bluuebunny/crossref_metadata_2025 huggingface dataset:
Geochemical and ecotoxicological assessment of iron- and steel-making slags for potential use in environmental applications
Authors: Wendling Laura A. , Binet Monique T. , Yuan Zheng , Gissi Francesca , Koppel Darren J. , Adams Merrin S.
Published: August 2013

Prior to the productive use of iron- and steel-making slags as environmental amendments, a risk assessment supported by material characterization concomitant with leaching and ecotoxicological testing is necessary. Five iron- and steel-making slags were characterized geochemically, and the leachability of their elemental constituents was assessed. The toxicity of slag leachate to microalgae (Chlorella sp.), cladocerans (Ceriodaphnia dubia), and bacteria (Vibrio fischeri) was related to elemental composition. Slag leachates with the highest concentrations of dissolved elements were the most toxic (10% effective concentration [EC10] ∼1%), whereas those with the lowest concentrations of elements were the least toxic (EC10 63–85%). It was not possible to determine which elements caused the observed toxicity; however, comparisons with contaminant guidelines and published toxicity data identified several elements of potential environmental concern. Low to moderate activities were measured for radionuclides in the U and Th decay chains in slags. Based on these data, some of the slags examined herein are potentially suitable for use as environmental amendments following ≥10 times dilution to ameliorate potential toxic effects because of leachate pH. Environ Toxicol Chem 2013;32:2602–2610. © 2013 SETAC
Post‐depositional processes: What really happens to new atmospheric iron in the ocean's surface?
Authors: Bressac Matthieu , Guieu Cécile
Published: August 2013

Abiotic iron removal processes such as scavenging can significantly and rapidly modify iron distribution in the dissolved‐colloidal‐particulate continuum. Therefore, these processes could be considered, in addition to ligand complexation, as a major control on atmospheric iron dissolution in seawater. In this work, we investigated the seasonal abiotic processes occurring once dust deposited on surface seawater using a series of artificial seeding experiments (allowing us to take into consideration the settling of particles on a 1 m depth layer). Here, we demonstrate that atmospheric dissolved iron concentration ([DFe]) is driven by the processes governed by the dissolved organic matter (DOM) pool. Following artificial dust seeding, an order magnitude range increase in the [DFe] (12 – 181 nmol L−1) was observed depending on the season. Under high and fresh DOM conditions (spring and summer), the rapid formation of aggregates induced a negative feedback on the [DFe] through scavenging, while a fraction of the DFe was likely organically complexed. In contrast, in low‐DOM surface waters (winter), aggregation was not observed, allowing a very large transient increase in [DFe] (181 nmol L−1) before being removed by adsorption onto settling particles. A key result of the findings is that depending on the age and quantity of DOM, the “lithogenic carbon pump” is likely a major pathway for organic carbon export. Modeling studies should therefore relate both atmospheric iron dissolution in seawater and the intensity of the subsequent biological response, to the age and quantity of DOM.
Late‐interseismic state of a continental plate‐bounding fault: Petrophysical results from DFDP‐1 wireline logging and core analysis, Alpine Fault, New Zealand
Authors: Townend J. , Sutherland R. , Toy V. G. , Eccles J. D. , Boulton C. , Cox S. C. , McNamara D.
Published: August 2013

We present a geophysical characterization at 0.1–100 m scales of a major plate‐bounding continental fault in a late‐interseismic state. The Alpine Fault produces MW∼8 earthquakes every 200–400 years and last ruptured in 1717 AD. Wireline geophysical logs and rock cores extending from one side of the Alpine Fault to the other were acquired in two boreholes drilled in 2011 at Gaunt Creek during the first phase of the Deep Fault Drilling Project (DFDP‐1). These data document ambient conditions under which the next Alpine Fault earthquake will occur. Principal component analysis of the wireline logging data reveals that >80% of the variance is accounted for by electrical, acoustic, and natural gamma properties, and preliminary multivariate classification enables the lithologies of sections of missing core to be reconstructed from geophysical measurements. The fault zone exhibits systematic variations in properties consistent with common processes of progressive alteration and comminution near the principal slip zone, superimposed on different protolith compositions. Our observations imply that the fault zone has the opposite sense of elastic asymmetry at 0.1–100 m scales to that of the crustal‐scale orogen imaged by remote geophysical methods. On the basis of the fault‐zone scale asymmetry, the bimaterial interface model of preferred earthquake rupture directions implies a northeastward direction of preferred Alpine Fault rupture. On‐going characterization of the structural and hydraulic architecture of the Alpine Fault will improve our understanding of the relationship between in situ conditions, earthquake rupture processes, and the hazards posed by future earthquakes.
Heterogeneous magnesium isotopic composition of the lower continental crust: A xenolith perspective
Authors: Teng Fang‐Zhen , Yang Wei , Rudnick Roberta L. , Hu Yan
Published: August 2013

