bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocyte Polarization Is Essential for the Productive Entry of the Hepatitis B Virus
Authors: Schulze Andreas , Mills Kerry , Weiss Thomas S. , Urban Stephan 
Published: September 2011

Abstract

Human hepatitis B virus (HBV) is characterized by a high species specificity and a distinct liver tropism. Within the liver, HBV replication occurs in differentiated and polarized hepatocytes. Accordingly, the

in vitro

HBV infection of primary human hepatocytes (PHHs) and the human hepatoma cell line, HepaRG, is restricted to differentiated, hepatocyte-like cells. Though preparations of PHH contain up to 100% hepatic cells, cultures of differentiated HepaRG cells are a mixture of hepatocyte-like and biliary-like epithelial cells. We used PHH and HepaRG cells and compared the influence of virus inoculation dose, cell differentiation, and polarization on productive HBV infection. At multiplicities of genome equivalents (mge) >8,000, almost 100% of PHHs could be infected. In contrast, only a subset of HepaRG cells stained positive for HBcAg at comparable or even higher mge. Infection predominantly occurred at the edges of islands of hepatocyte-like HepaRG cells. This indicates a limited accessibility of the HBV receptor, possibly as a result of its polar sorting. Multidrug resistance protein 2 (MRP2), a marker selectively transported to the apical (i.e., canalicular) cell membrane, revealed two polarization phenotypes of HepaRG cells. HBV infection within the islands of hepatocyte-like HepaRG cells preferentially occurred in cells that resemble PHH, exhibiting canalicular structures. However, disruption of cell-cell junctions allowed the additional infection of cells that do not display a PHH-like polarization.

Conclusion:

HBV enters hepatocytes via the basolateral membrane. This model, at least partially, explains the difference of PHH and HepaRG cells in infection efficacy, provides insights into natural HBV infection, and establishes a basis for optimization of the HepaRG infection system. (Hepatology 2012)
Induction of Heme Oxygenase 1 Prevents Progression of Liver Fibrosis in Mdr2 Knockout Mice
Authors: Barikbin Roja , Neureiter Daniel , Wirth Jan , Erhardt Annette , Schwinge Dorothee , Kluwe Johannes , Schramm Christoph , Tiegs Gisa , Sass Gabriele 
Published: September 2011

Abstract

Induction or overexpression of the heme-degrading enzyme, heme oxygenase 1 (HO-1), has been shown to protect mice from liver damage induced by acute inflammation. We have investigated the effects of HO-1 induction in a mouse model of chronic liver inflammation and fibrogenesis with progression to hepatocellular carcinoma (HCC) (Mdr2ko; FVB.129P2-Abcb4tm1Bor). HO-1 was induced in vivo by treatment with cobalt protoporphyrin IX, starting at week 5 or 12 of mice lifespan, and continued for 7 weeks. Our results showed that HO-1 induction reduced liver damage and chronic inflammation by regulating immune cell infiltration or proliferation as well as tumor necrosis factor receptor signaling. Fibrosis progression was significantly reduced by HO-1 induction in mice with mild, as well as established, portal and lobular fibrosis. HO-1 induction significantly suppressed hepatic stellate cell activation. During established fibrosis, HO-1 induction was able to revert portal inflammation and fibrosis below levels observed at the start of treatment. Moreover, hepatocellular proliferation and signs of dysplasia were decreased after HO-1 induction.

Conclusion:

Induction of HO-1 interferes with chronic inflammation and fibrogenesis and, in consequence, might delay progression to HCC. (Hepatology 2012;)
Extrinsic and local glutamatergic inputs of the rat hippocampal CA1 area differentially innervate pyramidal cells and interneurons
Authors: Takács Virág T. , Klausberger Thomas , Somogyi Peter , Freund Tamás F. , Gulyás Attila I. 
Published: September 2011

