bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluctuations of Raikot Glacier during the past 70 years: a case study from the Nanga Parbat massif, northern Pakistan
Authors: Schmidt Susanne , Nüsser Marcus
Published: February 2010

The Himalaya has some of the largest glacier concentrations outside the polar regions. Despite this, long-term measurements detecting the impact of global warming and changing precipitation patterns on glaciers are rare. The Nanga Parbat massif in northern Pakistan is an exception. The cartographer and glaciologist R. Finsterwalder investigated glacier dynamics of this mountain massif in the 1930s, and several other studies document changes since then. The aim of this study is to detect and analyse the changes of Raikot Glacier over the past seven decades. We use a multitemporal and multiscale approach, based on repeat terrestrial images, additional historical data and remotely sensed imagery (Corona, ASTER, Landsat, QuickBird). The multitemporal approach covers the period 1934–2007. While the analyses show a total glacier retreat of ~200 m in 73 years, this general trend was interrupted by a significant glacier advance between the 1950s and 1980s. Although down-wasting processes can be inferred from an increase in debris-covered area, a general trend of reduced glacier thickness does not appear significant over the whole observation period.
The effects of meltwater percolation on the seasonal isotopic signals in an Arctic snowpack
Authors: Moran Tara , Marshall Shawn
Published: February 2010

We investigate the evolution of snow temperature, water content, density and stable water isotopes of δ18O at four Arctic snow-pit sites during early-season melt, in order to understand the effects of melt on snowpack stratigraphies and seasonal isotopic signals. We relate isotopic changes observed at these sites to temperature reconstructions derived from a 33 year firn-core record drilled on the same icefield. Decreases in seasonal isotopic amplitudes observed at all but one snow-pit site coincide with the percolation of more enriched meltwater into the snowpack, suggesting that meltwater percolation is the dominant process causing isotopic redistribution in Arctic snowpacks during the melt season. The decrease in isotopic range was accompanied by increases in mean δ18O values at all snow-pit sites. Positive degree-day (PDD) calculations are used to relate the amount of melt observed at the low-elevation snow-pit sites to the firn-core site. Results based on PDD values suggest an average overestimation of 1.1°C in average annual temperature reconstructions from the firn-core site from 1967 to 2006, with the possibility of errors in excess of 3°C during high-melt years.
Using radar-sounding data to identify the distribution and sources of subglacial water: application to Dome C, East Antarctica
Authors: Carter Sasha Peter , Blankenship Donald D. , Young Duncan A. , Holt John W.
Published: February 2010

Basal radar reflectivity is the most important measurement for the detection of subglacial water. However, dielectric loss in the overlying ice column complicates the determination of basal reflectivity. Dielectric attenuation is a function of ice temperature and impurity concentration. Temperature distribution is a function of climate history, basal heat flow and vertical strain rate, all of which can be partially inferred from the structure of dated internal layers. Using 11 dated layers, isotope records from Dome C, East Antarctica, and a model of the spatial variation of geothermal flux, we calculate the vertical strain rate and accumulation-rate history, allowing identification of areas where the basal melt rate exceeds 1.5 mm a−1. The accumulation-rate history and vertical strain rates are then used as inputs for a transient temperature model. The model outputs for the present-day temperature distribution are then combined with depth-dependent ionic concentrations to model dielectric loss and infer basal reflectivity. The resulting reflection coefficients are consistent (∼−5 dB) across a variety of subglacial water bodies. We also identify a high reflectivity >−15 dB in Concordia Trench and along suspected subglacial water-flow routes in Vincennes Basin. Highland areas tend to have highly variable reflection coefficients near −30 dB, consistent with an ice–bedrock interface. This combined model also identifies three areas of enhanced basal melting along Concordia Ridge, Concordia Subglacial Lake and Vincennes Basin. Melt at Concordia Subglacial Lake exceeds 5 mm a−1. The inferred basal melt at these locations is not possible without enhanced geothermal flux. We demonstrate how radar-sounding data can provide both input and verification for a self-consistent model of vertical strain, vertical temperature distribution and meltwater distribution.
Identification and characteristics of surge-type glaciers on Novaya Zemlya, Russian Arctic
Authors: Grant Katie L. , Stokes Chris R. , Evans Ian S.
Published: February 2010

We present a comprehensive new inventory of surge-type glaciers on the Novaya Zemlya archipelago, using high-resolution (up to 4 m) satellite imagery from 1976/77 (Hexagon), 1989 (Landsat TM), 2001 (Landsat ETM+) and 2006 (ASTER). A total of 692 glaciers and their forelands were observed for glaciological and geomorphological criteria indicative of glacier surging (e.g. looped moraines, heavy surface crevassing, surface potholes, thrust-block moraines, concertina eskers). This enabled the identification of 32 potential surge-type glaciers (compared with four previously identified) representing 4.6% of the total but 18% by glacier area. We assess the characteristics of surge-type glaciers. Surge-type glaciers are statistically different from non-surge-type glaciers in terms of their area, length, surface slope, minimum elevation, mid-range elevation and terminus type. They are typically long (median length 18.5 km), large (median area 106.8 km2) outlet glaciers, with relatively low overall surface slopes (median slope 1.7°) and tend to terminate in water (marine or lacustrine). They are predominantly directed towards and located in the more maritime western region of the Russian Arctic, and we suggest that surge occurrence might be related to large and complex catchment areas that receive increased delivery of precipitation from the Barents Sea.
An Analysis of the Effects of Cooperative Advertising on Tourism
Authors: McKinney William B. , Hazeldine Mary F. , Chawla Sudhir K.
Published: February 2010

