bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells
Authors: Mahajan Simmi , Cervera Ana , MacLeod Megan , Fillatreau Simon , Perona‐Wright Georgia , Meek Stephen , Smith Andrew , MacDonald Andrew , Gray David 
Published: June 2007

AbstractWe have addressed the role of the inducible costimulator (ICOS) in the development of T cell help for B cells and in the generation, survival and reactivation of memory CD4 T cells and B cells. We find that while T cell help for all antibody isotypes (including IgG2c) is impaired in ICOS knockout (ICOS‐KO) mice, the IFN‐γ response is little affected, indicating a defect in helper function that is unrelated to cytokine production. In addition, the ICOS‐negative T cells do not accumulate in B cell follicles. Secondary (memory), but not primary, clonal proliferation of antigen‐specific B cells is impaired in ICOS‐KO mice, as is the generation of secondary antibody‐secreting cells. Analysis of endogenous CD4 memory cells in ICOS‐KO mice, using MHC class II tetramers, reveals normal primary clonal expansion, formation of memory clones and long‐term (10 wk) survival of memory cells, but defective expansion upon reactivation in vivo. The data point to a role of ICOS in supporting secondary, memory and effector T cell responses, possibly by influencing cell survival. The data also highlight differences in ICOS dependency of endogenous T cell proliferation in vivo compared to that of adoptively transferred TCR‐transgenic T cells.
IL‐27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1
Authors: Neufert Clemens , Becker Christoph , Wirtz Stefan , Fantini Massimo C. , Weigmann Benno , Galle Peter R. , Neurath Markus F. 
Published: June 2007

AbstractIL‐27 is an IL‐12‐related cytokine frequently present at sites of inflammation that can promote both anti‐ and pro‐inflammatory immune responses. Here, we have analyzed the mechanisms how IL‐27 may drive such divergent immune responses. While IL‐27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti‐inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL‐27 suppressed the development of adaptive, TGF‐β‐induced Forkhead box transcription factor p3‐positive (Foxp3+) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg development was STAT1 independent, suggesting that IL‐27 utilizes different signaling pathways to shape T cell‐driven immune responses. Our data thus demonstrate that IL‐27 controls the development of Th17 and iTreg cells via differential effects on STAT1.
OSP/claudin‐11‐induced EAE in mice is mediated by pathogenic T cells primarily governed by OSP192Y residue of major encephalitogenic region OSP179–207
Authors: Kaushansky Nathali , Hemo Reut , Eisenstein Miriam , Ben‐Nun Avraham 
Published: June 2007

AbstractPathogenic autoimmunity against oligodendrocyte‐specific protein (OSP/claudin‐11), recently implicated in multiple sclerosis (MS) pathophysiology, has been poorly investigated as compared to that against other myelin encephalitogens. Using recombinant soluble mouse OSP (smOSP) and overlapping peptides thereof, we show that smOSP‐induced chronic EAE in C57BL/6J mice is primarily associated with CD4+ T cells reactive against OSP179–207 and OSP22–46, the major and minor encephalitogenic regions, respectively, and with a predominant B cell response against OSP22–46. The encephalitogenic OSP179–207‐specific T cells recognized OSP190–202 as minimal stimulatory epitope, while minimal encephalitogenic sequence was OSP191–199. Further delineation and structural bioinformatic analysis of the major encephalitogenic region suggested four overlapping potential I‐Ab core epitopes, predicting OSP192Y as major TCR‐contact residue shared by OSP 188–196, OSP190–198, and OSP191–199 cores, albeit at different MHC‐II pockets. Accordingly, substitution at OSP192Y yielded OSP188–192A‐202, a non‐stimulatory/non‐encephalitogenic altered peptide ligand (APL) that was antagonistic for OSP188–202‐specific encephalitogenic T cells. Systemic administration of OSP188–192A‐202 suppressed OSP188–202‐induced EAE and fully reversed smOSP‐induced EAE. These data suggest that a single epitopic residue (OSP192Y) governs the selection and control of most pathogenic T cells associated with smOSP‐induced EAE in H‐2b mice. This may impact profoundly on peripheral self‐tolerance to OSP and on potential APL‐mediated therapy of OSP‐related autoimmune pathogenesis.
Sandstone dissolution landforms in the Furnas Formation, southern Brazil
Authors: Sérgio de Melo Mário , César Fonseca Giannini Paulo 
Published: June 2007

