bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic Stem Cells Are Not the Direct Target of Spontaneous Leukemic Transformation in p18INK4C-Null Reconstituted Mice
Authors: Yuan Youzhong , Yu Hui , Boyer Matthew J. , Song Xianmin , Cao Shaonan , Shen Hongmei , Cheng Tao
Published: January 2006

Cell cycle inhibitors are important regulators in normal tissue regeneration and disruption of the regulators are involved in cancer development. Our recent study showed that the absence of the CDK inhibitor p18INK4C (p18) enhances self-renewal of normal hematopoietic stem cell (HSC) in vivo, whereas previous studies by others showed an increased incidence of leukemogenesis in older p18-null mice. Here, we have examined potential leukemogenesis during experimentally induced regeneration of HSC in the absence of p18 in order to gauge the relation between these two processes. Reconstituted mice with p18-deficient HSCs under the condition of repetitive proliferative stress (serial transplantation) were followed for >3 years. T cell leukemia from the p18−/− origin was recapitulated 24 months after secondary transplantation. However, no myeloid leukemia was found in the recipients. The T cell leukemia–initiating cells (mainly in a CD3lo cell subset) did not share the same immunophenotype with normal HSCs and, in fact, the function of HSCs was significantly compromised with decreased abundance in the leukemic mice. Furthermore, we found that the p15 or p16 gene promoters were frequently methylated in the leukemic cells but not in HSCs. Our present study argues against the possibility of overgrowth of p18-null HSCs leading to a leukemic phenotype. The data also support the notion that p18 has an independent role in T cell maintenance such that CD3+CD8+ cells, unlike HSCs, are more accessible to leukemogenic transformation after the loss of p18. (Cancer Res 2006; 66(1): 343-51)
Interleukin-12 Up-Regulates Fas Expression in Human Osteosarcoma and Ewing's Sarcoma Cells by Enhancing Its Promoter Activity
Authors: Zhou Zhichao , Lafleur Elizabeth A. , Koshkina Nadezhda V. , Worth Laura L. , Lester Malisa S. , Kleinerman Eugenie S.
Published: December 2005

Interleukin-12 (IL-12) has shown significant antitumor activity in several preclinical animal tumor models. Our previous studies showed that IL-12 inhibited tumor growth in human osteosarcoma and Ewing's sarcoma animal model. Decreased Fas expression in osteosarcoma increased the lung metastatic potential. In this study, we further examined the mechanism of IL-12 antitumor activity and showed that IL-12 significantly increased Fas expression in both human osteosarcoma cells LM7 and Ewing's sarcoma cells TC71. Up-regulation of Fas expression increased their sensitivity to Fas-induced cell apoptosis. Constructs of the Fas promoter linked to a luciferase reporter gene were used to determine the promoter activity. IL-12 increased Fas promoter activity 4.2- and 4.9-fold in TC71 and LM7 cells, respectively. Time course studies have shown that recombinant IL-12 stimulated Fas promoter activity at 2 hours, reached the peak level at 4 hours, and then declined at 24 hours. To investigate whether IL-12 specifically enhanced Fas promoter activity, we determined whether another gene (E1A) was able to stimulate Fas promoter activity. We also evaluated effect of IL-12 on the topoisomerase IIα promoter. The results indicated that E1A but not IL-12 stimulated topoisomerase IIα promoter activity. E1A failed to increase Fas promoter activity. We also found that κB-Sp1 element at position −295 to −286 in Fas promoter was essential for IL-12-induced activation, and nuclear factor-κB transcription factor was activated after IL-12 treatment in TC71 cells. These results indicate that IL-12 up-regulates Fas expression in human osteosarcoma and Ewing's sarcoma by enhancing Fas promoter activity. Understanding this mechanism may lead to new therapeutic approaches for the treatment of sarcoma involving the use of IL-12. (Mol Cancer Res 2005;3(12):685–91)
Comprehensive Profiling of 8p11-12 Amplification in Breast Cancer
Authors: Gelsi-Boyer Véronique , Orsetti Béatrice , Cervera Nathalie , Finetti Pascal , Sircoulomb Fabrice , Rougé Carole , Lasorsa Laurence , Letessier Anne , Ginestier Christophe , Monville Florence , Esteyriès Séverine , Adélaïde José , Esterni Benjamin , Henry Catherine , Ethier Stephen P. , Bibeau Frédéric , Mozziconacci Marie-Joëlle , Charafe-Jauffret Emmanuelle , Jacquemier Jocelyne , Bertucci François , Birnbaum Daniel , Theillet Charles , Chaffanet Max
Published: December 2005