A 2 × 2 factorial experimental design was used to test the effect of cooperative advertising on an individual's propensity to visit an area. Cooperative advertising and co-op programs both refer to advertising communication whose sponsorship and cost are shared by more than one
party. The term partner refers to either other cities/towns or various types of business entities. For the tourism industry the main object of co-op programs is to create demand for an area as a tourist destination of choice and demand for local goods/services offered by co-op partners. Results
showed that visitor preference for cooperative advertisements increased in situations where advertisements were viewed for low effectiveness, that is, the level of advertising or copy effectiveness/believability was low. This was especially true for historical and average city types. Differences
in visiting preferences between business and leisure travelers were not supported by the data. It is suggested that small towns embrace cooperative advertising strategies to help attract tourists.
Evaluating Historical Districts: Exploring the Use of Photographs and Slide Experiments
Authors: Naoi Taketo , Airey David , Iijima Shoji
Published: February 2010

This study explores approaches and methods to investigate visitors' evaluation of historical districts. Personal interviews with use of repertory grid analysis and laddering analysis and slide experiments with photographs were conducted with a sample of students to reveal relationships
between various evaluative components. The results of the two sets of methods are examined in a comparative manner to obtain abundant insights into evaluations of historical districts and the efficacy of these methods. The results provide insights into issues raised by past studies. Particularly,
they shed light on the complex nature of visitors' evaluation of historical districts, as represented by the mixed effects of the presence of other people, commercialization, and modernity. Personal interviews and slide experiments are found to be mutually complementary in that, while the
former illuminate the complex relationships between components of subjects' evaluations, the latter depict these relationships in a more holistic and simple form by uncovering the commonality between the elicited components. The findings of the slide experiments also suggest room for further
attempts to elicit evaluative components. Further studies of this kind with different groups of subjects and in different field settings would provide further insights into this complex area.
Independent Bicycle Tourism: A Whole Tourism Systems Perspective
Authors: Lamont Matthew
Published: February 2010

Leiper's model of whole tourism systems is a useful conceptual framework for generic research into tourism. However, several limitations can be identified regarding its capacity to describe elements that comprise whole tourism systems involving independent bicycle tourism. This article
draws on a combination of empirical evidence, existing literature, and critical analysis to demonstrate how two geographic elements of whole tourism systems, transit routes and tourist destination regions, can be reconceptualized to better reflect tourist flows associated with independent
bicycle tourism. It is suggested that for independent bicycle tourists, the concept of a destination is multidimensional. Furthermore, two distinct transit routes used by such tourists are identified. An adapted model of whole tourism systems specific to independent bicycle tourism is proposed
and implications for theory and practice are discussed as are avenues for future research.
Tourism Destination Attractiveness: Attractions, Facilities, and People as Predictors
Authors: Vengesayi Sebastian , Mavondo Felix T. , Reisinger Yvette
Published: February 2010

This article examines the influence of tourist attractions, destination support services, and people related factors on the attractiveness of a tourism destination. A sample consists of 275 tourists visiting major tourism destinations. Through moderated regression of models the study
identifies the main contributors to destination attractiveness. Destination attractions are found to be the core determinants of the attractiveness; destination support facilities and services, and people-related factors are the secondary determinants. Support facilities and services and people-related
factors explain equivalent variances suggesting they are complementary rather than substitutes.
Expectation Maximization Algorithm Cluster Analysis for UK National Trust Visitors
Authors: Cang Shuang
Published: February 2010

This article aims to investigate the segmenting of UK National Trust (NT) visitors based on behavior and motivation for the visit. The main focus of the article is to apply the more powerful, robust, and stable expectation maximization (EM) algorithm cluster analysis method together
with PCA (without varimax rotation), which is rarely used in a tourism context, to the NT data set. This study identifies four clusters of NT visitors, and also identifies the most important items (questions) in the classification of NT visitors, which is the satisfaction with the NT service.
The intracluster inequality, which means the diversity of the cluster, is also analyzed. Each cluster has its own characteristics and the results of cluster analysis will be useful for future NT marketing management to maximize the benefit to the NT. The diversity of each cluster is also discussed.
Ant Colony Optimization Approach for Estimating Tourism Receipts and Expenditures: The Case of Turkey
Authors: Toksari M. Duran , Toksari Murat
Published: February 2010