AbstractThe Furnas Formation (Silurian to Devonian of the Paraná Basin) consists of medium to coarse sandstones (quartzarenites) cemented by kaolinite, which reduces its porosity and makes the rock more resistant. A Mesozoic crustal upwarping called the Ponta Grossa Arch and subsequent erosion gave origin to the Devonian Scarp, which is a cuesta supported by the sandstones. The scarp serves as a boundary line for the Second Paraná Plateau, a step of the en échelon relief in the State of Paraná in southern Brazil. In the outcropping areas the sandstones display a ubiquitous phenomenon of superficial exfoliation by dissolution of the kaolinitic mesodiagenetic cement and reprecipitation of microcrystalline telodiagenetic kaolinite. The dissolution of kaolinite contributes to the development of small scale superficial landforms such as alveoles, runnels, dissolution basins, concavities at the base of rocky walls, polygonal joints, anastomosing tunnels and erosion columns. In the Quebra‐Perna River area near the Devonian Scarp, the sandstones of the Furnas Formation show many features of significant subterranean erosion, such as ‘furnas’ (collapsed hollows), ponds, wet and dry depressions, sinkholes, tunnels and grikes. Such features are associated with the presence of brittle structures (faults, fractures, dikes) in two directions: the main one, NE–SW, corresponds to reactivations of the Proterozoic basement of the Paraná Basin and the secondary one, NW–SE, runs parallel to the Ponta Grossa Arch axis. Furnas and other associated features frequently occur at the crossing of such structures. These findings indicate that the great features of subterranean erosion are the result of kaolinite dissolution, which intensifies along structural directions, in a region of scarped relief and steep hydraulic gradient. As a consequence, the Furnas Formation displays landforms that are characteristic of a both structural and karstic aquifer. Copyright © 2007 John Wiley & Sons, Ltd.
Improving power in genome‐wide association studies: weights tip the scale
Authors: Roeder Kathryn , Devlin B. , Wasserman Larry 
Published: June 2007

AbstractThe potential of genome‐wide association analysis can only be realized when they have power to detect signals despite the detrimental effect of multiple testing on power. We develop a weighted multiple testing procedure that facilitates the input of prior information in the form of groupings of tests. For each group a weight is estimated from the observed test statistics within the group. Differentially weighting groups improves the power to detect signals in likely groupings. The advantage of the grouped‐weighting concept, over fixed weights based on prior information, is that it often leads to an increase in power even if many of the groupings are not correlated with the signal. Being data dependent, the procedure is remarkably robust to poor choices in groupings. Power is typically improved if one (or more) of the groups clusters multiple tests with signals, yet little power is lost when the groupings are totally random. If there is no apparent signal in a group, relative to a group that appears to have several tests with signals, the former group will be down‐weighted relative to the latter. If no groups show apparent signals, then the weights will be approximately equal. The only restriction on the procedure is that the number of groups be small, relative to the total number of tests performed. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Optimal designs for two‐stage genome‐wide association studies
Authors: Skol Andrew D. , Scott Laura J. , Abecasis Gonçalo R. , Boehnke Michael 
Published: June 2007

AbstractGenome‐wide association (GWA) studies require genotyping hundreds of thousands of markers on thousands of subjects, and are expensive at current genotyping costs. To conserve resources, many GWA studies are adopting a staged design in which a proportion of the available samples are genotyped on all markers in stage 1, and a proportion of these markers are genotyped on the remaining samples in stage 2. We describe a strategy for designing cost‐effective two‐stage GWA studies. Our strategy preserves much of the power of the corresponding one‐stage design and minimizes the genotyping cost of the study while allowing for differences in per genotyping cost between stages 1 and 2. We show that the ratio of stage 2 to stage 1 per genotype cost can strongly influence both the optimal design and the genotyping cost of the study. Increasing the stage 2 per genotype cost shifts more of the genotyping and study cost to stage 1, and increases the cost of the study. This higher cost can be partially mitigated by adopting a design with reduced power while preserving the false positive rate or by increasing the false positive rate while preserving power. For example, reducing the power preserved in the two‐stage design from 99 to 95% that of the one‐stage design decreases the two‐stage study cost by ∼15%. Alternatively, the same cost savings can be had by relaxing the false positive rate by 2.5‐fold, for example from 1/300,000 to 2.5/300,000, while retaining the same power. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Powerful designs for genetic association studies that consider twins and sibling pairs with discordant genotypes
Authors: Wessel Jennifer , Schork Andrew J. , Tiwari Hemant K. , Schork Nicholas J. 
Published: June 2007