In human carcinomas, especially breast cancer, chromosome arm 8p is frequently involved in complex chromosomal rearrangements that combine amplification at 8p11-12, break in the 8p12-21 region, and loss of 8p21-ter. Several studies have identified putative oncogenes in the 8p11-12 amplicon. However, discrepancies and the lack of knowledge on the structure of this amplification lead us to think that the actual identity of the oncogenes is not definitively established. We present here a comprehensive study combining genomic, expression, and chromosome break analyses of the 8p11-12 region in breast cell lines and primary breast tumors. We show the existence of four amplicons at 8p11-12 using array comparative genomic hybridization. Gene expression analysis of 123 samples using DNA microarrays identified 14 genes significantly overexpressed in relation to amplification. Using fluorescence in situ hybridization analysis on tissue microarrays, we show the existence of a cluster of breakpoints spanning a region just telomeric to and associated with the amplification. Finally, we show that 8p11-12 amplification has a pejorative effect on survival in breast cancer. (Mol Cancer Res 2005;3(12):655–67)
Identification of Mitogen-Activated Protein Kinase Signaling Pathways That Confer Resistance to Endoplasmic Reticulum Stress in Saccharomyces cerevisiae
Authors: Chen Yijun , Feldman Douglas E. , Deng Changchun , Brown James A. , De Giacomo Anthony F. , Gaw Allison F. , Shi Gongyi , Le Quynh T. , Brown J. Martin , Koong Albert C.
Published: December 2005

Hypoxia activates all components of the unfolded protein response (UPR), a stress response initiated by the accumulation of unfolded proteins within the endoplasmic reticulum (ER). Our group and others have shown previously that the UPR, a hypoxia-inducible factor–independent signaling pathway, mediates cell survival during hypoxia and is required for tumor growth. Identifying new genes and pathways that are important for survival during ER stress may lead to the discovery of new targets in cancer therapy. Using the set of 4,728 homozygous diploid deletion mutants in budding yeast, Saccharomyces cerevisiae, we did a functional screen for genes that conferred resistance to ER stress–inducing agents. Deletion mutants in 56 genes showed increased sensitivity under ER stress conditions. Besides the classic UPR pathway and genes related to calcium homeostasis, we report that two additional pathways, including the SLT2 mitogen-activated protein kinase (MAPK) pathway and the osmosensing MAPK pathway, were also required for survival during ER stress. We further show that the SLT2 MAPK pathway was activated during ER stress, was responsible for increased resistance to ER stress, and functioned independently of the classic IRE1/HAC1 pathway. We propose that the SLT2 MAPK pathway is an important cell survival signaling pathway during ER stress. This study shows the feasibility of using the yeast deletion pool to identify relevant mammalian orthologues of the UPR. (Mol Cancer Res 2005;3(12):669–77)
The Emerging Role of the COP9 Signalosome in Cancer
Authors: Richardson Katharine S. , Zundel Wayne
Published: December 2005

In the last several years, multiple lines of evidence have suggested that the COP9 signalosome (CSN) plays a significant role in the regulation of multiple cancers and could be an attractive target for therapeutic intervention. First, the CSN plays a key role in the regulation of Cullin-containing ubiquitin E3 ligases that are central mediators of a variety of cellular functions essential during cancer progression. Second, several studies suggest that the individual subunits of the CSN, particularly CSN5, might regulate oncogenic and tumor suppressive functions independently of, or coordinately with, the CSN holocomplex. Thus, deregulation of CSN subunit function can have a dramatic effect on diverse cellular functions, including the maintenance of DNA fidelity, cell cycle control, DNA repair, angiogenesis, and microenvironmental homeostasis that are critical for tumor development. Additionally, clinical studies have suggested that the expression or localization of some CSN subunits correlate to disease progression or clinical outcome in a variety of tumor types. Although the study of CSN function in relation to tumor progression is in its infancy, this review will address current studies in relation to cancer initiation, progression, and potential for therapeutic intervention. (Mol Cancer Res 2005;3(12):645–53)
Association Analysis of the GSK-3β T–50C Gene Polymorphism with Schizophrenia and Bipolar Disorder
Authors: Szczepankiewicz Aleksandra , Skibinska Maria , Hauser Joanna , Slopien Agnieszka , Leszczynska-Rodziewicz Anna , Kapelski Paweł , Dmitrzak-Weglarz Monika , Czerski Piotr M. , Rybakowski Janusz K.
Published: January 2006

Glycogen synthase kinase-3β (GSK-3β) has been implicated in the pathogenesis of major psychoses. In this paper, the T–50C polymorphism of the GSK-3β gene has been studied in patients with schizophrenia (n = 432), patients with bipolar disorder (n = 416) and in a healthy control group (n = 408). Consensus diagnosis by at least two psychiatrists was made for each patient, according to DSM-IV and ICD-10 criteria, using the Structured Clinical Interview for DSM-IV Axis I Disorders. Genotypes were established by the polymerase chain reaction-restriction fragment length polymorphism method. We have found a trend towards an association for the C allele in the whole group of schizophrenic patients (p = 0.088) and for the heterozygous T/C genotype of bipolar patients (0.095). Significant differences of genotype distribution and allele frequencies of the T–50C polymorphism were found in the female group of bipolar II patients (p = 0.015 for genotypes and p = 0.009 for alleles). In conclusion, this polymorphism may be associated with female gender in bipolar II disorder.
Mechanisms of Intraseasonal Amplification of the Cold Siberian High
Authors: Takaya Koutarou , Nakamura Hisashi
Published: January 2006

Mechanisms of intraseasonal amplification of the Siberian high are investigated on the basis of composite anomaly evolution for its strongest events at each of the grid points over Siberia. At each location, the amplification of the surface high is associated with formation of a blocking ridge in the upper troposphere. Over central and western Siberia, what may be called “wave-train (Atlantic-origin)” type is common, where a blocking ridge forms as a component of a quasi-stationary Rossby wave train propagating across the Eurasian continent. A cold air outbreak follows once anomalous surface cold air reaches the northeastern slope of the Tibetan Plateau.

