bluuebunny/crossref_metadata_2025 huggingface dataset:
Explaining country and cross‐border liquidity commonality in international equity markets
Authors: Zhang Zheng , Cai Jun , Cheung Yan Leung
Published: April 2009

Using a large cross section of intraday data from 25 developed countries, we study commonality in liquidity, both within and across international equity markets, over 15‐minute intervals. Within‐country and cross‐border liquidity commonalities are found to be significant and, after controlling for country and industry effects, relate to such firm‐specific measures as size, bid–ask spread, and the extent of analyst coverage. Additionally, within‐country liquidity commonality is lower for firms with depository receipts cross listed in New York or London. Cross‐border liquidity commonality is particularly high for firms with relatively high actual ownership by foreign institutions. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 29:630–652, 2009
Neural integration of iconic and unrelated coverbal gestures: A functional MRI study
Authors: Green Antonia , Straube Benjamin , Weis Susanne , Jansen Andreas , Willmes Klaus , Konrad Kerstin , Kircher Tilo
Published: April 2009

Gestures are an important part of interpersonal communication, for example by illustrating physical properties of speech contents (e.g., “the ball is round”). The meaning of these so‐called iconic gestures is strongly intertwined with speech. We investigated the neural correlates of the semantic integration for verbal and gestural information. Participants watched short videos of five speech and gesture conditions performed by an actor, including variation of language (familiar German vs. unfamiliar Russian), variation of gesture (iconic vs. unrelated), as well as isolated familiar language, while brain activation was measured using functional magnetic resonance imaging. For familiar speech with either of both gesture types contrasted to Russian speech‐gesture pairs, activation increases were observed at the left temporo‐occipital junction. Apart from this shared location, speech with iconic gestures exclusively engaged left occipital areas, whereas speech with unrelated gestures activated bilateral parietal and posterior temporal regions. Our results demonstrate that the processing of speech with speech‐related versus speech‐unrelated gestures occurs in two distinct but partly overlapping networks. The distinct processing streams (visual versus linguistic/spatial) are interpreted in terms of “auxiliary systems” allowing the integration of speech and gesture in the left temporo‐occipital region. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Dissociating networks of imitation
Authors: Menz Mareike M. , McNamara Adam , Klemen Jane , Binkofski Ferdinand
Published: April 2009

The investigation of imitation, which consists of observation and later reproduction of voluntary actions, promises insights into the complex processes of human actions. Although several aspects concerning the component neural processes necessary for action execution are known, our current understanding of the neural networks underlying these remains sparse. The present study applies independent component analysis (ICA) to functional magnetic resonance imaging (fMRI) data acquired during imitation of abstract gestures and object‐related actions. This enables identification of neural networks underlying the production of these imitations. The explorative approach of ICA is complemented by an analysis of time courses from the maxima of each component. Four independent networks were active during delayed imitation. These can be assigned to the aspects of (1) action perception, (2) motor preparation and action execution, (3) encoding and retrieval into and from working memory, as well as (4) the dynamic integration of object affordances into the action. At least two of these networks participate in action preparation, one contains areas involved with motor working memory and one includes areas which are connected to the true action execution. The fourth network only shows activity shortly before an object‐related action is imitated. This indicates a late integration of object affordances into the movement as the time course of activity in this network pertains to action rather than perception of the object. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Time‐varied characteristics of acupuncture effects in fMRI studies
Authors: Bai Lijun , Qin Wei , Tian Jie , Liu Peng , Li LinLing , Chen Peng , Dai Jianping , Craggs Jason G. , von Deneen Karen M. , Liu Yijun
Published: April 2009