The present study develops two forms to estimate tourism receipts and expenditures to Turkey based on ant colony optimization (ACO) approach. ACO approach is first used to estimate tourism receipts and expenditures. Tourism has become one of the largest and most rapidly growing sectors
in the world economy during the second half of the 20th century. So forecasting correctly tourism receipts and expenditures is vital for economics. ACO is a multiagent system in which the behavior of each ant is inspired by the foraging behavior of real ants to solve an optimization problem.
Ant Colony Optimization Tourism Receipt Estimation (ACOTRE) model uses the gross national product (GNP), balance of receipt – expenditure, rate of tourism receipts in the export earnings, and average expenditure per foreigner. Furthermore, Ant Colony Optimization Tourism Expenditure
Estimation (ACOTEE) model uses the GNP, balance of receipt – expenditure, rate of tourism expenditure in the import earnings, and average expenditure per citizen. Linear and quadratic forms of both ACOTRE and ACOTEE are proposed and quadratic models of both provided better fit solution.
The proposed models can be used as an alternative solution for estimating tourism receipts to any country. The ACOTRE and ACOTEE models plan the tourism receipts to Turkey until 2025 under some scenarios.
How do we Get Baby Boomers and Future Seniors on Motorcoaches?
Authors: Hung Kam , Petrick James F.
Published: February 2010

The world population is aging. The large number of baby boomers and their substantial consumption power suggests a potential market for tourism businesses. This study investigated how the industry has responded to the change of market. A case study was conducted with the Bus Owners
Association of Québec (APAQ) in Québec, Canada to reveal some of the practices that the organization has implemented in order to get baby boomers on motorcoaches. Results of the study suggest that marketers need to closely monitor the changing profile of baby boomers and constantly
renovate tourism products/services in order to respond to emerging customers' needs. Based on the case study and past literature, marketing implications on how to effectively target baby boomers and future seniors are suggested.
Sex Tourism in Northern Cyprus: Investigating the Current Situation
Authors: Cansel Aril , Ekiz Erdogan H. , Bavik Ali
Published: February 2010

Tourism and sex have commonalities in providing services that satisfy basic physiological and psychological needs of human beings. Traveling to different places for relaxation, excitement and/or fun seeking and related services are long been considered as areas of research in tourism
marketing. In this sense, this article deals with controversial side of tourism, sex tourism, by investigating the current situation in an unrecognized country on a Mediterranean island. This article argues that, although it is not been spoken out loud by the government officials and tourism
scholars, “sex tourism,” by being the fourth “S” after sea, sun, and sand, has the potential to put Turkish Republic of Northern Cyprus (TRNC) on the international tourism map, again. Results of several interviews with “involved parties” and review of the
published work suggested that ongoing body trade in Northern Cyprus is a “civilized one” where sex workers are willingly work and consider this as their “summer jobs.”
The Role of Large Mammals and Protected Areas to Tourist Satisfaction in the Northern Circuit, Tanzania
Authors: Okello Moses Makonjio , Grasty Katie
Published: February 2010

The quality of a tourist trip through diversifying attractions and tourist experiences enhances destination loyalty and tourism satisfaction. The Northern Circuit of Tanzania contains six parks that bring many tourists to the country. Information was gathered about tourist satisfaction
and attractions in for each protected area in the area. Tourists were most satisfied with Ngorongoro Conservation Area followed by Serengeti and Lake Manyara because of the high density, diversity, and visibility of large mammals. The large mammals mostly sought by tourists were large mammals
rather than only members of the Big Five. Kilimanjaro and Arusha had a relatively low popularity compared to Ngorongoro, Serengeti and Lake Manyara parks. It is recommended that the unique contribution of each of the protected areas be highlighted for each protected area in a joint tourism
planning and marketing endeavor.
Are spurred cyathia a key innovation? Molecular systematics and trait evolution in the slipper spurges (Pedilanthus clade:Euphorbia, Euphorbiaceae)
Authors: Cacho N. Ivalú , Berry Paul E. , Olson Mark E. , Steinmann Victor W. , Baum David A.
Published: February 2010

The study of traits that play a key role in promoting diversification is central to evolutionary biology. Floral nectar spurs are among the few plant traits that correlate with an enhanced rate of diversification, supporting the claim that they are key innovations. Slight changes in spur morphology could confer some degree of premating isolation, explaining why clades with spurs tend to include more species than their spurless close relatives. We explored whether the cyathial nectar spur of the Pedilanthus clade (Euphorbia) may also function as a key innovation. We estimated the phylogeny of the Pedilanthus clade using one plastid (matK) and three nuclear regions (ITS and twoG3pdhloci) and used our results and a Yule model of diversification to test the hypothesis that the cyathial spur correlates with an increased diversification rate. We found a lack of statistical support for the key innovation hypothesis unless specific assumptions regarding the phylogeny apply. However, the young age (hence small size) of the group may limit our ability to detect a significant increase in diversification rate. Additionally, our results confirm previous species designations, indicate higher homoplasy in cyathial than in vegetative features, and suggest a possible Central American origin of the group.
Patterns of genetic diversity in colonizing plant species: Nassauvia lagascae var. lanata (Asteraceae: Mutisieae) on Volcán Lonquimay, Chile
Authors: López Patricio G. , Tremetsberger Karin , Stuessy Tod F. , Gómez‐González Susana , Jiménez Alejandra , Baeza Carlos M.
Published: February 2010

