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Critical Differences (critical + difference)
Selected AbstractsKinetic perspectives of T cell antigen receptor signalingIMMUNOLOGICAL REVIEWS, Issue 1 2003Makio Iwashima Summary: T-cell activation consists of multiple layers of signaling events. Interleukin-2 production is of interest for many, since its expression determines a critical difference between partial and full T-cell activation. To achieve full activation of T cells, it is necessary for the T-cell antigen receptor (TCR) to be engaged for an extended period of time. However, why extended stimulation is required for full T-cell activation is not understood at the molecular level. In this review, orchestrated events of TCR signal transduction will be analyzed in a kinetic manner and connected toward the understanding of the mechanism of T-cell activation. Based on recent results, a model of the mechanism that dictates the threshold between partial and full T-cell activation is proposed. [source] Distal enhancer of the mouse FGF-4 gene and its human counterpart exhibit differential activity: Critical role of a GT boxMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2005Brian Boer Abstract Previous studies have shown that there is a strict requirement for fibroblast growth factor-4 (FGF-4) during mammalian embryogenesis, and that FGF-4 expression in embryonic stem (ES) cells and embryonal carcinoma (EC) cells are controlled by a powerful downstream distal enhancer. More recently, mouse ES cells were shown to express significantly more FGF-4 mRNA than human ES cells. In the work reported here, we demonstrate that mouse EC cells also express far more FGF-4 mRNA than human EC cells. Using a panel of FGF-4 promoter/reporter gene constructs, we demonstrate that the enhancer of the mouse FGF-4 gene is approximately tenfold more active than its human counterpart. Moreover, we demonstrate that the critical difference between the mouse and the human FGF-4 enhancer is a 4 bp difference in the sequence of an essential GT box. Importantly, we demonstrate that changing 4 bp in the human enhancer to match the sequence of the mouse GT box elevates the activity of the human FGF-4 enhancer to the same level as that of the mouse enhancer. We extended these studies by examining the roles of Sp1 and Sp3 in FGF-4 expression. Although we demonstrate that Sp3, but not Sp1, can activate the FGF-4 promoter when artificially tethered to the FGF-4 enhancer, we show that Sp3 is not essential for expression of FGF-4 mRNA in mouse ES cells. Finally, our studies with human EC cells suggest that the factor responsible for mediating the effect of the mouse GT box is unlikely to be Sp1 or Sp3, and this factor is either not expressed in human EC cells or it is not sufficiently active in these cells. Mol. Reprod. Dev. © 2005 Wiley-Liss, Inc. [source] The "Income Gap" and the Health of Arts NonprofitsNONPROFIT MANAGEMENT & LEADERSHIP, Issue 3 2000Arthur C. Brooks This article addresses the widening gap between costs and revenues for many arts nonprofits; it examines the most common explanations for the problem, categorizes possible solutions, and suggests practical strategies for implementation. This study suggests that a critical difference exists between large and small arts firms, which in turn implies a different set of strategies for each. Whereas large organizations do well to leverage technological innovations, diversify product lines, and expand audiences through educational outreach, smaller organizations tend to see greater returns from efforts to expand their philanthropic base. [source] 15-Deoxy ,12,14 -prostaglandin J2 suppresses transcription by promoter 3 of the human thromboxane A2 receptor gene through peroxisome proliferator-activated receptor , in human erythroleukemia cellsFEBS JOURNAL, Issue 18 2005Adrian T. Coyle In humans, thromboxane (TX) A2 signals through two receptor isoforms, thromboxane receptor (TP), and TP,, which are transcriptionally regulated by distinct promoters, Prm1 and Prm3, respectively, within the single TP gene. The aim of the current study was to investigate the ability of the endogenous peroxisome proliferator-activated receptor (PPAR), ligand 15-deoxy-,12,14 -prostaglandin J2 (15d-PGJ2) to regulate expression of the human TP gene and to ascertain its potential effects on the individual TP, and TP, isoforms. 15d-PGJ2 suppressed Prm3 transcriptional activity and TP, mRNA expression in the platelet progenitor megakaryocytic human erythroleukemia (HEL) 92.1.7 cell line but had no effect on Prm1 or Prm2 activity or on TP, mRNA expression. 15d-PGJ2 also resulted in reductions in the overall level of TP protein expression and TP-mediated intracellular calcium mobilization in HEL cells. 