When studying the neural responses to acupuncture with a block‐designed paradigm, its temporal dynamics predicted by the general linear model (GLM) conforms to typical “on‐off” variations during a limited period of the experiment manipulation. Despite a lack of direct evidence associating its psychophysiological response, numerous clinical reports suggest that acupuncture can provide pain relief beyond a needling session. Therefore, a typical GLM analysis may be insensitive or inappropriate for identifying altered neural responses resulting from acupuncture. We developed a new approach to investigate the dynamics underlying sustained effects of acupuncture. Specifically, we designed two separate models to evaluate the baseline activities (prior to stimulation) and neural activities in sequential epochs, using three block‐designed functional runs: acupuncture at acupoint ST36, nonmeridian point (NMP) stimulation, and a visual task. We found that the activity patterns during rest were associated with the stimulus types and that the resting activities might be even higher than that of stimulation phases. Such effects of the elevated activity during rest may reduce or eliminate the activity during stimulus conditions or even reverse the sign of brain activation using conventional GLM analysis. Moreover, such sustained responses, followed by acupuncture at ST36 and NMP, exhibited distinct patterns in wide brain structures, particularly in the limbic system and brainstem. These findings may pose great implications for the design and interpretation of a range of acupuncture neuroimaging studies. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Visuo‐attentional and sensorimotor alpha rhythms are related to visuo‐motor performance in athletes
Authors: Del Percio Claudio , Babiloni Claudio , Bertollo Maurizio , Marzano Nicola , Iacoboni Marco , Infarinato Francesco , Lizio Roberta , Stocchi Massimiliano , Robazza Claudio , Cibelli Giuseppe , Comani Silvia , Eusebi Fabrizio
Published: April 2009

This study tested the two following hypotheses: (i) compared with non‐athletes, elite athletes are characterized by a reduced cortical activation during the preparation of precise visuo‐motor performance; (ii) in elite athletes, an optimal visuo‐motor performance is related to a low cortical activation. To this aim, electroencephalographic (EEG; 56 channels; Be Plus EB‐Neuro) data were recorded in 18 right‐handed elite air pistol shooters and 10 right‐handed non‐athletes. All subjects performed 120 shots. The EEG data were spatially enhanced by surface Laplacian estimation. With reference to a baseline period, power decrease/increase of alpha rhythms during the preshot period indexed the cortical activation/deactivation (event‐related desynchronization/synchronization, ERD/ERS). Regarding the hypothesis (i), low‐ (about 8–10 Hz) and high‐frequency (about 10–12 Hz) alpha ERD was lower in amplitude in the elite athletes than in the non‐athletes over the whole scalp. Regarding the hypothesis (ii), the elite athletes showed high‐frequency alpha ERS (about 10–12 Hz) larger in amplitude for high score shots (50%) than for low score shots; this was true in right parietal and left central areas. A control analysis confirmed these results with another indicator of cortical activation (beta ERD, about 20 Hz). The control analysis also showed that the amplitude reduction of alpha ERD for the high compared with low score shots was not observed in the non‐athletes. The present findings globally suggest that in elite athletes (experts), visuo‐motor performance is related to a global decrease of cortical activity, as a possible index of spatially selective cortical processes (“neural efficiency”). Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Mutations in the hepatitis C virus polymerase that increase RNA binding can confer resistance to cyclosporine A #
Authors: Liu Zhe , Robida John M. , Chinnaswamy Sreedhar , Yi Guanghui , Robotham Jason M. , Nelson Heather B. , Irsigler Andre , Kao Cheng C. , Tang Hengli
Published: April 2009

Hepatitis C virus (HCV) infection leads to acute and chronic liver diseases, and new classes of anti-HCV therapeutics are needed. Cyclosporine A (CsA) inhibits HCV replication and CsA derivatives that lack the immunosuppressive function are currently in clinical trials as candidate anti-HCV drugs. Here we characterize several independently derived HCV replicons with varying levels of CsA resistance due to mutations in nonstructural protein 5B (NS5B), the HCV-encoded polymerase. Mutant HCV replicons engineered with these mutations showed resistance to CsA. The mutations reside in two distinct patches in the polymerase: the template channel and one face of a concave surface behind the template channel. Mutant NS5B made by cells expressing the HCV replicon had increased ability to bind to RNA in the presence of CsA. Purified recombinant NS5B proteins containing the mutations were better at de novo initiated RNA synthesis than the wild-type control. Furthermore, the mutant proteins were able to bind RNA with ≈8-fold higher affinity. Last, mutation near the template channel alleviated the lethal phenotype of a mutation in the concave patch, P540A. This intramolecular compensation for the HCV replicase function by amino acid changes in different domains was further confirmed in an infectious cell culture-derived virus system. Conclusion: An increased level of CsA resistance is associated with distinct mutations in the NS5B gene that increase RNA binding in the presence of CsA, and the intramolecular communications between residues of the thumb and the C-terminal domains are important for HCV replicase function. (Hepatology 2009.)
Shy and soft‐spoken: shyness, pragmatic language, and socio‐emotional adjustment in early childhood
Authors: Coplan Robert J. , Weeks Murray
Published: April 2009

