bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent Protein LANA2 from Kaposi's Sarcoma-Associated Herpesvirus Interacts with 14-3-3 Proteins and Inhibits FOXO3a Transcription Factor
Authors: Muñoz-Fontela Cesar , Marcos-Villar Laura , Gallego Pedro , Arroyo Javier , Da Costa Marco , Pomeranz Karen M. , Lam Eric W.-F. , Rivas Carmen
Published: November 2006

The Kaposi's sarcoma-associated herpesvirus latent protein LANA2 has been suggested to have an important role in the transforming activity of the virus based on its capacity to inhibit p53 and PKR-dependent apoptosis as well as the interferon-dependent response. Here, we describe a novel interaction between LANA2 and both the phosphoserine/phosphothreonine-binding 14-3-3 proteins and the transcription factor FOXO3a. In addition, our results indicate that LANA2 inhibits the transcriptional activity of FOXO3a and blocks the G
2
/M arrest induced by 14-3-3 protein overexpression. These results suggest a novel mechanism by which LANA2 may promote tumorigenesis.
Preferential Activation of Toll-Like Receptor Nine by CD46-Utilizing Adenoviruses
Authors: Iacobelli-Martinez Milena , Nemerow Glen R.
Published: November 2006

Adenoviruses (Ads) are responsible for respiratory, ocular, and gastrointestinal illnesses in humans. While the majority of serotypes utilize coxsackievirus-adenovirus receptor (CAR) as their primary attachment receptor, subgroup B and subgroup D Ad37 serotypes use CD46. Given the propensity of Ad vectors to activate host immune responses, we sought to investigate their potential for type I interferon induction. We found that CD46 Ads were capable of alpha interferon (IFN-α) induction by peripheral blood mononuclear cells and that plasmacytoid dendritic cells (pDCs) were the principal producers of this cytokine. IFN-α induction correlated with the permissivity of pDCs to CD46- but not CAR-utilizing Ad serotypes. A role for Toll-like receptor 9 (TLR9) recognition of Ad was supported by the requirement for viral DNA and efficient endosomal acidification and by the ability of a TLR9-inhibitory oligonucleotide to attenuate IFN-α induction. Cell lines expressing TLR9 that are permissive to infection by both CAR- and CD46-utilizing serotypes showed a preferential induction of TLR9-mediated events by CD46-utilizing Ads. Specifically, the latter virus types induced higher levels of cytokine expression and NF-κB activation in HeLa cells than CAR-dependent Ad types, despite equivalent infection rates. Therefore, infectivity alone is not sufficient for TLR9 activation, but this activation instead is regulated by a specific receptor entry pathway. These data reveal a novel mode of host immune recognition of Ad with implications for Ad pathogenesis and for the use of unconventional Ad vectors for gene delivery and vaccine development.
CXCR3-Dependent Recruitment of Antigen-Specific T Lymphocytes to the Liver during Murine Cytomegalovirus Infection
Authors: Hokeness Kirsten L. , Deweerd Elizabeth S. , Munks Michael W. , Lewis Casey A. , Gladue Ronald P. , Salazar-Mather Thais P.
Published: November 2006

Innate inflammatory events promoting antiviral defense in the liver against murine cytomegalovirus (MCMV) infection have been characterized. However, the mechanisms that regulate the selective recruitment of inflammatory T lymphocytes to the liver during MCMV infection have not been defined. The studies presented here demonstrate the expression of monokine induced by gamma interferon (IFN-γ; Mig/CXCL9) and IFN-γ-inducible protein 10 (IP-10/CXCL10) in liver leukocytes and correlate their production with the infiltration of MCMV-specific CD8 T cells into the liver. Antibody-mediated neutralization of CXCL9 and CXCL10 and studies using mice deficient in CXCR3, the primary known receptor for these chemokines, revealed that CXCR3-dependent mechanisms promote the infiltration of virus-specific CD8 T cells into the liver during acute infection with MCMV. Furthermore, CXCR3 functions augmented the hepatic accumulation of CD8 T-cell IFN-γ responses to MCMV. Evaluation of protective functions demonstrated enhanced pathology that overlapped with transient increases in virus titers in CXCR3-deficient mice. However, ultimate viral clearance and survival were not compromised. Thus, CXCR3-mediated signals support the accumulation of MCMV-specific CD8 T cells that contribute to, but are not exclusively required for, protective responses in a virus-infected tissue site.
Retrotransposon-based S-SAP as a platform for the analysis of genetic variation and linkage in globe artichoke
Authors: Acquadro Alberto , Portis Ezio , Moglia Andrea , Magurno Franco , Lanteri Sergio
Published: November 2006

A high copy number of retrotransposon sequences are present and widely dispersed in plant genomes. Their activity generates a considerable degree of sequence polymorphism. Here, we report the cloning of CYRE-5, a long-terminal repeat carrying retrotransposon-like sequence in Cynara cardunculus L., and its exploitation to develop a DNA fingerprinting assay across 22 accessions, including both cultivated (globe artichoke and cultivated cardoon) and wild (wild cardoon) types. The effectiveness of the sequence-specific amplified polymorphism (S-SAP) platform is compared with that of amplified fragment length polymorphism (AFLP). A genetic linkage analysis, based on a hybrid population between 2 globe artichoke varietal types, resulted in the inclusion of 29 S-SAP loci in the core genetic map, confirming their dispersed distribution across the globe artichoke genome.
Increased muscle oxidative potential following resistance training induced fibre hypertrophy in young men
Authors: Tang Jason E. , Hartman Joseph W. , Phillips Stuart M.
Published: November 2006

