For comparison, HCV from patient sera or chimeric mice was 30%-80

For comparison, HCV from patient sera or chimeric mice was 30%-80% ApoB associated.[4] A third difference between virus produced in tissue culture and virus produced in animal models is its specific infectivity. Virus produced in tissue culture (FL-J6/JFH variant; HCV in cell culture [HCVcc]) has a specific infectivity of approximately 1 TCID50/1,230 genomes, whereas the specific infectivity of virus produced in either mice or chimpanzees was 1 TCID50 per 10-150 viral genomes.[19] We determined specific infectivity of the

two viral variants, expressed buy Tanespimycin as TCID50/RNA copies at various time points (Fig. 7E). The specific infectivity of the JFH-HS increased gradually in the first 21 days, then reached a plateau, whereas the specific infectivity of JFH-FBS did not change. The average specific infectivity of virus produced by cells that were fully differentiated in HS was 1 TCID50 per 236 viral genomes, compared to an average specific infectivity of 1/2513 for JFH-FBS (Fig. 7F). The overall specific infectivity of JFH-HS is now similar to the highest

specific infectivity that was reported previously for HCVcc,[5] corresponding to the small low-density peak in that study. In this study, we investigated the effects of HS on tissue culture of Huh7.5 cells. We compared the standard tissue culture protocol, using media supplemented with 10% FBS, to the use of media supplemented with 2% HS. Cells cultured in HS media undergo rapid growth arrest and show increased expression of hepatocyte

differentiation markers (α1AT and ALB). In HS-supplemented media, the expression of cell-contact EGFR inhibitors list medchemexpress proteins claudin-1, occludin, and e-cadherin was also increased. These factors are indicative of differentiated epithelial cells. Because previous reports have shown that claudin-1 and occludin are entry factors and confer infection of nonpermissive cell types,[20, 21] the increase in claudin-1 and occludin likely plays a role in the increase in viral titers in HS media. The level of expression of other HCV-entry receptors (CD81, SR-B1, and NPC1L1) did not change when Huh7.5 cells were cultured in media with HS. Expression of key lipid metabolism regulators (LXR-α, PPAR-α, and PPAR-γ) was increased, and consistent with this, the lipid droplet content of these cells was highly increased. We showed that VLDL secretion was restored, a complex process that requires the integration of various biogenesis, modification, and transportation steps.[12] All these factors have been implicated in the life cycle of HCV, and, in particular, HCV has been shown to hijack the VLDL secretion machinery for egress.[25] Consistent with this, we have shown that under these new tissue culture conditions, production of JFH-1 increased more than 1,000-fold. The virus produced under these conditions more closely emulates HCV that is found in serum of patients and animal models, was associated with ApoB, had a lower density, and was highly infectious.

For comparison, HCV from patient sera or chimeric mice was 30%-80

For comparison, HCV from patient sera or chimeric mice was 30%-80% ApoB associated.[4] A third difference between virus produced in tissue culture and virus produced in animal models is its specific infectivity. Virus produced in tissue culture (FL-J6/JFH variant; HCV in cell culture [HCVcc]) has a specific infectivity of approximately 1 TCID50/1,230 genomes, whereas the specific infectivity of virus produced in either mice or chimpanzees was 1 TCID50 per 10-150 viral genomes.[19] We determined specific infectivity of the

two viral variants, expressed APO866 as TCID50/RNA copies at various time points (Fig. 7E). The specific infectivity of the JFH-HS increased gradually in the first 21 days, then reached a plateau, whereas the specific infectivity of JFH-FBS did not change. The average specific infectivity of virus produced by cells that were fully differentiated in HS was 1 TCID50 per 236 viral genomes, compared to an average specific infectivity of 1/2513 for JFH-FBS (Fig. 7F). The overall specific infectivity of JFH-HS is now similar to the highest

specific infectivity that was reported previously for HCVcc,[5] corresponding to the small low-density peak in that study. In this study, we investigated the effects of HS on tissue culture of Huh7.5 cells. We compared the standard tissue culture protocol, using media supplemented with 10% FBS, to the use of media supplemented with 2% HS. Cells cultured in HS media undergo rapid growth arrest and show increased expression of hepatocyte