The goal of this study was to examine the moderating role of pragmatic language in the relations between shyness and indices of socio‐emotional adjustment in an unselected sample of early elementary school children. In particular, we sought to explore whether pragmatic language played a protective role for shy children. Participants were n=167 children aged 6–7 years, recruited from grade 1 classrooms in public elementary schools. Multi‐source assessment was used to measure child shyness, pragmatic language ability, and indices of social and emotional difficulties at school. Results indicated several significant shyness‐by‐pragmatic‐language interactions in the prediction of outcome variables. The pattern of results indicated a clear buffering effect of pragmatic language, with associations between shyness and adjustment difficulties exacerbated at lower levels of pragmatic language, and attenuated at higher levels. Results are discussed in terms of the specific positive benefits of pragmatic language for shy children and the implications for ameliorative intervention programs. Copyright © 2009 John Wiley & Sons, Ltd.
The chemokine CCL20 and its receptor CCR6 in human malignancy with focus on colorectal cancer
Authors: Ghadjar Pirus , Rubie Claudia , Aebersold Daniel M. , Keilholz Ulrich
Published: April 2009

Chemokines are a superfamily of small chemotactic cytokines, which interact with their G‐protein‐coupled receptors. These interactions regulate multiple physiological functions, particularly tissue architecture and compartment‐specific migration of white blood cells. It has been found that the chemokine/chemokine receptor system has been utilized by cancer cells for migration and metastasis. The chemokine receptor CCR6 is expressed in colorectal cancer and several other cancer types, and stimulation by its physiological chemokine ligand CCL20 has been reported to promote cancer cell proliferation and migration in vitro. Moreover, CCR6/CCL20 interactions apparently play a role in organ selectiveliver metastasis of colorectal cancer. Here, we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCR6 and CCL20 in the formation of colorectal cancer liver metastasis, providing a potential basis for novel treatment strategies. © 2009 UICC
Parathyroid hormone‐related protein confers chemoresistance by blocking apoptosis signaling via death receptors and mitochondria
Authors: Gagiannis Sarah , Müller Martina , Uhlemann Sebastian , Koch Andreas , Melino Gerry , Krammer Peter H. , Nawroth Peter P. , Brune Maik , Schilling Tobias
Published: April 2009

Parathyroid hormone (PTH) has a central role in the regulation of serum calcium and phosphate, whereas parathyroid hormone‐related peptide (PTHrP) has important developmental roles. In addition, PTHrP has been discovered as a causative agent of hypercalcemia of malignancy. PTHrP is also expressed in many tumors, and expression often correlates with unfavorable prognosis. We have investigated the effects of PTHrP on apoptosis signaling pathways initiated by DNA damaging chemotherapeutic drugs. Stimulation experiments of the CD95‐, the TNF‐R‐, and the TRAIL‐R‐death receptor systems in Saos human osteosarcoma cells revealed that PTHrP can block signaling via each of these death receptors. Furthermore, our findings demonstrate a link between PTHrP and the mitochondrial apoptosis pathway. PTHrP down‐regulates expression of pro‐apoptotic Bcl‐2 family members like Bax and PUMA and up‐regulates expression of antiapoptotic molecules like Bcl‐2 and Bcl‐xl. It is of clinical relevance that PTHrP and anticancer drugs show opposing interactions on death receptor‐triggered as well as on mitochondrial apoptosis pathways. In addition, PTHrP induces chemoresistance by interference with p53 family‐dependent apoptosis signaling pathways and p53‐mediated transactivation of apoptosis target genes. Inhibition of CD95‐ and Bax gene transactivation is a mechanism by which PTHrP reduced the apoptosis response and treatment sensitivity of tumor cells. Our data indicate that PTHrP inhibits major apoptosis signaling pathways by blocking signaling via p53, death receptors and mitochondria and, consequently, confers chemoresistance of cancer cells. Thus, beyond its importance in development and differentiation, we describe an important role for PTHrP in tumorigenesis. © 2009 UICC
A novel human fibronectin cryptic sequence unmasked by the insertion of the angiogenesis‐associated extra type III domain B
Authors: Balza Enrica , Sassi Francesca , Ventura Elisa , Parodi Arianna , Fossati Sara , Blalock William , Carnemolla Barbara , Castellani Patrizia , Zardi Luciano , Borsi Laura
Published: April 2009