Some evidence suggests that resistance training may lower relative muscle mitochondrial content via “dilution” of the organelle in a larger muscle fibre. Such an adaptation would reduce fatigue resistance, as well as compromise oxidative ATP synthesis and the capacity for fatty-acid oxidation. We investigated the effect of resistance training on mitochondrial enzymes of the citric acid cycle (citrate synthase; CS) and β-oxidation (β-hydroxyacyl CoA dehydrogenase; β-HAD), as well as markers of the potential for glucose phosphorylation (hexokinase; HK) and glycolysis (phosphofructokinase; PFK). Twelve untrained men (21.9 ± 0.5 y; 1.79 ± 0.03 m; 83.2 ± 3.2 kg) participated in a 12 week progressive resistance-training program. Muscle biopsies were taken from the vastus lateralis before (PRE) and after (POST) training. Training increased mean muscle fibre cross-sectional area (p < 0.05) and the activities of CS (PRE = 4.53 ± 0.44 mol·kg protein–1·h–1; POST = 5.63 ± 0.40 mol·kg protein–1·h–1; p < 0.001) and β-HAD (PRE = 2.55 ± 0.28 mol·kg protein–1·h–1; POST = 3.11 ± 0.21 mol·kg protein–1·h–1; p < 0.05). The activity of HK increased 42% (p < 0.05), whereas the activity of PFK remained unchanged. We conclude that resistance training provides a stimulus for improving muscle oxidative potential, as reflected by the increased activities of CS and β-HAD following resistance training induced hypertrophy.
Ruthenium(III) acetylacetonate [Ru(acac)3] — An efficient chemoselective catalyst for the tetrahydropyranylation (THP) of alcohols and phenols under solvent-free conditions
Authors: Varala Ravi , Adapa Srinivas R
Published: November 2006

A catalytic amount of ruthenium(III) acetylacetonate (2 mol%) [Ru(acac)3] enables solvent-free tetrahydropyranylation of different types of alcohols and phenols at ambient temperature in moderate to excellent yields. Notably, selective monoprotection of diols can be achieved chemoselectively. Furthermore, the catalyst could be recovered and reused if necessary.Key words: tetrahydropyranyl ethers, protecting groups, ruthenium(III) acetylacetonate, alcohols, thiols.
Probiotic bacteria as potential detoxification tools: assessing their heavy metal binding isotherms
Authors: Ibrahim Fandi , Halttunen Teemu , Tahvonen Raija , Salminen Seppo
Published: November 2006

Dietary exposure to heavy metals may have detrimental effects on human and animal health, even at low concentrations. Specific probiotic bacteria may have properties that enable them to bind toxins from food and water. We assessed the interaction of probiotic bacteria with cadmium and lead in vitro as an initial screening step to identify strains for heavy metal decontamination in food and intestinal models. Binding isotherms for cadmium and lead were characterized for Lactobacillus rhamnosus LC-705, Propionibacterium freudenreichii subsp. shermanii JS and a mix of them used by the food industry. Differences among the strains and their combinations in binding performance at a range of concentrations between 0.1 and 100 mg·L–1 were evaluated with the Langmuir model for biosorption. The effects of pH, contact time, and viability on the binding capacities were also investigated. All strains and their combinations were found to bind cadmium and lead efficiently at low concentration ranges commonly observed in foods. However, the two strains and their combinations differed significantly in their maximum binding capacities and affinities represented by the Langmuir constants Qmax and b, respectively. The binding seemed to occur instantaneously and in a pH-dependent manner, which can be perfectly described by a segmented linear–plateau model.Key words: probiotics, cadmium, lead, binding, Langmuir.
Physical and genetic map of the Spiroplasma kunkelii CR2-3x chromosome
Authors: Dally Ellen L , Barros Thereza S.L , Zhao Yan , Lin ShaoPing , Roe Bruce A , Davis Robert E
Published: November 2006

Spiroplasma kunkelii (class Mollicutes) is the characteristically helical, wall-less bacterium that causes corn stunt disease. A combination of restriction enzyme analysis, pulsed-field gel electrophoresis (PFGE), and Southern hybridization analysis was used to construct a physical and genetic map of the S. kunkelii CR2-3x chromosome. The order of restriction fragments on the map was determined by analyses of reciprocal endonuclease double digests employing I-CeuI, AscI, ApaI, EagI, SmaI, BssHII, BglI, and SalI; adjacent fragments were identified on two-dimensional pulsed-field electrophoresis gels. The size of the chromosome was estimated at 1550 kb. Oligonucleotide pairs were designed to prime the amplification of 26 S. kunkelii gene sequences in the polymerase chain reaction (PCR). Using PCR amplicons as probes, the locations of 27 S. kunkelii putative single-copy genes were positioned on the map by Southern hybridization analyses of chromosomal fragments separated in PFGE. The nucleotide sequence of the single ribosomal RNA operon was determined and its location mapped to a chromosomal segment bearing recognition sites for SalI, SmaI, EagI, and I-CeuI.Key words: Spiroplasma kunkelii CR2-3x, corn stunt spiroplasma, mollicutes, genome mapping, two-dimensional pulsed-field gel electrophoresis.
Genotypic characteristics of therrnoperon and genome of indigenous soybeanBradyrhizobiain cropping zones of China
Authors: Yang Jiang Ke , Zhang Wei Tao , Yuan Tian Ying , Zhou Jun Chu
Published: November 2006

