Laboratory Investigation - Table of Contents alert Volume 94 Issue 5

If you are unable to see the message below, click here to view.

TABLE OF CONTENTS Volume 94, Issue 5 (May 2014) In this issue Inside the USCAP Journals Research Articles Also new AOP Sign up for e-alerts Recommend to your library Web feed Subscribe Inside the USCAP Journals Top Inside the USCAP Journals 2014 94: 476-477; 10.1038/labinvest.2014.56 Full Text Research Articles Top HEPATIC AND PANCREATIC SYSTEMS Tapasin modification on the intracellular epitope HBcAg18–27 enhances HBV-specific CTL immune response and inhibits hepatitis B virus replication in vivo Hepatitis-B virus (HBV)-specific cytotoxic T lymphocyte (CTL) activity plays a key role in controlling the outcome of HBV infection. The authors proposed that combining the CTL-stimulatory ability of HBcAg18-27 with the cell-penetrating property of cytoplasmic transduction peptide (CTP) and the chaperone tapasin would elicit a robust and specific HBV immune response. The CTP-HBcAg18-27-Tapasin fusion protein induces an HBV-specific CTL immune response, causes liver inflammatory cell infiltration, and inhibits hepatitis B virus replication through activation of the JAK/STAT signaling pathway. Xiaohua Chen, Yuyan Tang, Yi Zhang, Meng Zhuo, Zhenghao Tang, Yongsheng Yu and Guoqing Zang 2014 94: 478-490; advance online publication, March 10, 2014; 10.1038/labinvest.2014.6 Abstract | Full Text Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation This paper explains the influence of metabolically evoked inflammation (carbohydrate, cholesterol) and non-metabolic inflammatory triggers (LPS, IL1β), on the development of murine nonalcoholic steatohepatitis (NASH). Only the metabolic triggers aggravate steatosis and lead to an infiltration of neutrophils as well as activation of AP-1, a hallmark of lipotoxicity. Furthermore, they induce metabolic risk factors (insulin resistance, dyslipidemia) associated with NASH development in humans, which are not observed for the non-metabolic triggers. Wen Liang, Jan H Lindeman, Aswin L Menke, Debby P Koonen, Martine Morrison, Louis M Havekes, Anita M van den Hoek and Robert Kleemann 2014 94: 491-502; advance online publication, February 24, 2014; 10.1038/labinvest.2014.11 Abstract | Full Text Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling This study examines the relationship between diabetes and nonalcoholic steatohepatitis (NASH). Hyperglycemia induces production of advanced glycation end-products (AGEs). AGEs stimulate hepatic stellate cell (HSC) activation, leading to hepatic fibrosis by inhibition of expression of AGE receptor-1 and induction of expression of receptor for AGEs. The antioxidant curcumin eliminates the effects of AGEs on the divergent regulation of these two receptors in HSC by interrupting the AGEs-caused activation of leptin signaling. Youcai Tang and Anping Chen 2014 94: 503-516; advance online publication, March 10, 2014; 10.1038/labinvest.2014.42 Abstract | Full Text Loss of HNF6 expression correlates with human pancreatic cancer progression Loss of transcription factor HNF6 strongly correlates with pancreatic cancer progression in humans, and mouse models of acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasm formation recapitulate the dynamics of HNF6 expression in human pancreatic cancer progression. These studies suggest that HNF6 acts a tumor suppressor in the pancreas. Kelly R Pekala, Xidi Ma, Peter A Kropp, Christine P Petersen, Courtney W Hudgens, Christine H Chung, Chanjuan Shi, Nipun B Merchant, Anirban Maitra, Anna L Means and Maureen A Gannon 2014 94: 517-527; advance online publication, March 17, 2014; 10.1038/labinvest.2014.47 Abstract | Full Text BLOOD, LYMPHATICS, IMMUNE SYSTEM AND STEM CELLS An aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress the Th17 response in allergic rhinitis patients A predominant Th17 population is a marker of allergic rhinitis (AR). The aryl hydrocarbon receptor (AhR) regulates the differentiation of T lymphocytes and dendritic cells (DCs) after activation by the ligand ITE. ITE induces secretion of IL-10 and inhibits IL-1β and IL-6 production in DCs, and promotes IL-10 production and suppresses IL-17 expression in CD4+T cells, thus inhibiting the Th17-suppression of AR. The AhR-DC-Th17 axis may therefore be an important pathway in the treatment of AR. Ping Wei, Guo-hua Hu, Hou-yong Kang, Hong-bing Yao, Wei Kou, Hong Liu, Cheng Zhang and Su-ling Hong 2014 94: 528-535; advance online publication, February 10, 2014; 