differentiation markers (α1AT and ALB). In HS-supplemented media, the expression of cell-contact selleck screening library medchemexpress proteins claudin-1, occludin, and e-cadherin was also increased. These factors are indicative of differentiated epithelial cells. Because previous reports have shown that claudin-1 and occludin are entry factors and confer infection of nonpermissive cell types,[20, 21] the increase in claudin-1 and occludin likely plays a role in the increase in viral titers in HS media. The level of expression of other HCV-entry receptors (CD81, SR-B1, and NPC1L1) did not change when Huh7.5 cells were cultured in media with HS. Expression of key lipid metabolism regulators (LXR-α, PPAR-α, and PPAR-γ) was increased, and consistent with this, the lipid droplet content of these cells was highly increased. We showed that VLDL secretion was restored, a complex process that requires the integration of various biogenesis, modification, and transportation steps.[12] All these factors have been implicated in the life cycle of HCV, and, in particular, HCV has been shown to hijack the VLDL secretion machinery for egress.[25] Consistent with this, we have shown that under these new tissue culture conditions, production of JFH-1 increased more than 1,000-fold. The virus produced under these conditions more closely emulates HCV that is found in serum of patients and animal models, was associated with ApoB, had a lower density, and was highly infectious.

In SLCO1B3 polymorphism, insertion (ins)/ins, ins/wild, and wild/

In SLCO1B3 polymorphism, insertion (ins)/ins, ins/wild, and wild/wild genotype was present in 2.3%, 20.5%, and 77.3% of the cases, respectively, while in 0.2%, 10.5%, and 89.4% of the controls, respectively. The allele frequency of L1 insertion was 12.5% of the cases, which was significantly greater than the controls

(5.4%, P=0.012, odds ratio 2.5 [95% CI: 1.3-4.9]). The c.1738C>T mutation in SLCO1B1 was not observed in both cases and www.selleckchem.com/products/Deforolimus.html controls. [Conclusions] The genotype of L1 retrotransposon insertion in SLCO1B3 was observed more frequently in Japanese patients with drug-induced cholestasis than controls. As L1 insertion potentially impairs the function of OATP1B3, the individuals with this polymorphism might be predisposed to acquired cholestasis. KPT-330 manufacturer Disclosures: The following people have nothing to disclose: Tatehiro Kagawa, Kazuya Anzai, Kota Tsuruya, Yoshitaka Arase, Shunji Hirose, Koichi Shiraishi, Tetsuya Mine Aim: The performance of single and repeated brush cytology in detecting dysplasia or cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) prior to liver transplantation, and patients’ survival during follow-up was compared to the histopathology of the explanted liver. Methods: All consecutive PSC patients undergoing liver transplantation in Sweden between 1999 and 2013 were evaluated (n=255). Patients

were categorized using histopathology of the explanted liver to determine the presence

of CCA or dysplasia. Sensitivity, specificity, 上海皓元医药股份有限公司 and other measures of test performance were calculated for single and repeated brush cytology, with or without fluorescence in situ hybridization (FISH). Survival after liver transplantation was analyzed using Kaplan-Meier estimate. Results: Brush cytology was done before liver transplantation in 117 of the 225 patients, of whom 65 patients were brushed more than once. The sensitivity and specificity of brush cytology for diagnosing dysplasia or CCA increased from 50% and 81% respectively in patients with one sampling, to 100% and 83% respectively in patients where repeated examinations were performed (table 1). When considering only the subgroup where FISH was also done in addition to brush cytology (n=64), the presence of aneuploidy increased the sensitivity of brush cytology in this subgroup from 83% to 95%, while the finding of only diploid cells increased specificity from 90% to 95%. Survival after liver transplantation was significantly lower in the group with pre-transplantation undiagnosed CCA in the explanted liver p<0.001). Conclusion: In PSC patients, the utilization of repeated brush cytology or the combination with FISH results in increased sensitivity and specificity for the detection of dysplasia or CCA.

