bluuebunny/crossref_metadata_2025 huggingface dataset:
Social cognition in anorexia nervosa: Specific difficulties in decoding emotional but not nonemotional mental states
Authors: Brockmeyer Timo , Pellegrino Judith , Münch Hannah , Herzog Wolfgang , Dziobek Isabell , Friederich Hans‐Christoph
Published: June 2016

Objective

Building on recent models of anorexia nervosa (AN) that emphasize the importance of impaired social cognition in the development and maintenance of the disorder, the present study aimed at examining whether women with AN have more difficulties with inferring other people's emotional and nonemotional mental states than healthy women.

Method

Social cognition was assessed in 25 adult women with AN and 25 age‐matched healthy women. To overcome limitations of previous research on social cognition in AN, the processing of social information was examined in a more complex and ecologically valid manner. The Movie for the Assessment of Social Cognition (MASC) reflects complex real‐life social interaction and allows for disentangling emotional and non‐emotional mental state inference as well as different types of errors in mentalizing.

Results

Women with AN showed poorer emotional mental state inference, whereas non‐emotional mental state inference was largely intact. Groups did not differ in undermentalizing (overly simplistic theory of mind) and overmentalizing (overly complex or over‐interpretative mental state reasoning). Performance in the MASC was independent of levels of eating disorder psychopathology and symptoms of depression and anxiety.

Discussion

The findings suggest that AN is associated with specific difficulties in emotional mental state inference despite largely intact nonemotional mental state inference. Upon replication in larger samples, these findings advocate a stronger emphasis on socio‐emotional processing in AN treatment. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:883–890)
The regulation of inflammation by oxidized phospholipids
Authors: Freigang Stefan
Published: June 2016

During inflammation or under conditions of oxidative stress, the polyunsaturated fatty acid side chains of phospholipids in cellular membranes or lipoproteins can be oxidatively modified. This process generates a complex mixture of structurally diverse oxidized phospholipid (OxPL) species, each of which may exert distinct biological effects. The presence of OxPLs has been documented in acute and chronic microbial infections, metabolic disorders, and degenerative diseases. It is now well recognized that OxPLs actively influence biological processes and contribute to the induction and resolution of inflammation. While many pro‐ and anti‐inflammatory effects have been documented for bulk OxPL preparations, we are only beginning to understand the exact molecular mechanisms and signaling events that mediate the individual proinflammatory or anti‐inflammatory bioactivities of discrete isolated OxPL species. Here, we review the current knowledge on the regulation of inflammation by OxPLs and summarize recent studies that establish cyclopentenone‐containing OxPLs as a category of potent anti‐inflammatory lipid mediators.
Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice
Authors: Maier Barbara B. , Hladik Anastasiya , Lakovits Karin , Korosec Ana , Martins Rui , Kral Julia B. , Mesteri Ildiko , Strobl Birgit , Müller Mathias , Kalinke Ulrich , Merad Miriam , Knapp Sylvia
Published: June 2016

Protecting the integrity of the lung epithelial barrier is essential to ensure respiration and proper oxygenation in patients suffering from various types of lung inflammation. Type I interferon (IFN‐I) has been associated with pulmonary epithelial barrier function, however, the mechanisms and involved cell types remain unknown. We aimed to investigate the importance of IFN‐I with respect to its epithelial barrier strengthening function to better understand immune‐modulating effects in the lung with potential medical implications. Using a mouse model of pneumococcal pneumonia, we revealed that IFN‐I selectively protects alveolar epithelial type II cells (AECII) from inflammation‐induced cell death. Mechanistically, signaling via the IFN‐I receptor on AECII is sufficient to promote AECII survival. The net effects of IFN‐I are barrier protection, together with diminished tissue damage, inflammation, and bacterial loads. Importantly, we found that the protective role of IFN‐I can also apply to sterile acute lung injury, in which loss of IFN‐I signaling leads to a significant reduction in barrier function caused by AECII cell death. Our data suggest that IFN‐I is an important mediator in lung inflammation that plays a protective role by antagonizing inflammation‐associated cell obstruction, thereby strengthening the integrity of the epithelial barrier.
Alkyl esters content and other quality parameters in oil mill: A response surface methodology study
Authors: Alcalá Sonia , Ocaña María Teresa , Cárdenas José Rafael , Miquel Miguel Ángel , Vilar Juan , Espínola Francisco , Moya Manuel
Published: June 2016

The quality of the olives oil can be altered during their processing. This paper studies the influence that the washing of olive oils has on their alkyl esters content and on other quality parameters. A Central Composite Rotatable Design (CCRD) with five center points has been used to modify the factors, rotational frequency of the motor of the vertical centrifuge (between 34 and 47 Hz) and percentage of added water (between 6 and 34%). Results show that the content in alkyl esters of olive oils increases by the flow from the decanter to the vertical centrifuge. The use of water in the vertical centrifuge decreases the content in ethyl and methyl esters 0.8 and 0.6 mg/kg, respectively, per percentage unit of added water. The acidity, peroxide index, K232, chlorophyll, and carotenoid contents are slightly altered by the oil flow from the decanter to vertical centrifuge, but not by operating factors. K270, total polyphenols and orthodiphenols change with the speed of the vertical centrifuge, but water does not affect them. For the normal operation frequency of the centrifuge (50 Hz), K270 is increased about 14%, while the total polyphenols and orthodiphenols decrease by 27 and 62%, respectively.