The angiogenesis‐associated extra‐domain B (EDB) of fibronectin (FN) is a complete type III repeat of 91 amino acids. Its expression is modulated by the alternative splicing pattern of the FN pre‐mRNA. FN containing the EDB (B‐FN) is undetectable in tissues of healthy adults, with rare exceptions such as the female reproductive system where tissue remodeling and angiogenesis are recurrent physiological processes. On the contrary, B‐FN is expressed at high levels in neoplastic tissues and during angiogenesis; consequently, it is considered an excellent marker of angiogenesis. Here, we report on a novel FN cryptic sequence, localized on the FN type III repeat 8 (immediately downstream of the EDB) that is unmasked by the insertion of the EDB. This sequence is specifically recognized by the high‐affinity monoclonal antibody, C6, that selectively recognizes B‐FN by means of ELISA, immunohistochemical and Western blot assays. The variable regions of C6 were cloned and a divalent covalently linked mini‐antibody was generated. Biodistribution studies using the radioiodinated C6 mini‐antibody on tumor‐bearing mice demonstrated an efficient tumor targeting. This antibody represents a new tool for the study of the potential biological functions of hindered sequences that the inclusion of the EDB renders accessible, and likewise makes its epitope an additional angiogenesis target. © 2009 UICC.
+331G/A variant in the progesterone receptor gene, postmenopausal hormone use and risk of breast cancer
Authors: Kotsopoulos Joanne , Tworoger Shelley S. , DeVivo Immaculata , Hankinson Susan E. , Hunter David J. , Willett Walter C. , Chen Wendy Y.
Published: April 2009

A functional promoter polymorphism in the progesterone receptor (PR) gene previously has been associated with an increased risk of postmenopausal breast cancer. Whether the relationship between genetic variation in PR and risk of breast cancer is modified by postmenopausal hormone (PMH) use is unknown. Thus, we conducted a case–control study nested within the prospective Nurses' Health Study to evaluate if the risk of breast cancer associated with having the +331 A risk allele was modified by PMH use. Genotyping of this SNP was available for 1,664 postmenopausal breast cancer cases and 2,391 controls. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer. Women who were carriers of 1 or both variant A alleles had a 31% increased risk of developing breast cancer (95% CI 1.04–1.65). PMH use significantly modified the association between the +331G/A polymorphism and risk (p‐interaction <0.05). Among never users of PMH, women who were variant carriers had a significantly increased risk of breast cancer compared to those with the wild‐type genotype (OR = 2.57; 95% CI 1.64–4.02). The +331G/A polymorphism was not associated with breast cancer risk among past (OR = 1.23; 95% CI 0.77–1.97) or current (OR = 1.14; 95% CI 0.84–1.56) PMH users. The data from this large prospective study provide evidence for a 2‐fold increased risk of developing postmenopausal breast cancer among never users of PMH with the +331G/A SNP. This finding adds to the evidence that the PR has an important etiologic role in breast cancer and should be evaluated in future studies. © 2009 UICC
Anti‐endoglin monoclonal antibodies are effective for suppressing metastasis and the primary tumors by targeting tumor vasculature
Authors: Uneda Shima , Toi Hirofumi , Tsujie Tomoko , Tsujie Masanori , Harada Naoko , Tsai Hilda , Seon Ben K.
Published: April 2009

Anti‐metastatic activity of an antitumor agent is exceedingly important because metastasis is the primary cause of death for most solid cancer patients. In this report, we show that 3 anti‐endoglin (ENG) monoclonal antibodies (mAbs) SN6a, SN6j and SN6k which define individually distinct epitopes of ENG of tumor vasculature are capable of suppressing tumor metastases in the multiple metastasis models. The metastasis models were generated by i.v., s.c. (into flank) or mammary gland fat pad injection of 4T1 murine mammary carcinoma cells and splenic injection of two types of colon26 murine colorectal carcinoma cells. Individual mAbs were injected i.v. via the tail vein of mice. SN6a and SN6j effectively suppressed the formation of metastatic colonies of 4T1 in the lung in all of the three 4T1 metastatic models. In addition, these mAbs were effective for suppressing the primary tumors of 4T1 in the skin and mammary fat pad. These mAbs effectively suppressed microvessel density and angiogenesis in tumors as measured by the Matrigel plug assay in mice. No significant side effects of the administered mAbs were detected. Furthermore, SN6a and SN6j extended survival of the tumor‐bearing mice. SN6j, SN6k and their immunoconjugates with deglycosylated ricin A‐chain were all effective for suppressing hepatic metastasis of colon26. The findings in the present study are clinically relevant in view of the ongoing clinical trial of a humanized (chimerized) form of SN6j. © 2009 UICC
Constitutively active MEK1 is sufficient to induce epithelial‐to‐mesenchymal transition in intestinal epithelial cells and to promote tumor invasion and metastasis
Authors: Lemieux Étienne , Bergeron Sébastien , Durand Véronique , Asselin Claude , Saucier Caroline , Rivard Nathalie
Published: April 2009

