bluuebunny/crossref_metadata_2025 huggingface dataset:
A humble servant: The work of Helen L. Brownson and the early years of information science research
Authors: Jayroe Tina J.
Published: September 2012

Helen Brownson was a federal government employee from 1942 to 1970. At a time when scientific data were becoming exceedingly hard to manage, Brownson was instrumental in coordinating national and international efforts for more efficient, cost‐effective, and universal information exchange. Her most significant contributions to documentation/information science were during her years at the National Science Foundation's Office of Scientific Information. From 1951 to 1966, Brownson played a key role in identifying and subsequently distributing government funds toward projects that sought to resolve information‐handling problems of the time: information access, preservation, storage, classification, and retrieval. She is credited for communicating the need for information systems and indexing mechanisms to have stricter criteria, standards, and evaluation methods; laying the foundation for present‐day NSF‐funded computational linguistics projects; and founding several pertinent documentation/information science publications including the Annual Review of Information Science and Technology.
Governance of open content creation: A conceptualization and analysis of control and guiding mechanisms in the open content domain
Authors: Schroeder Andreas , Wagner Christian
Published: September 2012

The open content creation process has proven itself to be a powerful and influential way of developing text‐based content, as demonstrated by the success of Wikipedia and related sites. Distributed individuals independently edit, revise, or refine content, thereby creating knowledge artifacts of considerable breadth and quality. Our study explores the mechanisms that control and guide the content creation process and develops an understanding of open content governance. The repertory grid method is employed to systematically capture the experiences of individuals involved in the open content creation process and to determine the relative importance of the diverse control and guiding mechanisms. Our findings illustrate the important control and guiding mechanisms and highlight the multifaceted nature of open content governance. A range of governance mechanisms is discussed with regard to the varied levels of formality, the different loci of authority, and the diverse interaction environments involved. Limitations and opportunities for future research are provided.
Phillip V. Tobias as an anatomist†
Authors: Štrkalj Goran , Pather Nalini
Published: September 2012

The article outlines the career of the renowned South African scientist Phillip Vallentine Tobias. While he made substantial contributions to a number of scientific disciplines, Tobias spent most of his career teaching anatomy at his alma mater, University of the Witwatersrand, Johannesburg, and saw himself primarily as an anatomist. The first part of this article presents Tobias' major contributions to science and demonstrates that his profound knowledge of anatomy was the basis of many of his groundbreaking research accomplishments. The second part of the article focuses on Tobias' career in anatomy and his significant contribution to anatomy teaching and administration, particularly in establishing and organizing the Anatomical Society of Southern Africa. The article also demonstrates how Tobias' academic career was constrained by the oppressive system of apartheid South Africa and how social engagement was an integral part of his intellectual activities. Clin. Anat. 2013. © 2012 Wiley Periodicals, Inc.
Stereoselectivity in the Salt–Cocrystal Products formed by Phenylglycinol or Phenylglycine with their Respective Sodium or Hydrochloride Salts
Authors: Brittain Harry G.
Published: September 2012

The salt and stereoselective cocrystal phenomena associated with 2‐phenylglycinol and 2‐phenylglycine have been studied using X‐ray powder diffraction and differential scanning calorimetry. The chiral identities of the free acids and their sodium salts, or the free bases and their chloride salts, were found to play a determining role as to whether a salt–cocrystal product could or could not be formed. In particular, when cocrystallization of an enantiomerically pure basic or zwitterionic substance with its enantiomerically pure acid addition salt was attempted, a salt–cocrystal was only obtained when the absolute configuration of the two reactants is opposite. On the other hand, it has been found that no stereoselectivity in salt–cocrystal formation existed in the cocrystallization of an enantiomerically pure acidic or zwitterionic substance with its enantiomerically pure base addition salt. Chirality 25:8–15, 2013. © 2012 Wiley Periodicals, Inc.
Manmade Vulnerability of the Cancun Beach System: The Case of Hurricane Wilma
Authors: Casarin Rodolfo Silva , Martinez Gabriel Ruiz , Mariño‐Tapia Ismael , Vanegas Gregorio Posada , Baldwin Edgar Mendoza , Mancera Edgar Escalante
Published: September 2012

Climate change and resultant coastal erosion and flooding have been the focus of many recent analyses. Often these studies overlook the effects of manmade modifications to the coastline which have reduced its resilience to storm events. In this investigation, we integrate previous reports, historical photo analysis, field work, and the application of numerical models to better understand the effects of Wilma, the most destructive hurricane to affect Cancun, Mexico. Huge waves (of significant height, >12 m), long mean wave periods (>12 s), devastating winds (>250 km/h), and powerful currents (>2 m/s) removed >7 million cubic meters of sand from the Cancun beach system, leaving 68% of the sub‐aerial beach as bedrock, and the rest considerably eroded. Numerical simulations show that the modifications to the barrier island imposed by tourist infrastructure have considerably increased the rigidity of the system, increasing the potential erosion of the beach under extreme conditions. If there were no structural barriers, a series of breaches could occur along the beach, allowing exchange of water and alleviating storm surge on other sections of the beach. If the effects caused by anthropogenic changes to Cancun are ignored, the analysis is inaccurate and misleading.
Characterization of Risks in Coastal Zones: A Review
Authors: Escudero Castillo Mireille , Mendoza Baldwin Edgar , Silva Casarin Rodolfo , Posada Vanegas Gregorio , Arganis Juaréz Maritza
Published: September 2012