Practical applications: Quality control of olive oils (virgin and extra virgin).

Olive‐oil production process: differences in the content of EE and TP between the vertical centrifuge way out and the decanter way out.
Controlling Cyclopeptide Backbone Conformation with β/α‐Hybrid Peptide–Heterocycle Scaffolds
Authors: Gentilucci Luca , Gallo Francesca , Meloni Fernanda , Mastandrea Marco , Del Secco Benedetta , De Marco Rossella
Published: June 2016

Cyclopeptides (CPs) have been recognized as excellent templates for the rational design of biologically active compounds. However, in the absence of constraining elements, even the small cyclotetrapeptides (CTPs) and cyclopentapeptides (CPPs) may show conformational heterogeneity, with the occurrence of mixtures ofcis/trans‐peptide bonds. In this paper, we discuss the synthesis of CTP and CPP model compounds containing 5‐aminomethyloxazolidine‐2,4‐dione (Amo)‐dipeptide scaffolds, which combine a β/α‐hybrid dipeptide structure & a Freidinger lactam‐like heterocycle. Depending on the stereochemistry, the dipeptide scaffolds were shown to efficiently promote well‐defined turn structures within the CP sequences, by taking advantage of the particular local constraints, and by establishing extra intramolecular hydrogen‐bonding interactions.
H9 subtype influenza vaccine in MDCK single‐cell suspension culture with stable expression of TMPRSS2: Generation and efficacy evaluation
Authors: Feng Lei , Tang Yinghua , Wu Peipei , Chu Xuan , Wang Weifeng , Hou Jibo
Published: June 2016

Vaccination is the most effective way to protect chickens from avian influenza pandemics. Mammalian cells, especially MDCK cells, are being investigated as a good alternative to the embryonated chicken eggs for avian influenza vaccine production. In this work, we developed a new MDCK cell line, which has two main features: single‐cell suspension growth and stable expression of human TMPRSS2 protein (transmembrane protease serine S1 member 2) anchored on cells membrane, named MDCK‐Sus‐TMPRSS2. Reverse‐transcription polymerase chain reaction, western blot analysis and indirect immunofluorescence assay were employed to detect the expression of TMPRSS2 in the MDCK‐Sus‐TMPRSS2 cells. Then, H9 subtype avian influenza virus, NJ02/01 strain, was adapted in MDCK‐Sus‐TMPRSS2 cells with serial blind passages and propagated in stirred bioreactor with 9.5 log2/25 μL hemagglutination titers for inactivated avian influenza vaccine production without addition of exogenous trypsin. The MDCK‐Sus‐TMPRSS2 cell‐derived H9 subtype avian influenza vaccine could induce high titers of hemagglutiniton inhibition antibodies in specific pathogen‐free chickens and protect chickens against heterologous H9 subtype influenza virus challenge, showing lower virus shedding rate and sickness rate than in the egg‐derived vaccines group. High titers of H9 subtype‐specific antibodies above 6 log2 were maintained for 6 months in commercial chickens vaccinated by the MDCK‐Sus‐TMPRSS2 cells derived H9 subtype avian influenza vaccine and there were no negative effects on body weight increase in these chickens. Taken together, the results of this work revealed that MDCK‐Sus‐TMPRSS2 cell line could be a promising and safe substitute for embryonated chicken eggs as a host cell line for H9 subtype avian influenza virus propagation.
Catalytic Dry Reforming for Biomass‐Based Fuels Processing: Progress and Future Perspectives
Authors: Colmenares Juan Carlos , Colmenares Quintero Ramón Fernando , Pieta Izabela S.
Published: June 2016

We describe and review recent research on potential biomass‐derived fuels consisting of methanol, ethanol, butanol, and carboxylic acids. These fuels possess a volumetric energy densities of 15.6–22.7, 20.9–26.8, and 24.6 (levulinic acid) MJ L−, respectively. We recognize biomass as a valuable, sustainable, and economic fuel source in comparison to fossil fuels. First, we discuss, characterize, and compare all mentioned fuels. Second, we review recent research developments in the continuous pre‐processing for syngas production for biofuels production, specifically concentrating on dry reforming and the catalytic effects on the effluent and process efficiency. Finally, we discuss the future prospects and research needs to realize this technology on a global scale.
Acute and subacute toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the shallow-water coral Porites divaricata: Application of a novel exposure protocol
Authors: Renegar D. Abigail , Turner Nicholas R. , Riegl Bernhard M. , Dodge Richard E. , Knap Anthony H. , Schuler Paul A.
Published: June 2016