It is found through the potential vorticity (PV) inversion technique that interaction between the upper-level stationary Rossby wave train and preexisting surface cold anomalies is essential for the strong amplification of the surface high. Upper-level PV anomalies associated with the wave train reinforce the cold anticyclonic anomalies at the surface by inducing anomalous cold advection that counteracts the tendency of the thermal anomalies themselves to migrate eastward as surface thermal Rossby waves. The surface cold anomalies thus intensified, in turn, act to induce anomalous vorticity advection aloft that reinforces the blocking ridge and cyclonic anomalies downstream of it that constitute the propagating wave train. The baroclinic development of the anomalies through this vertical coupling is manifested as a significant upward flux of wave activity emanating from the surface cold anomalies, which may be interpreted as dissipative destabilization of the incoming external Rossby waves.
Understanding Parameter Invariance in Unidimensional IRT Models
Authors: Rupp André A. , Zumbo Bruno D.
Published: January 2006

One theoretical feature that makes item response theory (IRT) models those of choice for many psychometric data analysts is parameter invariance, the equality of item and examinee parameters from different examinee populations or measurement conditions. In this article, using the well-known fact that item and examinee parameters are identical only up to a set of linear transformations specific to the functional form of a given IRT model, violations of these transformations for unidimensional IRT models are investigated using analytical, numerical, and visual tools. Because item parameter drift (IPD) constitutes a lack of invariance (LOI) at the individual item level or item set level, the magnitudes and effects of IPD on examinee response probabilities and true scores are algebraically derived and connected to empirical results from a recent simulation study. Thus, this article facilitates a deeper understanding of the exact statistical formulation of parameter invariance as a fundamental property of latent variable measurement and explicates some practical consequences of LOI for decision making.
A Comparison of the Bootstrap-F, Improved General Approximation, and Brown-Forsythe Multivariate Approaches in a Mixed Repeated Measures Design
Authors: Seco Guillermo Vallejo , Izquierdo Marcelino Cuesta , García M. Paula Fernández , Díez F. Javier Herrero
Published: January 2006

The authors compare the operating characteristics of the bootstrap- F approach, a direct extension of the work of Berkovits, Hancock, and Nevitt, with Huynh’s improved general approximation (IGA) and the Brown-Forsythe (BF) multivariate approach in a mixed repeated measures design when normality and multisample sphericity assumptions do not hold. The results of the simulation show that the three approaches adequately control Type I error when data are generated from normal or slightly nonnormal distributions. However, when data are generated from distributions with moderate or severe skewness, the approaches tend to produce conservative Type I error rates, except the IGA test of the main effect, which has liberal Type I error rates in some conditions. With regard to power, it was found that the bootstrap- F approach can compete with the IGA approach but not with the BF approach: The power differences favoring the bootstrap- F approach are generally small, whereas those favoring the BF approach are substantial.
Testing the Hypothesis of a Homoscedastic Error Term in Simple, Nonparametric Regression
Authors: Wilcox Rand R.
Published: January 2006

Consider the nonparametric regression model Y = m( X)+ τ( X)ε, where X and ε are independent random variables, ε has a median of zero and variance σ2, τ is some unknown function used to model heteroscedasticity, and m( X) is an unknown function reflecting some conditional measure of location associated with Y, given X. This article considers the problem of testing H0:τ = 1, the hypothesis that the error term is homoscedastic. Several methods were considered, two of which were found that control the probability of a Type I error well in simulations. One is fast from a computational point of view, and the other is based in part on a bootstrap method. Neither dominates in terms of power.
A Single‐Dose Pharmacokinetic Study of Lasofoxifene in Healthy Volunteers and Subjects With Mild and Moderate Hepatic Impairment
Authors: Bramson Candace , Ouellet Daniele , Roman Doina , Randinitis Edward , Gardner Mark J.
Published: January 2006

Lasofoxifene, a selective estrogen receptor modulator for osteoporosis management, is metabolized primarily by hepatic oxidation and conjugation. This study compared the pharmacokinetics of 0.25 mg lasofoxifene in subjects with mild (Child‐Pugh grade A, n = 6) or moderate (Child‐Pugh grade B, n = 6) hepatic impairment and healthy volunteers (n = 6). Analysis of variance was used to calculate 90% confidence intervals for the ratios (impaired/healthy) of least squares mean log maximum plasma concentration (Cmax) and area under the curve (AUC) values. Lasofoxifene pharmacokinetics was similar between healthy and mild hepatic impairment subjects: ratios of Cmax and AUC from 0 to infinity (AUC[0‐∞]) were 101% (75.0–138) and 95.5% (77.9–117), respectively. In subjects with moderate hepatic impairment, ratios of Cmax and AUC[0‐∞] were 121% (89.6–165) and 138% (112–169), respectively; mean terminal half‐life was 252 hr compared to 193 hr in healthy subjects. Dose adjustment should not be required for subjects with mild to moderate hepatic impairment.
Psychological Treatment of Men Convicted of Gender Violence
Authors: Echeburúa Enrique , Fernández-Montalvo Javier , Amor Pedro J.
Published: January 2006