Interest in sustainable development for the natural, socio‐economic, and cultural resources of coastal zones is growing worldwide. On the other hand, the range of threats to coastal zones increasingly posed by hydro‐meteorological natural phenomena has led to a trend in the analysis and assessment of risks to these areas. The available literature dealing with coastal risk assessment is quite wide, focusing mainly on the risk evaluation of coastal flooding and erosion resulting directly from the occurrence of extreme natural events. The risk assessment methodologies are usually specific to the conditions and available data of each country, society or location, though most have evolved to assess the risk concept more precisely and rigorously. However, there are still very few studies that present feasible and effective methodologies, which lead to the effective integration of risk analysis at all levels. In Mexico coastal risk analysis has barely begun despite our extensive coastline, which is highly vulnerable to the threat of tropical cyclones. This paper aims to give a broad view of the risk assessment methodologies which already exist, in order to provide a starting point for future efforts in Mexico and elsewhere.
Apnea of Prematurity
Authors: Martin Richard J. , Wilson Christopher G.
Published: September 2012

Apnea of prematurity is a significant problem due to immaturity of the central neural control circuitry responsible for integrating afferent input and central rhythm. In this review, we provide an overview of the pathogenesis of apnea of prematurity—including our current understanding of the role that afferent input to the brain stem plays in synergy with the central pattern generation circuitry in the emergence of apnea of prematurity. We then discuss the interplay of apnea, bradycardia, desaturation, as well as the genesis of central, mixed, and obstructive apnea. Finally, we provide a summary of the physiological basis for current therapeutic approaches to treating apnea of prematurity, and conclude with an overview of proposed long‐term consequences of the resultant intermittent hypoxic episodes. © 2012 American Physiological Society.
Compr Physiol
2:2923‐2931, 2012.
Sensory Systems in the Control of Movement
Authors: Prochazka Arthur , Ellaway Peter
Published: September 2012

Animal movement is immensely varied, from the simplest reflexive responses to the most complex, dexterous voluntary tasks. Here, we focus on the control of movement in mammals, including humans. First, the sensory inputs most closely implicated in controlling movement are reviewed, with a focus on somatosensory receptors. The response properties of the large muscle receptors are examined in detail. The role of sensory input in the control of movement is then discussed, with an emphasis on the control of locomotion. The interaction between central pattern generators and sensory input, in particular in relation to stretch reflexes, timing, and pattern forming neuronal networks is examined. It is proposed that neural signals related to bodily velocity form the basic descending command that controls locomotion through specific and well‐characterized relationships between muscle activation, step cycle phase durations, and biomechanical outcomes. Sensory input is crucial in modulating both the timing and pattern forming parts of this mechanism. © 2012 American Physiological Society.Compr Physiol2:2615‐2627, 2012.
Cell Migration
Authors: Trepat Xavier , Chen Zaozao , Jacobson Ken
Published: September 2012

Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part, of cell locomotion, from large‐scale migrations of epithelial sheets during gastrulation, to the movement of individual cells during development of the nervous system. In an adult organism, cell migration is essential for proper immune response, wound repair, and tissue homeostasis, while aberrant cell migration is found in various pathologies. Indeed, as our knowledge of migration increases, we can look forward to, for example, abating the spread of highly malignant cancer cells, retarding the invasion of white cells in the inflammatory process, or enhancing the healing of wounds. This article is organized in two main sections. The first section is devoted to the single‐cell migrating in isolation such as occurs when leukocytes migrate during the immune response or when fibroblasts squeeze through connective tissue. The second section is devoted to cells collectively migrating as part of multicellular clusters or sheets. This second type of migration is prevalent in development, wound healing, and in some forms of cancer metastasis.© 2012 American Physiological Society.Compr Physiol2:2369‐2392, 2012.
Nonclassical Renin‐Angiotensin System and Renal Function
Authors: Chappell Mark C.
Published: September 2012

The renin‐angiotensin system (RAS) constitutes one of the most important hormonal systems in the physiological regulation of blood pressure through renal and nonrenal mechanisms. Indeed, dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies, including kidney injury, and blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or blockade of the angiotensin type 1 receptor (AT1R) by selective antagonists constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS within the kidney and other tissues that the system is actually composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE‐Ang II‐AT1R axis that promotes vasoconstriction, water intake, sodium retention, and other mechanisms to maintain blood pressure, as well as increase oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions. In contrast, the nonclassical RAS composed primarily of the AngII/Ang III‐AT2R pathway and the ACE2‐Ang‐(1‐7)‐AT7R axis generally opposes the actions of a stimulated Ang II‐AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and reduced oxidative stress. Moreover, increasing evidence suggests that these non‐classical RAS components contribute to the therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury, as well as contribute to normal renal function. © 2012 American Physiological Society.Compr Physiol2:2733‐2752, 2012.
Mass spectrometry made easy: The quest for simplicity
Authors: Schwab Nicolas V. , Eberlin Marcos N.
Published: September 2012