Previous research evaluating hydrocarbon toxicity to corals and coral reefs has generally focused on community-level effects, and results often are not comparable between studies because of variability in hydrocarbon exposure characterization and evaluation of coral health and mortality during exposure. Toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the coral Porites divaricata was assessed in a constant exposure toxicity test utilizing a novel toxicity testing protocol uniquely applicable to shallow-water corals, which considered multiple assessment metrics and evaluated the potential for post-exposure mortality and/or recovery. Acute and subacute effects (gross morphological changes, photosynthetic efficiency, mortality, and histologic cellular changes) were evaluated during pre-exposure (4 wk), exposure (48 h), and post-exposure recovery (4 wk) periods. Coral condition scores were used to determine a 48-h median effective concentration of 7442 μg/L. Significant physical and histological changes resulted from exposure to 640 μg/L and 5427 μg/L 1-methylnaphthalene, with a 1-d to 3-d delay in photosynthetic efficiency effects (ΔF/Fm). Pigmented granular amoebocyte area was found to be a potentially useful sublethal endpoint for this species. Coral mortality was used to estimate a 48-h median lethal concentration of 12 123 μg/L. Environ Toxicol Chem 2017;36:212–219. © 2016 SETAC
Effects of silver nanoparticles on the freshwater snail Physa acuta: The role of test media and snails’ life cycle stage
Authors: F. Gonçalves Sandra , D. Pavlaki Maria , Lopes Rafael , Hammes Julia , Gallego-Urrea Julián Alberto , Hassellöv Martin , Jurkschat Kerstin , Crossley Alison , Loureiro Susana
Published: June 2016

Silver nanoparticles (AgNPs) are widely used worldwide, most likely leading to their release into the environment and a subsequent increase of environmental concentrations. Studies of their deleterious effects on organisms is crucial to understand their environmental impacts. The freshwater snail Physa acuta was chosen to evaluate the potential deleterious effects of AgNPs and their counterpart AgNO3, through water-only exposures. The toxicity of AgNPs is greatly influenced by medium composition. Thus, 2 media were tested: artificial pond water (APW) and modified APW (adapted by removing calcium chloride). Acute tests (96 h) were performed with juvenile and adult snails in both media to assess lethality, and egg mass chronic tests were conducted with APW medium only to assess embryo viability and mortality, carried out until 90% hatching success was reached in the control. Acute toxicity increased with decreasing shell length for both silver forms (ion and nanoparticle); that is, juveniles were more sensitive than adults. Different test media led to dissimilar median lethal concentrations, with chloride playing an important role in toxicity, most likely by complexation with silver ions, which would reduce the bioavailability, uptake, and toxicity of silver. Chronic tests showed that hatching success was more sensitive to silver in the ionic form than in the particulate form. Different forms of silver, exposure media, and life cycle stages led to different patterns of toxicity, highlighting an impairment in the snails’ life cycle. Environ Toxicol Chem 2017;36:243–253. © 2016 SETAC
Mobility as an emergent property of biological organization: Insights from experimental evolution
Authors: Wallace Ian J. , Garland Theodore
Published: June 2016

Anthropologists accept that mobility is a critical dimension of human culture, one that links economy, technology, and social relations. Less often acknowledged is that mobility depends on complex and dynamic interactions between multiple levels of our biological organization, including anatomy, physiology, neurobiology, and genetics. Here, we describe a novel experimental approach to examining the biological foundations of mobility, using mice from a long‐term artificial selection experiment for high levels of voluntary exercise on wheels. In this experiment, mice from selectively bred lines have evolved to run roughly three times as far per day as those from nonselected control lines. We consider three insights gleaned from this experiment as foundational principles for the study of mobility from the perspective of biological evolution. First, an evolutionary change in mobility will necessarily be associated with alterations in biological traits both directly and indirectly connected to mobility. Second, changing mobility will result in trade‐offs and constraints among some of the affected traits. Third, multiple solutions exist to altering mobility, so that various combinations of adjustments to traits linked with mobility can achieve the same overall behavioral outcome. We suggest that anthropological knowledge of variation in human mobility might be improved by greater research attention to its biological dimensions.
Time and space in the middle paleolithic: Spatial structure and occupation dynamics of seven open‐air sites
Authors: Clark Amy E.
Published: June 2016

The spatial structure of archeological sites can help reconstruct the settlement dynamics of hunter‐gatherers by providing information on the number and length of occupations. This study seeks to access this information through a comparison of seven sites. These sites are open‐air and were all excavated over large spatial areas, up to 2,000 m2, and are therefore ideal for spatial analysis, which was done using two complementary methods, lithic refitting and density zones. Both methods were assessed statistically using confidence intervals. The statistically significant results from each site were then compiled to evaluate trends that occur across the seven sites. These results were used to assess the “spatial consistency” of each assemblage and, through that, the number and duration of occupations. This study demonstrates that spatial analysis can be a powerful tool in research on occupation dynamics and can help disentangle the many occupations that often make up an archeological assemblage.
Hunter‐gatherer mobility and embedded raw‐material procurement strategies in the mediterranean upper paleolithic
Authors: Tomasso Antonin , Porraz Guillaume
Published: June 2016

Since the early 1980s, the sourcing of lithic raw materials has become central to studies of the territorial range and mobility strategies of Pleistocene foraging societies. Results have been fruitful but somehow repetitive. We will discuss the embedded procurement strategy, which presumes that raw material acquisition was part of other subsistence activities rather than an autonomous technological task. We argue that this theoretical assumption, when taken as dogma, restricts the role of technology in human history and also underestimates the way some lithic resources may have affected the organization of past hunter‐gatherers. We base our discussion on the Upper Paleolithic (UP) from the Liguro‐Provençal arc, with examples from the Proto‐Aurignacian and the Epigravettian. Our regional record shows that in this context the movement of rocks over distances greater than 100 km was the norm rather than the exception. We argue that these long‐distance procurements mirror technical needs that were oriented toward the selection of high‐quality flints. We support the hypothesis that indirect procurement was an important component of regional socio‐economic networks.
VOLIN and KJON—Two novel hyperdiploid myeloma cell lines
Authors: Våtsveen Thea Kristin , Børset Magne , Dikic Aida , Tian Erming , Micci Francesca , Lid Ana H. B. , Meza‐Zepeda Leonardo A. , Coward Eivind , Waage Anders , Sundan Anders , Kuehl W. Michael , Holien Toril
Published: June 2016