AbstractThe two main glutamatergic pathways to the CA1 area, the Schaffer collateral/commissural input and the entorhinal fibers, as well as the local axons of CA1 pyramidal cells innervate both pyramidal cells and interneurons. To determine whether these inputs differ in their weights of activating GABAergic circuits, we have studied the relative proportion of pyramidal cells and interneurons among their postsynaptic targets in serial electron microscopic sections. Local axons of CA1 pyramidal cells, intracellularly labeled in vitro or in vivo, innervated a relatively high proportion of interneuronal postsynaptic targets (65.9 and 53.8%, in vitro and in vivo, respectively) in stratum (str.) oriens and alveus. In contrast, axons of in vitro labeled CA3 pyramidal cells in str. oriens and str. radiatum of the CA1 area made synaptic junctions predominantly with pyramidal cell spines (92.9%). The postsynaptic targets of anterogradely labeled medial entorhinal cortical boutons in CA1 str. lacunosum‐moleculare were primarily pyramidal neuron dendritic spines and shafts (90.8%). The alvear group of the entorhinal afferents, traversing str. oriens, str. pyramidale, and str. radiatum showed a higher preference for innervating GABAergic cells (21.3%), particularly in str. oriens/alveus. These data demonstrate that different glutamatergic pathways innervate CA1 GABAergic cells to different extents. The results suggest that the numerically smaller CA1 local axonal inputs together with the alvear part of the entorhinal input preferentially act on GABAergic interneurons in contrast to the CA3, or the entorhinal input in str. lacunosum‐moleculare. The results highlight differences in the postsynaptic target selection of the feed‐forward versus recurrent glutamatergic inputs to the CA1 and CA3 areas. © 2011 Wiley Periodicals, Inc.
Sex differences in sleep after a single oral morning dose of olanzapine in healthy volunteers
Authors: Giménez Sandra , Romero Sergio , Gich Ignasi , Clos Susana , Grasa Eva , Rosa‐María Antonijoan , Barbanoj Manuel‐José 
Published: September 2011

ObjectivePolysomnography abnormalities are frequent in schizophrenia and have been correlated with clinical variables. Because women with schizophrenia present a general better clinical outcome than men, we aimed to determine whether sex differences in antipsychotic‐induced effects on sleep could contribute to this difference.MethodsSingle oral morning doses of olanzapine (5 mg) were administered to 10 men and 10 women. Sleep variables were evaluated using traditional polysomnography Rechstschaffen and Kales criteria and all‐night sleep electroencephalogram spectral analysis. Drug plasma concentrations were also measured.ResultsSignificant sex‐by‐drug interactions were obtained in slow‐wave sleep. After olanzapine, women showed an increase in slow‐wave sleep, whereas men showed a decrease. We did not observe sex differences in olanzapine‐induced hypnotic effects. Neither did we find any significant differences in pharmacokinetic parameters between sexes. Significant sex effects were observed in deep sleep, with women showing longer periods than men.ConclusionOur results showed significant pharmacodynamic differences in olanzapine sleep effects between men and women. Further studies in clinical populations are needed to assess if these sex‐based differences suggest that optimal treatment and doses should differ between men and women. Copyright © 2011 John Wiley & Sons, Ltd.
Rapid nutrient load reduction during infiltration of managed aquifer recharge in an agricultural groundwater basin: Pajaro Valley, California
Authors: Schmidt C. M. , Fisher A. T. , Racz A. , Wheat C. G. , Los Huertos M. , Lockwood B. 
Published: September 2011

AbstractArtificial recharge of groundwater is an increasingly important method for augmenting groundwater supply and can have a positive or negative influence on the quality of water resources. We instrumented a managed aquifer recharge (MAR) pond in central coastal California to assess how patterns of infiltration and recharge affect the load of nitrate delivered to the underlying aquifer. The concentration of nitrate in infiltrating water consistently decreased during passage through the first metre of subsurface soils. Enrichment of 18O and 15 N in the residual nitrate in infiltrating water proceeded in a ratio of 1:2, indicating that denitrification plays a significant role in the quantitative reduction of nutrients exported during infiltration through shallow soils. The extent and rate of nitrate removal was spatially and temporally variable across the bottom of the recharge pond, with 30% to 60% of the nitrate load being removed over the first 6 weeks of managed aquifer recharge operation. During the period of highest N loading to the system, when the average infiltration rate was > 1 m/day, the recharge pond achieved a load reduction efficiency of 7 kg NO3−‐N/day/ha, which compares favourably to nitrate load reductions achieved by treatment wetlands. Groundwater mounding and water composition below the recharge pond suggest that recharge and subsequent lateral transport occur heterogeneously in the underlying aquifer. Nitrate concentrations in the aquifer following infiltration were lowered primarily by dilution, with little evidence for additional denitrification occurring in the aquifer in comparison to high rates documented during shallow infiltration. Copyright © 2011 John Wiley & Sons, Ltd.
A novel treatment strategy for EGFR mutant NSCLC with T790M‐mediated acquired resistance
Authors: Taube Erika , Jokinen Elina , Koivunen Peppi , Koivunen Jussi P. 
Published: September 2011