In this article, the effectiveness of a psychological treatment program for men who are in prison for committing a serious offence of gender violence is tested. The sample consisted of 52 men who were imprisoned in eight Spanish prisons. The psychological treatment was a cognitive-behavioral program, in a group format, with 20 weekly sessions that lasted for 8 months. The results showed a significant improvement of irrational beliefs, about both women and violence, as a strategy to cope with everyday difficulties and a significant decrease of psychopathological symptomatology, anger, and hostility. On the other hand, results indicated that the only difference between the patients who dropped out of treatment and those who completed it was the level of initial motivation for treatment. Implications of this study for clinical practice and future research in this field are discussed.
Occupational Networking as Normative Control
Authors: Osnowitz Debra
Published: January 2006

With workforce flexibility and nonstandard, “contingent,” work have come new mechanisms for labor market mediation and workforce control. This study examines occupational connection and control in two groups of contract professionals. For these occupational practitioners, networking is a mechanism for labor market regulation as well as for finding work. Networking perpetuates occupational norms that demand commitment towork, accountability to clients, and reciprocity among colleagues. Adhering to occupational norms, contractors develop reputations that can enhance the likelihood of referrals from colleagues for contract assignments. Collegial exchange in an occupational labor market, therefore, exposes contractors to the informal sanctions of normative control.
An Update in the Management of Hepatitis B/HIV Coinfection
Authors: Daftary Monika N. , Goolsby Tiffany , Farhat Faria
Published: January 2006

With growing numbers of hepatitis B virus (HBV)/ HIVcoinfected patients and the complexity of treating both diseases together, new treatment options and guidelines are available. This article reviews treatment and management options for HBV/HIV-coinfected patients.
A Review of Pneumocystis Pneumonia
Authors: Lee Stephanie A.
Published: January 2006

Pneumocystis pneumonia remains one of the leading causes of morbidity and mortality in the HIV-infected population. Trimethoprim-sulfamethoxazole remains the drug of choice for both the treatment and prevention of this infection, although a high rate of side effects in HIV-infected patients often necessitates alternative treatment regimens. This article will review pneumocystis pneumonia, with a focus on the various therapeutic options, their side effects, and the immune reconstitution inflammatory syndrome as it relates to pneumocystis pneumonia infection.
Duality in Context
Authors: Yearwood Edilma L. , McClowry Sandee
Published: January 2006

The goal of this study was to explore the cultural meaning of parent-child communication behaviors in inner-city children at risk for common behavioral problems. Following participation in a preventive intervention called Insights Into Children's Temperament, 40 parents of first and second-grade children were interviewed. The data were analyzed using a constant comparative method derived from grounded-theory techniques. Findings indicate that a complex communication process was used by parents with their at-risk innercity school-age children. The immediacy of safety concerns for the child, the child's temperament, and the current parental state informed the choice of communication behaviors chosen by the parent. The ultimate goal of communication for these participants was to equip their children with tools to assist them to safely navigate their school and community environments. Participants also offered several recommendations that could be useful for practitioners and researchers to incorporate into their work with inner-city families.
Coping With Customer Complaints
Authors: Bell Simon J. , Luddington James A.
Published: January 2006

This article investigates the relationship between customer complaints and service personnel commitment to customer service. Positive and negative affectivity are considered as potential moderators of this relationship. Using data obtained from a survey of 432 retail service personnel in a national retail chain with 124 stores, the authors find that customer complaints are significantly and negatively associated with service personnel commitment to customer service. Higher levels of service employee positive affectivity significantly reduced this negative relationship. Contrary to expectations, high levels of negative affectivity also reduced the negative relationship between complaints and commitment to customer service. Potential explanations for these findings are provided, and implications for managers and future research are considered.
AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with the Wilms tumor gene, WT1
Authors: Nishida Sumiyuki , Hosen Naoki , Shirakata Toshiaki , Kanato Keisuke , Yanagihara Masashi , Nakatsuka Shin-ichi , Hoshida Yoshihiko , Nakazawa Tsutomu , Harada Yukie , Tatsumi Naoya , Tsuboi Akihiro , Kawakami Manabu , Oka Yoshihiro , Oji Yusuke , Aozasa Katsuyuki , Kawase Ichiro , Sugiyama Haruo
Published: December 2005

AML1-ETO, a chimeric gene frequently detected in acute myelogenous leukemia (AML), inhibits the differentiation of myeloid progenitors by suppressing genes associated with myeloid differentiation and increases the replating ability of clonogenic myeloid progenitors. However, AML1-ETO alone cannot induce AML and thus additional genetic events are required for the onset of AML. The Wilms tumor gene (WT1), which has been identified as the gene responsible for Wilms tumor, is expressed at high levels in almost all human leukemias. In this study, we have generated transgenic mice (WT1-Tg) that overexpress WT1 in hematopoietic cells to investigate the effects of WT1 on AML1-ETO-associated leukemogenesis. AML1-ETO-transduced bone marrow (BM) cells from WT1-Tg mice exhibited inhibition of myeloid differentiation at more immature stages and higher in vitro colony-forming ability compared with AML1-ETO-transduced BM cells from wild-type mice. Most importantly, all of the mice that received a transplant of AML1-ETO-transduced BM cells from the WT1-Tg mice rapidly developed AML. These results demonstrate that AML1-ETO may exert its leukemogenic function in cooperation with the expression of WT1.
Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs
Authors: Appel Silke , Bringmann Anita , Grünebach Frank , Weck Markus M. , Bauer Jürgen , Brossart Peter
Published: December 2005

