bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human fetal, cord blood, and adult lymphocyte progenitors have similar potential for generating B cells with a diverse immunoglobulin repertoire
Authors: Kolar Grant R. , Yokota Takafumi , Rossi Maria Isabel D. , Nath Swapan K. , Capra J. Donald 
Published: July 2004

AbstractSeveral characteristics of the immunoglobulin (Ig) repertoire in fetuses and adults set them apart from each other. Functionally, this translates into differences in the affinity and effectiveness of the humoral immune response between adults and the very young. At least 2 possibilities could explain these differences: (1) fetal and adult lymphocyte progenitors differ significantly in their potential to form a diverse repertoire, and (2) factors extrinsic to the immunoglobulin locus are more influential to the character of the repertoire. To address this we used nonobese diabetic-severe combined immunodeficient-β2 microglobulin knockout (NOD/SCID/β2m-/-) mice reconstituted with human B-cell progenitors to compare the immunoglobulin repertoire potential of human fetal, cord blood, and adult sources. We found nearly identical VH and JH gene segment use and only modest differences in the third complementarity determining region of the immunoglobulin heavy chain (HCDR3). We conclude that the repertoire potential is remarkably similar regardless of the age of the individual from which progenitors are derived. Age-related differences in the immunoglobulin repertoire and variance of B-cell responses to immunization appear to arise from selection rather than from changes in recombination of the immunoglobulin locus itself. From the standpoint of the Ig repertoire, an immune system reconstituted from fetal or neonatal stem cells would likely be as diverse as one generated from adult bone marrow.
The Fanconi anemia core complex associates with chromatin during S phase
Authors: Mi Jun , Kupfer Gary M. 
Published: July 2004

AbstractFanconi anemia (FA) is an autosomal recessive disease marked by bone marrow failure, birth defects, and cancer. The FA proteins FANCA, FANCC, FANCE, FANCF, FANCG, and FANCL participate in a core complex. We previously have shown that several members of this complex bind to chromatin until mitosis and that this binding increases after DNA damage. The purpose of the present study was to determine the dynamics of complex movement between cytoplasm and nuclear compartments. Fluorescent-tagged versions of FANCA, FANCC, and FANCG colocalize in cytoplasm and nucleus, chiefly in chromatin. At the G1-S border, the FA core complex exists as foci on chromatin, progressively diffusing and migrating to the nuclear periphery and becoming completely excluded from condensed chromosomes by mitosis. Chromatin fiber analysis shows FA proteins diffusely staining along chromatin fibers during G1-S and S phase. Treatment with the DNA cross-linker mitomycin C results in a diffusion of foci and increased binding of complex proteins to chromatin, as well as diffuse and increased complex binding to chromatin fibers. These data are consistent with the idea that the FA proteins function at the level of chromatin during S phase to regulate and maintain genomic stability.
A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo
Authors: Gunzer Matthias , Weishaupt Carsten , Hillmer Anja , Basoglu Yasmin , Friedl Peter , Dittmar Kurt E. , Kolanus Waldemar , Varga Georg , Grabbe Stephan 
Published: July 2004

AbstractFor activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen matrices as structural scaffold, we directly compared the kinetics of T-cell engagement and activation by functionally major APC types, ie, dendritic cells (DCs) and resting or activated B cells. Resting B cells engaged T cells in long-lived (several hours), adhesive, and leukocyte function-associated antigen-1 (LFA-1)-dependent conjugates in 3-D collagen as well as in intact lymph nodes in vivo. DCs and preactivated B cells, however, supported predominantly dynamic, short-lived (minutes), and sequential contacts to T cells that were dependent on high cytoskeletal activity of the APCs but could not be inhibited by anti-LFA-1 treatment. Naive T cells were most strongly activated by DCs and activated B cells, whereas resting B cells were 100-fold less efficient to induce T-cell proliferation. Thus, in the same 3-D environment, naive T cells respond with a spectrum of different interaction modes dependent on the type and activation state of the APCs. Thereby, more dynamic interaction kinetics is positively correlated with higher T-cell priming efficiency. (Blood. 2004;104: 2801-2809)
Proinflammatory Cytokine Impairment of Insulin-Like Growth Factor I-Induced Protein Synthesis in Skeletal Muscle Myoblasts Requires Ceramide
Authors: Strle Klemen , Broussard Suzanne R. , McCusker Robert H. , Shen Wen-Hong , Johnson Rodney W. , Freund Gregory G. , Dantzer Robert , Kelley Keith W. 
Published: July 2004