Mass spectrometry (MS) is generally viewed as a highly complex and demanding technique, full of difficulties and apprehensions. Ease and simplicity have been infrequently used descriptors of MS but a series of revolutionary developments is turning a complex technique into a model of simplicity, making MS easier than ever. Focusing on spray‐based ambient desorption/ionization techniques, we discuss how previously unthinkable goals for MS – (1) to bring it to a real world open atmosphere environment; (2) to perform fast, selective, and highly sensitive chemical and biochemical MS analysis with ease while (3) avoiding pre‐separation and sample work‐up for samples in their natural environment and therefore, at the end, (4) to make MS accessible in wherever MS is needed and by whoever needs it – have become feasible. Without compromising the unique combination of high speed, selectivity, sensitivity and separation competences, simplicity has become a new MS attribute – a fifth ‘S’ in the unique 5 S set of MS trademark features. Copyright © 2012 John Wiley & Sons, Ltd.
Using dopamine research to generate rational cannabinoid drug policy
Authors: Loewinger G.C. , Oleson E.B. , Cheer J.F.
Published: September 2012

The recent rise in the recreational use of synthetic cannabinoids (e.g. ‘K2’ and ‘Spice’) has been accompanied by a corresponding increase in regulation. Besides prohibition of specific compounds and general class bans in over forty states, five synthetic cannabinoids (CB) are federally regulated under a ‘temporary’ ban and are currently under a formal review to determine whether to permanently schedule them. Whether through explicit prohibition of specific chemicals, or potential de facto bans of unofficially scheduled compounds through the analogue act, scheduling CBs may significantly impede researching their therapeutic utility and elucidating physiological roles of the endogenous CB system. We argue that a review of neuroscience research suggests that synthetic CBs that act like Δ9‐tetrahydrocannabinol (THC) by directly binding to and stimulating CB receptors (i.e. direct agonists), as well as novel drugs that indirectly stimulate these receptors by increasing levels of endogenous CB neurotransmitters (i.e. indirect agonists) have therapeutic value. Specifically, neurochemical research into how CBs influence mesolimbic dopamine release, a reliable and consistent marker of drugs’ rewarding/reinforcing effects, provides the most useful indication of CB abuse liability, and may have implications for the generation of rational drug policy. It demonstrates that direct CB receptor agonists, but not indirect agonists, increase mesolimbic dopamine release. Thus, while direct CB receptor agonists pose an abuse liability, indirect agonists do not. We recommend regulatory agencies revise policies that treat these separate CB classes similarly and to curb regulation aimed at any CB receptor agonists as Schedule I, as this ignores their medicinal properties. Copyright © 2012 John Wiley & Sons, Ltd.
Effects ofCO2enrichment on photosynthesis, growth, and nitrogen metabolism of the seagrassZostera noltii
Authors: Alexandre Ana , Silva João , Buapet Pimchanok , Björk Mats , Santos Rui
Published: September 2012

Seagrass ecosystems are expected to benefit from the global increase inCO2in the ocean because the photosynthetic rate of these plants may be Ci‐limited at the currentCO2level. As well, it is expected that lower external pHwill facilitate the nitrate uptake of seagrasses if nitrate is cotransported with H+across the membrane as in terrestrial plants. Here, we investigate the effects ofCO2enrichment on both carbon and nitrogen metabolism of the seagrassZostera noltiiin a mesocosm experiment where plants were exposed for 5 months to two experimentalCO2concentrations (360 and 700 ppm). Both the maximum photosynthetic rate (Pm) and photosynthetic efficiency (α) were higher (1.3‐ and 4.1‐fold, respectively) in plants exposed toCO2‐enriched conditions. On the other hand, no significant effects ofCO2enrichment on leaf growth rates were observed, probably due to nitrogen limitation as revealed by the low nitrogen content of leaves. The leaf ammonium uptake rate and glutamine synthetase activity were not significantly affected by increasedCO2concentrations. On the other hand, the leaf nitrate uptake rate of plants exposed toCO2‐enriched conditions was fourfold lower than the uptake of plants exposed to currentCO2level, suggesting that in the seagrassZ. noltiinitrate is not cotransported with H+as in terrestrial plants. In contrast, the activity of nitrate reductase was threefold higher in plant leaves grown at high‐CO2concentrations. Our results suggest that the global effects ofCO2on seagrass production may be spatially heterogeneous and depend on the specific nitrogen availability of each system. Under aCO2increase scenario, the natural levels of nutrients will probably become limiting forZ. noltii. This potential limitation becomes more relevant because the expected positive effect ofCO2increase on nitrate uptake rate was not confirmed.
Quantitative proteomic analysis reveals that lipopolysaccharide induces mitogen‐activated protein kinase‐dependent activation in human microglial cells
Authors: Byun Kyunghee , Young Kim Jin , Bayarsaikhan Enkhjargal , Kim Daesik , Jeong Goo‐Bo , Yun Ki Na , Kyeong Min Hye , Kim Seung U. , Yoo Jong Shin , Lee Bonghee
Published: September 2012