Four genetic assays, 16S rRNA restriction fragment length polymorphism (RFLP), 16S rRNA sequencing, 16S–23S rRNA intergenetic spacer (IGS) RFLP, and amplified fragment length polymorphism (AFLP), were conducted to determine the genotypic characteristics of 44 indigenous strains of Bradyrhizobium from soybean (Glycine max L.) cropping zones of China. The results generated from different assays showed that soybean bradyrhizobial isolates comprised four genomic groups. Group I was composed of strains mainly isolated from the North and Northeast plains of China. All four assays confirmed this group as phylogenetically divergent from all the reference strains. Strains of the group may represent a new species. Strains in Group II isolated from a variety of geographic regions were ascribed to B. liaoningense. Strains in Group III, mainly isolated from Central and East China, were closely related to the reference strains of B. japonicum. Strains in Group IV belonged to B. elkanii.Key words: soybean bradyrhizobia, 16S rRNA RFLP, 16S–23S IGS RFLP, AFLP.
Comment on “Are survival rates for northern spotted owls biased?”Appears in Can. J. Zool.83: 1386–1390.
Authors: Franklin A.B. , Nichols J.D. , Anthony R.G. , Burnham K.P. , White G.C. , Forsman E.D. , Anderson D.R.
Published: November 2006

Loehle et al. recently estimated survival rates from radio-telemetered northern spotted owls ( Strix occidentalis caurina (Merriam, 1898)) and suggested that survival rates estimated for this species from capture–recapture studies were negatively biased, which subsequently resulted in the negatively biased estimates of rates of population change (λ) reported by Anthony et al. (Wildl. Monogr. No. 163, pp. 1–47 (2006)) . We argue that their survival estimates were inappropriate for comparison with capture–recapture estimates because (i) the manner in which they censored radio-telemetered individuals had the potential to positively bias their survival estimates, (ii) their estimates of survival were not valid for evaluating bias, and (iii) the size and distribution of their radiotelemetry study areas were sufficiently different from capture–recapture study areas to preclude comparisons. In addition, their inferences of negative bias in rates of population change estimated by Anthony et al. were incorrect and reflected a misunderstanding about those estimators.
SYNTHESIS AND PHOTOLUMINESCENCE PROPERTIES OF Er3+, Eu3+ IONS ACTIVATED SrAl12O19
Authors: SINGH VIJAY , ZHU JUN-JIE
Published: November 2006

Synthesis of Er 3+, Eu 3+ ions activated strontium hexa-aluminate phosphor using the combustion method is described. An efficient phosphor can be prepared by this method at reaction temperatures as low as 500°C in a few minutes. Powder X-ray diffraction and the optical properties were studied by photoluminescence spectra.
Neopluralism
Authors: McFarland Andrew S.
Published: November 2006

▪ Abstract  Neopluralism is one of a class of research findings or social science models—such as elitism, pluralism, and corporatism—that refer to the structure of power and policy making in some domain of public policy. Originating from Robert Dahl's pluralism model in Who Governs? (1961), neopluralism evolved in the study of American politics through discarding or modifying some of Dahl's ideas, while adding new concerns about agenda building, the logic of collective action, special-interest subgovernments, social movements, advocacy coalitions, and the theory of political processes. Neopluralism is normally a finding of complex action in policy systems, but neopluralism does not assume that complexity implies fairness of representation, nor does it assume interest group elimination of autonomous action by governmental agencies.
Case-based learning of blood oxygen transport
Authors: Cliff William H.
Published: November 2006

A case study about carbon monoxide poisoning was used help students gain a greater understanding of the physiology of oxygen transport by the blood. A review of student answers to the case questions showed that students can use the oxygen-hemoglobin dissociation curve to make meaningful determinations of oxygen uptake and delivery. However, the fact that many students had difficulty locating the effect of carbon monoxide poisoning in the process of external respiration suggests that these students have not built a robust model of how oxygen distributes itself between the plasma and hemoglobin. This suggests that more determined emphasis on how oxygen enters the blood and how it is partitioned between hemoglobin and the plasma would help students develop more accurate mental models of how oxygen moves from the lungs to the tissues.
PGC-1α: a key regulator of energy metabolism
Authors: Liang Huiyun , Ward Walter F.
Published: November 2006

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a member of a family of transcription coactivators that plays a central role in the regulation of cellular energy metabolism. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis. PGC-1α stimulates mitochondrial biogenesis and promotes the remodeling of muscle tissue to a fiber-type composition that is metabolically more oxidative and less glycolytic in nature, and it participates in the regulation of both carbohydrate and lipid metabolism. It is highly likely that PGC-1α is intimately involved in disorders such as obesity, diabetes, and cardiomyopathy. In particular, its regulatory function in lipid metabolism makes it an inviting target for pharmacological intervention in the treatment of obesity and Type 2 diabetes.
Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety
Authors: Masuki Shizue , Eisenach John H. , Johnson Christopher P. , Dietz Niki M. , Benrud-Larson Lisa M. , Schrage William G. , Curry Timothy B. , Sandroni Paola , Low Phillip A. , Joyner Michael J.
Published: November 2006