Our work demonstrates the utility of these infectious systems for

Our work demonstrates the utility of these infectious systems for studying HBV biology and the virus’ interactions with host hepatocyte genetics and physiology. Disclosures: The following people have nothing to disclose: Robert E. Schwartz, Amir Shlomai, Vyas Ramanan, Ankit Bhatta, Ype P. De Jong, Sangeeta Bhatia, Charles M. Rice “
“The A kinase anchor protein 12 (AKAP12) is a central mediator of protein kinase A and protein

kinase C signaling. Although AKAP12 has been described to act as http://www.selleckchem.com/products/poziotinib-hm781-36b.html a tumor suppressor and its expression is frequently down-regulated in several human malignancies, the underlying molecular mechanisms responsible for the AKAP12 reduction are poorly understood. We therefore analyzed the expression of AKAP12 and its genetic and epigenetic regulatory mechanisms in human hepatocarcinogenesis. Based on tissue microarray analyses (n = 388) and western immunoblotting, we observed Linsitinib ic50 a significant reduction of AKAP12 in cirrhotic

liver (CL), premalignant lesions (DN), and hepatocellular carcinomas (HCCs) compared to histologically normal liver specimens (NL). Analyses of array comparative genomic hybridization data (aCGH) from human HCCs revealed chromosomal losses of AKAP12 in 36% of cases but suggested additional mechanisms underlying the observed reduction of AKAP12 expression in hepatocarcinogenesis. Quantitative methylation analysis by MassARRAY of NL, CL, DN, and HCC tissues, as well as of various tumorigenic and nontumorigenic liver cell lines revealed specific hypermethylation of the AKAP12α promoter but not of the AKAP12β promoter in HCC

specimens and in HCC cell lines. Consequently, restoration experiments performed with 5-aza-2′deoxycytidine drastically increased AKAP12α mRNA MCE levels in a HCC cell line (AKN1) paralleled by AKAP12α promoter demethylation. As hypermethylation is not observed in CL and DN, we investigated microRNA-mediated posttranscriptional regulation as an additional mechanism to explain reduced AKAP12 expression. We found that miR-183 and miR-186 are up-regulated in CL and DN and are able to target AKAP12. Conclusion: In addition to genetic alterations, epigenetic mechanisms are responsible for the reduction of the tumor suppressor gene AKAP12 in human hepatocarcinogenesis. (HEPATOLOGY 2010;.) A kinase anchor proteins (AKAPs) are a diverse group of functionally related scaffolding proteins that target protein kinase A (PKA) and other enzymes, thereby coordinating a range of signaling events.1 Human AKAP12 (synonymous: Gravin/AKAP250) is a large protein up-regulated in contact-inhibited cells and down-regulated by Src, Ras, and PKC.2 Interestingly, AKAP12 is able to modulate both protein kinase A and C, indicating that this protein is involved in the regulation of several signaling pathways. Other effects of AKAP12 are direct sequestration of cyclin D1, inhibition of ERK2 activation, and actin cytoskeleton interaction.

An initial abdominal

sonography showed a well-defined, cy

An initial abdominal

sonography showed a well-defined, cystic-appearance mass lesion with a diameter of 6 cm localized between the portal hilus and the pancreatic head. On contrast-enhanced computed tomography (CT), a well-defined hypodense lesion about 6 cm adjacent to the pancreatic head existed with a mural solid nodular component (Figure 1A). A conventional magnetic resonance imaging (MRI) and a diffusion-weighted MRI (DW-MRI) were performed to determine the nature of the lesion and the relationship between adjacent structures. Contrast-enhanced and diffusion-weighted images revealed a lesion located in the gastroduodenal ligament with enhancing septa and solid mural component with diffusion restriction (Figures 1B–D). BMS-354825 mw The lesion was assumed as malignant according to these imaging features and the patient was prepared for surgery. On histopathologic examination, the tumor was diagnosed as a benign schwannoma (Figure 2). Schwannomas, also known as neurilemmomas, are benign nerogenic tumors that arise from Schwann cells that line the sheaths of peripheral nerves. Schwannomas are commonly located in the soft tissues of the head and neck, extremities, and mediastinum. Although a frequent tumor, schwannomas are seldom found in the abdomen. Intra-abdominal schwannomas are very rare tumors that are difficult to diagnose preoperatively