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells of the immune system with the unique ability to initiate and maintain primary immune responses. In order to better characterize the functional and phenotypic features of DCs, a subtractive cDNA library to identify differentially expressed genes in monocyte-derived DCs (MDCs) was constructed. Using this approach, we found that the epithelial transcription factor ESE-3, which was previously shown to be exclusively expressed in cells of epithelial origin, is differentially expressed in MDCs. This was further confirmed by reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot analyses. The expression of ESE-3 is up-regulated upon maturation of MDCs and inhibited by treating the cells with IL-10 or IFN-γ. Knockdown experiments using siRNA suggest that ESE-3 plays an important role during MDC development. Our results might help to improve the phenotypic characterization of DCs and lead to a better understanding of the cellular mechanisms involved in antigen presentation and T-cell stimulation.
Polymorphisms in the IL10 but not in the IL1beta and IL4 genes are associated with inhibitor development in patients with hemophilia A
Authors: Astermark Jan , Oldenburg Johannes , Pavlova Anna , Berntorp Erik , Lefvert Ann-Kari ,   for the MIBS Study Group
Published: December 2005

The aim of the Malmö International Brother Study (MIBS) is to evaluate host genetic factors associated with the development of inhibitory antibodies in patients with hemophilia. Factor VIII gene mutations and genetic polymorphisms of the IL1beta, IL4, and IL10 genes, known to influence antibody production in autoimmune diseases, were analyzed in 164 patients (124 with severe, 26 with moderate, and 14 with mild disease) in 78 unrelated families with hemophilia A. Seventy-seven (47%) patients in 54 families had a history of inhibitors (57 high responding, 20 low responding). Inversions were found in 36 families (75 patients). There was no association between the development of inhibitor and the IL1beta Taq I RFLP alleles in exon 5 or the –590 C/T single nucleotide polymorphism (SNP) in the promoter region of IL4. There was, however, a strong association between an allele with 134 bp in one of the CA repeat microsatellites, IL10G, located in the promoter region of the IL10 gene, and the development of inhibitor (odds ratio [OR], 4.4; 95% confidence interval [95% CI], 2.1-9.5; P < .001). The association was consistent in the subgroup of families with severe hemophilia and inversions. IL10 is the first gene located outside the causative factor VIII gene mutation to be associated with inhibitor development.
Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity
Authors: Perez Francisco A , Curtis Wendy R , Palmiter Richard D
Published: December 2005

Background

Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations in theparkingene which encodes an E3 ubiquitin-protein ligase. Parkin is thought to be critical for protecting dopaminergic neurons from toxic insults by targeting misfolded or oxidatively damaged proteins for proteasomal degradation. Surprisingly, mice with targeted deletions ofparkindo not recapitulate robust behavioral or pathological signs of parkinsonism. Since Parkin is thought to protect against neurotoxic insults, we hypothesized that the reason Parkin-deficient mice do not develop parkinsonism is because they are not exposed to appropriate environmental triggers. To test this possibility, we challenged Parkin-deficient mice with neurotoxic regimens of either methamphetamine (METH) or 6-hydroxydopamine (6-OHDA). Because Parkin function has been linked to many of the pathways involved in METH and 6-OHDA toxicity, we predicted that Parkin-deficient mice would be more sensitive to the neurotoxic effects of these agents.

Results

We found no signs consistent with oxidative stress, ubiquitin dysfunction, or degeneration of striatal dopamine neuron terminals in aged Parkin-deficient mice. Moreover, results from behavioral, neurochemical, and immunoblot analyses indicate that Parkin-deficient mice are not more sensitive to dopaminergic neurotoxicity following treatment with METH or 6-OHDA.

Conclusion

Our results suggest that the absence of a robust parkinsonian phenotype in Parkin-deficient mice is not due to the lack of exposure to environmental triggers with mechanisms of action similar to METH or 6-OHDA. Nevertheless, Parkin-deficient mice could be more sensitive to other neurotoxins, such as rotenone or MPTP, which have different mechanisms of action; therefore, identifying conditions that precipitate parkinsonism specifically in Parkin-deficient mice would increase the utility of this model and could provide insight into the mechanism of AR-JP. Alternatively, it remains possible that the absence of parkinsonism in Parkin-deficient mice could reflect fundamental differences between the function of human and mouse Parkin, or the existence of a redundant E3 ubiquitin-protein ligase in mouse that is not found in humans. Therefore, additional studies are necessary to understand why Parkin-deficient mice do not display robust signs of parkinsonism.
Work factors and smoking cessation in nurses' aides: a prospective cohort study
Authors: Eriksen Willy
Published: December 2005

Background

The prevalence of smoking in nursing personnel remains high. The aim of this study was to identify work factors that predict smoking cessation among nurses' aides.

Methods

Of 2720 randomly selected, Norwegian nurses' aides, who were smoking at least one cigarette per day when they completed a questionnaire in 1999, 2275 (83.6 %) completed a second questionnaire 15 months later. A wide spectrum of work factors were assessed at baseline. Respondents who reported smoking 0 cigarettes per day at follow-up were considered having stopped smoking. The odds ratios and 95 % confidence intervals of stopping smoking were derived from logistic regression models.