AbstractGH and IGF-I control over 80% of postnatal growth. We recently established that TNFα impairs the ability of IGF-I to increase protein synthesis and promote expression of myogenin in myoblasts. Here we extend these results by showing that ceramide, a second messenger in both TNFα and IL-1β receptor signaling pathways, is a key downstream sphingosine-based lipid that leads to IGF-I resistance. A cellpermeable ceramide analog, C2-ceramide, inhibits IGF-I-induced protein synthesis by 65% and blocks the ability of IGF-I to increase expression of two key myogenic factors, myogenin and MyoD. Identical results were obtained with both TNFα and IL-1β (1 ng/ml). Consistent with these data, neutral sphingomyelinase (N-SMase), an enzyme that catalyzes formation of ceramide from sphingomyelin, blocks IGF-I-induced protein synthesis and expression of both myogenin and MyoD. The possibility that cytokine-induced ceramide production is required for disruption of IGF-I biologic activity was confirmed by treating C2C12 myoblasts with inhibitors of all three ceramide-generating pathways. A N-SMase inhibitor, glutathione, as well as an acidic sphingomyelinase (A-SMase) inhibitor, D609, reverse the cytokine inhibition of IGF-I-induced protein synthesis by 80% and 45%, respectively. Likewise, an inhibitor of de novo ceramide synthesis, FB1, causes a 50% inhibition. Similarly, all three inhibitors significantly impair the ability of both TNFα and IL-1β to suppress IGF-I-driven expression of myogenin. These experiments establish that ceramide, derived both from sphingomyelin and de novo synthesis, is a key intermediate by which proinflammatory cytokines impair the ability of IGF-I to promote protein synthesis and expression of critical muscle-specific transcription factors.
Thyroid Hormone Regulates Oligodendrocyte Accumulation in Developing Rat Brain White Matter Tracts
Authors: Schoonover Christopher M. , Seibel Melissa M. , Jolson Dawn M. , Stack Mary Jo , Rahman Rounak J. , Jones Sidney A. , Mariash Cary N. , Anderson Grant W. 
Published: July 2004

AbstractThyroid hormone (TH) is necessary for normal axonal myelination. Myelin basic protein (MBP) is a structural protein essential for myelin function. In this study, we demonstrate that perinatal hypothyroidism regulates MBP mRNA levels via indirect mechanisms. We observed decreased MBP mRNA accumulation in the hypothyroid rat brain at postnatal (PN) d 10 and 50. Acute TH replacement did not rescue hypothyroid MBP mRNA levels at PN5, 10, or 50. TH is necessary for normal intrahemispheric commissure development including the anterior commissure (AC) and the corpus callosum (CC). We determined that perinatal hypothyroidism decreases AC area and cellularity in the developing rat brain by PN10 and 50. In the developing CC, hypothyroidism initially increases area and cellularity by PN5, but then ultimately decreases area and cellularity by PN50. MBP-expressing oligodendrocytes are a recognized target of TH and are responsible for myelination within intrahemispheric commissures. We found that hypothyroidism reduces the number of mature oligodendrocytes within both the AC and CC. This reduction is noted at PN5, 10, and 50 in the AC and by PN10 and 50 in the CC. Together, these data suggest that TH regulates MBP mRNA levels through indirect mechanisms. These data demonstrate the complex mechanisms whereby TH regulates myelination in the developing brain.
Ghrelin Degradation by Serum and Tissue Homogenates: Identification of the Cleavage Sites
Authors: De Vriese Carine , Gregoire Francoise , Lema-Kisoka Roger , Waelbroeck Magali , Robberecht Patrick , Delporte Christine 
Published: July 2004