AbstractThe purpose of our study was to identify novel kinase inhibitors for the treatment of genetic subsets of non‐small cell lung cancer (NSCLC). NSCLC cell lines (n = 8) with known oncogenic backgrounds (K‐Ras, EGFR and EML4‐ALK) were exposed to several kinase inhibitors and analyzed for cell growth/cytotoxicity and signaling. Gö6976, a classical protein kinase C inhibitor, showed high potency against mutated EGFR and was further validated in vitro using additional NSCLC lines (n = 4) and Ba/F3 models and in vivo using a xenograft model. Gö6976 was identified to be a potent inhibitor of mutated EGFR with IC50 values from 0.033 nM to 3.3 μM and down regulating phosphorylation of EGFR, AKT and ERK1/2 at concentrations in the range of the IC50 values. Gö6976 has only a minor effect on wild‐type EGFR and cell lines independent of signaling from the mutant EGFR. Most importantly, the activity of Gö6976 remains unchanged despite the presence of the T790M‐mediated resistance, and it prevents the occurrence of this resistance in vitro. Gö6976 was also shown to significantly reduce tumor growth in an in vivo xenograft model with a EGFR‐mutated NSCLC cell line containing T790M. These findings demonstrate that Gö6976 acts as a potent inhibitor of mutant EGFR despite the presence of T790M, the most important mechanism of acquired resistance for EGFR tyrosine kinase inhibitors, in both in vitro and in vivo models.
Global microRNA expression profiling of microdissected tissues identifies miR‐135b as a novel biomarker for pancreatic ductal adenocarcinoma
Authors: Munding Johanna B. , Adai Alex T. , Maghnouj Abdelouahid , Urbanik Aleksandra , Zöllner Hannah , Liffers Sven T. , Chromik Ansgar M. , Uhl Waldemar , Szafranska‐Schwarzbach Anna E. , Tannapfel Andrea , Hahn Stephan A. 
Published: September 2011

AbstractPancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis resulting from being diagnosed at an advanced stage. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed. MicroRNAs (miRNAs), considered a new class of biomarkers and therapeutic targets, may be able to fulfill those needs. Combining tissue microdissection with global miRNA array analyses, cell type‐specific miRNA expression profiles were generated for normal pancreatic ductal cells, acinar cells, PDAC cells derived from xenografts and also from macrodissected chronic pancreatitis (CP) tissues. We identified 78 miRNAs differentially expressed between ND and PDAC cells providing new insights into the miRNA‐driven pathophysiological mechanisms involved in PDAC development. Having filtered miRNAs which are upregulated in the three pairwise comparisons of PDAC vs. ND, PDAC vs. AZ and PDAC vs. CP, we identified 15 miRNA biomarker candidates including miR‐135b. Using relative qRT‐PCR to measure miR‐135b normalized to miR‐24 in 75 FFPE specimens (42 PDAC and 33 CP) covering a broad range of tumor content, we discriminated CP from PDAC with a sensitivity and specificity of 92.9% [95% CI=(80.5, 98.5)] and 93.4% [95% CI=(79.8, 99.3)], respectively. Furthermore, the area under the curve (AUC) value reached of 0.97 was accompanied by positive and negative predictive values of 95% and 91%, respectively. In conclusion, we report pancreatic cell‐specific global miRNA profiles, which offer new candidate miRNAs to be exploited for functional studies in PDAC. Furthermore, we provide evidence that miRNAs are well‐suited analytes for development of sensitive and specific aid‐in‐diagnosis tests for PDAC.
The effect of storage medium on the elution of monomers from composite materials
Authors: Polydorou Olga , Huberty Catherine , Wolkewitz Martin , Bolek Richard , Hellwig Elmar , Kümmerer Klaus 
Published: September 2011

AbstractThe aim of this study was to evaluate the effect of four different storage media on the elution of monomers from two composite materials. Samples (n = 10, diameter: 4.5 mm, thickness: 2 mm) of two different composite materials (Ceram X™ & Filtek™ Supreme XT) were stored after polymerization in four different media (NaCl, saliva, ethanol 75% & acetone) for 24 h, 7 days, and 28 days. From the storage medium of each tested time period, samples were prepared and analyzed by LC‐MS/MS, for the elution of BisGMA, TEGDMA, HEMA, Bisphenol A, and two types of UDMA. No monomers were detected in the samples of Ceram X™, independently of the storage medium used. In the samples of Filtek™ Supreme XT, no Bisphenol A, HEMA, and UDMA 1 were found. BisGMA was detected only in the ethanol and acetone samples. The amount of BisGMA eluted in acetone was significant higher compared with ethanol 75% (p < 0.0001). TEGDMA was the only monomer that could be detected in all tested storage media. Storage in acetone resulted in higher release of TEGDMA when compared with other media. The amount of TEGDMA released in saliva was similar to the one released in ethanol 75%. It can be concluded that acetone is not a suitable medium for elution experiments and although ethanol 75% can simulate saliva concerning the elution of TEGDMA, it does not represent a laboratory substitute of saliva with respect to the elution of monomers like BisGMA. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Higher premenarcheal bone mass in elite gymnasts is maintained into young adulthood after long-term retirement from sport: A 14-year follow-up
Authors: Erlandson Marta C , Kontulainen Saija A , Chilibeck Phil D , Arnold Cathy M , Faulkner Robert A , Baxter-Jones Adam DG 
Published: September 2011