Multiple myeloma can be divided into two distinct genetic subgroups: hyperdiploid (HRD) or nonhyperdiploid (NHRD) myeloma. Myeloma cell lines are important tools to study myeloma cell biology and are commonly used for preclinical screening and testing of new drugs. With few exceptions human myeloma cell lines are derived from NHRD patients, even though about half of the patients have HRD myeloma. Thus, there is a need for cell lines of HRD origin to enable more representative preclinical studies. Here, we present two novel myeloma cell lines, VOLIN and KJON. Both of them were derived from patients with HRD disease and shared the same genotype as their corresponding primary tumors. The cell lines' chromosomal content, genetic aberrations, gene expression, immunophenotype as well as some of their growth characteristics are described. Neither of the cell lines was found to harbor immunoglobulin heavy chain translocations. The VOLIN cell line was established from a bone marrow aspirate and KJON from peripheral blood. We propose that these unique cell lines may be used as tools to increase our understanding of myeloma cell biology. © 2016 Wiley Periodicals, Inc.
Evolution of a Shallow Water Wave‐Dominated Shipwreck Site: Fougueux (1805), Gulf of Cadiz
Authors: Fernández‐Montblanc T. , Quinn R. , Izquierdo A. , Bethencourt M.
Published: June 2016

The evolution of the shallow water wave‐dominated Fougueux wreck site in the Gulf of Cadiz was investigated through repeat bathymetric surveys, wave‐ and current‐velocity field measurements, and numerical modeling. This multidisciplinary approach was used to understand the relationships between scouring, morphodynamic change, and hydrodynamic forcing. Field experiments and numerical models indicate that wave processes dominate site evolution. Numerical model outputs indicate current velocity, bed shear stress, orbital velocity, and specially wave fraction breaking (with an increase of 45% and 135% for weak and significant storm conditions, respectively) are all amplified at the site. Scour pits 0.8 m depth inshore and 0.4 m depth offshore of the wreck are developed in response to hydrodynamic forcing. Time‐lapse bathymetric surveys quantify seasonal geomorphological change at the Fougueux. Up to 1.2 m of sediment is deposited and 0.7 m of sediment eroded in response to seasonal wave climate variation (an increase of 0.5 m for mean significant wave height, 0.9 m for significant wave height corresponding to 99% of nonexceedance probability, and 0.4 m·s−1 for mean near‐bed orbital velocity during winter conditions). A two‐dimensional scour model reproduces observed seasonal scour changes. Results have direct applications at all stages of a wreck site investigation.
Post hoc Analysis for Detecting Individual Rare Variant Risk Associations Using Probit Regression Bayesian Variable Selection Methods in Case‐Control Sequencing Studies
Authors: Larson Nicholas B. , McDonnell Shannon , Albright Lisa Cannon , Teerlink Craig , Stanford Janet , Ostrander Elaine A. , Isaacs William B. , Xu Jianfeng , Cooney Kathleen A. , Lange Ethan , Schleutker Johanna , Carpten John D. , Powell Isaac , Bailey‐Wilson Joan , Cussenot Olivier , Cancel‐Tassin Geraldine , Giles Graham , MacInnis Robert , Maier Christiane , Whittemore Alice S. , Hsieh Chih‐Lin , Wiklund Fredrik , Catolona William J. , Foulkes William , Mandal Diptasri , Eeles Rosalind , Kote‐Jarai Zsofia , Ackerman Michael J. , Olson Timothy M. , Klein Christopher J. , Thibodeau Stephen N. , Schaid Daniel J.
Published: June 2016

Rare variants (RVs) have been shown to be significant contributors to complex disease risk. By definition, these variants have very low minor allele frequencies and traditional single‐marker methods for statistical analysis are underpowered for typical sequencing study sample sizes. Multimarker burden‐type approaches attempt to identify aggregation of RVs across case‐control status by analyzing relatively small partitions of the genome, such as genes. However, it is generally the case that the aggregative measure would be a mixture of causal and neutral variants, and these omnibus tests do not directly provide any indication of which RVs may be driving a given association. Recently, Bayesian variable selection approaches have been proposed to identify RV associations from a large set of RVs under consideration. Although these approaches have been shown to be powerful at detecting associations at the RV level, there are often computational limitations on the total quantity of RVs under consideration and compromises are necessary for large‐scale application. Here, we propose a computationally efficient alternative formulation of this method using a probit regression approach specifically capable of simultaneously analyzing hundreds to thousands of RVs. We evaluate our approach to detect causal variation on simulated data and examine sensitivity and specificity in instances of high RV dimensionality as well as apply it to pathway‐level RV analysis results from a prostate cancer (PC) risk case‐control sequencing study. Finally, we discuss potential extensions and future directions of this work.
Human glioblastoma‐associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples
Authors: Szulzewsky Frank , Arora Sonali , de Witte Lot , Ulas Thomas , Markovic Darko , Schultze Joachim L. , Holland Eric C. , Synowitz Michael , Wolf Susanne A. , Kettenmann Helmut
Published: June 2016

Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b+ human glioblastoma‐associated microglia/monocytes (hGAMs) to CD11b+ microglia isolated from non‐tumor samples. Hierarchical clustering and principal component analysis showed a clear separation of the two sample groups and we identified 334 significantly regulated genes in hGAMs. In comparison to human control microglia hGAMs upregulated genes associated with mitotic cell cycle, cell migration, cell adhesion, and extracellular matrix organization. We validated the expression of several genes associated with extracellular matrix organization in samples of human control microglia, hGAMs, and the hGAMs‐depleted fraction via qPCR. The comparison to murine GAMs (mGAMs) showed that both cell populations share a significant fraction of upregulated transcripts compared with their respective controls. These genes were mostly related to mitotic cell cycle. However, in contrast to murine cells, human GAMs did not upregulate genes associated to immune activation. Comparison of human and murine GAMs expression data to several data sets of in vitro‐activated human macrophages and murine microglia showed that, in contrast to mGAMs, hGAMs share a smaller overlap to these data sets in general and in particular to cells activated by proinflammatory stimulation with LPS + INFγ or TNFα. Our findings provide new insights into the biology of human glioblastoma‐associated microglia/monocytes and give detailed information about the validity of murine experimental models. GLIA 2016 GLIA 2016;64:1416–1436
Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1‐CX3CR1 signaling in a mouse model of retinitis pigmentosa
Authors: Zabel Matthew K. , Zhao Lian , Zhang Yikui , Gonzalez Shaimar R. , Ma Wenxin , Wang Xu , Fariss Robert N. , Wong Wai T.
Published: June 2016

Retinitis pigmentosa (RP), a disease characterized by the progressive degeneration of mutation‐bearing photoreceptors, is a significant cause of incurable blindness in the young worldwide. Recent studies have found that activated retinal microglia contribute to photoreceptor demise via phagocytosis and proinflammatory factor production, however mechanisms regulating these contributions are not well‐defined. In this study, we investigate the role of CX3CR1, a microglia‐specific receptor, in regulating microglia‐mediated degeneration using the well‐established rd10 mouse model of RP. We found that in CX3CR1‐deficient (CX3CR1GFP/GFP) rd10 mice microglial infiltration into the photoreceptor layer was significantly augmented and associated with accelerated photoreceptor apoptosis and atrophy compared with CX3CR1‐sufficient (CX3CR1GFP/+) rd10 littermates. CX3CR1‐deficient microglia demonstrated increased phagocytosis as evidenced by (1) having increased numbers of phagosomes in vivo, (2) an increased rate of phagocytosis of fluorescent beads and photoreceptor cellular debris in vitro, and (3) increased photoreceptor phagocytosis dynamics on live cell imaging in retinal explants, indicating that CX3CR1 signaling in microglia regulates the phagocytic clearance of at‐risk photoreceptors. We also found that CX3CR1 deficiency in retinal microglia was associated with increased expression of inflammatory cytokines and microglial activation markers. Significantly, increasing CX3CL1‐CX3CR1 signaling in the rd10 retina via exogenous intravitreal delivery of recombinant CX3CL1 was effective in (1) decreasing microglial infiltration, phagocytosis and activation, and (2) improving structural and functional features of photoreceptor degeneration. These results indicate that CX3CL1‐CX3CR1 signaling is a molecular mechanism capable of modulating microglial‐mediated degeneration and represents a potential molecular target in therapeutic approaches to RP. GLIA 2016;64:1479–1491
Cortico‐cortical and motor evoked potentials to single and paired‐pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study
Authors: Boulogne Sébastien , Andre‐Obadia Nathalie , Kimiskidis Vasilios K , Ryvlin Philippe , Rheims Sylvain
Published: June 2016

Background

Paired‐pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single‐pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico‐cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS.

Objective

The work was intended (i) to verify that the well‐established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico‐cortical connections through modulations of CCEP.

Methods

Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single‐pulse DES (1–3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS‐induced MEPs in two patients.

Results

MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally.

Conclusion

PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico‐cortical connections.Hum Brain Mapp 37:3767–3778, 2016. ©2016 Wiley Periodicals, Inc.
Long‐Term Effects of Famine on Chronic Diseases: Evidence from China's Great Leap Forward Famine
Authors: Hu Xue Feng , Liu Gordon G. , Fan Maoyong
Published: June 2016

We evaluate the long‐term effects of famine on chronic diseases using China's Great Leap Forward Famine as a natural experiment. Using a unique health survey, we explore the heterogeneity of famine intensity across regions and find strong evidence supporting both the adverse effect and the selection effect. The two offsetting effects co‐exist and their magnitudes vary in different age cohorts at the onset of famine. The selection effect is dominant among the prenatal/infant famine‐exposed cohort, while the adverse effect appears dominant among the childhood/puberty famine‐exposed cohort. The net famine effects are more salient in rural residents and non‐migrants subsamples. Gender differences are also found, and are sensitive to smoking and drinking behaviors. Our conclusion is robust to various specifications. Copyright © 2016 John Wiley & Sons, Ltd.
Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study
Authors: Cui Jeffrey , Chen Chi‐Hua , Lo Min‐Tzu , Schork Nicholas , Bettencourt Ricki , Gonzalez Monica P. , Bhatt Archana , Hooker Jonathan , Shaffer Katherine , Nelson Karen E. , Long Michelle T. , Brenner David A. , Sirlin Claude B. , Loomba Rohit , for the Genetics of NAFLD in Twins Consortium
Published: June 2016