AbstractThe endogenous ligand for the GH secretagogue receptor is ghrelin, a peptide recently purified from the stomach. Ghrelin is n-octanoylated on the Ser3 residue, and this modification is essential for its interaction with the receptor. The degradation of ghrelin by rat and human serum, purified commercial enzymes, and tissues homogenates was analyzed by combining HPLC and mass spectrometry. In serum, ghrelin was desoctanoylated, without proteolysis. The desoctanoylation was significantly reduced by phenylmethylsulfonyl fluoride, a serine proteases and esterases inhibitor. In rat serum, the carboxylesterase inhibitor bis-p-nitrophenyl-phosphate totally inhibited ghrelin desoctanoylation, and a correlation was found between ghrelin desoctanoylation and carboxylesterase activity. Moreover, purified carboxylesterase degraded ghrelin. Thus, carboxylesterase could be responsible for ghrelin desoctanoylation in that species. In human serum, ghrelin desoctanoylation was partially inhibited by eserine salicylate and sodium fluoride, two butyrylcholinesterase inhibitors, but not by bis-p-nitrophenyl-phosphate and EDTA. Purified butyrylcholinesterase was able to degrade ghrelin, and there was a correlation between the butyrylcholinesterase and ghrelin desoctanoylation activities in human sera. This suggested that several esterases, including butyrylcholinesterase, contributed to ghrelin desoctanoylation in human serum. In contact with tissues homogenates, ghrelin was degraded by both desoctanoylation and N-terminal proteolysis. We identified five cleavage sites in ghrelin between residues -Ser2-(acyl)Ser3- (stomach and liver), -(acyl?)Ser3-Phe4- (stomach, liver, and kidney), -Phe4-Leu5- (stomach and kidney), -Leu5-Ser6- and -Pro7-Glu8- (kidney). In all cases, the resulting fragments were biologically inactive.
Coordinate Transcription of the ADAMTS-1 Gene by Luteinizing Hormone and Progesterone Receptor
Authors: Doyle Kari M. H. , Russell Darryl L. , Sriraman Venkataraman , Richards JoAnne S. 
Published: July 2004

AbstractADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs) is a multifunctional protease that is expressed in periovulatory follicles. Herein we show that induction of ADAMTS-1 message in vivo and transcription of the ADAMTS-1 promoter in cultured granulosa cells are dependent on separable but coordinate actions of LH and the progesterone receptor (PR). To analyze the molecular mechanisms by which LH and PR regulate this gene, truncations and site-specific mutants of ADAMTS-1 promoter-luciferase reporter constructs (ADAMTS-1-Luc) were generated and transfected into rat granulosa cell cultures. Three regions of the promoter were found to be important for basal activity, two of which were guanine cytosine-rich binding sites for specificity proteins Sp1/Sp3 and the third bound a nuclear factor 1-like factor. Despite the absence of a consensus PR DNA response element in the proximal ADAMTS-1 promoter, cotransfection of a PRA (or PRB) expression vector stimulated ADAMTS-1 promoter activity, a response that was reduced by the PR antagonist ZK98299. Forskolin plus phorbol myristate acetate also increased promoter activity and, when added to cells cotransfected with PRA, ADAMTS-1 promoter activity increased further. Activation of the ADAMTS-1 promoter by PRA involves functional CAAT enhancer binding protein β, nuclear factor 1-like factor, and three Sp1/Sp3 binding sites as demonstrated by transfection of mutated promoter constructs. In summary, LH and PRA/B exert distinct but coordinate effects on transactivation of the ADAMTS-1 gene in granulosa cells in vivo and in vitro with PR acting as an inducible coregulator of the ADAMTS-1 gene.
Genomic Organization of Mouse Orexin Receptors: Characterization of Two Novel Tissue-Specific Splice Variants
Authors: Chen Jing , Randeva Harpal S. 
Published: July 2004