The effect of colonization on the distribution of genetic diversity within and among populations in relation to species characteristics remains an open empirical question. The objective of this study was to contrast genetic diversity within and among established and colonizing populations of Nassauvia lagascae var. lanata on Volcán Lonquimay (Araucanía Region, Chile), which erupted on 25 December 1988, and relate genetic diversity to biological characteristics of the populations. We analyzed a total of 240 individuals from 15 populations distributed along the Andes Cordillera using AFLP and obtained a total of 307 AFLP bands, of which 97.7% are polymorphic. Values of population differentiation (FST) did not differ significantly among established and colonizing populations, but colonizing populations did have reduced levels of genetic divergence (as indicated by private and rare bands) and genetic variation (e.g., Shannon index). We conclude that a founder effect through limited numbers of founding propagules derived from nearby source populations has not yet been compensated for by subsequent population growth and migration. Low rates of secondary dispersal via running water, kin‐structure within populations, and slow population growth seem to contribute to the slow recovery of genetic diversity.
The role of nodding stems in the goldenrod–gall–fly interaction: A test of the “ducking” hypothesis
Authors: Wise Michael J. , Abrahamson Warren G. , Cole Julia A.
Published: February 2010

Herbivores are among the most pervasive selective forces acting on plants, and the number of plant chemicals that presumably evolved for defense against herbivory is immense. In contrast, biologists are only beginning to appreciate the important roles that architectural traits can play in antiherbivore defense. One putative architectural‐resistance trait is the nodding stem apex of some goldenrods (Solidago; Asteraceae). Individuals of S. altissima genets that undergo temporary nodding in the late spring (i.e., “candy‐cane” ramets) have been shown to be more resistant than individuals of erect‐stemmed genets to certain apex‐attacking herbivores. We tested the hypothesis that the greater resistance of candy‐cane ramets is accomplished by the ramets’ “ducking” from the herbivores. In a greenhouse experiment, nodding candy‐cane ramets were significantly more resistant to oviposition by the gall‐inducing fly Eurosta solidaginis than were ramets of the same genets that had been experimentally straightened. The straightened candy‐cane stems were just as susceptible to ovipositions as were ramets of erect‐stemmed genets. Thus, ducking indeed appears to confer a resistance advantage to candy‐cane genets of S. altissima.
Biogeography of Cedrela (Meliaceae, Sapindales) in Central and South America
Authors: Muellner Alexandra N. , Pennington Terence D. , Koecke A. Valerie , Renner Susanne S.
Published: February 2010

Dated phylogenies have helped clarify the complex history of many plant families that today are restricted to the world's tropical forests, but that have Eocene, Oligocene, and Miocene fossils from the northern hemisphere. One such family is the Meliaceae. Here we infer the history of the neotropical Meliaceae genus Cedrela (17 species), the sister clade of which today is restricted to tropical Asia. Sequences from the nuclear ribosomal spacer region and five plastid loci obtained for all ingroup species and relevant outgroups were used to infer species relationships and for molecular‐clock dating under two Bayesian relaxed clock models. The clock models differed in their handling of rate autocorrelation and sets of fossil constraints. Results suggest that (1) crown group diversification in Cedrela started in the Oligocene/Early Miocene and intensified in the Late Miocene and Early Pliocene, and (2) Central American Cedrela species do not form a clade, implying reentry into Central America after the closure of the Panamanian Isthmus. At present, Cedrela is distributed in both dry and humid habitats, but morphological features suggest an origin in dry forest under seasonal climates, fitting with Miocene and Pliocene Cedrela fossils from deciduous forests.
Measuring wood specific gravity…Correctly
Authors: Williamson G. Bruce , Wiemann Michael C.
Published: February 2010

The specific gravity (SG) of wood is a measure of the amount of structural material a tree species allocates to support and strength. In recent years, wood specific gravity, traditionally a forester's variable, has become the domain of ecologists exploring the universality of plant functional traits and conservationists estimating global carbon stocks. While these developments have expanded our knowledge and sample of woods, the methodologies employed to measure wood SG have not received as much scrutiny as SG's ecological importance. Here, we reiterate some of the basic principles and methods for measuring the SG of wood to clarify past practices of foresters and ecologists and to identify some of the prominent errors in recent studies and their consequences. In particular, we identify errors in (1) extracting wood samples that are not representative of tree wood, (2) differentiating wood specific gravity from wood density, (3) drying wood samples at temperatures below 100°C and the resulting moisture content complications, and (4) improperly measuring wood volumes. In addition, we introduce a new experimental technique, using applied calculus, for estimating SG when the form of radial variation is known, a method that significantly reduces the effort required to sample a tree's wood.
Characterization of polymorphic microsatellite loci in Haageocereus (Trichocereeae, Cactaceae)
Authors: Arakaki Mónica , Soltis Douglas E. , Soltis Pamela S. , Speranza Pablo R.
Published: February 2010

• Premise of the study: Microsatellites were isolated from two species of the genus Haageocereus (H. tenuis and H. pseudomelanostele) to be applied in studies of genetic diversity and population structure.

• Methods and Results: Five loci were employed in a preliminary study of genetic diversity and population differentiation in two rare (H. tenuis and H. repens) and two widespread (H. acranthus and H. pseudomelanostele) species, yielding between one and 44 alleles per locus. All five loci were polymorphic, with overall levels of observed and expected heterozygosities ranging from 0.478 to 0.871 and from 0.564 to 0.956, respectively. Three additional loci were scored in H. pseudomelanostele. These eight plus the remaining 11 loci were amplified from putative parents of three hybrids involving Haageocereus and Espostoa.