Constitutive activation of the MAP kinase kinase MEK1 induces oncogenic transformation in intestinal epithelial cells. Loss of cell–cell adhesion followed by the dissociation of epithelial structures is a prerequisite for increased cell motility and tumor invasion. This phenotypic switch is designated epithelial‐to‐mesenchymal transition (EMT). EMT also plays an important role in determining the dissemination of tumors. However, the role of MEK1 in intestinal EMT, tumor invasion and metastasis has not been elucidated. To determine the functions of activated MEK1 in intestinal tumorigenesis, we established intestinal epithelial cell lines that overexpress wild‐type MEK1 (wtMEK) or activated MEK1 (caMEK). Our results indicate that expression of caMEK is sufficient to induce EMT as confirmed with the induction of N‐cadherin, vimentin, Snail1 and Snail2, whereas a reduction in E‐cadherin, occludin, ZO‐1 and cortical F‐actin was noted. The Snail1 and Snail2 promoter analyses revealed that Egr‐1 and Fra‐1, an AP‐1 protein, are responsible for MEK1‐induced Snail1 and Snail2 expression, respectively. Cells expressing activated MEK1 clearly acquired an invasive capacity when compared to wtMEK‐expressing cells. Zymography studies confirmed elevated levels of MMP2 and MMP9 activities in media of caMEK‐expressing cells. Importantly, cells expressing activated MEK1 induced tumors with short latency in correlation with their ability to induce experimental metastasis in vivo and to express factors known to promote colorectal cancer cell metastasis. In conclusion, our results demonstrate, for the first time, that constitutive activation of MEK1 in intestinal epithelial cells is sufficient to induce an EMT associated with tumor invasion and metastasis. © 2009 UICC
Compensatory inter vivos gifts
Authors: Hochguertel Stefan , Ohlsson Henry
Published: April 2009

Parents' transfer motives are important for understanding, e.g., macroeconomics, income (re)distribution, savings, and public finance. Using data from six biennial waves of the Health and Retirement Study 1992–2002, we estimate censored regression models with nested multilevel error components. First, we interpret our findings that inter vivos transfers from parents to children are gifts, rather than temporary help to overcome liquidity constraints. Second, inter vivos gifts are compensatory in the sense that lifetime poorer children will receive higher transfers than their lifetime richer siblings. Third, inter vivos gifts do not, however, make up the entire difference in lifetime incomes. Copyright © 2009 John Wiley & Sons, Ltd.
NF‐κB and estrogen receptor α interactions: Differential function in estrogen receptor‐negative and ‐positive hormone‐independent breast cancer cells
Authors: Gionet Nathalie , Jansson Deidre , Mader Sylvie , Pratt M.A. Christine
Published: April 2009