15d-PGJ2 suppression of Prm3 transcriptional activity and TP, mRNA expression was found to occur through a novel mechanism involving direct binding of PPAR,,retinoic acid X receptor (RXR) heterodimers to a PPAR, response element (PPRE) composed of two imperfect hexameric direct repeat (DR) sequences centred at ,159 and ,148, respectively, spaced by five nucleotides (DR5). These data provide direct evidence for the role of PPAR, in the regulation of human TP gene expression within the vasculature and point to further critical differences in the modes of transcriptional regulation of TP, and TP, in humans. Moreover, these data highlight a further link between enhanced risk of cardiovascular disease in diabetes mellitus associated with increased synthesis and action of thromboxane A2 (TXA2). [source] How to test different density-dependent fecundity hypotheses in an increasing or stable populationJOURNAL OF ANIMAL ECOLOGY, Issue 1 2006MIGUEL FERRER Summary 1We report on a simulation study of increasing and stable populations working under two different hypotheses of density dependence of fecundity: the habitat heterogeneity hypothesis (HHH) and the individual adjustment hypothesis (IAH). Our aim is to find critical differences between the two regulatory hypotheses in natural populations. 2Populations under HHH show a strong negative relationship between fecundity and the coefficient of variation of fecundity. We also found a strong negative relationship between fecundity and skewness, demonstrating that, as fecundity decreases, the form of the distribution of brood sizes changes, being more left-skewed due to more territories failing to produce any offspring. 3This strong relationship was found only in the simulations of populations under HHH; whether increasing or stable, and under different ratios of good : poor territories and different population sizes. In contrast, no relationship between mean fecundity and skewness was found among simulations under IAH. 4Populations under IAH also showed a significant relationship between mean fecundity and the coefficient of variation of fecundity, but with a lower slope than in populations under HHH. 5In conclusion, skewness was found to be an adequate critical test that showed significant and strong relationships with mean fecundity only in populations under HHH, whether increasing or stable. This test is useful for species with a discrete distribution of offspring with a small number of integer categories, including most of the bird and mammal species. [source] Reciprocal distribution of two congeneric trees, Betula platyphylla var. japonica and Betula maximowicziana, in a landscape dominated by anthropogenic disturbances in northeastern JapanJOURNAL OF BIOGEOGRAPHY, Issue 12 2005Katsuhiro Osumi Abstract Aim, Information has been compiled on disturbance regimes and the life-history characteristics of Betula platyphylla var. japonica (Miq.) Hara and B. maximowicziana Regel to investigate the impact of humans on the present distribution patterns of these two congeneric tree species. Location, The study area is in the central region of the northern Kitakami Mountain Range, located in the northeast of Honshu Island, Japan. Methods, First, the present distributions of B. maximowicziana and B. platyphylla var. japonica were mapped at the landscape scale. To examine the factors affecting the distribution patterns, topographic features and past land use were taken into account. Second, life-history traits of both species were clarified at various growth stages either by fieldwork or through a literature search. Previous studies have provided some information on seed production, seed dispersal, seedling dynamics, sprouting, and growth. In the present study, field observations and experiments were conducted regarding seed-bank formation, size and age at reproduction, and the life span of canopy trees. Results,Betula platyphylla var. japonica and B. maximowicziana were spatially segregated in the studied landscape (14,000 ha). The distribution of each species was correlated more strongly with land use at the beginning of the twentieth century than with site environmental factors such as altitude or slope angle. Betula platyphylla var. japonica was distributed more frequently on former grasslands, whereas B. maximowicziana was almost exclusively limited to past old-growth forests. As typical pioneers, the two species showed similar life-history traits but differed in several critical points. Betula platyphylla var. japonica has a vigorous sprouting ability, which might increase its resistance to burning and logging, whereas B. maximowicziana forms a persistent seed bank in the soil, indicating an advantage in regenerating in disturbances found in forest communities. Other critical differences were detected in age-related characteristics such as minimum age of reproduction and life span. Main conclusions, The earlier reproductive maturity and the shorter life span of B. platyphylla var. japonica indicate a shorter population cycle than that for B. maximowicziana. The latter would be excluded from grasslands that were burned frequently, as a result of the longer time span before initial reproduction and its poor sprouting ability. In contrast, B. platyphylla var. japonica would be excluded from old-growth forests, where disturbance was infrequent, owing to its shorter life span and lack of a persistent seed bank. [source] Comparing health care delivery systems , initiating a student exchange project between Europe and the United StatesMEDICAL