We report 26 high‐precision whole‐rock Mg isotopic analyses for two suites of well‐characterized granulite xenoliths from Chudleigh and McBride, North Queensland, Australia, in order to constrain the behavior of Mg isotopes during deep crustal processes and the Mg isotopic composition of the lower continental crust. Previous studies suggest that the Chudleigh granulites are a suite of cogenetic cumulates crystallized from mafic magmas that intruded into and assimilated the preexisting lower crust via combined assimilation and fractional crystallization (AFC). The δ26Mg values of the xenoliths range from −0.31 to −0.21‰ and correlate with radiogenic isotopes, reflecting mixing of mantle‐derived mafic magma (δ26Mg = −0.31‰) with preexisting isotopically heavy crustal materials (δ26Mg = ∼ +0.5‰) through the AFC process. The McBride granulites range compositionally from mafic to felsic, and originated as cumulates, solidified mafic/felsic melts, and restites that formed during basaltic underplating and reworking of preexisting lower crust. Their δ26Mg values vary widely from −0.72 to +0.19‰. The large Mg isotopic variation in the McBride xenoliths reflects both distinct source compositions and metamorphic enrichment of garnet, which is isotopically light. Based on these results, the lower continental crust has a heterogeneous Mg isotopic composition, with a weighted average δ26Mg of −0.18‰. The bulk continental crust, based on available data, has an average Mg isotopic composition of −0.19‰, and is slightly heavier than the mantle. The highly heterogeneous Mg isotopic distribution in the crust indicates that chemical weathering not only modifies the upper crust compositions but also significantly influences lower crust compositions through emplacement of upper crustal materials into the deep crust.
Petrological variability of recent magmatism at Axial Seamount summit, Juan de Fuca Ridge
Authors: Dreyer Brian M. , Clague David A. , Gill James B.
Published: August 2013

A combined study of mapping, observational, age constraint, and geochemical data at the summit of Axial Seamount, Juan de Fuca Ridge, has revealed its recent petrological history. Multiple basalt types erupted at the summit in a time sequence. At least three different magma batches have been present beneath the Axial Summit caldera during the last millennium, each with a range in differentiation. The first, prior to 1100 CE, was compositionally diverse, dominantly aphyric T‐MORB. The second, from ∼1220 to 1300 CE, was dominantly plagioclase‐phyric, more mafic N‐MORB erupted mostly in the central portion of the caldera. Since ∼1400 CE, lavas have been more differentiated, and nearly aphyric T‐MORB mostly erupted in the caldera's rift zones. Parental magmas vary subtly due to small coupled differences in the degree of melting and sources, but all share a uniform differentiation trend indicating pooling at similar depths. Thus, melts percolate through melt‐rich lenses that remain partially isolated in space and/or time. Centennial magmatic timescales at Axial Seamount are similar to those for fast spreading ridge segments. The fluctuation between aphyric and plagioclase‐phyric lava likely reflects different pathways or velocities of melt migration.
Geologic history of the summit of Axial Seamount, Juan de Fuca Ridge
Authors: Clague David A. , Dreyer Brian M. , Paduan Jennifer B. , Martin Julie F. , Chadwick William W. , Caress David W. , Portner Ryan A. , Guilderson Thomas P. , McGann Mary L. , Thomas Hans , Butterfield David A. , Embley Robert W.
Published: August 2013

Multibeam (1 m resolution) and side scan data collected from an autonomous underwater vehicle, and lava samples, radiocarbon‐dated sediment cores, and observations of flow contacts collected by remotely operated vehicle were combined to reconstruct the geologic history and flow emplacement processes on Axial Seamount's summit and upper rift zones. The maps show 52 post‐410 CE lava flows and 20 precaldera lava flows as old as 31.2 kyr, the inferred age of the caldera. Clastic deposits 1–2 m thick accumulated on the rims postcaldera. Between 31 ka and 410 CE, there are no known lava flows near the summit. The oldest postcaldera lava (410 CE) is a pillow cone SE of the caldera. Two flows erupted on the W rim between ∼800 and 1000 CE. From 1220 to 1300 CE, generally small eruptions of plagioclase phyric, depleted, mafic lava occurred in the central caldera and on the east rim. Larger post‐1400 CE eruptions produced inflated lobate flows of aphyric, less‐depleted, and less mafic lava on the upper rift zones and in the N and S caldera. All caldera floor lava flows, and most uppermost rift zone flows, postdate 1220 CE. Activity shifted from the central caldera to the upper S rift outside the caldera, to the N rift and caldera floor, and then to the S caldera and uppermost S rift, where two historical eruptions occurred in 1998 and 2011. The average recurrence interval deduced from the flows erupted over the last 800 years is statistically identical to the 13 year interval between historical eruptions.
The influence of recent Antarctic ice sheet retreat on simulated sea ice area trends
Authors: Swart N. C. , Fyfe J. C.
Published: August 2013