Microglial cells act as the first and main form of active immune defense in the central nervous system related to inflammation and neurodegenerative disease. Lipopolysaccharide (LPS) induces many genes encoding inflammatory mediators, including cytokines such as tumor necrosis factor‐α, interleukin‐1β, (IL‐1β), and IL‐6, chemokines, and prostaglandins in microglial cells. Quantitative proteomics methods with isobaric chemical labeling using tandem mass tags and 2D‐nano LC‐ESI‐MS/MS were used to systematically analyze proteomic changes in microglia responding to LPS stimulation. As a result, we found that the expression level of 21 proteins in human microglial cells changed after activation. Among those, one of the strong mitogen‐activated protein kinase (MAPK) regulator proteins, CMPK1 was highly upregulated after LPS stimulation in human microglial cells. We detected and validated upregulation of MAPK including ERK1/2, p38, and SAPK/JNK by immunohistochemistry and Western blotting. NFκB, strong transcription factor of CMPK1, was translocated to the nucleus from the cytosol by high contents screening after LPS stimulation. Taken together, we conclude that MAPK signaling plays an important role in LPS‐induced human microglial activation related to inflammatory response.
Mechanisms to limit higher mode effects in a controlled rocking steel frame. 2: Large‐amplitude shake table testing
Authors: Wiebe Lydell , Christopoulos Constantin , Tremblay Robert , Leclerc Martin
Published: September 2012

This paper presents the results of 56 large‐amplitude shake table tests of a 30% scale eight‐storey controlled rocking steel frame. No significant damage or residual deformations were observed after any of the tests. The frame had four possible configurations on the basis of combinations of two higher mode mitigation mechanisms. The first mitigation mechanism was formed by allowing the upper section of the frame to rock, so as to better control the mid‐height overturning moment. The second mitigation mechanism was formed by replacing the conventional first‐storey brace with a self‐centering energy dissipative (SCED) brace, so as to better control the base shear. The mechanisms had little effect during records where higher mode effects were not apparent, but they substantially reduced the shear and overturning moment envelopes, as well as the peak floor accelerations, during more demanding records. The reduction in storey shears led to similarly reduced brace force demands. Although the peak force demands in the columns were not reduced by as much as the frame overturning moments, using an upper rocking joint allowed the column demands to be estimated without the need to assume a lateral force distribution. The tests demonstrated that multiple force‐limiting mechanisms can be used to provide better control of peak seismic forces without excessive increases in drift demands, thus enabling more reliable capacity design. These results are expected to be widely applicable to structures where the peak seismic forces are significantly influenced by higher mode effects. Copyright © 2012 John Wiley & Sons, Ltd.
IFITm1 Is a Tight Junction Protein That Inhibits Hepatitis C Virus Entry
Authors: Wilkins Courtney , Woodward Jessica , Lau Daryl T.-Y. , Barnes Amy , Joyce Michael , McFarlane Nicola , McKeating Jane A. , Tyrrell Lorne D. , Gale Michael
Published: September 2012

Type 1 interferon (IFN) continues to be the foundation for the current standard of care combination therapy for chronic hepatitis C virus (HCV) infection, yet the component interferon-stimulated genes (ISGs) that mediate the antiviral actions of IFN are not fully defined. Interferon-induced transmembrane protein 1 (IFITM1) is an ISG product that suppresses early stage infection by a number of viruses through an unknown mechanism of action. Moreover, the actions of IFITM1 on HCV infection are not fully elucidated. Here we identify IFITM1 as a hepatocyte tight junction protein and a potent anti-HCV effector molecule. IFITM1 expression is induced early during IFN treatment of hepatocytes and accumulates at hepatic tight junctions in HCV-infected human patient liver during IFN therapy. Additionally, we found that IFITM1 interacts with HCV coreceptors, including CD81 and occludin, to disrupt the process of viral entry. Thus, IFITM1 is an anti-HCV ISG whose actions impart control of HCV infection through interruption of viral coreceptor function.

Conclusion:

This study defines IFITM1 as an ISG effector with action against HCV entry. Design of therapy regimens to enhance IFITM1 expression should improve the virologic response among HCV patients undergoing treatment with type I IFN.
Therapeutic Effect of Cytotoxic T Lymphocyte Antigen 4/Immunoglobulin on a Murine Model of Primary Biliary Cirrhosis
Authors: Dhirapong Amy , Yang Guo-Xiang , Nadler Steven , Zhang Weici , Tsuneyama Koichi , Leung Patrick , Knechtle Stuart , Ansari Aftab A. , Coppel Ross L. , Liu Fu-Tong , He Xiao-Song , Gershwin Eric M.
Published: September 2012

Collectively, the data in both humans and murine models of human primary biliary cirrhosis (PBC) suggest that activated T cells, particularly CD8 T cells, play a critical role in biliary cell destruction. Under physiological conditions, T-cell activation involves two critical signals that involve the major histocompatibility complex and a set of costimulatory molecules, which include a receptor on T cells termed cytotoxic T lymphocyte antigen 4 (CTLA-4). Germane to the studies reported herein, signaling by CTLA-4 has the potential to modulate costimulation and induce inhibitory signals. In this study, we have taken advantage of our well-defined murine model of PBC, in which mice are immunized with 2-octynoic acid coupled to bovine serum albumin (2OA-BSA), leading to the production of high-titer antimitochondrial autoantibodies (AMAs) and portal cellular infiltrates. To investigate the potential of CTLA-4-Ig (immunoglobulin) as an immunotherapeutic agent, we treated mice both before and after induction of autoimmune cholangitis. First, we demonstrate that CTLA-4-Ig treatment, begun 1 day before 2OA-BSA immunization, completely inhibits the manifestations of cholangitis, including AMA production, intrahepatic T-cell infiltrates, and bile duct damage. However, and more critically, treatment with CTLA-4-Ig, initiated after the development of autoimmune cholangitis in previously immunized mice, also resulted in significant therapeutic benefit, including reduced intrahepatic T-cell infiltrates and biliary cell damage, although AMA levels were not altered.