• Conclusions: These markers will facilitate analysis of genetic diversity, hybridization, and population differentiation throughout Haageocereus and Espostoa.
Dibutyl Phthalate-Induced Thymic Stromal Lymphopoietin Is Required for Th2 Contact Hypersensitivity Responses
Authors: Larson Ryan P. , Zimmerli Simone C. , Comeau Michael R. , Itano Andrea , Omori Miyuki , Iseki Masanori , Hauser Conrad , Ziegler Steven F.
Published: February 2010

Thymic stromal lymphopoietin (TSLP) is an IL-7–related cytokine, produced by epithelial cells, that has been linked to atopic dermatitis and asthma; however, it remains unclear how TSLP shapes the adaptive immune response that causes these allergic disorders. In this study, we demonstrate a role for TSLP in a Th2 model of contact hypersensitivity in mice. TSLP is required for the development of Th2-type contact hypersensitivity induced by the hapten FITC in combination with the sensitizing agent dibutyl phthalate. TSLPR-deficient mice exhibited a dramatically reduced response, including markedly reduced local infiltration by eosinophils, Th2 cytokine production, and serum IgE levels, following FITC sensitization and challenge. The reduced response by TSLPR-deficient mice is likely due to decreased frequency and reduced T cell stimulatory function of skin-derived Ag-bearing FITC+CD11c+ dendritic cells in draining lymph nodes following FITC sensitization. These data suggest that skin-derived dendritic cells are direct or indirect targets of TSLP in the development of type 2 immune responses in the skin, where TSLP drives their maturation, accumulation in skin draining lymph nodes, and ability to induce proliferation of naive allergen-specific T cells.
Thymic Stromal Lymphopoietin-Activated Plasmacytoid Dendritic Cells Induce the Generation of FOXP3+ Regulatory T Cells in Human Thymus
Authors: Hanabuchi Shino , Ito Tomoki , Park Woon-Ryon , Watanabe Norihiko , Shaw Joanne L. , Roman Eulogia , Arima Kazuhiko , Wang Yui-Hsi , Voo Kui Shin , Cao Wei , Liu Yong-Jun
Published: February 2010

Human thymus contains major dendritic cell (DC) subsets, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs). We previously showed that mDCs, educated by thymic stromal lymphopoietin (TSLP) produced by the epithelial cells of the Hassall’s corpuscles, induced differentiation of CD4+CD25− thymocytes into Forkhead Box P3+ (FOXP3+) regulatory T cells (TR) within the medulla of human thymus. In this study, we show that pDCs expressed the TSLP receptor and IL-7 receptor α complexes upon activation and became responsive to TSLP. TSLP-activated human pDCs secrete macrophage-derived chemokine CCL-22 and thymus- and activation-regulated chemokine CCL-17 but not Th1- or Th2-polarizing cytokines. TSLP-activated pDCs induced the generation of FOXP3+ TR from CD4+CD8−CD25− thymocytes, which could be strongly inhibited by Th1-polarizing cytokine IL-12 or Th2-polarizing cytokine IL-4. Interestingly, the FOXP3+ TR induced by the TSLP-pDCs expressed more IL-10 but less TGF-β than that induced by the TSLP-mDCs. These data suggest that TSLP expressed by thymic epithelial cells can activate mDCs and pDCs to positively select the FOXP3+ TR with different cytokine production potential in human thymus. The inability of TSLP to induce DC maturation without producing Th1- or Th2-polarizing cytokines may provide a thymic niche for TR development.
Modulation of T Lymphocyte Function by the Pregnane X Receptor
Authors: Dubrac Sandrine , Elentner Andreas , Ebner Susanne , Horejs-Hoeck Jutta , Schmuth Matthias
Published: February 2010

The pregnane X receptor (PXR) is a ligand-activated transcription factor regulating genes central to drug and hormone metabolism in the liver. Previous reports indicated that PXR is expressed in PBMC, but the role of PXR in immune cells remains unknown. In this paper, we report increased PXR expression in mouse and human T lymphocytes upon immune activation. Furthermore, pharmacologic activation of PXR inhibits T lymphocyte proliferation and anergizes T lymphocytes by decreasing the expression of CD25 and IFN-γ and decreasing phosphorylated NF-κB and MEK1/2. Although these effects are preceded by an increase of suppressor of cytokine signaling 1, a master switch for IFN-γ expression, in a PXR-dependent manner, T-bet expression remains unchanged. Conversely, PXR-deficient mice exhibit an exaggerated T lymphocyte proliferation and increased CD25 expression. Furthermore, PXR-deficient lymphocytes produce more IFN-γ and less of the anti-inflammatory cytokine IL-10. In summary, these results reveal a novel immune-regulatory role of PXR in T lymphocytes and identify suppressor of cytokine signaling 1 as an early signal in PXR-mediated T lymphocyte suppression.
Dendritic Cell Inhibition Is Connected to Exhaustion of CD8+ T Cell Polyfunctionality during Chronic Hepatitis C Virus Infection
Authors: Rodrigue-Gervais Ian Gaël , Rigsby Hawley , Jouan Loubna , Sauvé Dominike , Sékaly Rafick-Pierre , Willems Bernard , Lamarre Daniel
Published: February 2010