Abstract
Sports that impact-load the skeleton during childhood and adolescence increase determinants of bone strength such as bone mineral content and density; however, it is unclear if this benefit is maintained after retirement from the sport. The purpose of this study was to assess whether the previously reported higher bone mass in a group of premenarcheal gymnasts was still apparent 10 years after the cessation of participation and withdrawal of the gymnastics loading stimulus. In 1995, 30 gymnasts 8 to 15 years of age were measured and compared with 30 age-matched nongymnasts. Twenty-five former gymnasts and 22 nongymnasts were measured again 14 years later (2009 to 2010). Gymnasts had been retired from gymnastics training and competition for an average of 10 years. Total body (TB), lumbar spine (LS), and femoral neck (FN) bone mineral content (BMC) was assessed at both measurement occasions by dual-energy X-ray absorptiometry (DXA). Multivariate analysis of covariance (MANCOVA) was used to compare former gymnasts' and nongymnasts' BMC while controlling for differences in body size and maturation (covariates: age, height, weight, and years from menarche [1995] or age at menarche [2009 to 2010]). Premenarcheal gymnasts (measured in 1995) had significantly greater size-adjusted TB, LS, and FN BMC (p &lt; 0.05) (15%, 17%, and 12%, respectively) than nongymnasts. Ten years after retirement, gymnasts had maintained similar size-adjusted TB, LS, and FN BMC differences (p &lt; 0.05) (13%, 19%, and 13%, respectively) when compared with nongymnasts. Bone mass benefits in premenarcheal gymnasts were still apparent even after long-term (10 years) removal of the gymnastics loading stimulus. © 2012 American Society for Bone and Mineral Research
Subtrochanteric/femoral shaft Versus hip fractures: Incidences and identification of risk factors
Authors: Maravic Milka , Ostertag Agnès , Cohen-Solal Martine 
Published: September 2011

Abstract
Subtrochanteric and femoral shaft (ST/FS) fractures are now considered to be fragility fractures in osteoporotic patients. Although rare, there is growing evidence of the burden that they constitute. Little is known about the change over time in incidence of ST/FS fractures. We assessed the incidence of ST/FS fractures and the associated risk factors from 2002 to 2009 compared with those of hip fractures. Data were obtained from the French National Database, which includes all hospital discharge codes from acute care facilities. Hospitalizations for primary surgical management of neck/trochanteric (hip) and ST/FS fractures in patients aged above 50 years were selected and described for different age groups. Incidences per million populations were calculated using the estimated French population adjusted for each year, age, and gender. We studied the change for each fracture site. The comorbidity factors related to these fractures were assessed in 2009 using multivariate logistic regression. From 2002 to 2009, the adjusted incidence of hip fractures decreased continuously from 4368 to 3662 in women (p &lt; 0.0001), and a mild increase from 1476 to 1384 in men (p &lt; 0.0001) after an initial decrease. In contrast, the incidence of ST/FS increased significantly in both genders (from 353 to 395 in women, from 146 to 159 in men). In 2009, the incidence of ST/FS in the general population remained low, reaching the levels of 412 in women and 168 in men, but were 2966 and 1461 in women and men aged &gt;89 years. The adjusted risk of having a ST/FS fracture was significantly higher in a context of obesity (odds ratio [OR]: 2.26; 1.95–2.61) and dementia (OR: 1.23; 1.16–1.30), but decreased with age (OR: 0.83; 0.79–0.88) and hypertension (OR: 0.90; 0.86–0.95). In conclusion, ST/FS fractures mainly affect elderly people and incidence increased significantly from 2002 to 2009. Obesity and dementia are the risk factors associated with these rare fractures, compared with regular hip fractures. © 2012 American Society for Bone and Mineral Research
Atorvastatin suppresses inflammatory response induced by oxLDL through inhibition of ERK phosphorylation, IκBα degradation, and COX‐2 expression in murine macrophages
Authors: Shao Qin , Shen Ling‐Hong , Hu Liu‐Hua , Pu Jun , Jing Qing , He Ben 
Published: September 2011