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients ( n = 14) and healthy controls ( n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to −40 mmHg while wearing deflated antishock trousers. “Sham” venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 ± 5 beats/min vs. 19 ± 3 beats/min in control subjects at −40 mmHg ( P < 0.01). LBNP with trouser inflation markedly blunted the HR responses in the patients (9 ± 2 beats/min) and controls (2 ± 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 ± 2 vs. 19 ± 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients ( P < 0.05), but they were not related to the HR responses during LBNP or mental stress ( P > 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.
Time-Dependent, Layer-Specific Modulation of Sensory Responses Mediated by Neocortical Layer 1
Authors: Shlosberg Dan , Amitai Yael , Azouz Rony
Published: November 2006

An essential component of feedback and top-down information in the cortical column arrives at layer 1 (L1) where it contacts distal dendrites of pyramidal neurons. Although much is known about the anatomical organization of L1 fibers, their contribution to sensory information processing remains to be determined. We assessed the physiological significance of L1 inputs by performing extracellular recordings in vivo from neurons in the primary somatosensory cortex of rodents. We found that blocking activity in L1 increases whisker-evoked response magnitude and variance, suggesting that L1 exerts an inhibitory influence on whisker responses. However, when pairing L1 stimulation with whisker deflection, the interval between the stimuli determined the outcome of the interaction, with facilitation of sensory responses dominating the short intervals (≤10 ms) and suppression prevailing at longer intervals (>10 ms). These temporal interactions resulted in a time-dependent regulation of direction tuning of cortical neurons. The synaptic mechanisms underlying L1 inputs’ influences were examined using whole cell recordings in vitro while pairing L1 and white-matter stimulations. We found time-dependent, layer-specific differences in synaptic summation of the two inputs, with supralinearity at shorter intervals and sublinearity at longer intervals that resulted mainly from shunting inhibition. Taken together, our results demonstrate that L1 inputs impose a time- and layer-specific regulation on sensory-evoked responses. This in turn may lead to a dynamic transmission of sensory information in the somatosensory cortex.
Long-Lasting, Context-Dependent Modification of Stepping in the Cat After Repeated Stumbling-Corrective Responses
Authors: McVea D. A. , Pearson K. G.
Published: November 2006

A consistent feature of animal locomotion is the capacity to maintain stable movements in changing environments. Here we describe long-term modification of the swing movement of the hind leg in cats in response to repeatedly impeding the movement of the leg. While studying phase transitions in the hind legs, we discovered that repetitively evoking the stumbling-corrective reaction led to long-lasting increases in knee flexion and step height during swing to avoid the impediment. These increases were apparent after nearly 20 stimuli and maximal after about 120 stimuli and, in some animals, they persisted for ≥24 h after presentation of the stimuli. Furthermore, these long-lasting changes were context dependent and did not generalize to other environments; when walking was observed in an environment distinct from that used in training, the hind-limb kinematics returned to normal. To gain insight into what regions of the nervous system might be involved in this long-term modification, we examined the changes in stepping in decerebrate cats after multiple perturbed steps. In this situation, there was a short-term increase in step height, although this increase was smaller than that evoked in intact animals and persisted for <1 min after termination of the stimuli. Thus induction of the long-term increase in step height requires the forebrain. We propose that the conditioned change in leg movement is related to a general ability of animals to adapt locomotor movements to new features of the environment.
Starlikeness and convexity of a class of analytic functions
Authors: Tuneski Nikola , Irmak Hüseyin
Published: November 2006

Let be the class of analytic functions in the unit disk that
are normalized with f(0) = f′(0) − 1 = 0 and let −1 ≤ B < A ≤ 1. In this paper we study the class Gλ,α = {f ∈ :|(1 − α + αzf″(z)/f′(z))/zf′(z)/f(z)−(1 − α)| < λ, z∈}, 0 ≤ α ≤ 1, and give sharp sufficient conditions that embed it into the classes
S∗[A, B] = {f ∈ :zf′(z)/f(z)≺(1 + Az)/(1 + Bz)}
and K(δ) = {f ∈ :1 + zf″(z)/f′(z)≺(1 − δ)(1 + z)/(1 − z) + δ}, where “≺” denotes the usual subordination. Also, sharp upper
bound of |a2| and of the Fekete‐Szegö functional is given for the class Gλ,α.
Unsolid and fluid strong varieties of partial algebras
Authors: Busaman S. , Denecke K.
Published: November 2006