Observations indicate that dynamic mass loss from the Antarctic ice sheet has been accelerating over recent decades, leading to a freshening of the Southern Ocean. Here we quantify the effect of several rates and spatial distributions of freshwater forcing on simulated sea ice area trends. In contrast to a previous study, our simulations show that the freshwater effect on sea ice trends over the historical period is small and fails to reproduce the observed regional pattern of trends, when using observationally consistent rates of freshwater forcing. The Coupled Model Intercomparison Project Phase 5 (CMIP5) models do not represent this dynamic ice sheet mass loss, and it has been suggested that this deficiency may significantly influence the simulated sea ice trends. We show that when accounting for internal variability, the average CMIP5 sea ice area trend is statistically consistent with the observed trend, and accounting for ice sheet derived freshwater forcing has little influence.
Evaluation of liver disease progression in the German hepatitis C virus (1b)-contaminated anti-D cohort at 35 years after infection
Authors: Wiese Manfred , Fischer Janett , Löbermann Micha , Göbel Uwe , Grüngreiff Kurt , Güthoff Wolfgang , Kullig Ulrike , Richter Franziska , Schiefke Ingolf , Tenckhoff Hannelore , Zipprich Alexander , Berg Thomas , Müller Tobias
Published: August 2013

The natural course of HCV infection remains controversial. The German HCV (1b)-contaminated anti-D cohort provides an ideal population to investigate the natural course of HCV infection in a large, homogenous cohort of young women from the date of HCV inoculation. Our previous follow-up studies at 20 and 25 years after infection suggested slow fibrosis progression rates in this unique cohort. The aim of our prospective, community-based, multicenter study was to reevaluate the liver disease progression in 718 patients of the original anti-D cohort at 35 years after infection. Patients with self-limited HCV infection (n = 189) were compared to those who failed to eliminate the virus spontaneously (n = 529), comprising patients who were treatment naïve (n = 197) or achieved a sustained virological response (SVR; n = 149), respectively, failed to clear the virus (non-SVR; n = 183) after antiviral therapy. In the overall cohort, 9.3% of patients showed clinical signs of liver cirrhosis at 35 years after infection. Liver disease progression largely depended on HCV infection status. The highest proportion of patients with clinical signs of end-stage liver disease was observed in the non-SVR group (15.3%), whereas decreased cirrhosis rates were detected in the SVR group (6%) and in patients with self-limited HCV infection (1.1%;

P

= 6.2 × 10−6). Overall survival was significantly enhanced after SVR, compared to treatment-naïve patients or non-SVR (

P

= 0.027).

Conclusion :

The present study provides further evidence for a mild, but significant, disease progression at 35 years after infection in the German HCV (1b)-contaminated anti-D cohort. Patients with self-limited HCV infection or SVR after antiviral treatment were protected from progressive liver disease and showed the best clinical long-term outcome.
Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes reveals a stable hierarchy of gene expression
Authors: Bolen Christopher R. , Ding Siyuan , Robek Michael D. , Kleinstein Steven H.
Published: August 2013

Despite activating similar signaling cascades, the type I and type III interferons (IFNs) differ in their ability to antagonize virus replication. However, it is not clear whether these cytokines induce unique antiviral states, particularly in the liver, where the clinically important hepatitis B and C viruses cause persistent infection. Here, clustering and promoter analyses of microarray-based gene expression profiling were combined with mechanistic studies of signaling pathways to dynamically characterize the transcriptional responses induced by these cytokines in Huh7 hepatoma cells and primary human hepatocytes. Type I and III IFNs differed greatly in their level of interferon-stimulated gene (ISG) induction with a clearly detectable hierarchy (IFN-β > IFN-α > IFN-λ3 > IFN-λ1 > IFN-λ2). Notably, although the hierarchy identified varying numbers of differentially expressed genes when quantified using common statistical thresholds, further analysis of gene expression over multiple timepoints indicated that the individual IFNs do not in fact regulate unique sets of genes. The kinetic profiles of IFN-induced gene expression were also qualitatively similar with the important exception of IFN-α. While stimulation with either IFN-β or IFN-λs resulted in a similar long-lasting ISG induction, IFN-α signaling peaked early after stimulation then declined due to a negative feedback mechanism. The quantitative expression hierarchy and unique kinetics of IFN-α reveal potential specific roles for individual IFNs in the immune response, and elucidate the mechanism behind previously observed differences in IFN antiviral activity. While current clinical trials are focused on IFN-λ1 as a potential antiviral therapy, the finding that IFN-λ3 invariably possesses the highest activity among type III IFNs suggests that this cytokine may have superior clinical activity. (HEPATOLOGY 2014;59:1262-1272)
Antismooth Muscle and Antiactin Antibodies Are Indirect Markers of Histological and Biochemical Activity of Autoimmune Hepatitis
Authors: Couto Claudia A. , Bittencourt Paulo L. , Porta Gilda , Abrantes-Lemos Clarice P. , Carrilho Flair J. , Guardia Bianca D. , Cançado Eduardo L.R.
Published: August 2013

Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4–69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2–6] times) after a mean follow-up evaluation of 70 [20–185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected

de novo

in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (

P

< 0.001).