Conclusion:

These data suggest that an optimized regimen with CTLA-4-Ig has the potential to serve as an investigative therapeutic tool in patients with PBC.
Hepatopulmonary syndrome: Favorable outcomes in the MELD exception era
Authors: Iyer Vivek N. , Swanson Karen L. , Cartin-Ceba Rodrigo , Dierkhising Ross A. , Rosen Charles B. , Heimbach Julie K. , Wiesner Russell H. , Krowka Michael J.
Published: September 2012

Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality, regardless of the cause or severity of liver disease. Liver transplantation (LT) improves survival in HPS. We present the largest consecutive series of HPS patients specifically addressing long-term survival relative to the degree of hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan-Meier methodology. LT was accomplished in 49 HPS patients. Post-LT survival (1, 3, 5, and 10 years) did not differ between groups based on baseline partial pressure of arterial oxygen (PaO2) obtained at the time of HPS diagnosis. Improvements in overall survival at 1, 3, and 5 years post-LT in those HPS patients transplanted after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively) did not reach statistical significance (5-year

P

= 0.09). Model for Endstage Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since January 1 2002 with post-LT survival of 19/21 patients and one wait-list death.

Conclusion:

Long-term outcome after LT in HPS is favorable, with a trend towards improved survival in the MELD exception era since 2002 as compared to earlier HPS transplants. Survival after LT was not associated with PaO2 levels at the time of HPS diagnosis.
MicroRNA-10a Is Involved in the Metastatic Process by Regulating Eph Tyrosine Kinase Receptor A4-Mediated Epithelial-Mesenchymal Transition and Adhesion in Hepatoma Cells
Authors: Yan Yan , Luo Yue-Chen , Wan Hai-Ying , Wang Jun , Zhang Pei-Pei , Liu Min , Li Xin , Li Shengping , Tang Hua
Published: September 2012

MicroRNAs (miRNAs) have been reported to be associated with the development of cancers. However, the function of miRNAs in human hepatocellular carcinoma (HCC) remains largely undefined. Here we found that overexpression of miR-10a promoted the migration and invasion of QGY-7703 and HepG2 cells

in vitro

but suppressed metastasis

in vivo

. Cell adhesion assays showed that miR-10a suppressed HCC cell-matrix adhesion, which could explain the results of the

in vivo

animal experiments. The Eph tyrosine kinase receptor,

EphA4

, was identified as the direct and functional target gene of miR-10a. Knockdown of

EphA4

phenocopied the effect of miR-10a and ectopic expression of

EphA4

restored the effect of miR-10a on migration, invasion, and adhesion in HCC cells. We further demonstrated that miR-10a and

EphA4

regulated the epithelial-mesenchymal transition process and the β1-integrin pathway to affect cell invasion and adhesion.

Conclusion:

Our findings highlight the importance of miR-10a in regulating the metastatic properties of HCC by directly targeting

EphA4

and may provide new insights into the pathogenesis of HCC.
Hepatic fat loss in advanced nonalcoholic steatohepatitis: Are alterations in serum adiponectin the cause?
Authors: van der Poorten David , Samer Caroline F. , Ramezani-Moghadam Mehdi , Coulter Sally , Kacevska Marina , Schrijnders Dennis , Wu Lindsay E. , McLeod Duncan , Bugianesi Elisabetta , Komuta Mina , Roskams Tania , Liddle Christopher , Hebbard Lionel , George Jacob
Published: September 2012

Advanced liver fibrosis in nonalcoholic steatohepatitis (NASH) is often accompanied by a reduction in hepatic fat to the point of complete fat loss (burnt-out NASH), but the mechanisms behind this phenomenon have not been elucidated. Adiponectin is raised in cirrhosis of any cause and has potent antisteatotic activity. In this study we examined 65 patients with advanced biopsy-proven NASH (fibrosis stage 3-4) and 54 with mild disease (fibrosis stage 0-1) to determine if disappearance of steatosis correlated with changes in serum adiponectin. All patents had fasting blood tests and anthropometric measures at the time of liver biopsy. Liver fat was accurately quantitated by morphometry. Serum adiponectin was measured by immunoassay. When compared to those with early disease, patients with advanced NASH were more insulin-resistant, viscerally obese, and older, but there was no difference in liver fat content or adiponectin levels. Adiponectin had a significant negative correlation with liver fat percentage in the whole cohort (

r

= −0.28,

P

< 0.01), driven by patients with advanced NASH (

r

= −0.40,

P

< 0.01). In advanced NASH, for each 4 μg/L increase in adiponectin there was an odds ratio OR of 2.0 (95% confidence interval [CI]: 1.3-3.0,

P

< 0.01) for a 5% reduction in hepatic fat. Adiponectin was highly and significantly associated with almost complete hepatic fat loss or burnt-out NASH (12.1 versus 7.4 μg/L,

P

= 0.001) on multivariate analysis. A relationship between adiponectin, bile acids, and adipocyte fexaramine activation was demonstrated

in vivo

and

in vitro

, suggestive of hepatocyte-adipocyte crosstalk.