A partial algebra consists of a setAand an indexed set of partial operations . Partial operations occur in the algebraic description of partial recursive functions and Turing machines. A pair of termsp≈qover the partial algebra𝒜is said to be a strong identity in𝒜if the right‐hand side is defined whenever the left‐hand side is defined and vice versa, and both are equal. A strong identityp≈qis called a strong hyperidentity if when the operation symbols occurring inpandqare replaced by terms of the same arity, the identity which arises is satisfied as a strong identity. If every strong identity in a strong variety of partial algebras is satisfied as a strong hyperidentity, the strong variety is called solid. In this paper, we consider the other extreme, the case when the set of all strong identities of a strong variety of partial algebras is invariant only under the identical replacement of operation symbols by terms. This leads to the concepts of unsolid and fluid varieties and some generalizations.
On the asymptotics of the real solutions to the general sixthPainlevé equation
Authors: Qin Huizeng , Lu Youmin
Published: November 2006

We study the general sixth Painlevé equation, develop, and justify the
existence of several groups of asymptotics of its real solutions. Our methods also justify the differentiability of the asymptotics. Particular attention is paid to the solutions between 0 and 1. We find the asymptotics of all real solutions between 0 and 1 of the sixth Painlevé equation as x → +∞.
Probabilistic Sensitivities for Fatigue Analysis of Turbine Engine Disks
Authors: Millwater Harry R. , Osborn R. Wesley
Published: November 2006

A methodology is developed and applied that determines the sensitivities
of the probability‐of‐fracture of a gas turbine disk fatigue analysis with respect
to the parameters of the probability distributions describing the random variables.
The disk material is subject to initial anomalies, in either low‐ or high‐frequency
quantities, such that commonly used materials (titanium, nickel, powder nickel)
and common damage mechanisms (inherent defects or surface damage) can be considered.
The derivation is developed for Monte Carlo sampling such that the existing failure samples
are used and the sensitivities are obtained with minimal additional computational time.
Variance estimates and confidence bounds of the sensitivity estimates are developed.
The methodology is demonstrated and verified using a multizone probabilistic fatigue analysis
of a gas turbine compressor disk analysis considering stress scatter, crack
growth propagation scatter, and initial crack size as random variables.
Towards a Holistic, Yet Gene‐Centered Analysis of Gene Expression Profiles: A Case Study of Human Lung Cancers
Authors: Guo Yuchun , Eichler Gabriel S. , Feng Ying , Ingber Donald E. , Huang Sui
Published: November 2006

Genome‐wide gene expression profile studies encompass increasingly large number of samples, posing a challenge to their presentation and interpretation without losing the notion that each transcriptome constitutes a complex biological entity. Much like pathologists who visually analyze information‐rich histological sections as a whole, we propose here an integrative approach. We use a self‐organizing maps‐based software, the gene expression dynamics inspector (GEDI) to analyze gene expression profiles of various lung tumors. GEDI allows the comparison of tumor profiles based on direct visual detection of transcriptome patterns. Such intuitive “gestalt” perception promotes the discovery of interesting relationships in the absence of an existing hypothesis. We uncovered qualitative relationships between squamous cell tumors, small‐cell tumors, and carcinoid tumor that would have escaped existing algorithmic classifications. These results suggest that GEDI may be a valuable explorative tool that combines global and gene‐centered analyses of molecular profiles from large‐scale microarray experiments.
Mutant p53 Protects Cells from 12-O-Tetradecanoylphorbol-13-Acetate–Induced Death by Attenuating Activating Transcription Factor 3 Induction
Authors: Buganim Yosef , Kalo Eyal , Brosh Ran , Besserglick Hila , Nachmany Ido , Rais Yoach , Stambolsky Perry , Tang Xiaohu , Milyavsky Michael , Shats Igor , Kalis Marina , Goldfinger Naomi , Rotter Varda
Published: November 2006

Mutations in p53 are ubiquitous in human tumors. Some p53 mutations not only result in loss of wild-type (WT) activity but also grant additional functions, termed “gain of function.” In this study, we explore how the status of p53 affects the immediate response gene activating transcription factor 3 (ATF3) in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-protein kinase C (PKC) pathway. We show that high doses of TPA induce ATF3 in a WT p53-independent manner correlating with PKCs depletion and cell death. We show that cells harboring mutant p53 have attenuated ATF3 induction and are less sensitive to TPA-induced death compared with their p53-null counterparts. Mutagenesis analysis of the ATF3 promoter identified the regulatory motifs cyclic AMP-responsive element binding protein/ATF and MEF2 as being responsible for the TPA-induced activation of ATF3. Moreover, we show that mutant p53 attenuates ATF3 expression by two complementary mechanisms. It interacts with the ATF3 promoter and influences its activity via the MEF2 site, and additionally, it attenuates transcriptional expression of the ATF3 activator MEF2D. These data provide important insights into the molecular mechanisms that underlie mutant p53 gain of function. (Cancer Res 2006; 66(22): 1750-9)
Oxidative Stress Induces Premature Senescence by Stimulating Caveolin-1 Gene Transcription through p38 Mitogen-Activated Protein Kinase/Sp1–Mediated Activation of Two GC-Rich Promoter Elements
Authors: Dasari Arvind , Bartholomew Janine N. , Volonte Daniela , Galbiati Ferruccio
Published: November 2006