Results

Compared with working 1–9 hours per week, working 19–36 hours per week (odds ratio (OR) = 0.35; 95 % confidence interval (CI) = 0.13 – 0.91), and working more than 36 hours per week (i.e. more than full-time job) (OR = 0.27; CI = 0.09 – 0.78) were associated with reduced odds of smoking cessation, after adjustments for daily consumption of cigarettes at baseline, age, gender, marital status, and having preschool children. Adjusting also for chronic health problems gave similar results.

Conclusion

There seems to be a negative association between hours of work per week and the odds of smoking cessation in nurses' aides. It is important that health institutions offer workplace-based services with documented effects on nicotine dependence, such as smoking cessation courses, so that healthcare workers who want to stop smoking, especially those with long working hours, do not have to travel to the programme or to dedicate their leisure time to it.
Cystathionine β-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children
Authors: Dutta Samikshan , Sinha Swagata , Chattopadhyay Anindita , Gangopadhyay Prasanta Kumar , Mukhopadhyay Jotideb , Singh Manoranjan , Mukhopadhyay Kanchan
Published: December 2005

Background

Cystathionine β-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR). A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups.

Methods

The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR. One hundred and ninety MR cases were recruited after psychometric evaluation. Hundred and thirty-eight control subjects, two hundred and sixty-seven parents of MR probands and thirty cardiovascular disorder (CVD) patients were included for comparison. Peripheral blood was collected after obtaining informed written consent. The T833C/844ins68 polymorphism was investigated by PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, followed by statistical analysis.

Results

The genotypic distribution of the polymorphism was within the Hardy-Weinberg equilibrium. A slightly increased genotypic frequency was observed in the Indian control population as compared to other Asian populations. Both haplotype-based haplotype relative risk analysis and transmission disequilibrium test reveled lack of association of the T833C/844ins68 polymorphism with MR; nevertheless, the relative risk calculated was higher (>1) and in a limited number of informative MR families, preferential transmission of the double mutant from heterozygous mothers to the MR probands was noticed (χ2 = 4.00, P < 0.05).

Conclusion

This is the first molecular genetic study of CBS gene dealing with T833C/844ins68 double mutation in MR subjects. Our preliminary data indicate lack of association between T833C/844ins68 polymorphism with MR. However, higher relative risk and biased transmission of the double mutation from heterozygous mothers to MR probands are indicative of a risk of association between this polymorphism with mental retardation.
Peroxisome proliferator-activated receptor γ contributes to T lymphocyte apoptosis during sepsis
Authors: Soller Mathias , Tautenhahn Anja , Brüne Bernhard , Zacharowski Kai , John Stefan , Link Hartmut , von Knethen Andreas
Published: December 2005

In the last two decades, extensive research failed to significantly improve the outcome of patients with sepsis. In part, this drawback is based on a gap in our knowledge about molecular mechanisms understanding the pathogenesis of sepsis. During sepsis, T cells are usually depleted. Recent studies in mice and human cells suggested a role of the peroxisome proliferator-activated receptor γ (PPARγ) in provoking apoptosis in activated T lymphocytes. Therefore, we studied whether expression/activation of PPARγ might contribute to T cell death during sepsis. We observed PPARγ up-regulation in T cells of septic patients. In contrast to controls, PPARγ expressing cells from septic patients responded with apoptosis when exposed to PPARγ agonists. Cell demise was attenuated by SR-202, a synthetic PPARγ antagonist, and specificity was further verified by excluding a proapoptotic response to a PPARα agonist. We propose that up-regulation of PPARγ sensitizes T cells of septic patients to undergo apoptosis. PPARγ activation in T cells requires an exogenous PPARγ agonist, which we identified in sera of septic patients. Septic sera were used to study reporter gene expression containing a PPAR-responsive element. We conclude that PPARγ plays a significant role in T cell apoptosis, contributing to lymphocyte loss in sepsis. Thus, inhibition of PPARγ may turn out to be beneficial for patients suffering from lymphopenia during sepsis.
A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: two isoforms of CD33 are generated by alternative splicing
Authors: Hernández-Caselles Trinidad , Martínez-Esparza María , Pérez-Oliva Ana B , Quintanilla-Cecconi Ana M , García-Alonso Ana , Alvarez-López D María Rocío , García-Peñarrubia Pilar
Published: December 2005

The expression of CD33, a restricted leukocyte antigen considered specific for myeloid lineage, has been studied extensively on lymphoid cells. We demonstrated that wide subsets of mitogen- or alloantigen-activated human T and natural killer (NK) cells express CD33 at protein and nucleic acid levels. CD33+ and CD33– T and NK cell populations showed identical surface expression of activation markers such as CD25, CD28, CD38, CD45RO, or CD95. Myeloid and lymphoid CD33 cDNA were identical. However, lymphoid CD33 protein had lower molecular weight, suggesting cell type-specific, post-translational modifications. Additionally, reverse transcriptase-polymerase chain reaction and Northern blot analysis showed an unknown CD33 isoform (CD33m) expressed on all CD33+ cell lines or T cell clones tested. CD33m was identical to CD33 (CD33M) in the signal peptide, the immunoglobulin (Ig) domain C2, the transmembrane, and the cytoplasmic regions but lacked the extracellular ligand-binding variable Ig-like domain encoded by the second exon. CD33m mRNA was mostly detected on NKL and myeloid cell lines but poorly expressed on B cell lines and T lymphocytes. The CD33m extracellular portion was successfully expressed as a soluble fusion protein on transfected human cells, suggesting a functional role on cell membranes. Cross-linking of CD33 diminished the cytotoxic activity of NKL cells against K562 and P815 target cells, working as an inhibitory receptor on NK cells. These data demonstrate that CD33 expression is not restricted to the myeloid lineage and could exist as two different splicing variants, which could play an important role in the regulation of human lymphoid and myeloid cells.
Infants' ERP Responses to Novel and Familiar Stimuli Change Over Time: Implications for Novelty Detection and Memory
Authors: Wiebe Sandra A. , Cheatham Carol L. , Lukowski Angela F. , Haight Jennifer C. , Muehleck Abigail J. , Bauer Patricia J.
Published: January 2006