Abstract
In humans and rat, orexins orchestrate divergent actions through their G protein-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R). Orexins also play an important physiological role in mouse, but the receptors through which they function are not characterized. To characterize the physiological role(s) of orexins in the mouse, we cloned and characterized the mouse orexin receptor(s), mOX1R and mOX2R, using rapid amplification of cDNA (mouse brain) ends, RT-PCR, and gene structure analysis. The mOX1R cDNA encodes a 416-amino acid (aa) receptor. We have identified two alternative C terminus splice variants of the mOX2R; mOX2αR (443 aa) and mOX2βR (460 aa). Binding studies in human embryonic kidney 293 cells transfected with mOX1R, mOX2αR, and the mOX2βR revealed specific, saturable sites for both orexin-A and -B. Activation of these receptors by orexins induced inositol triphosphate (IP3) turnover. However, human embryonic kidney 293 cells transfected with mOXRs demonstrated no cAMP response to either orexin-A or orexin-B challenge, although forskolin and GTPγS revealed a dose-dependent increase in cAMP. Although, orexin-A and -B showed no difference in binding characteristics between the splice variants; interestingly, orexin-B led to an increase in IP3 production at all concentrations in the mOX2βR variant. Orexin-A, however, showed no difference in IP3 production between the two variants. Additionally, in the mouse, we demonstrate that these splice variants are distributed in a tissue-specific manner, where OX2αR mRNA was undetectable in skeletal muscle and kidney. Moreover, food deprivation led to a greater increase in hypothalamic mOX2βR gene expression, compared with both mOX1R and mOX2αR. This potentially implicates a fundamental physiological role for these splice variants.
Development of Sensitive Immunoassays for Free and Total Human Glandular Kallikrein 2
Authors: Väisänen Ville , Eriksson Susann , Ivaska Kaisa K , Lilja Hans , Nurmi Martti , Pettersson Kim 
Published: July 2004

AbstractBackground: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity.Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer.Results: All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 μg/L. The median total hK2 concentration was 0.022 μg/L (range, 0.0015–0.37 μg/L). hK2 concentrations were 0.1–58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41–50 and 51–60 years of age. The ratio of hK2 to PSA steadily decreased from 5–30% at PSA &lt;1 μg/L to 1–2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 μg/L (range, 0.0015–16.2 μg/L). The median free hK2 concentration was 0.070 (range, 0.005–12.2) μg/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%).Conclusions: The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.
Stripping for the wolf: Rethinking representations of gender in children's literature
Authors: MARSHALL ELIZABETH 
Published: July 2004

ABSTRACTSThis essay seeks to broaden theoretical paradigms commonly used in the social sciences to analyze representations of gender, especially girlhood, in children's literature. In particular, this project seeks to add to liberal feminist frameworks for conceptualizing textual representations of gender and sexuality in literacy studies. Liberal feminisms theorize gender through the lens of sex‐role theory, a paradigm in which social roles are allocated to men and to women on the basis of biological sex. The author acknowledges this important theoretical tradition, which brings attention to sex‐role stereotypes in children's literature, and approaches the topic of gender representation from another perspective. Drawing on feminist and literary theories informed by poststructuralism, the author analyzes how discourses of femininity produce the contested subjectivity of the “girl.” Through a textual analysis of four variants of “Little Red Riding Hood,” the author illustrates how poststructural feminist literary theory allows for a reading of the girl as less a natural category than as the product of evolving, culturally situated, and contradictory discourses. In this wayanother possible direction for analyzing gender in children's literature is offered.
Postsecondary education and some dimensions of literacy development: An exploration of longitudinal evidence
Authors: BRAY GAYLE BABBITT , PASCARELLA ERNEST T. , PIERSON CHRISTOPHER T. 
Published: July 2004