AbstractGenetic association studies are becoming commonplace due to the availability of cost‐effective yet sophisticated DNA sequencing and genotyping resources and technologies. In addition, technologies designed to identify molecular and subclinical phenotypes that reflect disease pathogenesis are continually being developed and refined (consider, e.g., imaging technologies, microarray‐based gene expression and proteomic platforms, histological analyses of excised tissues, etc.). Unfortunately, the large‐scale use of many of these molecular and subclinical phenotyping technologies in genetic association studies is difficult logistically and is currently cost‐prohibitive. In this paper, we consider efficient designs for testing the association between particular genetic variations and expensive, yet appropriate, subclinical phenotypes of relevance to a disease that take advantage of twins or sibling pairs discordant for genotypes at the locus (or loci) being tested. We demonstrate that including genotypically discordant twins or siblings in an association study can result in a substantial increase in power over designs that use monozygotic twins or only unrelated individuals. We ultimately argue that, from a practical standpoint, sampling from existing family or twin‐based cohorts in which: (1) follow‐up studies of a genetic association are warranted in order to assess the in vivo significance of an association with respect to more refined pathological phenotypes; and/or (2) large‐scale, genome‐wide linkage and association studies have been pursued that have focused on clinical endpoints for which the study subjects have consented to more elaborate follow‐up studies, is a powerful way to test associations. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Quantitative trait association in parent offspring trios: Extension of case/pseudocontrol method and comparison of prospective and retrospective approaches
Authors: Wheeler Eleanor , Cordell Heather J. 
Published: June 2007

AbstractThe case/pseudocontrol method provides a convenient framework for family‐based association analysis of case‐parent trios, incorporating several previously proposed methods such as the transmission/disequilibrium test and log‐linear modelling of parent‐of‐origin effects. The method allows genotype and haplotype analysis at an arbitrary number of linked and unlinked multiallelic loci, as well as modelling of more complex effects such as epistasis, parent‐of‐origin effects, maternal genotype and mother‐child interaction effects, and gene‐environment interactions. Here we extend the method for analysis of quantitative as opposed to dichotomous (e.g. disease) traits. The resulting method can be thought of as a retrospective approach, modelling genotype given trait value, in contrast to prospective approaches that model trait given genotype. Through simulations and analytical derivations, we examine the power and properties of our proposed approach, and compare it to several previously proposed single‐locus methods for quantitative trait association analysis. We investigate the performance of the different methods when extended to allow analysis of haplotype, maternal genotype and parent‐of‐origin effects. With randomly ascertained families, with or without population stratification, the prospective approach (modeling trait value given genotype) is found to be generally most effective, although the retrospective approach has some advantages with regard to estimation and interpretability of parameter estimates when applied to selected samples. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Expression and function of water channels (aquaporins) in migrating malignant astrocytes
Authors: McCoy Eric , Sontheimer Harald 
Published: June 2007

AbstractAquaporins (AQP) constitute the principal pathway for water movement across biological membranes. Consequently, their expression and function is important for cell volume regulation. Glioma cells quickly adjust their cell volume in response to osmotic challenges or spontaneously as they invade into the narrow and tortuous extracellular spaces of the brain. These cell volume changes are likely to engage water movements across the cell membrane through AQP. AQP expression in glioma cells is poorly understood. In this study, we examined the expression of AQP in several commonly used human glioma cell lines (D54, D65, STTG1, U87, U251) and in numerous acute patient biopsies by PCR, Western blot, and immunocytochemistry and compared them to nonmalignant astrocytes and normal brain. All glioma patient biopsies expressed AQP1, AQP4 and some expressed AQP5. However, when isolated and grown as cell lines they lose all AQP proteins except a few cell lines that maintain expression of AQP1 (D65, U251, GBM62). Reintroducing either AQP1 or AQP4 stably into glioma cell lines allowed us to show that each AQP is sufficient to restore water permeability. Yet, only the presence of AQP1, but not AQP4, enhanced cell growth and migration, typical properties of gliomas, while AQP4 enhanced cell adhesion suggesting differential biological roles for AQP1 and AQP4 in glioma cell biology. © 2007 Wiley‐Liss, Inc.
Genetic programming approach for flood routing in natural channels
Authors: Sivapragasam C. , Maheswaran R. , Venkatesh Veena 
Published: June 2007

AbstractIn recognition of the non‐linear relationship between storage and discharge existing in most river systems, non‐linear forms of the Muskingum model have been proposed, together with methods to calibrate the model parameters. However, most studies have focused only on routing a typical hypothetical flood hydrograph characterized by a single peak. In this study, we demonstrate that the storage–discharge relationship adopted for the non‐linear Muskingum model is not adequate for routing flood hydrographs in natural channels, which are often characterized by multiple peaks. As an alternative, an evolutionary algorithm‐based modelling approach, i.e. genetic programming (GP), is proposed, which is found to route complex flood hydrographs accurately. The proposed method is applied for constructing a routing model for a channel reach along the Walla Walla River, USA. The GP model performs extremely well with a root‐mean‐square error (RMSE) of 0·73 m3 s−1 as against an RMSE of 3·26 m3 s−1 for routing the multi‐peaked hydrograph. The advantage of GP lies in the fact that, unlike other models, it establishes the routing relationship in an easy and simple mathematical form. Copyright © 2007 John Wiley & Sons, Ltd.
The effect of refreezing on the isotopic composition of melting snowpack
Authors: Zhou Shiqiao , Nakawo Masayoshi , Hashimoto Shigemasa , Sakai Akiko 
Published: June 2007