Nonalcoholic fatty liver disease is associated with metabolic risk factors including hypertension and dyslipidemia and may progress to liver fibrosis. Studies have shown that hepatic steatosis and fibrosis are heritable, but whether they have a significant shared gene effect is unknown. This study examined the shared gene effects between hepatic steatosis and fibrosis and their associations with metabolic risk factors. This was a cross‐sectional analysis of a prospective cohort of well‐characterized, community‐dwelling twins (45 monozygotic, 20 dizygotic twin pairs, 130 total subjects) from southern California. Hepatic steatosis was assessed with magnetic resonance imaging‐proton density fat fraction and hepatic fibrosis with magnetic resonance elastography. A standard bivariate twin additive genetics and unique environment effects model was used to estimate the proportion of phenotypic variance between two phenotypes accounted for by additive genetic effects and individual‐specific environmental effects. Genetic correlations estimated from this model represent the degree to which the genetic determinants of two phenotypes overlap. Mean (± standard deviation) age and body mass index were 47.1 (±21.9) years and 26.2 (±5.8) kg/m2, respectively. Among the cohort, 20% (26/130) had hepatic steatosis (magnetic resonance imaging‐proton density fat fraction ≥5%), and 8.2% (10/122) had hepatic fibrosis (magnetic resonance elastography ≥3 kPa). Blood pressure (systolic and diastolic), triglycerides, glucose, homeostatic model assessment of insulin resistance, insulin, hemoglobin A1c, and low high‐density lipoprotein had significant shared gene effects with hepatic steatosis. Triglycerides, glucose, homeostatic model assessment of insulin resistance, insulin, hemoglobin A1c, and low high‐density lipoprotein had significant shared gene effects with hepatic fibrosis. Hepatic steatosis and fibrosis had a highly significant shared gene effect of 0.756 (95% confidence interval 0.716‐1, P < 0.0001). Conclusions: Genes involved with steatosis pathogenesis may also be involved with fibrosis pathogenesis. (Hepatology 2016;64:1547‐1558)
Lack of immunological DNA sensing in hepatocytes facilitates hepatitis B virus infection
Authors: Thomsen Martin K. , Nandakumar Ramya , Stadler Daniela , Malo Antje , Valls Roser Marin , Wang Fan , Reinert Line S. , Dagnæs‐Hansen Frederik , Hollensen Anne Kruse , Mikkelsen Jacob Giehm , Protzer Ulrike , Paludan Søren R.
Published: June 2016

Hepatitis B virus (HBV) is a major human pathogen, and about one third of the global population will be exposed to the virus in their lifetime. HBV infects hepatocytes, where it replicates its DNA and infection can lead to acute and chronic hepatitis with a high risk of liver cirrhosis and hepatocellular carcinoma. Despite this, there is limited understanding of how HBV establishes chronic infections. In recent years it has emerged that foreign DNA potently stimulates the innate immune response, particularly type 1 interferon (IFN) production; and this occurs through a pathway dependent on the DNA sensor cyclic guanosine monophosphate‐adenosine monophosphate synthase and the downstream adaptor protein stimulator of IFN genes (STING). In this work we describe that human and murine hepatocytes do not express STING. Consequently, hepatocytes do not produce type 1 IFN in response to foreign DNA or HBV infection and mice lacking STING or cyclic guanosine monophosphate‐adenosine monophosphate synthase exhibit unaltered ability to control infection in an adenovirus‐HBV model. Stimulation of IFN production in the murine liver by administration of synthetic RNA decreases virus infection, thus demonstrating that IFN possesses anti‐HBV activity in the liver. Importantly, introduction of STING expression specifically in hepatocytes reconstitutes the DNA sensing pathway, which leads to improved control of HBV in vivo. Conclusion: The lack of a functional innate DNA‐sensing pathway in hepatocytes hampers efficient innate control of HBV infection; this may explain why HBV has adapted to specifically replicate in hepatocytes and could contribute to the weak capacity of this cell type to clear HBV infection. (Hepatology 2016;64:746‐759)
Inhibition of epoxyeicosatrienoic acid production in rats with cirrhosis has beneficial effects on portal hypertension by reducing splanchnic vasodilation
Authors: Di Pascoli Marco , Zampieri Francesca , Verardo Alberto , Pesce Paola , Turato Cristian , Angeli Paolo , Sacerdoti David , Bolognesi Massimo
Published: June 2016