Conclusion

: With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. (Hepatology 2014;59:592–600)
Kupffer Cell-Derived IL-10 Plays a Key Role in Maintaining Humoral Immune Tolerance in Hepatitis B Virus-Persistent Mice
Authors: Xu Long , Yin Wenwei , Sun Rui , Wei Haiming , Tian Zhigang
Published: August 2013

The liver is considered as a unique lymphoid organ favoring the induction of immune tolerance, rather than immunity. Biologists and clinicians alike have a long-standing interest in how the liver induces systemic immune tolerance, but the mechanism has not yet been well elucidated. Here, we employed hepatitis B virus (HBV)-carrier mice generated by hydrodynamically injecting phosphor-adeno-associated virus/HBV1.2 plasmid as a model for adult chronic HBV infection, which we found were unable to respond to hepatitis B surface antigen vaccination. Humoral tolerance induced in HBV-carrier mice could be transferred into Rag1−/− mice, because anti-HBV immunity in immunologically reconstituted Rag1−/− mice was inhibited by adoptive transfer of splenocytes from HBV-carrier mice. Humoral tolerance needed at least 7 days for induction and persisted to 3 months after a single HBV plasmid injection. Kupffer cell (KC) depletion or interleukin (IL-10) deficiency broke this humoral tolerance, and exogenous injection of IL-10 could effectively induce this tolerance.

Conclusion

: KCs in HBV-carrier mice expressed more IL-10 and mediated the systemic tolerance induction in an IL-10-dependent manner. This previously undescribed humoral tolerance regarding HBV infection will help to explore new approaches to reverse liver-sustained systemic immune tolerance in liver disease. (Hepatology 2014;59:443–452)
Mesenchymal Stem Cells Alleviate Bacteria-Induced Liver Injury in Mice by Inducing Regulatory Dendritic Cells
Authors: Zhang Yi , Cai Wei , Huang Qingrong , Gu Yuting , Shi Yufang , Huang Jiefang , Zhao Fang , Liu Qiang , Wei Xunbin , Jin Min , Wu Changping , Xie Qing , Wan Bing , Zhang Yanyun
Published: August 2013

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by sudden and severe impairment of liver function. Mesenchymal stem cells (MSCs) have been proposed as a promising therapeutic approach for FHF. In this study we used

Propionibacterium acnes

(

P. acnes

)-primed, lipopolysaccharide (LPS)-induced liver injury in mice as an animal model of human FHF. We demonstrated that administration of MSCs significantly ameliorated liver injury and improved the survival rates of mice subjected to

P. acnes

plus LPS-induced FHF. Allogeneic MSCs showed similar treatment efficacy as autologous MSCs did in FHF. Treatment efficacy of MSCs could be attributed to decreased infiltration and activation of CD4+ T cells in the liver, inhibition of T helper 1 cells, and induction of regulatory T cells (Tregs). Moreover, decreased DNA copies of

P. acnes

were detected in the liver of MSC-treated mice. Intriguingly, a distinct liver population of CD11c+MHCIIhiCD80loCD86lo regulatory dendritic cells (DCs) was induced by MSCs. Moreover, these DCs induced Treg differentiation through transforming growth factor-β production. Further mechanistic studies demonstrated that MSC-derived prostaglandin E2 and one of its receptors, EP4, played essential roles in the differentiation of CD11c+B220− DC precursors into regulatory DCs in a phosphoinositide 3-kinase-dependent manner.

Conclusion

: MSCs induce regulatory DCs from CD11c+B220− DC precursors. This study elucidates an immunoregulatory mechanism of MSCs and lays a foundation for application of MSCs in FHF therapy. (Hepatology 2014;59:671–682)
Quantitative Proteomics Identifies the Membrane-Associated Peroxidase Gpx8 as a Cellular Substrate of the Hepatitis C Virus NS3–4A Protease
Authors: Morikawa Kenichi , Gouttenoire Jérôme , Hernandez Céline , Dao Thi Viet Loan , Tran Huong T.L. , Lange Christian M. , Dill Michael T. , Heim Markus H. , Donzé Olivier , Penin François , Quadroni Manfredo , Moradpour Darius
Published: August 2013

The hepatitis C virus (HCV) NS3–4A protease is not only an essential component of the viral replication complex and a prime target for antiviral intervention but also a key player in the persistence and pathogenesis of HCV. It cleaves and thereby inactivates two crucial adaptor proteins in viral RNA sensing and innate immunity, mitochondrial antiviral signaling protein (MAVS) and TRIF, a phosphatase involved in growth factor signaling, T-cell protein tyrosine phosphatase (TC-PTP), and the E3 ubiquitin ligase component UV-damaged DNA-binding protein 1 (DDB1). Here we explored quantitative proteomics to identify novel cellular substrates of the NS3–4A protease. Cell lines inducibly expressing the NS3–4A protease were analyzed by stable isotopic labeling using amino acids in cell culture (SILAC) coupled with protein separation and mass spectrometry. This approach identified the membrane-associated peroxidase GPx8 as a

bona fide

cellular substrate of the HCV NS3–4A protease. Cleavage by NS3–4A occurs at Cys 11, removing the cytosolic tip of GPx8, and was observed in different experimental systems as well as in liver biopsies from patients with chronic HCV. Overexpression and RNA silencing studies revealed that GPx8 is involved in viral particle production but not in HCV entry or RNA replication.