Silmitasertib cell line with certainty because of the lack of specific radiological features. The main

differential diagnosis of schwannoma in the abdominal cavity should include gastrointestinal stromal tumor (GIST), primary or secondary lymphoma, and adenocarcinoma. Ultrasonography, CTs, and MRIs are effective tools for evaluating the lesions found in the abdomen preoperatively in localization and differentiating diagnoses. A DW-MRI is being increasingly used in the evaluation of benign or malignant states. This kind of MRI measures the rate of microscopic water diffusion in tissues. Tumor cellularity reduces the extracellular matrix and therefore may play a major role in diffusion restriction. In this case, the well-encapsulated cystic mass showed enhancing septa and a solid mural component with diffusion restriction. Thus, the lesion was assumed to be malignant according to these imaging features, but the MCE tumor was diagnosed as a benign schwannoma after a histopathologic examination. However, a DW-MRI provided more information in differentiating the benign or malignant conditions. Misdiagnosis for benign processes as in this case should be taken into account, and thus histopathological verification is often still required because of the importance of excluding malignancies, especially before informing the patient. Contributed by “
“A gastroscopy was performed on a 76 year old lady one year after being diagnosed with celiac disease, due to recurrent gut symptoms, despite full compliance with gluten-free diet.

In this line, our results indicating an oncogenic role of the NRF

In this line, our results indicating an oncogenic role of the NRF2 pathway in preneoplastic lesions should be considered for their possible translational value. Further investigation is warranted to verify NRF2 activation in human preneoplastic stages as well. If so, targeting this pathway would offer new therapeutic options in stages of progression that could dramatically change the evolution of the disease. We thank G. Diaz for support in statistical analysis, M. Angioni and A. Follenzi for generation and characterization of RH

cells, B. Martinoglio for qRT-PCR, and F. Natale for editing the article. CP-673451 nmr Additional Supporting Information may be found in the online version of this article. “
“Background and Aim:  The prevalence of allergic disorders, including asthma, atopic dermatitis, and allergic rhinitis has been increasing, and the prevalence of Helicobacter pylori (H. pylori) infection has been decreasing. Chronic bacterial infection during childhood is reported to protect the development of allergic diseases. The aim of the present study was to identify whether H. pylori infection influences the prevalence of allergic rhinitis, which has become a serious social problem, especially in the developed countries. Methods:  We initially

investigated the association between the prevalence of H. pylori and pollinosis symptoms in 97 healthy volunteers. We had investigated the association between the serum H. pylori–immunoglobulin (Ig) G antibodies and specific IgE antibodies for pollen, mites,

and house dust in 211 consecutive patients. Results:  There were 52.2% (36/69) Smad inhibitor of H. pylori-negative volunteers with allergic symptoms, which was significantly higher than H. pylori-positive volunteers (14.3%, 4/28, P < 0.05). The risk of pollinosis symptoms by H. pylori infection was 0.148 (95% confidence interval): 0.046–0.475, P < 0.05). The prevalence of H. pylori infection increased according to age, whereas that of specific IgE-positive patients gradually decreased. Among the IgE-positive patients, the prevalence of H. pylori-negative patients was significantly higher than H. pylori-positive patients who were younger in age (P < 0.05). Conclusion: H. pylori infection decreased the pollinosis effects, especially among the younger 上海皓元医药股份有限公司 volunteers. However, the prevalence of pollinosis in patients who were 50 years or older were almost same between H. pylori-positive and H. pylori-negative patients; therefore, the recent increase of pollinosis might relate to not only H. pylori infection, but also change in social environment. “
“Histone deacetylases 1 and 2 (HDAC1 and HDAC2) are ubiquitously expressed in tissues, including the liver, and play critical roles in numerous physiopathological processes. Little is known regarding the role of HDAC1 and HDAC2 in liver regeneration.

In this line, our results indicating an oncogenic role of the NRF

In this line, our results indicating an oncogenic role of the NRF2 pathway in preneoplastic lesions should be considered for their possible translational value. Further investigation is warranted to verify NRF2 activation in human preneoplastic stages as well. If so, targeting this pathway would offer new therapeutic options in stages of progression that could dramatically change the evolution of the disease. We thank G. Diaz for support in statistical analysis, M. Angioni and A. Follenzi for generation and characterization of RH

cells, B. Martinoglio for qRT-PCR, and F. Natale for editing the article. Afatinib in vitro Additional Supporting Information may be found in the online version of this article. “
“Background and Aim:  The prevalence of allergic disorders, including asthma, atopic dermatitis, and allergic rhinitis has been increasing, and the prevalence of Helicobacter pylori (H. pylori) infection has been decreasing. Chronic bacterial infection during childhood is reported to protect the development of allergic diseases. The aim of the present study was to identify whether H. pylori infection influences the prevalence of allergic rhinitis, which has become a serious social problem, especially in the developed countries. Methods:  We initially