Although chronic viral infections have evolved mechanisms to interfere with aspects of pathogen recognition by dendritic cells (DCs), the role that these APCs play in virus-specific T cell exhaustion is unclear. Herein we report that NS3-dependent suppression of Toll/IL-1 domain-containing adapter-inducing IFN-β– and IFN-β promoter stimulator-1– but not MyD88-coupled pathogen-recognition receptor–induced synthesis of proinflammatory cytokines (IL-12 and TNF-α) from DCs by hepatitis C virus (HCV) is a distinctive feature of a subgroup of chronically infected patients. The result is decreased CD8+ T cell polyfunctional capacities (production of IFN-γ, IL-2, TNF-α, and CD107a mobilization) that is confined to HCV specificities and that relates to the extent to which HCV inhibits DC responses in infected subjects, despite comparable plasma viral load, helper T cell environments, and inhibitory programmed death 1 receptor/ligand signals. Thus, subjects in whom pathogen-recognition receptor signaling in DCs was intact exhibited enhanced polyfunctionality (i.e., IL-2-secretion and CD107a). In addition, differences between HCV-infected patients in the ability of CD8+ T cells to activate multiple functions in response to HCV did not apply to CD8+ T cells specific for other immune-controlled viruses (CMV, EBV, and influenza). Our findings identify reversible virus evasion of DC-mediated innate immunity as an additional important factor that impacts the severity of polyfunctional CD8+ T cell exhaustion during a chronic viral infection.
PI3K-Dependent Upregulation of Mcl-1 by Human Cytomegalovirus Is Mediated by Epidermal Growth Factor Receptor and Inhibits Apoptosis in Short-Lived Monocytes
Authors: Chan Gary , Nogalski Maciej T. , Bentz Gretchen L. , Smith M. Shane , Parmater Alexander , Yurochko Andrew D.
Published: February 2010

Monocytes are a primary target for human CMV (HCMV) infection and are a key cell type responsible for hematogenous dissemination of the virus. Biologically, these cells have a short lifespan of 1–3 d in the circulation, yet infected cells remain viable for weeks despite the lack of viral antiapoptotic gene expression during this period. To understand the mechanism by which HCMV inhibits the initial phase of monocyte apoptosis, we focused on the viral modulation of early prosurvival cell signaling events after infection. We demonstrate in this study that the viral upregulation of the PI3K pathway promotes an early block in apoptosis after infection. Temporal transcriptome and protein analyses revealed Mcl-1, a member of the Bcl-2 family, was transiently induced in a PI3K-dependent manner during the early stages of HCMV infection. In accord with the survival studies, virally induced levels of Mcl-1 expression dissipated to mock levels by 72 h postinfection. Through the use of Mcl-1–specific small interfering RNA, we confirmed the functional role that Mcl-1 plays as a key early regulator of apoptosis in monocytes. Lastly, we showed that HCMV engagement and activation of the epidermal growth factor receptor during viral binding triggered the upregulation of Mcl-1. Overall, our data indicates that activation of the epidermal growth factor receptor/PI3K signaling pathway, via the PI3K-dependent upregulation of Mcl-1, is required to circumvent apoptosis in naturally short-lived monocytes during the early stages of HCMV infection, thus ensuring the early steps in the viral persistence strategy.
Diet-Induced Obesity Impairs the T Cell Memory Response to Influenza Virus Infection
Authors: Karlsson Erik A. , Sheridan Patricia A. , Beck Melinda A.
Published: February 2010

The Centers for Disease Control and Prevention has suggested that obesity may be an independent risk factor for increased severity of illness from the H1N1 pandemic strain. Memory T cells generated during primary influenza infection target internal proteins common among influenza viruses, making them effective against encounters with heterologous strains. In male, diet-induced obese C57BL/6 mice, a secondary H1N1 influenza challenge following a primary H3N2 infection led to a 25% mortality rate (with no loss of lean controls), 25% increase in lung pathology, failure to regain weight, and 10- to 100-fold higher lung viral titers. Furthermore, mRNA expression for IFN-γ was >60% less in lungs of obese mice, along with one third the number of influenza-specific CD8+ T cells producing IFN-γ postsecondary infection versus lean controls. Memory CD8+ T cells from obese mice had a >50% reduction in IFN-γ production when stimulated with influenza-pulsed dendritic cells from lean mice. Thus, the function of influenza-specific memory T cells is significantly reduced and ineffective in lungs of obese mice. The reality of a worldwide obesity epidemic combined with yearly influenza outbreaks and the current pandemic makes it imperative to understand how influenza virus infection behaves differently in an obese host. Moreover, impairment of memory responses has significant implications for vaccine efficacy in an obese population.
Endoplasmic Reticulum Aminopeptidase Associated with Antigen Processing Defines the Composition and Structure of MHC Class I Peptide Repertoire in Normal and Virus-Infected Cells
Authors: Blanchard Nicolas , Kanaseki Takayuki , Escobar Hernando , Delebecque Frédéric , Nagarajan Niranjana A. , Reyes-Vargas Eduardo , Crockett David K. , Raulet David H. , Delgado Julio C. , Shastri Nilabh
Published: February 2010