In cirrhosis, 11,12‐epoxyeicosatrienoic acid (EET) induces mesenteric arterial vasodilation, which contributes to the onset of portal hypertension. We evaluated the hemodynamic effects of in vivo inhibition of EET production in experimental cirrhosis. Sixteen control rats and 16 rats with carbon tetrachloride‐induced cirrhosis were studied. Eight controls and eight rats with cirrhosis were treated with the specific epoxygenase inhibitor N‐(methylsulfonyl)‐2‐(2‐propynyloxy)‐benzenehexanamide (MS‐PPOH; 20 mg/kg/day) for 3 consecutive days. Portal blood flow and renal and splenic resistive indexes were calculated through echographic measurements, while portal and systemic pressures were measured through polyethylene−50 catheters. Small resistance mesenteric arteries were connected to a pressure servo controller in a video‐monitored perfusion system, and concentration‐response curves to phenylephrine and acetylcholine were evaluated. EET levels were measured in tissue homogenates of rat liver, kidney, and aorta, using an enzyme‐linked immunosorbent assay. Urinary Na+ excretion function was also evaluated. In rats with cirrhosis, treatment with MS‐PPOH significantly reduced portal blood flow and portal pressure compared to vehicle (13.6 ± 5.7 versus 25.3 ± 7.1 mL/min/100 g body weight, P < 0.05; 9.6 ± 1.1 versus 12.2 ± 2.3 mm Hg, P < 0.05; respectively) without effects on systemic pressure. An increased response to acetylcholine of mesenteric arteries from rats with cirrhosis (50% effect concentration ‐7.083 ± 0.197 versus ‐6.517 ± 0.73 in control rats, P < 0.05) was reversed after inhibition of EET production (‐6.388 ± 0.263, P < 0.05). In liver, kidney, and aorta from animals with cirrhosis, treatment with MS‐PPOH reversed the increase in EET levels. In both controls and rats with cirrhosis, MS‐PPOH increased urinary Na+ excretion. Conclusion: In rats with cirrhosis, in vivo inhibition of EET production normalizes the response of mesenteric arteries to vasodilators, with beneficial effects on portal hypertension. (Hepatology 2016;64:923‐930)
Vertical sleeve gastrectomy activates GPBAR‐1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice
Authors: Ding Lili , Sousa Kyle M. , Jin Lihua , Dong Bingning , Kim Byung‐Wook , Ramirez Ricardo , Xiao Zhenzhou , Gu Ying , Yang Qiaoling , Wang Jie , Yu Donna , Pigazzi Alessio , Schones Dustin , Yang Li , Moore David , Wang Zhengtao , Huang Wendong
Published: June 2016

Vertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries used for the remission of obesity and diabetes. However, the precise molecular mechanism by which VSG exerts its beneficial effects remains elusive. We report that the membrane‐bound G protein‐coupled bile acid receptor, GPBAR‐1 (also known as TGR5), is required to mediate the effects of anti‐obesity, anti‐hyperglycemia, and improvements of fatty liver of VSG in mice. In the absence of TGR5, the beneficial metabolic effects of VSG in mice are lost. Moreover, we found that the expression of TGR5 increased significantly after VSG, and VSG alters both BA levels and composition in mice, resulting in enhancement of TGR5 signaling in the ileum and brown adipose tissues, concomitant with improved glucose control and increased energy expenditure. Conclusion: Our study elucidates a novel underlying mechanism by which VSG achieves its postoperative therapeutic effects through enhanced TGR5 signaling. (Hepatology 2016;64:760‐773)
SIRT1‐mediated transcriptional regulation of SOX2 is important for self‐renewal of liver cancer stem cells
Authors: Liu Limei , Liu Chungang , Zhang Qianzhen , Shen Junjie , Zhang Heng , Shan Juanjuan , Duan Guangjie , Guo Deyu , Chen Xuejiao , Cheng Jiamin , Xu Yanmin , Yang Zhi , Yao Chao , Lai Maode , Qian Cheng
Published: June 2016

Hepatocellular carcinoma (HCC) is a highly aggressive liver tumor containing cancer stem cells (CSCs), which participate in tumor invasion, therapeutic resistance, and tumor relapse leading to poor outcome and limited therapeutic options. Histone deacetylatase sirtuin 1 (SIRT1) has been shown to be up‐regulated in human cancers; however, its role in liver CSCs is unknown. In this study, we explored the biological functions of SIRT1 in liver CSCs. Our data show that SIRT1 is highly expressed in liver CSCs and decreases during differentiation. In addition, high levels of SIRT1 predict a decreased probability of survival in patients with HCC. SIRT1 is responsible for the maintenance of self‐renewal and tumorigenicity of liver CSCs, and overexpression of exogenous SIRT1 can restore self‐renewal of non‐CSCs. We demonstrated that SOX2 is a main downstream regulator of SIRT1‐mediated self‐renewal and tumorigenicity potential of liver CSCs. Mechanistically, SIRT1 regulates transcription of the SOX2 gene by way of chromatin‐based epigenetic changes, which are dependent on DNA methylation. This effect is achieved by alternation of histone modification and interaction with DNA methyltransferase 3A, resulting in hypermethylation of SOX2 promoter. Furthermore, we demonstrated that insulin growth factor signaling plays an important role in maintaining SIRT1 expression through increased SIRT1 protein stability. Conclusions: These findings highlight the importance of SIRT1 in the biology of liver CSCs and suggest that SIRT1 may serve as a molecular target for HCC therapy. (Hepatology 2016;64:814‐827)
Finding the Latent Semantics of Haptic Interaction Research: A Systematic Literature Review of Haptic Interaction Using Content Analysis and Network Analysis
Authors: Song Joobong , Lim Ji Hyoun , Yun Myung Hwan
Published: June 2016