investigated the association between the prevalence of H. pylori and pollinosis symptoms in 97 healthy volunteers. We had investigated the association between the serum H. pylori–immunoglobulin (Ig) G antibodies and specific IgE antibodies for pollen, mites,

and house dust in 211 consecutive patients. Results:  There were 52.2% (36/69) Autophagy Compound Library price of H. pylori-negative volunteers with allergic symptoms, which was significantly higher than H. pylori-positive volunteers (14.3%, 4/28, P < 0.05). The risk of pollinosis symptoms by H. pylori infection was 0.148 (95% confidence interval): 0.046–0.475, P < 0.05). The prevalence of H. pylori infection increased according to age, whereas that of specific IgE-positive patients gradually decreased. Among the IgE-positive patients, the prevalence of H. pylori-negative patients was significantly higher than H. pylori-positive patients who were younger in age (P < 0.05). Conclusion: H. pylori infection decreased the pollinosis effects, especially among the younger 上海皓元医药股份有限公司 volunteers. However, the prevalence of pollinosis in patients who were 50 years or older were almost same between H. pylori-positive and H. pylori-negative patients; therefore, the recent increase of pollinosis might relate to not only H. pylori infection, but also change in social environment. “
“Histone deacetylases 1 and 2 (HDAC1 and HDAC2) are ubiquitously expressed in tissues, including the liver, and play critical roles in numerous physiopathological processes. Little is known regarding the role of HDAC1 and HDAC2 in liver regeneration.

In this line, our results indicating an oncogenic role of the NRF

In this line, our results indicating an oncogenic role of the NRF2 pathway in preneoplastic lesions should be considered for their possible translational value. Further investigation is warranted to verify NRF2 activation in human preneoplastic stages as well. If so, targeting this pathway would offer new therapeutic options in stages of progression that could dramatically change the evolution of the disease. We thank G. Diaz for support in statistical analysis, M. Angioni and A. Follenzi for generation and characterization of RH

cells, B. Martinoglio for qRT-PCR, and F. Natale for editing the article. learn more Additional Supporting Information may be found in the online version of this article. “
“Background and Aim:  The prevalence of allergic disorders, including asthma, atopic dermatitis, and allergic rhinitis has been increasing, and the prevalence of Helicobacter pylori (H. pylori) infection has been decreasing. Chronic bacterial infection during childhood is reported to protect the development of allergic diseases. The aim of the present study was to identify whether H. pylori infection influences the prevalence of allergic rhinitis, which has become a serious social problem, especially in the developed countries. Methods:  We initially

investigated the association between the prevalence of H. pylori and pollinosis symptoms in 97 healthy volunteers. We had investigated the association between the serum H. pylori–immunoglobulin (Ig) G antibodies and specific IgE antibodies for pollen, mites,

and house dust in 211 consecutive patients. Results:  There were 52.2% (36/69) selleck chemicals of H. pylori-negative volunteers with allergic symptoms, which was significantly higher than H. pylori-positive volunteers (14.3%, 4/28, P < 0.05). The risk of pollinosis symptoms by H. pylori infection was 0.148 (95% confidence interval): 0.046–0.475, P < 0.05). The prevalence of H. pylori infection increased according to age, whereas that of specific IgE-positive patients gradually decreased. Among the IgE-positive patients, the prevalence of H. pylori-negative patients was significantly higher than H. pylori-positive patients who were younger in age (P < 0.05). Conclusion: H. pylori infection decreased the pollinosis effects, especially among the younger 上海皓元医药股份有限公司 volunteers. However, the prevalence of pollinosis in patients who were 50 years or older were almost same between H. pylori-positive and H. pylori-negative patients; therefore, the recent increase of pollinosis might relate to not only H. pylori infection, but also change in social environment. “
“Histone deacetylases 1 and 2 (HDAC1 and HDAC2) are ubiquitously expressed in tissues, including the liver, and play critical roles in numerous physiopathological processes. Little is known regarding the role of HDAC1 and HDAC2 in liver regeneration.