Conclusion:

Serum adiponectin levels in advanced NASH are independently associated with hepatic fat loss. Adiponectin may in part be responsible for the paradox of burnt-out NASH.
The perceptions of dislocated workers under the Workforce Investment Act
Authors: Wilson Michael S. , Brown James M.
Published: September 2012

This descriptive qualitative case study investigated the perceptions of dislocated workers offered program services through the Workforce Investment Act's (WIA) Dislocated Worker program in Minnesota. This research focused on recently dislocated workers who lost their jobs through no fault of their own and hence were eligible for unemployment insurance. Semistructured interviews were conducted with a total of nine participants, who described their perceptions of their experiences of being offered services by the Minnesota Dislocated Worker program. The participants' perceptions were analyzed based on socially responsible human resource development. Participants confirmed they had reservations about using government services, and were stressed about career counseling and job search services. These results may stimulate further debate regarding public policies affecting dislocated workers, and implications for practice are provided along with future research suggestions.
Ultra‐deep sequencing reveals hidden HIV‐1 minority lineages and shifts of viral population between the main cellular reservoirs of the infection after therapy interruption
Authors: Rozera Gabriella , Abbate Isabella , Ciccozzi Massimo , Presti Alessandra Lo , Bruselles Alessandro , Vlassi Chrysoula , D'Offizi Gianpiero , Narciso Pasquale , Giombini Emanuela , Bartolini Barbara , Ippolito Giuseppe , Capobianchi Maria R.
Published: September 2012

Viral quasispecies population dynamics between monocytes and T‐lymphocytes were analyzed in patients after highly active antiretroviral therapy (HAART) interruption, during a follow‐up of 3–6 months. V3 env region underwent ultra‐deep pyrosequencing. Co‐receptor usage prediction was performed by Position Specific Score Matrix Analysis. Phylogenetic trees were constructed to evaluate the relationships between the variants. Gene flow was also investigated. Even though at the moment of therapy interruption monocyte‐derived HIV‐1 genomes presented higher genetic heterogeneity than that of T‐lymphocytes, at subsequent times, this difference in genetic heterogeneity disappeared, due to different waves of expansion and reduction of quasispecies variability associated with monocytes and T‐lymphocytes. Phylogenetic analysis and gene flow evaluation supported the hypothesis of extensive interchange of variants between cellular compartments of the infection. A spread of proviral X4 lineages hidden in monocytes to T cells was observed, but this was not associated with an overall shift towards CXCR4 using variants during the observation period. J. Med. Virol. 84:839–844, 2012. © 2012 Wiley Periodicals, Inc.
Immunological and viral features in patients with overactive bladder associated with human T‐cell lymphotropic virus type 1 infection
Authors: Santos Silvane Braga , Oliveira Paulo , Luna Tania , Souza Anselmo , Nascimento Márcia , Siqueira Isadora , Tanajura Davi , Muniz André Luiz , Glesby Marshall J. , Carvalho Edgar M.
Published: September 2012

The majority of patients infected with human T‐cell lymphotropic virus‐type 1 (HTLV‐1) are considered carriers, but a high frequency of urinary symptoms of overactive bladder, common in HTLV‐1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) have been documented in these patients. The aim of this study was to determine if immunological and viral factors that are seen in HAM/TSP are also observed in these patients. Participants were classified as HTLV‐1 carriers (n = 45), HTLV‐1 patients suffering from overactive bladder (n = 45) and HAM/TSP (n = 45). Cells from HTLV‐1 overactive bladder patients produced spontaneously more proinflammatory cytokines than carriers. TNF‐α and IL‐17 levels were similar in HAM/TSP and HTLV‐1 overactive bladder patients. High proviral load was found in patients with overactive bladder and HAM/TSP and correlated with proinflammatory cytokines. In contrast with findings in patients with HAM/TSP, serum levels of Th1 chemokines were similar in HTLV‐1 overactive bladder and carriers. Exogenous addition of regulatory cytokines decreased spontaneous IFN‐γ production in cell cultures from HTLV‐1 overactive bladder patients. The results show that HTLV‐1 overactive bladder and HAM/TSP patients have in common some immunological features as well as similar proviral load profile. The data show that HTLV‐1 overactive bladder patients are still able to down regulate their inflammatory immune response. In addition, these patients express levels of chemokines similar to carriers, which may explain why they have yet to develop the same degree of spinal cord damage as seen in patients with HAM/TSP. These patients present symptoms of overactive bladder, which may be an early sign of HAM/TSP. J. Med. Virol. 84:1809–1817, 2012. © 2012 Wiley Periodicals, Inc.
Gender differences in hepatitis C seroprevalence and suboptimal vaccination and hepatology services uptake amongst substance misusers
Authors: Marufu Muchandidemba , Williams Hugh , Hill Samuel L , Tibble Jeremy , Verma Sumita
Published: September 2012