Estrogen receptor (ER)‐positive breast cancer cells have low levels of constitutive NF‐κB activity while ER negative (−) cells and hormone‐independent cells have relatively high constitutive levels of NF‐κB activity. In this study, we have examined the aspects of mutual repression between the ERα and NF‐κB proteins in ER+ and ER− hormone‐independent cells. Ectopic expression of the ERα reduced cell numbers in ER+ and ER− breast cancer cell lines while NF‐κB‐binding activity and the expression of several NF‐κB‐regulated proteins were reduced in ER− cells. ER overexpression in ER+/E2‐independent LCC1 cells only weakly inhibited the predominant p50 NF‐κB. GST‐ERα fusion protein pull downs and in vivo co‐immunoprecipitations of NF‐κB:ERα complexes showed that the ERα interacts with p50 and p65 in vitro and in vivo. Inhibition of NF‐κB increased the expression of diverse E2‐regulated proteins. p50 differentially associated directly with the ER:ERE complex in LCC1 and MCF‐7 cells by supershift analysis while p65 antibody reduced ERα:ERE complexes in the absence of a supershift. ChIP analysis demonstrated that NF‐κB proteins are present on an endogenous ERE. Together these results demonstrate that the ER and NF‐κB undergo mutual repression, which may explain, in part, why expression of the ERα in ER− cells does not confer growth signaling. Secondly, the acquisition of E2‐independence in ER+ cells is associated with predominantly p50:p50 NF‐κB, which may reflect alterations in the ER in these cells. Since the p50 homodimer is less sensitive to the presence of the ER, this may allow for the activation of both pathways in the same cell. J. Cell. Biochem. 107: 448–459, 2009. © 2009 Wiley‐Liss, Inc.
Megakaryocytic programming by a transcriptional regulatory loop: A circle connecting RUNX1, GATA‐1, and P‐TEFb
Authors: Goldfarb Adam N.
Published: April 2009

Transcription factors originally identified as drivers of erythroid differentiation subsequently became linked to megakaryopoiesis, reflecting the shared parentage of red cells and platelets. The divergent development of megakaryocytic and erythroid progenitors relies on signaling pathways that impose lineage‐specific transcriptional programs on non‐lineage‐restricted protein complexes. One such signaling pathway involves RUNX1, a transcription factor upregulated in megakaryocytes and downregulated in erythroid cells. In this pathway, RUNX1 engages the erythro‐megakaryocytic master regulator GATA‐1 in a megakaryocytic transcriptional complex whose activity is highly dependent on the P‐TEFb kinase complex. The implications of this pathway for normal and pathological megakaryopoiesis are discussed. J. Cell. Biochem. 107: 377–382, 2009. © 2009 Wiley‐Liss, Inc.
HACE1: A novel repressor of RAR transcriptional activity
Authors: Zhao Jianhua , Zhang Zhenping , Vucetic Zivjena , Soprano Kenneth J. , Soprano Dianne Robert
Published: April 2009

The diverse biological actions of retinoic acid (RA) are mediated by RA receptors (RARs) and retinoid X receptors (RXRs). While the coregulatory proteins that interact with the ligand‐dependent AF‐2 in the E region are well studied, the ligand‐independent N‐terminal AF‐1 domain‐interacting partners and their influence(s) on the function of RARs are poorly understood. HECT domain and Ankyrin repeat containing E3 ubiquitin–protein ligase (HACE1) was isolated as a RARβ3 AB region interacting protein. HACE1 interacts with RARβ3 both in in vitro GST pull‐down and in cell‐based coprecipitation assays. The interaction sites map to the N terminus of RARβ3 and the C terminus of HACE1. HACE1 functionally represses the transcriptional activity of RARα1, RARβ isoforms 1, 2, and 3, but not RARγ1 in luciferase reporter assays. In addition, HACE1 represses the endogenous RAR‐regulated genes CRABP II, RIG1 and RARβ2, but not RAI3 in CAOV3 cells. Mutation of the putative catalytic cysteine (C876 of LF HACE1), which is indispensable for its E3 ubiquitin ligase activity, does not alter the repressive effect of HACE1 on the transcriptional activity of RARβ3. On the other hand, HACE1 inhibits the RA dependent degradation of RARβ3. It is possible that the repression of RAR‐regulated transcription by HACE1 is due to its ability to inhibit the RA‐dependent degradation of RARs. J. Cell. Biochem. 107: 482–493, 2009. © 2009 Wiley‐Liss, Inc.
Redox‐sensitive regulation of gene expression in human primary macrophages exposed to inorganic arsenic
Authors: Bourdonnay Emilie , Morzadec Claudie , Fardel Olivier , Vernhet Laurent
Published: April 2009