Conclusion

: We provide proof-of-concept for the use of quantitative proteomics to identify cellular substrates of a viral protease and describe GPx8 as a novel proviral host factor targeted by the HCV NS3–4A protease. (Hepatology 2014;59:423–433)
Nonalcoholic Fatty Liver Disease, Hepatic Insulin Resistance, and Type 2 Diabetes
Authors: Birkenfeld Andreas L. , Shulman Gerald I.
Published: August 2013

Nonalcoholic fatty liver disease (NAFLD), hepatic insulin resistance, and type 2 diabetes are all strongly associated and are all reaching epidemic proportions. Whether there is a causal link between NAFLD and hepatic insulin resistance is controversial. This review will discuss recent studies in both humans and animal models of NAFLD that have implicated increases in hepatic diacylglycerol (DAG) content leading to activation of novel protein kinase Cε (PKCε) resulting in decreased insulin signaling in the pathogenesis of NAFLD-associated hepatic insulin resistance and type 2 diabetes. The DAG-PKCε hypothesis can explain the occurrence of hepatic insulin resistance observed in most cases of NAFLD associated with obesity, lipodystrophy, and type 2 diabetes. (Hepatology 2014;59:713–723)
Hepatocytes as a Source of Cholangiocytes in Injured Liver
Authors: Lemaigre Frédéric P.
Published: August 2013

Cellular reprogramming—the ability to interconvert distinct cell types with defined factors—is transforming the field of regenerative medicine. However, this phenomenon has rarely been observed

in vivo

without exogenous factors. Here, we report that activation of Notch, a signaling pathway that mediates lineage segregation during liver development, is sufficient to reprogram hepatocytes into biliary epithelial cells (BECs). Moreover, using lineage tracing, we show that hepatocytes undergo widespread hepatocyte-to-BEC reprogramming following injuries that provoke a biliary response, a process requiring Notch. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under injury conditions.
Steroid Use in Acute Liver Failure
Authors: Karkhanis Jamuna , Verna Elizabeth C. , Chang Matthew S. , Stravitz Todd R. , Schilsky Michael , Lee William M. , Brown Robert S.
Published: August 2013

Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998–2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% versus 66%,

P

= 0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%,

P

= 0.03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH < 7.4 (OR 3.09) were significantly associated with mortality. Although steroid use was associated with a marginal benefit in SS overall (35% versus 23%,

P

= 0.047), this benefit did not persistent in multivariate analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and alanine aminotransferase (1.02) were the only significant predictors of SS.

Conclusion

: Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate, or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores. (Hepatology 2014;59:612–621)
The effect of early‐life stress on memory systems supporting instrumental behavior
Authors: Patterson Tara K. , Craske Michelle G. , Knowlton Barbara J.
Published: August 2013

People experiencing early‐life stress (ELS) exhibit increased incidence of behaviors that lead to addiction and obesity as adults. Many of these behaviors may be viewed as resulting from an overreliance on habits as opposed to goal‐directed instrumental behavior. This increased habitization may result from alterations in the interactions between dorsolateral striatum‐dependent and hippocampus‐dependent learning systems. As an initial examination of this idea, we investigated the effect of ELS on instrumental learning and extinction. In Experiment 1, we examined the effect of ELS in two groups of people, one trained on a continuous reinforcement schedule and one trained on a partial reinforcement schedule. We found that people who experienced ELS had a diminished effect of the partial reinforcement schedule on extinction. In Experiment 2, we again manipulated reinforcement schedule and also challenged declarative memory by requiring subjects to perform a concurrent task. We found that the declarative challenge did not affect extinction responding in the non‐ELS group. In a moderate‐ELS group, we observed a diminished sensitivity to the reinforcement schedule during extinction only under divided attention. In the high‐ELS group, we observed a reduced sensitivity to reinforcement schedule even in the absence of the declarative memory challenge, consistent with Experiment 1. Our results suggest that ELS reduces the tendency to use declarative, hippocampus‐dependent memory in instrumental tasks in favor of habits. ELS may affect hippocampal development, thus altering the interaction between memory systems and potentially contributing to poor health outcomes. © 2013 Wiley Periodicals, Inc.
Hippocampus and striatum: Dynamics and interaction during acquisition and sleep‐related motor sequence memory consolidation
Authors: Albouy Geneviève , King Bradley R. , Maquet Pierre , Doyon Julien
Published: August 2013