As interest in multimodal and tangible interfaces is increasing in the field of human–robot interaction and virtual reality, haptics has been researched across areas such as engineering, computer science, psychology, and neuroscience. The main objective of the study was to construct a comprehensive review of the current haptic‐related literature based on quantitative data derived from content analysis and network analysis. Using the results of content analysis and network analysis of 6,000 research articles on haptic interaction, the haptic‐related literature was classified into two categories: 1) studies on technologies providing haptic stimuli and 2) studies on the human perception of haptic stimuli. Emotions in haptic feedback and haptic perception characteristics of various body sites were identified as potential research topics for further investigation. Greater research effort on understanding human haptic sensation and perception using the proposed systematic approach could accelerate the development of haptic interaction technology.
The Impact of Image Dimensions toward Online Consumers’ Perceptions of Product Aesthetics
Authors: Park Jungkun , Gunn Frances
Published: June 2016

Marketers and industrial designers devote considerable attention to the visual attributes of products, based on the premise that the visual appearance of products influences consumers’ judgments of the products’ attributes. This research investigated consumers’ perceptions about particular types of innovative products (revolutionary technology‐driven products), with 275 consumers sample purchased from an independent marketing company. To achieve the main goal, interrelations among image of product and aesthetics of product have been examined using structural equation modeling with two psychological moderators: consumer innovativeness and needs for uniqueness. The results of this study provide evidence that individual differences in uniqueness motivation moderated how online consumers’ perceptions of a product's image characteristics influenced perceptions of value showing consumers’ need for uniqueness was more influential toward perceptions of the product's value than perceptions of functional value. Consequently, these findings expand understanding of the consumer characteristics that respond to perceptions of products’ epistemic value.
Acceptance of the virtual item auctioning system in online games: The role of intrinsic motivation, extrinsic motivation, and trust
Authors: Altin Gumussoy Cigdem
Published: June 2016

The virtual item auctioning system (VIAS) has economic potential as millions of online players trade their virtual items in an auction‐based environment. However, little empirical research has been conducted about understanding the factors affecting the decision to use the VIAS in online games. To address this gap, the current study uses the technology acceptance model (TAM) to explore the effects of extrinsic motivation‐perceived usefulness, intrinsic motivation‐flow, and trust on the decision to use the VIAS in online games. Three hundred and twenty‐eight surveys were gathered from the users of VIAS in online games. The research model was tested with the structural equation modeling technique, using AMOS 20. The results showed that intrinsic motivation is more important than extrinsic motivation in explaining the use of the VIAS. Furthermore, trust is a strong predictor of both intrinsic and extrinsic motivation. We conclude the study with the discussion of the findings, managerial implications, and suggestions for future research. © 2016 Wiley Periodicals, Inc.
New Sterol Derivatives from the Marine Sponge Xestospongia sp.
Authors: Cheng Zhongbin , Liu Dong , de Voogd Nicole J. , Proksch Peter , Lin Wenhan
Published: June 2016

Chemical examination of a marine sponge Xestospongia sp. resulted in the isolation of 20 sterol derivatives (1 – 20), including eight new sterols namely aragusterols J – L (1 – 3), (5α,7α,12β,22E)‐7,12,18‐trihydroxystigmast‐22‐en‐3‐one (4), (5α,7α,12β,24R)‐ and (5α,7α,12β,24S)‐7,12,20‐trihydroxystigmastan‐3‐one (5/6), and (5α,7α,12β,22E,24R)‐ and (5α,7α,12β,22E,24S)‐7,12,20‐trihydroxyergost‐22‐en‐3‐one (7/8). The structures of new compounds were determined through extensive spectroscopic analyses and chemical conversion. The sterol diversity was mainly characterized by the presence of a cyclopropane unit at side chain, while compound 4 with 18‐hydroxymethyl group was found in stigmasterol family for the first time. Cytotoxic test revealed the inhibitory effects of compounds 1, 4, and 17 against human leukemia cell line K562 with IC50 values of 18.3, 24.1, and 34.3 μm, respectively.
Visualizing liver anatomy, physiology and pharmacology using multiphoton microscopy
Authors: Wang Haolu , Liang Xiaowen , Gravot Germain , Thorling Camilla A. , Crawford Darrell H. G. , Xu Zhi Ping , Liu Xin , Roberts Michael S.
Published: June 2016

Multiphoton microscopy (MPM) has become increasingly popular and widely used in both basic and clinical liver studies over the past few years. This technology provides insights into deep live tissues with less photobleaching and phototoxicity, which helps us to better understand the cellular morphology, microenvironment, immune responses and spatiotemporal dynamics of drugs and therapeutic cells in the healthy and diseased liver. This review summarizes the principles, opportunities, applications and limitations of MPM in hepatology. A key emphasis is on the use of fluorescence lifetime imaging (FLIM) to add additional quantification and specificity to the detection of endogenous fluorescent species in the liver as well as exogenous molecules and nanoparticles that are applied to the liver in vivo. We anticipate that in the near future MPM‐FLIM will advance our understanding of the cellular and molecular mechanisms of liver diseases, and will be evaluated from bench to bedside, leading to real‐time histology of human liver diseases.

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Block‐Transitive and Point‐Primitive 2‐ Designs with Sporadic Socle
Authors: Zhang Xiaohong , Zhou Shenglin
Published: June 2016

The purpose of this paper is to classify all pairs , where is a nontrivial 2‐ design, and acts transitively on the set of blocks of and primitively on the set of points of with sporadic socle. We prove that there exists only one such pair : is the unique 2‐(176,8,2) design and , the Higman–Sims simple group.