Injecting drug users are the principal at risk group for blood borne viruses. The aim was to assess the feasibility of screening substance misusers for blood borne viruses, and to offer appropriate vaccinations/referral to hepatology services. This was a nurse led prospective 6‐month study based at a large Substance Misuse Service in south east England. Of the 196 consecutive individuals assessed, 81 were eligible for HBV immunization of whom only 33.3% completed a vaccination course. Prevalence of positive serological markers were: anti‐HBc 14.4%, HBsAg 1.5%, and HCV antibody 37.9%. Compared to men, women were more likely to accept blood borne virus testing (83.3% vs. 62.3%), have ever injected (89.6% vs. 76.3%), overdose (54.2% vs. 23.6%), be anti‐HBc positive (27.5% vs. 8.8%), drink alcohol above national recommended guidelines (41.7% vs. 25.7%), and have a positive HCV serology (55% vs. 30.4%) (P ≤ 0.05 for all). Of the 73 individuals identified with a positive HBsAg and or HCV antibody, only 14 (19.1%) were known to hepatology services and 8 (20%) of those eligible subsequently accepted a specialist referral. In conclusion, serological markers for blood borne viruses remain high in substance misusers (anti‐HBc 14.4%, HCV antibody 37.9%), with women more likely to be positive. Overall, only 33.3% and 20%, respectively, complete HBV vaccination and accept a hepatology referral. A multidisciplinary approach is paramount to address both the blood borne viruses and the substance misuse and realignment of hepatitis services to Substance Misuse Services may offer such a strategy. J. Med. Virol. 84:1737–1743, 2012. © 2012 Wiley Periodicals, Inc.
Impact of seminal cytomegalovirus replication on HIV‐1 dynamics between blood and semen
Authors: Gianella Sara , Mehta Sanjay R. , Strain Matthew C. , Young Jason A. , Vargas Milenka V. , Little Susan J. , Richman Douglas D. , Pond Sergei L. Kosakovsky , Smith Davey M.
Published: September 2012

The genital tract of individuals infected with human immunodeficiency virus type 1 (HIV‐1) is an anatomic compartment that supports local HIV‐1 and cytomegalovirus (CMV) replication. This study investigated the association of seminal CMV replication with changes in HIV‐1 clonal expansion, evolution and phylogenetic compartmentalization between blood and semen. Fourteen paired blood and semen samples were analyzed from four untreated subjects. Clonal sequences (n = 607) were generated from extracted HIV‐1 RNA (env C2‐V3 region), and HIV‐1 and CMV levels were measured in the seminal plasma by real‐time PCR. Sequence alignments were evaluated for: (i) viral compartmentalization between semen and blood samples using Slatkin–Maddison and FST methods, (ii) different nucleotide substitution rates in semen and blood, and (iii) association between proportions of clonal HIV‐1 sequences in each compartment and seminal CMV levels. Half of the semen samples had detectable CMV DNA, with at least one CMV positive sample for each patient. Seminal CMV DNA levels correlated positively with seminal HIV‐1 RNA levels (Spearman P = 0.05). A trend towards an association between compartmentalization of HIV‐1 sequences sampled from blood and semen and presence of seminal CMV was observed (Cochran Q test P = 0.12). Evolutionary rates between semen and blood HIV‐1 populations did not differ significantly, and there was no significant association between seminal CMV DNA levels and the frequency of non‐unique clonal HIV‐1 sequences in the semen. In conclusion, the effects of CMV replication on HIV‐1 viral and immunologic dynamics within the male genital tract are not significant enough to perturb evolution or disrupt compartmentalization in the genital tract. J. Med. Virol. 84:1703–1709, 2012. © 2012 Wiley Periodicals, Inc.
Distribution of hepatitis C virus genotypes in a diverse US integrated health care population
Authors: Manos M. Michele , Shvachko Valentina A. , Murphy Rosemary C. , Arduino Jean Marie , Shire Norah J.
Published: September 2012

Hepatitis C virus (HCV) genotypes influence response to therapy, and recently approved direct‐acting antivirals are genotype‐specific. Genotype distribution information can help to guide antiviral development and elucidate infection patterns. HCV genotype distributions were studied in a diverse cross‐section of patients in the Northern California Kaiser Permanente health plan. Associations between genotype and race/ethnicity, age, and sex were assessed with multivariate logistic regression models. The 10,256 patients studied were median age 56 years, 62% male, 55% White non‐Hispanic. Overall, 70% were genotype 1, 16% genotype 2, 12% genotype 3, 1% genotype 4, <1% genotype 5, and 1% genotype 6. Blacks (OR 4.5 [3.8–5.5]) and Asians (OR 1.2 [1.0–1.4]) were more likely to have genotype 1 than 2/3 versus non‐Hispanic Whites. Women less likely had genotype 1 versus 2/3 than did men (OR 0.86 [0.78–0.94]). Versus non‐Hispanic Whites, Asians (OR 0.38 [0.31–0.46]) and Blacks (OR 0.73 [0.63–0.84]) were less likely genotype1a than 1b; Hispanics (OR 1.3 [1.1–1.5]) and Native Americans (OR 1.9 [1.2–2.8]) more likely had genotype 1a than 1b. Patients age ≥65 years less likely had genotype 1a than 1b versus those age 45–64 (OR 0.34 [0.29–0.41]). The predominance of genotype 1 among all groups studied reinforces the need for new therapies targeting this genotype. Racial/ethnic variations in HCV genotype and subtype distribution must be considered in formulating new agents and novel strategies to successfully treat the diversity of hepatitis C patients. J. Med. Virol. 84:1744–1750, 2012. © 2012 Wiley Periodicals, Inc.
The intriguing case of silicon crystals unveiled in ancient mosaic tesserae
Authors: Di Martino Daniela , Galli Anna , Martini Marco
Published: September 2012