While several models of memory consolidation have previously associated hippocampal activity with declarative memory, there is now increasing evidence that the hippocampus also plays a crucial role in procedural memory. Here, we review recent human functional neuroimaging studies demonstrating that the hippocampus is involved in the acquisition and sleep‐related consolidation of procedural memories, and motor sequence‐based skills in particular. More specifically, we present evidence that hippocampal activity and its functional interactions with other brain structures, particularly competition with the striatum, contribute to initial learning of sequential motor behavior. Interestingly, these early cerebral representations in the hippocampus and striatum, which may interact through the prefrontal cortex, can even predict subsequent sleep‐related memory consolidation processes. We propose that sleep can reorganize the activity within, as well as the functional interactions between, these structures, ultimately favoring overnight performance enhancement. Finally, we conclude by offering insights into the respective roles of these structures in procedural memory consolidation processes. We argue that, in the context of motor sequence memory consolidation, the hippocampal system triggers subsequent sleep‐dependent performance enhancement whereas the striatal system is involved in the maintenance of the motor behavior over time. © 2013 Wiley Periodicals, Inc.
Evaluating the ability of a hydrologic model to replicate hydro‐ecologically relevant indicators
Authors: Shrestha Rajesh R. , Peters Daniel L. , Schnorbus Markus A.
Published: August 2013

It is a common practice to employ hydrologic models for assessing alterations to streamflow as a result of anthropogenically driven changes, such as riverine, land use, and climate change. However, the ability of the models to replicate different components of the hydrograph simultaneously is not clear. Hence, this study evaluates the ability of a standard hydrologic model set‐up: Variable Infiltration Capacity (VIC) hydrologic model for two headwater sub‐basins in the Fraser River (Salmon and Willow), British Columbia, Canada, with climate inputs derived from observations and statistically downscaled global climate models (GCMs); to simulate six general water resource indicators (WRIs) and 32 ecologically relevant indicators of hydrologic alterations (IHA). The results show a generally good skill of the observation‐driven VIC model in replicating most of the WRIs and IHAs. Although the WRIs, including annual volume, centre of timing, and seasonal flows, and the IHAs, including maximum and minimum flows, were reasonably well replicated, statistically significant differences in some of the monthly flows, number and duration of flow pulses, rise and fall rates, and reversals were noted. In the case of GCM‐driven results, additional monthly, maximum, and minimum flow indicators produced statistically significant differences. A number of issues with the model input/output data, hydrologic model parametrization and structure as well as downscaling methods were identified, which lead to such discrepancies. Therefore, there is a need to exercise caution in the use of model‐simulated indicators. Overall, the WRIs and IHAs can be useful tools for evaluating changes in an altered hydrologic system, provided the skill and limitations of the model in replicating these indicators are understood. © 2013 Her Majesty the Queen in Right of Canada. Hydrological Processes © 2013 John Wiley & Sons Ltd.
Supramolecular Nanofibers of Peptide Amphiphiles for Medicine
Authors: Webber Matthew J. , Berns Eric J. , Stupp Samuel I.
Published: August 2013

Peptide nanostructures are an exciting class of supramolecular systems that can be designed for novel therapies with great potential in advanced medicine. This paper reviews progress on nanostructures based on peptide amphiphiles capable of forming one‐dimensional assemblies that emulate in structure the nanofibers present in extracellular matrices. These systems are highly tunable using supramolecular chemistry, and can be designed to signal cells directly with bioactive peptides. Peptide amphiphile nanofibers can also be used to multiplex functions through co‐assembly and designed to deliver proteins, nucleic acids, drugs, or cells. We illustrate here the functionality of these systems, describing their use in regenerative medicine of bone, cartilage, the nervous system, the cardiovascular system, and other tissues. In addition, we highlight recent work on the use of peptide amphiphile assemblies to create hierarchical biomimetic structures with order beyond the nanoscale, and also discuss the future prospects of these supramolecular systems.
Progesterone reduces the expression of spinal cyclooxygenase‐2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain
Authors: Coronel M.F. , Labombarda F. , De Nicola A.F. , González S.L.
Published: August 2013

Background

Spinal cord injury (SCI) results in the development of chronic pain that is refractory to conventional treatment. Progesterone, a neuroprotective steroid, may offer a promising perspective in pain modulation after central injury. Here, we explore the impact of progesterone administration on the post‐injury inflammatory cascade involving the enzymes cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) at the spinal cord level. We also analyse pain behaviours, the profile of glial cell activation, and IκB‐α mRNA levels, as an index of NF‐κB transactivation.

Methods

We used biochemical, immunohistochemical and molecular techniques, as well as behavioural studies, to investigate the effects of progesterone in a well‐characterized model of central neuropathic pain.

Results

Injured animals receiving progesterone presented reduced mRNA levels of the proinflammatory enzymes, as well as decreased COX‐2 activity and nitrite levels, as compared to vehicle‐treated injured rats. Further, animals receiving the steroid exhibited lower levels of IκB‐α mRNA, suggesting decreased NF‐κB transactivation. Progesterone administration also attenuated the injury‐induced increase in the number of glial fibrillary acidic protein and OX‐42 positive cells both at early and late time points after injury, and prevented the development of mechanical and thermal allodynia. Further, when injured rats received early progesterone administration for a critical period of time after injury, they did not display allodynic behaviours even after the treatment had stopped.