EDUCATION, Issue 7 2001Elizabeth G Armstrong Background Cross-cultural contact among different health care systems can provide a framework for identifying the strengths and weaknesses of one's own healthcare system. However, such contact has rarely had much impact upon medical education curricula. Despite intense debate on reforming the healthcare delivery systems (HCDS) in Europe and the United States, there is very little formal representation of this interdisciplinary field in our educational programs. Description To address this problem, a medical student exchange program was conducted in which students developed case studies that produced comparative analyses of HCDS in Germany, Sweden, Denmark and the United States. Each case is intended to highlight critical differences among the systems. Evaluation Students and their faculty preceptors completed pre- and post-exchange questionnaires to assess perceived knowledge of the HCDS and the adequacy of time devoted to it in their curricula. Both perceived that too little attention was devoted to this content in their programs. Following the exchange, students described clear increases in perceived knowledge. Discussion Our common interest in curriculum reform was key to implementing the exchange. The written cases generated by the students are being developed as course material in some of the schools and a conference is planned to disseminate the cases and the implementation strategies for their inclusion in medical curricula. [source] Characterization of the Streptococcus sobrinus acid-stress response by interspecies microarrays and proteomicsMOLECULAR ORAL MICROBIOLOGY, Issue 5 2010A.R. Martinez Summary Streptococcus mutans and Streptococcus sobrinus are considered the primary organisms responsible for human dental caries. The ability to generate acids and to adapt to low pH conditions is directly associated with the cariogenic potential of these bacteria. To survive acidic conditions, both species have been shown to mount an acid-tolerance response (ATR). However, previous characterization of the S. sobrinus ATR identified critical differences in the mechanisms of acid adaptation between S. mutans and S. sobrinus. Here, interspecies microarray and proteomic approaches were used to identify novel, previously unrecognized genes and pathways that participate in the S. sobrinus acid-stress response. The results revealed that, among other things, metabolic alterations that enhance energy generation and upregulation of the malolactic fermentation enzyme activity constitute important acid-resistance properties in S. sobrinus. Some of these acid adaptive traits are shared by S. mutans and might be considered optimal targets for therapeutic treatments designed to control dental caries. [source] Differences between chloro-carbon and hydro-carbon precursors in low-temperature epitaxial growth of 4H-SiCPHYSICA STATUS SOLIDI - RAPID RESEARCH LETTERS, Issue 7 2010Siva Kotamraju Abstract The advantages of using the chlorinated carbon precursor chloromethane instead of the hydrocarbon precursor propane in low-temperature (1300 °C) epitaxial growth of 4H-SiC were investigated. Chloromethane was found to provide a much wider process window for variation of the C/Si ratio between the lower boundary corresponding to the formation of condensed silicon face and the upper boundary corresponding to polytype inclusions and polycrystalline degradation, which is critical for achieving high growth rates without epilayer quality degradation. Use of a high Cl/Si ratio provided by HCl addition in the propane-based epitaxial growth did not eliminate the critical differences between chloro-carbon and hydro-carbon precursors. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Transfer of maternally administered fusogenic liposome-DNA complexes into monkey fetuses in a pregnancy modelTHE JOURNAL OF GENE MEDICINE, Issue 5 2002Makoto Hirano Abstract Background Materno-fetal transfer of intravenously administered liposome-plasmid DNA complexes has been demonstrated only in mice. Studies on its materno-fetal transfer in the pregnant monkey model is needed because of critical differences in placental structure between primates including humans and rodents. Methods The reporter plasmid pEGFP-C1 was formulated in cationic lipid containing polybrene and vesicular stomatitis virus G protein. The fusogenic liposome-plasmid DNA complexes were intradermally injected into pregnant common marmosets (N=2), a New World monkey, near term. DNA extracted from fetal tissues was subjected to PCR for detection of the egfp gene. Confocal microscopy and immunostaining were performed to determine the sites of transgene expression in the fetal organs. Results The egfp gene was detected in fetal blood and major organs (heart, liver, lung). The encoded protein was mainly produced in the endothelial cells of blood vessels in the fetal lungs. Conclusions This is the first report on materno-fetal transfer of intradermally administered fusogenic liposome-plasmid DNA complexes and fetal expression of a transgene in primates. Copyright © 2002 John Wiley & Sons, Ltd. [source] | |||||||||||||