10.1038/labinvest.2014.8 Abstract | Full Text Myeloid expression of angiotensin-converting enzyme facilitates myeloid maturation and inhibits the development of myeloid-derived suppressor cells Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that suppress T cell function and the immune response. The authors show that the expression of angiotensin converting enzyme (ACE) inversely correlates with MDSC development. Thus, the finding that ACE expression increases the maturation status of immature MDSCs to cells with a pro-inflammatory phenotype has potential clinical application. Xiao Z Shen, Derick Okwan-Duodu, Wendell-Lamar Blackwell, Frank S Ong, Tea Janjulia, Ellen A Bernstein, Sebastien Fuchs, Serhan Alkan and Kenneth E Bernstein 2014 94: 536-544; advance online publication, March 10, 2014; 10.1038/labinvest.2014.41 Abstract | Full Text GENITOURINARY AND REPRODUCTIVE SYSTEMS Smad3 signaling activates bone marrow-derived fibroblasts in renal fibrosis This paper defines the signaling mechanisms underlying the activation of bone marrow-derived fibroblasts in the kidney following obstructive injury. Loss of Smad3 activity results in fewer bone marrow-derived fibroblasts, less myofibroblast activation, less α-SMA, reduced total collagen deposition, suppressed expression of extracellular matrix proteins, and less severe fibrosis in the affected kidney. Smad3 signaling therefore plays an essential role in the pathogenesis of renal fibrosis. Jiyuan Chen, Yunfeng Xia, Xia Lin, Xin-Hua Feng and Yanlin Wang 2014 94: 545-556; advance online publication, March 10, 2014; 10.1038/labinvest.2014.43 Abstract | Full Text HIF-mediated metabolic switching in bladder outlet obstruction mitigates the relaxing effect of mitochondrial inhibition Urethral obstruction results in growth and fibrosis of the urinary bladder. Previous work demonstrated a role of hypoxia-inducible factor (HIF) in this response. Here the authors demonstrate that HIF activation in obstructed bladder muscle involves mechanisms beyond HIF-1α accumulation, resulting in extensive metabolic adaptation. This upholds bladder contraction when mitochondrial respiration is limited. Mari Ekman, Bengt Uvelius, Sebastian Albinsson and Karl Swärd 2014 94: 557-568; advance online publication, March 3, 2014; 10.1038/labinvest.2014.48 Abstract | Full Text VISUAL AND AUDITORY SYSTEMS Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment This paper describes the mechanism of extracellular histone toxicity in retinal detachment. Histones released from detached retinas modulate the subretinal microenvironment by induction of interleukin-8, which is mediated through the ERK1/2- and p38 MAPK-dependent pathways and toll-like receptor 4. The vitreous body and hyaluronan can protect the retina from these toxic effects by inhibiting diffusion of histones. Hiroki Kawano, Takashi Ito, Shingo Yamada, Teruto Hashiguchi, Ikuro Maruyama, Toshio Hisatomi, Makoto Nakamura and Taiji Sakamoto 2014 94: 569-585; advance online publication, March 10, 2014; 10.1038/labinvest.2014.46 Abstract | Full Text MODELS AND TECHNIQUES Low invasive in vivo tissue sampling for monitoring biomarkers and drugs during surgery The applicability of solid phase microextraction for assessment of graft function in vivo is described in this study. By using biocompatible micro-probes, a wide range of compounds can be extracted/pre-concentrated directly from organs with no tissue damage. Examples of metabolic profiling of lung and liver, and drug metabolism are demonstrated. Barbara Bojko, Krzysztof Gorynski, German A Gomez-Rios, Jan M Knaak, Tiago Machuca, Erasmus Cudjoe, Vinzent N Spetzler, Michael Hsin, Marcelo Cypel, Markus Selzner, Mingyao Liu, Shaf Keshjavee and Janusz Pawliszyn 2014 94: 586-594; advance online publication, March 31, 2014; 10.1038/labinvest.2014.44 Abstract | Full Text Please note that you need to be a subscriber or site-licence holder to enjoy full-text access to Laboratory Investigation. In order to do so, please purchase a subscription. You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/nams/svc/myaccount (You will need to log in to be recognised as a nature.com registrant). For further technical assistance, please contact our registration department. For print subscription enquiries, please contact our subscription department. For other enquiries, please contact our customer feedback department. Nature Publishing Group | 75 Varick Street, 9th Floor | New York | NY 10013-1917 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.