Cellular senescence is believed to represent a natural tumor suppressor mechanism. We have previously shown that up-regulation of caveolin-1 was required for oxidative stress–induced premature senescence in fibroblasts. However, the molecular mechanisms underlying caveolin-1 up-regulation in senescent cells remain unknown. Here, we show that subcytotoxic oxidative stress generated by hydrogen peroxide application promotes premature senescence and stimulates the activity of a (−1,296) caveolin-1 promoter reporter gene construct in fibroblasts. Functional deletion analysis mapped the oxidative stress response elements of the mouse caveolin-1 promoter to the sequences −244/−222 and −124/−101. The hydrogen peroxide–mediated activation of both Cav-1 (−244/−222) and Cav-1 (−124/−101) was prevented by the antioxidant quercetin. Combination of electrophoretic mobility shift studies, chromatin immunoprecipitation analysis, Sp1 overexpression experiments, as well as promoter mutagenesis identifies enhanced Sp1 binding to two GC-boxes at −238/−231 and −118/−106 as the core mechanism of oxidative stress–triggered caveolin-1 transactivation. In addition, signaling studies show p38 mitogen-activated protein kinase (MAPK) as the upstream regulator of Sp1-mediated activation of the caveolin-1 promoter following oxidative stress. Inhibition of p38 MAPK prevents the oxidant-induced Sp1-mediated up-regulation of caveolin-1 protein expression and development of premature senescence. Finally, we show that oxidative stress induces p38-mediated up-regulation of caveolin-1 and premature senescence in normal human mammary epithelial cells but not in MCF-7 breast cancer cells, which do not express caveolin-1 and undergo apoptosis. This study delineates for the first time the molecular mechanisms that modulate caveolin-1 gene transcription upon oxidative stress and brings new insights into the redox control of cellular senescence in both normal and cancer cells. (Cancer Res 2006; 66(22): 10805-14)
Up-regulation of Heat Shock Protein 27 Induces Resistance to 17-Allylamino-Demethoxygeldanamycin through a Glutathione-Mediated Mechanism
Authors: McCollum Andrea K. , TenEyck Cynthia J. , Sauer Brian M. , Toft David O. , Erlichman Charles
Published: November 2006

17-Allylamino-demethoxygeldanamycin (17-AAG), currently in phase I and II clinical trials as an anticancer agent, binds to the ATP pocket of heat shock protein (Hsp90). This binding induces a cellular stress response that up-regulates many proteins including Hsp27, a member of the small heat shock protein family that has cytoprotective roles, including chaperoning of cellular proteins, regulation of apoptotic signaling, and modulation of oxidative stress. Therefore, we hypothesized that Hsp27 expression may affect cancer cell sensitivity to 17-AAG. In colony-forming assays, overexpression of Hsp27 increased cell resistance to 17-AAG whereas down-regulation of Hsp27 by siRNA increased sensitivity. Because Hsp27 is known to modulate levels of glutathione (GSH), we examined cellular levels of GSH and found that it was decreased in cells transfected with Hsp27 siRNA when compared with control siRNA. Treatment with buthionine sulfoximine, an inhibitor of GSH synthesis, also sensitized cells to 17-AAG. Conversely, treatment of Hsp27 siRNA–transfected cells with N-acetylcysteine, an antioxidant and GSH precursor, reversed their sensitivity to 17-AAG. A cell line selected for stable resistance to geldanamycin relative to parent cells showed increased Hsp27 expression. When these geldanamycin- and 17-AAG-resistant cells were transfected with Hsp27 siRNA, 17-AAG resistance was dramatically diminished. Our results suggest that Hsp27 up-regulation has a significant role in 17-AAG resistance, which may be mediated in part through GSH regulation. Clinical modulation of GSH may therefore enhance the efficacy of Hsp90-directed therapy. (Cancer Res 2006; 66(22): 10967-75)
Effectiveness and Efficiency of a Universal Newborn Hearing Screening in Germany
Authors: Neumann Katrin , Gross Manfred , Böttcher Peter , Euler Harald A. , Spormann-Lagodzinski Marlies , Polzer Melanie
Published: November 2006

The decision to mandate, finance, and implement a universal newborn hearing screening (UNHS) requires the evaluation of its therapy-directed benefit by comparing (1) a procedure employing a UNHS with (2) a targeted screening for at-risk babies for neonatal hearing disorders and (3) a procedure without systematic screening. In a cohort study the outcome of the UNHS program of Hessen in 2005 with 17,439 screened newborns was analyzed. Validity, effectiveness, and efficiency were evaluated and compared to a sample of 98 Hessian and 355 German children who were detected in 2005 as hearing-impaired but not by an UNHS. The UNHS group had a PASS rate of 97.0%. Forty-nine hearing-impaired children were diagnosed at a median age of 3.1 months and treated at a median age of 3.5 months. Corresponding values for the Hessian non-UNHS group were 17.8 and 21.0 months. For Germany the median age at diagnosis was 39.0 months. The age at therapy onset correlated negatively with parameters of speech/language and psychosocial development. A targeted screening would have resulted in a low sensitivity of 65.3%. Hence, a UNHS is the most effective way to an early therapy of neonatal hearing disorders with an optimal outcome.
Monozygotic Twins Suffering from Huntington’s Disease Show Different Cognitive and Behavioural Symptoms
Authors: Gómez-Esteban J.C. , Lezcano E. , Zarranz J.J. , Velasco F. , Garamendi Iñigo , Pérez Tomás , Tijero Beatriz
Published: November 2006