AbstractMacrophages crosstalk with oxidized low‐density lipoprotein (oxLDL), play a critical role in the initiation, progression, and subsequently stability of atherosclerotic plaques. Statins, inhibitors of HMG CoA (3‐hydroxy‐3‐methylglutaryl coenzyme A) reductase, reduce the expression of inflammatory proteins in addition to their lipid‐lowering action. However, the effect and detailed anti‐inflammation mechanisms of statins in macrophages induced by oxLDL remain unclearly. In the present study, we investigated the effect of atorvastatin on inflammatory response upon oxLDL stimulation in murine macrophages and analyzed the underlying mechanisms. Tumor necrosis factor (TNF)α and monocyte chemoattractant protein‐1 (MCP‐1) mRNA levels were assayed by real‐time PCR. The expression of cyclooxygenases‐2 (COX‐2) was detected by real‐time PCR and Western blotting. While mitogen‐activated protein kinase (MAPK) phosphorylation and IκBα degradation were determined by Western blotting. Our results showed that exposure of RAW264.7 cells to oxLDL, substantially changed the morphology of the cells and increased TNFα and MCP‐1 secretion. While pretreatment with atorvastatin resulted in a significant inhibition of oxLDL‐induced morphological alteration and inflammatory cytokines expression in a dose‐dependent fashion. Further investigation of the molecular mechanism revealed that oxLDL upregulated the transcription and protein expression of COX‐2 in a time‐dependent manner. Whereas, pretreatment with atorvastatin suppressed COX‐2 expression, MAPK activation and IκBα degradation. Thus, we conclude that the anti‐inflammatory effect of atorvastatin is mediated through the inhibition of proinflammatory COX‐2. Furthermore, suppression of ERK phosphorylation and IκBα degradation is involved in this regulation. Our findings provide a novel evidence that statins suppress inflammatory response, exert its anti‐atherogenic actions via against inflammation beyond cholesterol‐lowing effect. J. Cell. Biochem. 113: 611–618, 2012. © 2011 Wiley Periodicals, Inc.
A Simple and economical route to generate functional hepatocyte‐like cells from hESCs and their application in evaluating alcohol induced liver damage
Authors: Pal Rajarshi , Mamidi Murali Krishna , Das Anjan Kumar , Gupta Pawan Kumar , Bhonde Ramesh 
Published: September 2011

AbstractThe in vitro derived hepatocytes from human embryonic stem cells (hESC) is a promising tool to acquire improved knowledge of the cellular and molecular events underlying early human liver development under physiological and pathological conditions. Here we report a simple two‐step protocol employing conditioned medium (CM) from human hepatocellular carcinoma cell line, HepG2 to generate functional hepatocyte‐like cells from hESC. Immunocytochemistry, flow cytometry, quantitative RT‐PCR, and biochemical analyses revealed that the endodermal progenitors appeared as pockets in culture, and the cascade of genes associated with the formation of definitive endoderm (HNF‐3β, SOX‐17, DLX‐5, CXCR4) was consistent and in concurrence with the up‐regulation of the markers for hepatic progenitors [alpha‐feto protein (AFP), HNF‐4α, CK‐19, albumin, alpha‐1‐antitrypsin (AAT)], followed by maturation into functional hepatocytes [tyrosine transferase (TAT), tryptophan‐2, 3‐dioxygenase (TDO), glucose 6‐phosphate (G6P), CYP3A4, CYP7A1]. We witnessed that the gene expression profile during this differentiation process recapitulated in vivo liver development demonstrating a gradual down‐regulation of extra embryonic endodermal markers (SOX‐7, HNF‐1β, SNAIL‐1, LAMININ‐1, CDX2), and the generated hepatic cells performed multiple liver functions. Since prenatal alcohol exposure is known to provoke irreversible abnormalities in the fetal cells and developing tissues, we exposed in vitro generated hepatocytes to ethanol (EtOH) and found that EtOH treatment not only impairs the survival and proliferation, but also induces apoptosis and perturbs differentiation of progenitor cells into hepatocytes. This disruption was accompanied by alterations in the expression of genes and proteins involved in hepatogenesis. Our results provide new insights into the wider range of destruction caused by alcohol on the dynamic process of liver organogenesis. J. Cell. Biochem. 113: 19–30, 2012. © 2011 Wiley Periodicals, Inc.