Conclusions

Our results suggest that progesterone, by modulating early neuroinflammatory events triggered after SCI, may represent a useful strategy to prevent the development of central chronic pain.
Spermine‐alt‐poly(ethylene glycol) polyspermine as a safe and efficient aerosol gene carrier for lung cancer therapy
Authors: Kim You‐Kyoung , Cho Chong‐Su , Cho Myung‐Haing , Jiang Hu‐Lin
Published: August 2013

The clinical success of gene therapy critically depends upon the safety and efficiency of delivery system used. Although polyethylenimine (PEI) has been commonly used as an efficient cationic polymeric gene carrier due to its high transfection efficiency, its cytotoxicity and nondegradability limit the polymer's therapeutic applications in clinical trials. In this study, biocompatible polyspermine based on spermine (SPE) and poly(ethylene glycol) (PEG) diacrylate (SPE‐alt‐PEG) was synthesized using a Michael‐type addition reaction, and its ability as an alternative gene carrier for lung cancer therapy was evaluated. SPE‐alt‐PEG polyspermine was complexed with plasmid DNA, and the resulting complexes were characterized by particle size and surface charge by dynamic light scattering, complex formation and DNA protection ability by gel retardation, and complex shape by energy‐filtering transmission electron microscopy. The SPE‐alt‐PEG copolymer showed low cytotoxicity, and SPE‐alt‐PEG/DNA complexes showed efficacious transfection efficiency compared with 25 kDa PEI (PEI 25K). Also SPE‐alt‐PEG/GFP complexes were efficiently transferred into the lungs after aerosol administration without toxicity, and delivery of Pdcd4 gene as a therapeutic gene with SPE‐alt‐PEG polyspermine greatly reduced tumor size as well as tumor numbers in K‐rasLA1 lung cancer model mice compared relative to the effect observed for PEI 25K. These results suggest that SPE‐alt‐PEG has potential as a gene carrier for lung cancer gene therapy. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2230–2237, 2014.
Bone Loss After Bariatric Surgery: Discordant Results Between DXA and QCT Bone Density
Authors: Yu Elaine W , Bouxsein Mary L , Roy Adam E , Baldwin Chantel , Cange Abby , Neer Robert M , Kaplan Lee M , Finkelstein Joel S
Published: August 2013

Several studies, using dual-energy X-ray absorptiometry (DXA), have reported substantial bone loss after bariatric surgery. However, profound weight loss may cause artifactual changes in DXA areal bone mineral density (aBMD) results. Assessment of volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) may be less susceptible to such artifacts. We assessed changes in BMD of the lumbar spine and proximal femur prospectively for 1 year using DXA and QCT in 30 morbidly obese adults undergoing Roux-en-Y gastric bypass surgery and 20 obese nonsurgical controls. At 1 year, subjects who underwent gastric bypass surgery lost 37 ± 2 kg compared with 3 ± 2 kg lost in the nonsurgical controls (p < 0.0001). Spine BMD declined more in the surgical group than in the nonsurgical group whether assessed by DXA (−3.3 versus −1.1%, p = 0.034) or by QCT (−3.4 versus 0.2%, p = 0.010). Total hip and femoral neck aBMD declined significantly in the surgical group when assessed by DXA (−8.9 versus −1.1%, p < 0.0001 for the total hip and −6.1 versus −2.0%, p = 0.002 for the femoral neck), but no changes in hip vBMD were noted using QCT. Within the surgical group, serum P1NP and CTX levels increased by 82% ± 10% and by 220% ± 22%, respectively, by 6 months and remained elevated over 12 months (p < 0.0001 for all). Serum calcium, vitamin D, and PTH levels remained stable in both groups. We conclude that moderate vertebral bone loss occurs in the first year after gastric bypass surgery. However, striking declines in DXA aBMD at the proximal femur were not confirmed with QCT vBMD measurements. These discordant results suggest that artifacts induced by large changes in body weight after bariatric surgery affect DXA and/or QCT measurements of bone, particularly at the hip. © 2014 American Society for Bone and Mineral Research.
Deletion of a Single β-Catenin Allele in Osteocytes Abolishes the Bone Anabolic Response to Loading
Authors: Javaheri Behzad , Stern Amber Rath , Lara Nuria , Dallas Mark , Zhao Hong , Liu Ying , Bonewald Lynda F , Johnson Mark L
Published: August 2013