Monozygotic male twins, carrying the same number of trinucleotide repeats in the IT 15 Huntington disease (HD) gene, showed a different clinical course. Patient 1 presented with anxiety and chorea at the age of 40. Patient 2 showed persecution paranoia and motor impersistence at the age of 42. Both patients were monitored for 30 months using currently recommended motor and behaviour scales. No differences were observed in motor scoring besides small interevaluation fluctuations. However, on the cognitive and behaviour scales, patient 1 showed a significant worsening when compared with patient 2. Our cases support the belief that the motor symptoms and signs in HD are highly dependent on the trinucleotide expansion. However, the differences in the evolution of mental status in our patients suggest that other still unknown environmental factors are important in the phenotypic expression of Huntington’s disease.
Dexamethasone Alters Bronchoalveolar Lavage Fluid Proteome in a Mouse Asthma Model
Authors: Zhao Jing , Yeong Lai Han , Wong W.S. Fred
Published: November 2006

Background: Glucocorticoid is the most effective anti-inflammatory agent for asthma. The spectrum of protein targets that can be regulated by glucocorticoid in asthma is not fully understood. The present study tried to identify novel protein targets of dexamethasone in allergic airway inflammation by analyzing the proteome of mouse bronchoalveolar lavage (BAL) fluid. Methods: BALB/c mice sensitized and challenged with ovalbumin (OVA) showed increased pulmonary inflammatory cell infiltration, airway mucus production and serum OVA-specific IgE level. Dexamethasone inhibited all these allergic airway inflammation endpoints. BAL fluid proteins were resolved by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: The levels of 26 BAL fluid proteins were found to be markedly altered by dexamethasone. A family of chitinases (Ym1, Ym2 and acidic mammalian chitinase, AMCase), lungkine, gob-5, surfactant protein D and polymeric immunoglobulin receptor have been found for the first time to be downregulated by dexamethasone in allergic airways. The downregulatory effects were confirmed by immunoblotting and RT-PCR analyses. Dexamethasone was also shown to significantly inhibit lavage fluid chitinase bioactivity. In addition, dexamethasone promoted airway expression of vitamin D-binding protein, heptoglobin and α1-antitrypsin. Conclusions: Among all these newly identified protein targets of dexamethasone, AMCase and gob-5 have been shown to be pro-inflammatory in asthma. Downregulation of AMCase and gob-5 may be considered as two novel anti-inflammatory actions of glucocorticoid in asthma.
Reference Values of Total Serum IgE and Their Significance in the Diagnosis of Allergy in Young European Adults
Authors: Carosso Aurelia , Bugiani Massimiliano , Migliore Enrica , Antò Josep Maria , DeMarco Roberto
Published: November 2006

Allergic sensitization mediated by immunoglobulin E (IgE) is the basis of allergic diseases, and elevated total IgE, in spite of some well-known limitations, is frequently included as a diagnostic criterion for allergic diseases. The reference value of total IgE (IgE-t) in the literature (1.5–144 kU/l) was established almost 2 decades ago. The aim of this study was to establish IgE-t reference values, establishing an updated cutoff value able to identify atopic subjects, defined as a positive CAP-radioallergosorbent test to at least one of a panel of common allergens, among young European adults. The study included 6,670 subjects from 10 Western European countries within the framework of the European Community Respiratory Health Survey II. IgE-t and specific IgE (IgE-s) were measured for the main inhalant allergens; IgE-s in class 0 for all allergens (66.2%) characterized non-atopy. The reference values were estimated by means of linear regression using a 50% random subsample of non-atopic subjects. Two non-atopic subsamples were examined so that one subsample could be used to establish reference IgE-t values, and these values were compared to those in the second non-atopic subsample to validate the findings. Sensitivity and specificity for atopy were assessed on the other 50% of non-atopic and on all atopic subjects. The 95th percentile of IgE-t reference values in non-smokers was 148 kU/l in women and 169 kU/l in men, while it was 194 and 220 kU/l in female and male smokers, respectively: serum IgE-t above the 95th percentile identifies <32% and above the 99th percentile <20% of atopic adults (low sensitivity), but a serum IgE-t below the 95th percentile identifies >90% and below the 99th percentile identifies >95% of non-atopic adults (good specificity). Due to the adequate specificity, IgE-t values exceeding the normal limits confirm a suspected atopic status; however, because of the low sensitivity, values below the cutoff seem not to exclude an atopic status with sufficient accuracy.
On Being Small: Brain Allometry in Ants
Authors: Wehner Rüdiger , Fukushi Tsukasa , Isler Karin
Published: November 2006

Comparative neurobiologists have provided ample evidence that in vertebrates small animals have proportionally larger brains: in a double-logarithmic plot of brain weight versus body weight all data points conform quite closely to a straight line with a slope of less than one. Hence vertebrate brains scale allometrically, rather than isometrically, with body size. Here we extend the phylogenetic scope of such studies and the size range of the brains under investigation to the insects, especially ants. We show that the principle of (negative) allometry applies as well, but that ants have considerably smaller brains than any ant-sized vertebrate would have, and that this result holds even if the relatively higher exoskeleton weights of ants (as compared to endoskeleton weights of mammals) are taken into account. Finally, interspecific comparisons within one genus of ants, Cataglyphis, show that species exhibiting small colony sizes (of a few hundred individuals) have significantly smaller brains than species in which colonies are composed of several thousand individuals.
Introducing Robustness in Multi-Objective Optimization
Authors: Deb Kalyanmoy , Gupta Himanshu
Published: November 2006