Detection of novelty is an important cognitive ability early in development, when infants must learn a great deal about their world. Work with adults has identified networks of brain areas involved in novelty detection; this study investigated electrophysiological correlates of detection of novelty and recognition of familiarity in 9‐month‐old infants, using event‐related potentials (ERPs). Infants were familiarized with an event in the laboratory, then ERPs were recorded as they viewed repeated presentations of pictures of this familiar event and a novel event, along with single presentations of 30 trial‐unique events. A middle‐latency negative component was sensitive to degree of novelty, differing in amplitude and latency by stimulus condition and across repeated presentations. Long‐latency slow‐wave activity also related to stimulus condition. Findings have implications for our understanding of infants' detection of novel information and the processes that render the novel familiar.
A Comparison of Three Strategies to Reduce Student Procrastination in PSI
Authors: Lamwers Linda L. , Jazwinski Christine H.
Published: January 2006

Student procrastination in one the most serious drawbacks of self-paced learning. Our study investigated the effectiveness of three types of course contingencies (contracting, doomsday, and doomsday with tokens) designed to reduce student procrastination in a personalized system of instruction (PSI) course. Students participants (N = 610). Student progress was fastest, p < .001, and course completion was most likely, p <.01, in the contracting condition, which was also the most costly in terms of administrative effort.
Heterolytic Dissociation of C–H Bond of Methane over Ag+-exchanged Zeolites and Conversion of Methane into Higher Hydrocarbons in the Presence of Ethene or Benzene
Authors: Baba Toshihide , Inazu Koji
Published: December 2005

The heterolytic dissociation of CH4 over silver cationic clusters (Agn+) in Ag+-exchanged zeolites leads to the formation of silver hydride (Agn–H) and methyl cations, which then reacts with C2H4 to form C3H6. This process provides methane conversion of 13.2% at 673 K to afford higher hydrocarbons, such as toluene. Under these reaction conditions, H–ZSM-5 only catalyzes ethene conversion to higher hydrocarbons, such as butenes, and no methane conversion occurs. The reaction of CH4 with benzene also proceeds to form toluene and xylenes over Ag–ZSM-5 at 673 K. Zeolites prepared by exchange with other metal cations, including In and Ga, also activate CH4 in the presence of C2H4. Using 13C-labeled methane (13CH4) as a tracer, propene is shown to be a primary product for the ethene reaction based on the observation of a significant proportion of singly 13C-labeled propene (13CC2H6). In–ZSM-5 catalyzes the formation of not only propene, but also benzene and toluene. 13C label atoms are not found in the benzene thus produced, indicating that benzene originates entirely from C2H4. However, the occurrence of singly 13C-labeled toluene (13CC6H8) implies that toluene is formed by the reaction of benzene with 13CH4. The alternative reaction path, involving 13CC6H8 formation by reaction of propene with n-butenes generated by ethene dimerization, can be refuted by confirmation of the toluene origin through direct reaction of 13CH4 with benzene.
Syntheses and Characterization of Palladium(II) Complexes with Tridentate N-Heterocyclic Carbene Ligands Containing Aryloxy Groups and Their Application to Heck Reaction
Authors: Yagyu Takeyoshi , Oya Shoko , Maeda Masunobu , Jitsukawa Koichiro
Published: December 2005

Two palladium(II) complexes with tridentate N-heterocyclic carbene ligands containing aryloxy groups were prepared and characterized by X-ray crystallographic method. They showed good performance for Heck reaction.
Anomalous 13C NMR Chemical Shifts of High-spin Saddle Shaped Manganese(III) Octaethyltetraphenylporphyrin Complexes
Authors: Ikezaki Akira , Nakamura Mikio , Cheng Ru-Jen
Published: December 2005

NMR spectra of highly saddled Mn(III) porphyrinates such as Mn(OETPP)(CD3OD)2+ have been measured. The extraordinarily upfield shifted meso-13C signals, which reach as much as −492 ppm at 298 K, are ascribed to the dx2−y2–a2u, dxy–a1u, and dπ–3eg interactions, the former two of which occur only when the porphyrin ring is saddled.
An Efficient Energy Transfer Found in Triphenylene/Hexaazatriphenylene System with Electronic Complimentarity and Structural Similarity
Authors: Ishi-i Tsutomu , Tashiro Hiroshi , Kuwahara Rempei , Mataka Shuntaro , Yoshihara Toshitada , Tobita Seiji
Published: December 2005