The Wnt/β-catenin signaling pathway is essential for bone cell viability and function and for skeletal integrity. To determine if β-catenin in osteocytes plays a role in the bone anabolic response to mechanical loading, 18- to 24-week-old osteocyte β-catenin haploinsufficient mice (Dmp1-Cre × β-catenin fl/ + ; HET cKO) were compared with their β-catenin fl/fl (control) littermates. Trabecular bone volume (BV/TV) was significantly less (58.3%) in HET cKO females versus controls, whereas male HET cKO and control mice were not significantly different. Trabecular number was significantly less in HET cKO mice compared with controls for both genders, and trabecular separation was greater in female HET cKO mice. Osteoclast surface was significantly greater in female HET cKO mice. Cortical bone parameters in males and females showed subtle or no differences between HET cKO and controls. The right ulnas were loaded in vivo at 100 cycles, 2 Hz, 2500 µϵ, 3 days per week for 3 weeks, and the left ulnas served as nonloaded controls. Calcein and alizarin complexone dihydrate were injected 10 days and 3 days before euthanization, respectively. Micro-computed tomography (µCT) analysis detected an 8.7% and 7.1% increase in cortical thickness in the loaded right ulnas of male and female control mice, respectively, compared with their nonloaded left ulnas. No significant increase in new cortical bone formation was observed in the HET cKO mice. Histomorphometric analysis of control mice showed a significant increase in endocortical and periosteal mineral apposition rate (MAR), bone-formation rate/bone surface (BFR/BS), BFR/BV, and BFR/TV in response to loading, but no significant increases were detected in the loaded HET cKO mice. These data show that deleting a single copy of β-catenin in osteocytes abolishes the anabolic response to loading, that trabecular bone in females is more severely affected and suggest that a critical threshold of β-catenin is required for bone formation in response to mechanical loading. © 2014 American Society for Bone and Mineral Research
Ionospheric midlatitude electric current density inferred from multiple magnetic satellites
Authors: Shore R. M. , Whaler K. A. , Macmillan S. , Beggan C. , Olsen N. , Spain T. , Aruliah A.
Published: August 2013

A method for inferring zonal electric current density in the mid‐to‐low latitude F region ionosphere is presented. We describe a method of using near‐simultaneous overflights of the Ørsted and CHAMP satellites to define a closed circuit for an application of Ampère's integral law to magnetic data. Zonal current density from sources in only the region between the two satellites is estimated for the first time. Six years of mutually available vector magnetic data allows overlaps spanning the full 24 h range of local time twice. Solutions are computed on an event‐by‐event basis after correcting for estimates of main and crustal magnetic fields. Current density in the range ±0.1 μA/m2 is resolved, with the distribution of electric current largely matching known features such as the Appleton anomaly. The currents appear unmodulated at times of either high‐negative Dst or high F10.7, which has implications for any future efforts to model their effects. We resolve persistent current intensifications between geomagnetic latitudes of 30 and 50° in the postmidnight, predawn sector, a region typically thought to be relatively free of electric currents. The cause of these unexpected intensifications remains an open issue. We compare our results with current density predictions made by the Coupled Thermosphere‐Ionosphere‐Plasmasphere model, a self‐consistent, first‐principles, three‐dimensional numerical dynamic model of ionospheric composition and temperatures. This independent validation of our current density estimates highlights good agreement in the broad spatiotemporal trends we identify, which increases confidence in our results.
A simulation study of Io‐related Jovian decametric radiation: Control factor of occurrence probability
Authors: Matsuda K. , Katoh Y. , Terada N. , Misawa H.
Published: August 2013

Io‐Jupiter interaction leads to auroral emissions and Jovian decametric radiations (Io‐DAM). The longitudinal distribution of the Io‐DAM occurrence probability has been considered to be controlled by the footprint magnetic intensity of each hemisphere. Recent observations revealed that the brightness of the main auroral spot is mainly modulated by Io's magnetic latitude. In the present study, we propose that the Io‐DAM occurrence probability is controlled by the north‐south asymmetry of the footprint magnetic intensity, in addition to Io's magnetic latitude. Hall magnetohydrodynamic equations are solved in the corotating meridional plane, which includes the Jovian ionosphere of finite thickness. We assume that the ionospheric Pedersen conductance is inversely proportional to the footprint magnetic intensity; the conductance is nearly the same for both ionospheres at a longitude of 290°, while twice higher for the south than for the north at a longitude of 110°. Above the northern ionosphere, the parallel current density further than 20° downstream of the main spot is estimated to be 1.5–2.0 times larger for 290° than for 110°. This indicates that if the Io‐DAM lead angle is large, the suppressed Io‐DAM occurrence probability for the northern hemisphere around 110° would be caused by the north‐south asymmetry of the footprint magnetic intensity. A large current density conducted into the south around 110° would be the source of the Io‐D component, radiated from the southern hemisphere. The observed brightness of the Io‐related auroras is discussed in the context of the intensity of the parallel current density.
Wave breaking in developing and mature seas
Authors: Gemmrich Johannes , Zappa Christopher J. , Banner Michael L. , Morison Russel P.
Published: August 2013

In response to the growing need for robust validation data for Phillips (1985) breaking wave spectral framework, we contribute new field results observed from R/P FLIP for the breaking crest length distributions, Λ, during two different wind‐wave conditions, and breaking strength during one wind‐wave condition. The first experiment in Santa Barbara Channel had developing seas and the second experiment in the central Pacific Ocean south of Hawaii had mature seas. These are among the first experiments to use dissipation rate measurements probing up into the breaking crest together with simultaneous measurements of breaking crest length distributions. We directly measured the effective breaking strength parameter to be
in mature seas with wave age,
, of 40–47. We also found that the velocity scale of the breaking dissipation rate peak decreases with increasing wave age. Further, the breaking crest length spectrum falls off slower than the
behavior predicted by Phillips (1985). The integrated dissipation rate was consistently higher for mature seas compared to developing seas due to higher energy and momentum fluxes from the wind.