In optimization studies including multi-objective optimization, the main focus is placed on finding the global optimum or global Pareto-optimal solutions, representing the best possible objective values. However, in practice, users may not always be interested in finding the so-called global best solutions, particularly when these solutions are quite sensitive to the variable perturbations which cannot be avoided in practice. In such cases, practitioners are interested in finding the robust solutions which are less sensitive to small perturbations in variables. Although robust optimization is dealt with in detail in single-objective evolutionary optimization studies, in this paper, we present two different robust multi-objective optimization procedures, where the emphasis is to find a robust frontier, instead of the global Pareto-optimal frontier in a problem. The first procedure is a straightforward extension of a technique used for single-objective optimization and the second procedure is a more practical approach enabling a user to set the extent of robustness desired in a problem. To demonstrate the differences between global and robust multi-objective optimization principles and the differences between the two robust optimization procedures suggested here, we develop a number of constrained and unconstrained test problems having two and three objectives and show simulation results using an evolutionary multi-objective optimization (EMO) algorithm. Finally, we also apply both robust optimization methodologies to an engineering design problem.
Sylvia's Story
Authors: Davis Christine S.
Published: November 2006

This article, a story about a family with children with disabilities and the people who are helping them, shows the power of speaking in narratives, and the liberation of understanding in narratives. It looks at the issues of narrative truth, meaning, embodiment, believability, and empathy in the context of power, marginalization, and control. It illustrates that thinking through a narrative approach demarginalizes the Other and lets us form more equal connections through our joint life experiences.
Conversational Space and Participant Shame in Interviewing
Authors: Owens Erica
Published: November 2006

In this article, the author presents a “failed” interview that seemingly provided no usable data. The audiotape segments of participant talk were nearly inaudible and most of the interview could not be transcribed. Upon repeated readings of salvageable fragments, however, a pattern of silencing became noticeable. The author suggests that participant silence is a collaboratively produced constraint stemming from an unsuccessful subtextual negotiation about the linguistic environment of the interview. She explores the phenomenon of participant shame and the role of the researcher in expanding conversational space to allow for the expression of shameful storylines. Current notions of what is “sensitive” research unduly limit researcher's understandings of the collaborative and fragile nature of the interview setting. Research on any topic may turn sensitive if the participant's story includes elements that are potentially distressing and necessary to the storyline. Means for recognizing and accommodating participant shame during the interview process are suggested.
The Case of Trinity University
Authors: Twale Darla J. , Place A. William
Published: November 2006

The case of Trinity University is an ideal way to introduce graduate students in educational leadership preparation programs to the university culture and how it shapes the graduate curriculum, faculty expectations for student outcomes, and professional socialization processes. Master’s and doctoral students who take courses related to cultural issues, organizational behavior and change, and management and administrative strategies will have an opportunity to discuss these same processes at the postsecondary level and note how they compare and contrast to the cultural and organizational environments in the public schools. What students experience in both worlds (K-12 and higher) can inform their knowledge of leadership, mission, management, and culture. This case encourages students to address cultural change and the effects it will have on leader preparation in terms of the “alignment between espoused cultural values and actual management practices... [and how it can]... improve organizational performance” (Smart & St. John, 1996, p. 232).
Infrared study of goethites of varying crystallinity and particle size: I. Interpretation of OH and lattice vibration frequencies
Authors: Cambier P.
Published: November 2006

A detailed study of the IR spectrum of goethite is given with the aim of relating variations to crystalline order and particle size. The OH stretching vibrations are split into two active components at high frequency, plus two inactive ones at low frequency. Two different bending modes exist from site group splitting. Their active modes from factor group splitting are at lower frequencies than the uncoupled ones. The lattice bands at 630 and 400 cm−1 correspond to Fe-O or Fe-OH stretching, approximately parallel to a and c, and thus respectively sensitive and not sensitive to the particle shape, as long as it remains elongated along c.
Diagenetic carbonate and evaporite minerals in Rotliegend aeolian sandstones of the Southern North Sea: their nature and relationship to secondary porosity development
Authors: Pye K. , Krinsley D. H.
Published: November 2006

Deeply buried (> 3·5 km) Rotliegend aeolian sandstones in the Southern North Sea Basin display a number of interesting diagenetic features including (i) zoned iron-rich carbonate cements, (ii) anhydrite, halite and baryte cements, (iii) at least two generations of authigenic illite, and (iv) significant secondary porosity created by cement and framework-grain dissolution. The creation and destruction of secondary porosity is the result of changes in porewater chemistry during burial and subsequent uplift. Three pore-fluid regimes can be identified: (1) alkaline, oxidizing conditions during shallow to intermediate burial; (2) acid, reducing conditions during intermediate to deep burial; (3) alkaline, reducing conditions during deep burial and uplift. The transition from stage 1 to stage 2 was probably caused by expulsion of waters from the underlying Carboniferous shales. The transition to stage 3 probably began when faulting associated with uplift allowed invasion by alkaline fluids derived from Zechstein sediments.