaloric maltodextrin by intragastric gavage. Male C57BL6/J mice were fed for 27 weeks with an HFD in which 60% of calories are derived LY294002 from fat (D12492, Ssniff, Germany), or a normal diet (ND) (11% of calories from fat; 1320, Buparlisib nmr Genestil, France). See the Supporting Materials and Methods for detailed information on experimental designs and methods. Th2-biased BALB/c mice and C57BL6/J mice were subjected to a Lieber-De-Carli-derived alcohol diet.[14] There was no differences either in daily alcohol intake, serum ethanol level (Supporting Table S1), or alcohol metabolism between the two strains,

as attested by similar messenger RNA (mRNA) expression of cytochrome P4502E1, alcohol dehydrogenase, and aldehyde dehydrogenase (not shown). Moreover, livers from both strains of alcohol-fed mice showed negligible signs of inflammatory cell infiltration,

with no increase in hepatic expression of F4/80 and CCR2 mRNA (Fig. 1A; Supporting Fig. S1A), in the number of Gr-1-expressing cells (Fig. S1B), and in the density of F4/80-positive cells (Fig. 2A), thus providing a unique opportunity to study the role of resident macrophages. We next compared the macrophage phenotype of the two strains. Alcohol-fed C57BL6/J mice showed a 3- to 9-fold induction in hepatic M1 genes (inducible nitric oxide synthase [iNOS], tumor necrosis factor alpha [TNFα], and MCP1), whereas M2 markers (Arginase Thalidomide 1 [Arg1], mannose receptor C type 2 [Mrc2], and cluster of differentiation 163 [CD163]) were unchanged or slightly increased (Fig. 1A). In contrast, BALB/c mice showed no change in the hepatic expression of M1 genes in response to alcohol, but displayed a higher hepatic expression of M2 markers, including Arg1, Mrc2, and CD163, both in control and alcohol feeding conditions (Fig. 1A). M1-responsive C57BL6/J mice displayed significant steatosis, hepatocyte apoptosis, and elevation of serum transaminase levels, whereas M2 preponderant BALB/c mice were resistant (Fig. 1B,C). Analysis of pooled data from both strains of alcohol-fed mice further showed an inverse correlation between the ratio of M2/M1 mRNA expression and liver triglyceride levels or serum transaminase (Fig. 1D).