The MHC class I (MHC-I) molecules ferry a cargo of peptides to the cell surface as potential ligands for CD8+ cytotoxic T cells. For nearly 20 years, the cargo has been described as a collection of short 8-9 mer peptides, whose length and sequences were believed to be primarily determined by the peptide-binding groove of MHC-I molecules. Yet the mechanisms for producing peptides of such optimal length and composition have remained unclear. In this study, using mass spectrometry, we determined the amino acid sequences of a large number of naturally processed peptides in mice lacking the endoplasmic reticulum aminopeptidase associated with Ag processing (ERAAP). We find that ERAAP-deficiency changed the oeuvre and caused a marked increase in the length of peptides normally presented by MHC-I. Furthermore, we observed similar changes in the length of viral peptides recognized by CD8+ T cells in mouse CMV-infected ERAAP-deficient mice. In these mice, a distinct CD8+ T cell population was elicited with specificity for an N-terminally extended epitope. Thus, the characteristic length, as well as the composition of MHC-I peptide cargo, is determined not only by the MHC-I peptide-binding groove but also by ERAAP proteolysis in the endoplasmic reticulum.
Effect of Silicate‐Substitution on Attachment and Early Development of Human Osteoblast‐Like Cells Seeded on Microporous Hydroxyapatite Discs
Authors: Guth Katharina , Campion Charlie , Buckland Tom , Hing Karin A.
Published: February 2010

Hydroxyapatite (HA) is a well‐established graft material used in bone repair. Silicon‐substituted hydroxyapatite (SA; 0.8 wt% Si) has shown greater bone ingrowth and bone coverage than phase pure HA. To assess the effect of microporosity on sensitivity of cell attachment to surface physiochemistry, microporous SA and HA discs, and control Thermanox (TMX) discs were incubated with osteoblast‐like cells (5 × 104 HOS‐TE85 cells) under differing tissue culture conditions. To investigate early cellular attachment, organization, and differentiation, cells were also stained for integrin–α5 β1, actin, and runt‐related transcription factor (RUNX‐2), respectively, after incubation on HA, SA, and TMX discs for 3 days. No significant differences emerged between HA, SA, and TMX discs in mean numbers of cells attached in serum free medium (SFM) over 90 min incubation. In contrast, significantly more cells were attached to SA than HA after 180 min incubation in complete medium (C‐MEM) containing fetal calf serum (p < 0.05). Cell attachment to SA and HA discs pre‐conditioned in SFM supplemented with fibronectin (FN) was lower than discs pre‐conditioned in C‐MEM, suggesting sensitivity of an active FN conformation to the presence of co‐adsorbates. Confocal microscopy demonstrated significantly more co‐localization of integrin α5 β1 and actin on SA than HA. Translocalization of RUNX‐2 to the nucleus was stronger in cells incubated on SA. Microporosity did not diminish the effect of surface physiochemistry on cell adhesion, and enhanced cell attachment for SA appears to be mediated by differences in the quality of adsorbed protein rather than via direct effects of substrate chemistry.
Construction of Polyethyleneimine‐β‐cyclodextrin/pDNA Multilayer Structure for Improved In Situ Gene Transfection
Authors: Hu Yan , Cai Kaiyong , Luo Zhong , Hu Ran
Published: February 2010

This study reports in situ gene delivery from gene‐functionalized poly(D,L‐lactic acid) (PDLLA, Mw of around 2.0 × 105 g mol−1) films, which were constructed via layer‐by‐layer (LbL) assembly technique with low molecular weight polyethylenimine‐β‐cyclodextrin (PEI‐CD) conjugate and plasmid DNA (pDNA). PEI‐CD was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR), respectively. The buildup of multilayered PEI‐CD/pDNA pairs onto PDLLA films was monitored with contact angle measurements and UV–Vis spectrometer, respectively. A sustained release of pDNA from multilayered films was observed for 28 h. The mechanism of in situ gene delivery on PDLLA film was investigated in this study as well. Spherical PEI‐CD/pDNA complexes were formed and released following the deconstruction of multilayered films, which was confirmed by transmission electron microscopy (TEM) and gel electrophoresis, respectively. Surface mediated in situ gene transfection was achieved when culturing hepatoma G2 (HepG2) and human embryonic kidney 293 (HEK293) onto PEI‐CD/pDNA multilayered films. Furthermore, PEI‐CD improved the gene transfection efficiency when compared with that of PEI. Such gene‐functionalized biomaterial reported here has potential application in tissue engineering and implant technology.
Dual‐Growth‐Factor‐Releasing PCL Scaffolds for Chondrogenesis of Adipose‐Tissue‐Derived Mesenchymal Stem Cells
Authors: Lim Sung Mook , Jang Sung Hwan , Oh Se Heang , Yuk Soon Hong , Im Gun Il , Lee Jin Ho
Published: February 2010