These findings have important implications for screening non–inje

These findings have important implications for screening non–injection drug users in the United States, particularly since the prevalence of tattooing is on the rise and intravenous drug use is on the decline. The prevalence of tattoos in the United States has been increasing during the past decade, particularly among youths.22-25 Although little is known about the prevalence of body art among minority adolescents, one study of African American and Hispanic students from an inner city high school in Texas found that 10% of the African American students already had a tattoo by graduation, a rate that

is comparable to prior studies that evaluated predominantly white college students.26 A 2004 study among persons aged 18 to 50 years Rapamycin concentration in the United States found that 24% of respondents had at

least one tattoo, and an additional 21% of nontattooed respondents had considered tattoo placement.23 Tattooing is more common among those of low socioeconomic status23 despite its increased prevalence across all social groups, and it is also highly prevalent among soldiers. In one study, almost 36% of soldiers in the US Army had at least one tattoo, and 76% experienced bleeding after the procedure, which might promote transmission of blood-borne infections.27 The literature assessing the association between tattooing and HCV has heretofore been equivocal. Because of the wide variability of study 上海皓元 populations with regard to baseline risk of HCV exposure, previous work has been

risk-stratified by general population, blood donors, high-risk groups BAY 73-4506 mw (i.e., drug users, homeless persons, sex workers, and patients in sexually transmitted disease clinics), prisoners, and veterans. Although studies that recruited >1,000 veterans found an almost three-fold higher risk of HCV infection among veterans with a tattoo compared with those who did not have a tattoo,28-30 results from cross-sectional studies involving the general public, blood donors, and other high-risk groups have been inconsistent.21 A recent review article of the best available data on the risk of HCV infection from tattoo exposure found that most studies relied on descriptive statistics alone and failed to report measures of association, such as ORs and relative risk. In fact, meta-analysis of the existing literature was deferred because several of the studies that found no association between HCV infection and tattooing in the univariate analysis either did not include those exposures in the multivariate analysis or did not report the adjusted OR.21 Furthermore, few case-controlled studies completely excluded injection drug users and blood transfusion recipients.21 Our study confirms the association between tattoo exposure and hepatitis C infection in a very large ethnically diverse population of HCV cases and uninfected controls.

The value of the GWAS approach has been questioned recently, with

The value of the GWAS approach has been questioned recently, with the argument put forward that it “flatters to deceive” and fails to deliver the anticipated paradigm shift in disease understanding.8 In

this sense, therefore, PBC represents a triumph for GWASs because the PBC studies are likely to turn out to be landmarks in our understanding of the disease. It is also likely that the findings will translate into new approaches to therapy sooner than GWAS findings typically do, with modulation of the IL-12 pathway representing one obvious potential approach. The findings of these studies also, however, suggest that PBC may be not only an important disease to study in its own right but also an important paradigm for our understanding of immune regulation in humans as a result of its homogeneity and the diagnostic accuracy. It is often forgotten that PBC was a landmark disease GSK-3 assay in the study of autoimmunity and represented one of the first disease settings in which autoantibodies were described and in which the autoantigens associated with human disease were identified.19-21 We may now

be at the point at which PBC returns to the forefront of the study of the mechanistic immunobiology of autoimmunity. These are interesting times. “
“Over our term as editors for HEPATOLOGY, we have published over 1,645 original research articles as well as 160 reviews and meeting proceedings. These publications were cited over 32,000 上海皓元 times, and over 5.2 million downloads occurred. We are grateful

to our authors, reviewers, and, especially Rapamycin from my perspective, to our associate editors. The associate editors were comprised of a remarkable group of physician scientists. All of our associate editors, with the exception of Dr. Margaret Koziel, who was replaced by Dr. David Nelson, remained in this position for the entire term. During our tenure, this group of individuals undertook several professional moves, all for promotions, yet managed to maintain their excellent, timely overview of the flow of papers to and through the journal. During our term, we were privileged to be involved with a rapid evolution in discoveries regarding liver disease. We saw the emergence, in this journal, of descriptions of targeted therapy for hepatocellular cancer, the introduction of new treatments for hepatitis B and C, and new treatments for the complications of cirrhosis. We also saw more individualized medicine in hepatology with tests for interleukin-28B for interferon response and PNPLA3 for nonalcoholic fatty liver disease and hepatic fibrosis after liver transplant, as well as the rapid development of applications in the field of stem cell biology to liver disease. The introduction of Comments From the Editors, suggested by Dr. Greg Gores, and Master’s Perspective, suggested by Dr. Saul Karpen, were new additions to the journal, but also ones for which we received many favorable comments.