ABSTRACTSThis exploratory study analyzed longitudinal data from 18 institutions to track the literacy development of 1,054 students during the first three years of college. Reading comprehension and attitude toward literacy activities were assessed at the beginning and end of the study. Students responded annually to questionnaires about college experiences and provided background data. Linear regression procedures were used to predict growth on the outcome measures. With potential confounding influences on literacy growth controlled, students of color made smaller reading comprehension gains than white students, and women made smaller improvements in literacy attitude than men. For the overall sample, growth in comprehension was predicted by credit hours completed, number of assigned books read, instruction perceived as effective, and the number of natural sciences and engineering courses taken. Number of assigned and unassigned books read and involvement in course learning and library experiences predicted improved attitude toward literacy activities. However, the major finding of the study was that the college‐experience factors associated with literacy growth varied depending on students' race, sex, and levels of reading comprehension and attitude toward literacy activities prior to college.
Adaptive control with selective memory
Authors: Hill Jennifer Hsu , Ydstie B. Erik 
Published: July 2004

AbstractAdaptive control with selective memory updates the parameter estimates only when there is new information present. The information content increases and the estimator eventually stops. In this paper we use the Fisher information matrix and a variance estimator to measure the information content. The parameter estimates are updated only when the Information Matrix and/or the estimated variance of the prediction error increases. This gives an algorithm for adaptive control which converges to a linear time invariant controller. The resulting controller is robust with respect to bounded disturbances and small model/plant mismatch. Knowledge about overbounding sets for the parameter estimates or the disturbances are not needed. Simulation results using theoretical test cases illustrate near optimal performance for the converged parameters. Copyright © 2004 John Wiley & Sons, Ltd.
Identification of dual‐rate systems based on finite impulse response models
Authors: Ding Feng , Chen Tongwen 
Published: July 2004

AbstractTwo identification algorithms, a least squares and a correlation analysis based, are developed for dual‐rate stochastic systems in which the output sampling period is an integer multiple of the input updating period. The basic idea is to use auxiliary FIR models to predict unmeasurable noise‐free (true) outputs, and then use these and system inputs to identify parameters of underlying fast single‐rate models. The simulation results indicate that the proposed algorithms are effective. Copyright © 2004 John Wiley & Sons, Ltd.
Effects of vapor–liquid mass transfer on feasibility of reactive distillation
Authors: Nisoli Alberto , Doherty Michael F. , Malone Michael F. 
Published: July 2004

AbstractA cascade model including the Stefan–Maxwell model for mass transfer is developed to assess the feasibility of reactive distillation. The model fixed points are determined as a function of the Peclet number and other parameters, using a pseudo arc‐length continuation method. The approach is illustrated with two examples: a parametric study of an idealized ternary system, and the esterification of acetic acid to produce isopropyl acetate. In the limit of little or no reaction, the fixed points are independent of the mass‐transfer resistance, and a model based on phase equilibrium can be used for feasibility. When the chemical reaction rates or extents are more significant, the fixed points do depend on the Peclet number, and mass transfer can influence the feasible products. However, best estimates of the mass‐transfer parameters and the processing conditions typical of reactive distillation indicate that these effects are small for the examples studied. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1795–1813, 2004
Investigations on pulse broadening for catalyst screening in gas/liquid systems
Authors: Pennemann H. , Hessel V. , Kost H.‐J. , Löwe H. , de Bellefon C. 
Published: July 2004

AbstractIn connection with the development of a complete screening setup for organometallic catalysis, a micromixer–tube setup was investigated to optimize its serial transient operation mode. Because homogeneously dissolved catalysts and substrates in the liquid phase of a gas/liquid system are pulse‐injected into the two‐phase system, our investigations aim in finding a minimum in the signal broadening and maximizing the number of experiments per unit of time. Within this context, investigations of the residence time distribution of the whole setup, as well as the individual contributions of its respective components toward signal broadening, were undertaken by determining the effects on the residence time distribution by the gas/liquid ratio, the orientation of the residence time loop and the total flow rate. © 2004 American Institute of Chemical Engineers AIChE J, 50:1814–1823, 2004