Polycaprolactone/Pluronic F127 porous scaffolds are prepared using a modified melt‐molding particulate‐leaching method. The scaffolds are highly porous (about 90% porosity) and have open‐cellular pore structures. Growth factors (TGF‐β2, BMP‐7 or dual TGF‐β2/BMP‐7) can be easily immobilized on the pore surfaces of the PCL/F127 scaffolds via binding with heparin. The growth‐factor‐immobilized scaffolds can induce the chondrogenesis of ATMSCs seeded onto them. Using TGF‐β2 and BMP‐7 growth factors together leads to a better chondrogenic differentiation behavior than using single‐growth‐factor immobilized scaffolds.
Hypoxia Stabilizes Microtubule Networks and Decreases Tumor Cell Chemosensitivity to Anticancer Drugs Through Egr‐1
Authors: Peng Wan‐Xin , Pan Fei‐Yan , Liu Xiao‐Jin , Ning Shen , Xu Na , Meng Fan‐Li , Wang Yi‐Qian , Li Chao‐Jun
Published: February 2010

The hypoxic environment of solid tumor causes the tumor cells survive and which could protect them from death by facilitating resistance to therapy. Here, we provide evidence that hypoxia can increase tumor cell viability and proliferation through an Egr‐1‐dependant pathway. Hypoxia protected the microtubules from disassembly, and Egr‐1 was colocalized with microtubules in different cell cycle stages. Knockdown of Egr‐1 with its siRNA overcame the protection effect of hypoxia and increased the sensitivity of tumor cells to vinblastine under hypoxic conditions. Our results suggest a novel approach for increasing the sensitivity of tumor cells to chemotherapeutics that target microtubule assembly. Anat Rec, 293:414–420, 2010. © 2010 Wiley‐Liss, Inc.
Fetal Anatomy of the Human Carotid Sheath and Structures In and Around It
Authors: Miyake Naritomo , Hayashi Shogo , Kawase Tetsuaki , Cho Baik Hwan , Murakami Gen , Fujimiya Mineko , Kitano Hiroya
Published: February 2010

The aim of this study was to find basic rules governing the morphological development of the typical neurovascular sheath. We carried out histological examination of 15 paraffin‐embedded mid‐term fetuses at 9–25 weeks of gestation (three fetuses each at 9, 12, 15, 20, and 25 weeks). As the result, the vagus nerve showed a high propensity to change its topographical relationship with the common carotid artery (CCA) during 9–20 weeks of gestation: that is, from a primitive ventral course to a final dorsal course. The adventitia of the great arteries, which was distinct from other fascial structures, became evident by 15 weeks. The carotid sheath appeared at and after 20 weeks: it was clearly separated from the prevertebral lamina of the deep cervical fasciae, but fused with the pretracheal lamina covering the strap muscles. Thus the carotid sheath, as well as the topographical relationships of structures within it, seems to become established much later than the prevertebral and pretracheal laminae of the deep cervical fasciae. However, the adventitia of the cervical great arteries consistently becomes evident much earlier than the sheath, and it seems to be regarded as one of the basic components of the fetal deep cervical fasciae. Anat Rec, 293:438–445, 2010. © 2010 Wiley‐Liss, Inc.
Distribution Pattern of Muscle Fiber Types in the Perivertebral Musculature of Two Different Sized Species of Mice
Authors: Hesse Bettina , Fischer Martin S. , Schilling Nadja
Published: February 2010

Many physiological parameters scale with body size. Regarding limb muscles, it has been shown that the demands for relatively faster muscles, less postural work, and greater heat production in small mammals are met by lower proportions of Type I and conversely higher proportions of Type II fibers. To investigate possible adaptations of the perivertebral musculature, we investigated the proportion, spatial distribution, and cross‐sectional area (csa) of the different muscle fiber types in the laboratory and harvest mouse. Serial cross sections from the posterior thoracic to the lumbo‐sacral region were prepared and Type I, IIA, and IIB fibers identified using enzymehistochemistry. The general distribution of Type I and IIB fibers, as well as the more or less equal distribution of IIA fibers, resembles the pattern found in other mammals. However, the overall proportion of Type I fibers was very low in the laboratory mouse and particularly low in the harvest mouse. Muscular adaptations to a small body size were met primarily by increased Type IIA fiber proportions. Thereby, not all muscles or muscle regions similarly reflected the expected scaling effects. However, our results clearly show that body size is a critical factor when fiber‐type proportions are compared among different sized mammals. Anat Rec, 293:446–463, 2010. © 2010 Wiley‐Liss, Inc.
Intertopic information mining for query‐based summarization
Authors: Ouyang You , Li Wenjie , Li Sujian , Lu Qin
Published: February 2010

In this article, the authors address the problem of sentence ranking in summarization. Although most existing summarization approaches are concerned with the information embodied in a particular topic (including a set of documents and an associated query) for sentence ranking, they propose a novel ranking approach that incorporates intertopic information mining. Intertopic information, in contrast to intratopic information, is able to reveal pairwise topic relationships and thus can be considered as the bridge across different topics. In this article, the intertopic information is used for transferring word importance learned from known topics to unknown topics under a learning‐based summarization framework. To mine this information, the authors model the topic relationship by clustering all the words in both known and unknown topics according to various kinds of word conceptual labels, which indicate the roles of the words in the topic. Based on the mined relationships, we develop a probabilistic model using manually generated summaries provided for known topics to predict ranking scores for sentences in unknown topics. A series of experiments have been conducted on the Document Understanding Conference (DUC) 2006 data set. The evaluation results show that intertopic information is indeed effective for sentence ranking and the resultant summarization system performs comparably well to the best‐performing DUC participating systems on the same data set.