Mosaic glasses are very heterogeneous materials, and their characterization highly benefits from investigation by micro‐analytical techniques. In this regard, ancient mosaic tesserae belonging to Daphni Monastery (Greece, XI century) were analysed by micro‐Raman spectroscopy. In all the samples, some silicon nanocrystals were disclosed within the silica amorphous matrix of glass mosaics. This result, together with statistical analysis, suggests that a singular glass production site was the origin of all the investigated glass tesserae supporting the hypothesis of local glass making in contrast with raw materials supplied only from Middle East or Egypt. Copyright © 2012 John Wiley & Sons, Ltd.
Aspartic protease from Aspergillus (Eurotium) repens strain MK82 is involved in the hydrolysis and decolourisation of dried bonito (Katsuobushi)
Authors: Aoki Kenji , Matsubara Sayaka , Umeda Mayo , Tachibanac Shusaku , Doi Mikiharu , Takenaka Shinji
Published: September 2012

Background

Katsuobushi is a dried, smoked and fermented bonito used in Japanese cuisine. During the fermentation process with several Aspergillus species, the colour of Katsuobushi gradually changes from a dark reddish‐brown derived from haem proteins to pale pink. The change in colour gives Katsuobushi a higher ranking and price. This study aimed to elucidate the mechanism of decolourisation of Katsuobushi.

Results

A decolourising factor from the culture supernatant of Aspergillus (Eurotium) repens strain MK82 was purified to homogeneity. The purification was monitored by measuring the decolourising activity using equine myoglobin and bovine haemoglobin as substrates. It was found that the decolourising factor had protease activity towards myoglobin and haemoglobin. Complete inhibition of the enzyme by the inhibitor pepstatin A and the internal amino acid sequence classified the protein as an aspartic protease. The enzyme limitedly hydrolysed myoglobin between 1‐Met and 2‐Gly, 43‐Lys and 44‐Phe, and 70‐Leu and 71‐Thr. The purified enzyme decolourised blood of Katsuwonus pelamis (bonito) and a slice of dried bonito.

Conclusion

It is proposed that aspartic protease plays a role in the decolourisation of Katsuobushi by the hydrolysis of haem proteins that allows the released haem to aggregate in the dried bonito.
Analysis of zearalenone and α‐zearalenol in 100 foods and medicinal plants determined by HPLC‐FLD and positive confirmation by LC‐MS‐MS
Authors: Kong Wei‐Jun , Shen Hong‐Hong , Zhang Xiao‐Fei , Yang Xiao‐Li , Qiu Feng , Ou‐yang Zhen , Yang Mei‐Hua
Published: September 2012

Background

Mycotoxins, which may contaminate many foods and medicinal plants, are poisonous to humans. A high‐performance liquid chromatography with fluorescence detection (HPLC‐FLD) method was successfully developed for analysing the contamination levels of zearalenone (ZON) and its metabolite α‐zearalenol (α‐ZOL) in 100 widely consumed foods and medicinal plants in China. Samples were extracted with methanol–water (80:20, v/v), and cleaned up by using an immunoaffinity column.

Results

The limits of detection of this developed method for ZON and α‐ZOL were 4 µg kg−1 and 2.5 µg kg−1, respectively. Recoveries for the samples spiked with three levels (30, 60 and 300 µg kg−1 for ZON and α‐ZOL) ranged from 85.8% to 96.1% with relative standard deviation (RSD) of 2.6–7.1% for ZON, and from 89.9% to 98.7% with RSD of 1.9–9.2% for α‐ZOL. Twelve (12%) of these tested samples were contaminated with ZON at levels ranging from 5.3 to 295.8 µg kg−1. The most contaminated samples were Semen coicis, four of them in a concentration level exceeding 60 µg kg−1 ‘maximum level’ (range 68.9–119.6 µg kg−1). Positive samples were further confirmed by liquid chromatography–tandem mass spectrometry.

Conclusion

The results suggest that it is necessary to control ZON contamination in medicinal plants, especially Semen coicis. This is a successful study on the analysis of ZON and α‐ZOL in medicinal plants in China by HPLC‐FLD. Immunoaffinity clean‐up and HPLC‐FLD proved to have broad applicability in the field of simultaneously detecting ZON and α‐ZOL in foods and medicinal plants and other complicated matrices.© 2012 Society of Chemical Industry
An optimized approach for enrichment of glycoproteins from cell culture lysates using native multi‐lectin affinity chromatography
Authors: Lee Ling Y. , Hincapie Marina , Packer Nicolle , Baker Mark S. , Hancock William S. , Fanayan Susan
Published: September 2012

Lectins are capable of recognizing specific glycan structures and serve as invaluable tools for the separation of glycosylated proteins from nonglycosylated proteins in biological samples. We report on the optimization of native multi‐lectin affinity chromatography, combining three lectins, namely, concanavalin A, jacalin, and wheat germ agglutinin for fractionation of cellular glycoproteins from MCF‐7 breast cancer lysate. We evaluated several conditions for optimum recovery of total proteins and glycoproteins such as low pH and saccharide elution buffers, and the inclusion of detergents in binding and elution buffers. Optimum recovery was observed with overnight incubation of cell lysate with lectins at 4°C, and inclusion of detergent in binding and saccharide elution buffers. Total protein and bound recoveries were 80 and 9%, respectively. Importantly, we found that high saccharide strength elution buffers were not necessary to release bound glycoproteins. This study demonstrates that multi‐lectin affinity chromatography can be extended to total cell lysate to investigate the cellular glycoproteome.