In a donor–acceptor system with structural similarity and electronic complimentarity, an efficient energy transfer was observed from energy-donor triphenylenes to energy-acceptor hexaazatriphenylenes in a film state.
Synthesis of Single-crystal BaMo2O7 Nanowire Bundles: A General, Low-temperature Hydrothermal Approach to 1D Molybdenum Oxide-based Nanostructures
Authors: Gao Peng , Xie Yi , Ye Lina , Chen Ying , Li Zhen
Published: December 2005

Multicomponent BaMo2O7 single-crystalline nanowire bundles were synthesized by a hydrothermal crystallization process under mild conditions using cheap and simple bulky oxide and fluoride as precursors. This new strategy has been extended to prepare other 1D molybdenum oxide-based nanomaterials including alkaline earth metal molybdate compounds (such as BaMo3O10), transition-metal molybdate compounds (e.g., CdMoO4, PbMoO4, Ag6Mo10O33, etc.) and metal molybdenum oxide fluoride compounds (e.g., Ba2MoO3F4). Our experiments have also proved that this facile hydrothermal route is a general method for the synthesis of various multicomponent nanomaterials (such as tungstate, chromate, phosphate compounds).
Repetitive Two-step Method for Oligoarene Synthesis through Rapid Cross-coupling of Hydroxyphenylboronic Acids and Anhydrides
Authors: Ishikawa Shunpei , Manabe Kei
Published: December 2005

A two-step Suzuki–Miyaura coupling–triflation procedure, which features the use of hydroxyphenylboronic acids or anhydrides in the palladium-catalyzed cross-coupling step, has been developed for the synthesis of oligoarenes.
ASP, The Art and Science of Practice: Elements of a Theory of the Practice of Operations Research: Practice as a Business
Authors: Murphy Frederic H.
Published: December 2005

In the previous two articles in this series (Murphy 2005a, b), I looked at practice from the perspective of doing operations research (OR). Because OR practitioners have careers and often found businesses, we need to understand practice as a business. Operations research/management science (OR/MS) businesses face many of the same issues as other technology and consulting businesses. However, the product is intangible, creating marketing problems. The businesses operate in a complex ecology with different levels of competition and cooperation among OR and software firms, depending on their different areas of expertise. Social networks play an important role in the way individuals and companies market and develop new strands of practice.
The Operation Was a Success but the Patient Died: Aider Priorities Influence Decision Aid Usefulness
Authors: Brown Rex
Published: December 2005

The usefulness of quantitative decision aid is often impaired and its usage impeded by the misaligned priorities of analysts and the middlemen who employ them. Analysts’ professional orientation may dispose them to attend to analytic processes more than to deciders’ needs and to stick with outdated practices. As a result, their analyses may be technically sound but disregard key knowledge, make unrealistic assumptions, or answer the wrong questions. Middlemen’s financial or other conflicts of interest exacerbate such defects. Deciders may have to take more control of analyses (and analysts) and, for example, bypass middlemen.
Improving Supply-Chain-Reconfiguration Decisions at IBM
Authors: Kirkwood Craig W. , Slaven Matthew P. , Maltz Arnold
Published: December 2005

We developed a decision-support system for IBM’s supply-chain-configuration decisions. Managers and analysts used this prepackaged multiobjective decision-analysis procedure in facilitated workshops to analyze mid-level supply-chain configuration decisions based on 22 considerations covering cost, quality, customer responsiveness, strategic issues, and operating constraints. These multiattribute utility analyses incorporated uncertainty through expert estimates of probabilities and were implemented in a spreadsheet environment. We applied the approach to five IBM supply-chain decisions, and the results satisfied internal stakeholders that the analysis correctly included financial and nonfinancial considerations along with the associated risks and provided a useful audit trail for executive management. IBM now views this decision-support system as a potential template for future supply-chain decisions.
The Fifth Column: Why Maintenance Is Different or Why It’s More Important to Talk to Your Employees Than Your Equals
Authors: Woolsey Gene
Published: December 2005

A nameless consultant consults with some retiree consultants to solve management problems.
Ranking Sports Teams: A Customizable Quadratic Assignment Approach
Authors: Cassady C. Richard , Maillart Lisa M. , Salman Sinan
Published: December 2005

Ranking sports teams in the absence of full round-robin tournaments is big business, especially for NCAA Division I-A college football. The Bowl Championship Series awards millions of dollars each year to the conferences whose teams are awarded bids. We formulated the sports-team-ranking problem as a customizable quadratic-assignment problem. Decision makers can tailor our model to suit their personal definitions of the degree of victory for each game played and the relative distance between ranking positions. We developed a parameter-section procedure for determining these customized values and executed it using the 2004 college football season. Because the problem size is so large, we developed a heuristic solution procedure based on a genetic algorithm and local search techniques. This heuristic performs well on a special problem instance in which we can easily identify the optimal ranking. To examine the behavior of our approach, we implemented the heuristic for the 1999 through 2004 college football seasons. We concluded that our approach works best when the margin of victory of individual games is not considered, the location of games is considered, and the date of games is considered. Finally, we evaluated how our approach would have weighed in on several recent controversies in NCAA Division I-A college football and found that our approach generally agrees with traditional schools of thought regarding these controversies.