AbstractThe isotopic composition of solid and liquid portions of natural melting snowpack is investigated in detail by the separating of liquid water from snow grains at different depths of the snowpack. The slope of the δD–δ18O line for the liquid phase is found to be lower than for the solid phase. This is proved to be due to the isotopic fractionation occurring in the melt–freeze mass exchange within the snowpack. Melting of the snowpack has no clear impact on the δD–δ18O line for the solid phase, but the slope of the δD–δ18O line for the liquid shows an overall slight decrease in the melting period. When the snowpack is refrozen, the refreezing process would inevitably cause the slope of the solid phase to decrease because of the discrepancy between the slopes of the two phases. Thus the slope of the solid would become lower and lower as the diurnal melt–freeze episodes cycle throughout the melting season. This effect is then demonstrated by looking into the isotopic composition changes of glacier firn. The extent of the effect depends on the snowpack properties and environmental conditions. The slope changes also result in a decreasing trend in deuterium excess. Copyright © 2007 John Wiley & Sons, Ltd.
Stream Macroinvertebrate Community Affected by Point‐Source Metal Pollution
Authors: Doi Hideyuki , Takagi Atsushi , Kikuchi Eisuke 
Published: June 2007

AbstractThe impacts of mining activities on aquatic biota have been documented in many stream ecosystems. In mining streams, point‐source heavy metal pollution often appears in the stream. We hypothesize that this pollution is toxic to macroinvertebrates owing to high concentrations of metals and therefore affects macroinvertebrate community structure. We investigated macroinvertebrate community structure in mountain streams, including heavy metal‐polluted sites and neutral‐pH streams, to determine the relationship between community structure and environmental factors such as low pH and heavy metal concentrations. Based on multidimensional scaling ordination, the macroinvertebrate community at heavy metal pollution sites was remarkably different from that at the other sites. Inductively coupled plasma mass spectrometry revealed high concentrations of aluminum and iron in surface water at the polluted sites. Macroinvertebrate community structure at the metal pollution sites was significantly different from that at other sites in the same stream and in neutral‐pH streams. Thus, point‐source metal pollution may reduce the density and diversity of in situ macroinvertebrates. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of Interspecific Interactions between Microcystis aeruginosa and Chlorella pyrenoidosa on Their Growth and Physiology
Authors: Zhang Min , Kong Fanxiang , Xing Peng , Tan Xiao 
Published: June 2007

AbstractInteractions between Microcystis aeruginosa and Chlorella pyrenoidosa were analyzed by flow cytometry and by phytoplankton pulse‐amplitude‐modulated fluorimetry (Phyto‐PAM) in joint cultures as well as in cultures separated by dialysis membranes. Results showed that the growth of C. pyrenoidosa was greater than that of M. aeruginosa, and that the growth of M. aeruginosa but not the growth of C. pyrenoidosa was significantly inhibited by the interactions between M. aeruginosa and C. pyrenoidosa. Culture filtrates of these two algae showed no apparent effects on the growth of the competing species. For M. aeruginosa, decreases in esterase activity, chlorophyll a fluorescence, and maximum quantum yield were observed in joint cultures, indicating that the metabolic activity and photosynthetic capacity of M. aeruginosa were suppressed. Light limitation from the shading effect of C. pyrenoidosa may be the main reason for such inhibition. For C. pyrenoidosa, esterase activity was suppressed in membrane‐separated and joint cultures, suggesting that C. pyrenoidosa was probably affected by allelopathic substances secreted by M. aeruginosa. However, no significant difference was observed in the chlorophyll a fluorescence and maximum quantum yield of C. pyrenoidosa in the two cultures. In addition, interspecific interactions induced a reduction in size in both M. aeruginosa and C. pyrenoidosa, which may contribute to the development of C. pyrenoidosa dominance in the present study. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Subchronic (26‐ and 52‐week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models
Authors: Piret Jocelyne , Laforest Geneviève , Bussières Martin , Bergeron Michel G. 
Published: June 2007

AbstractThe safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26‐ and 52‐week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 ± 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 ± 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non‐irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non‐irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use. Copyright © 2007 John Wiley & Sons, Ltd.