Inorganic arsenic is an environmental contaminant toxic for key immune cells. We recently reported that low micromolar concentrations of arsenic trioxide (As2O3) alter functions and differentiation gene program of human macrophages. Particularly, prolonged treatment with As2O3 concomitantly reverses expression of a macrophage‐specific gene subset and triggers reactive oxygen species (ROS) production, suggesting a possible role of cell stress in As2O3 gene effects. This study was thus designed to determine whether redox‐sensitive signaling pathways could mediate gene expression in metalloid‐exposed macrophages. Our results show that As2O3‐dependent alterations of stress (HMOX1 and GCLM) and macrophage‐specific (MMP9, CCL22, and CXCL2) gene expression are not mediated by ROS or related signaling pathways. Notably, As2O3 alters neither activity of the redox‐sensitive transcription factor Sp1 nor that of AP‐1 or NF‐κB. In contrast, N‐acetylcysteine, a potent cysteine reductive compound, significantly prevents up‐regulation of HMOX1, GCLM, and CXCL2 genes, and repression of MMP9 and CCL22 genes induced by As2O3. In addition, we demonstrate that As2O3 markedly alters nuclear levels of Nrf2 and Bach1, two redox‐sensitive regulators of stress genes, and represses expression of the transcription factor EGR2 which is involved in mouse macrophage differentiation; such effects are reduced by N‐acetylcysteine. Finally, we report that genetic invalidation of EGR2 gene partially mimics metalloid effects; it significantly represses CCL22 gene expression and weakly induces that of CXCL2. In conclusion, our results demonstrate that As2O3 alters macrophage gene expression through redox‐sensitive signaling pathways unrelated to ROS production and reveal the transcription factor EGR2 as a new molecular target of arsenic. J. Cell. Biochem. 107: 537–547, 2009. © 2009 Wiley‐Liss, Inc.
MicroRNAs are involved in erythroid differentiation control
Authors: Yang Gui‐Hua , Wang Fang , Yu Jia , Wang Xiao‐Shuang , Yuan Jin‐Yun , Zhang Jun‐Wu
Published: April 2009

MicroRNAs (miRNAs) are a class of 17–25 nucleotides non‐coding RNA molecules that regulate gene expression by either translational inhibition or mRNAs degradation. We used miRNA array to characterize miRNA variation of K562 cells before and after hemin treatment. The differential expression of five miRNAs was validated by Northern blot analysis. Among them, miR‐126 exhibited up‐regulation while miR‐103, miR‐130a, miR‐210, and miR‐18b exhibited down‐regulation after hemin induction. The same expression tendency of the five miRNAs was observed following erythroid induction of CD34+ cells derived from human cord blood. miR‐103 was selected and examined for its role in erythroid differentiation. Over‐expression of miR‐103 in K562 could inhibit hemin‐induced K562 erythroid differentiation, which suggests this miRNA may take part in erythropoiesis. We confirmed that miR‐103 targeting mRNA of forkhead box J2 (FOXJ2), a transcription factor that was involved in the development of many tissues. Our results delineated the expression of miRNAs during erythroid differentiation and suggested regulatory roles of miRNAs in this process by targeting mRNAs related to erythropoiesis. J. Cell. Biochem. 107: 548–556, 2009. © 2009 Wiley‐Liss, Inc.
Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3
Authors: Kim Jang‐Hyun , Choi Joong‐Kook , Cinghu Senthilkumar , Jang Ju‐Won , Lee You‐Soub , Li Ying‐Hui , Goh Yun‐Mi , Chi Xin‐Zi , Lee Kyeong‐Sook , Wee Heejun , Bae Suk‐Chul
Published: April 2009

Runt‐related (RUNX) transcription factors play pivotal roles in neoplastic development and have tissue‐specific developmental roles in hematopoiesis (RUNX1), osteogenesis (RUNX2), as well as neurogenesis and thymopoiesis (RUNX3). RUNX3 is a tumor suppressor in gastric carcinoma, and its expression is frequently inactivated by DNA methylation or its protein mislocalized in many cancer types, including gastric and breast cancer. Jun‐activation domain‐binding protein 1 (Jab1/CSN5), a component of the COP9 signalosome (CSN), is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27Kip1, and Smad4. Here, we find that Jab1 facilitates nuclear export of RUNX3 that is controlled by CSN‐associated kinases. RUNX3 sequestered in the cytoplasm is rapidly degraded through a proteasome‐mediated pathway. Our results identify a novel mechanism of regulating nuclear export and protein stability of RUNX3 by the CSN complex. J. Cell. Biochem. 107: 557–565, 2009. © 2009 Wiley‐Liss, Inc.
PAK thread from amoeba to mammals
Authors: Kumar Anupam , Molli Poonam R. , Pakala Suresh B. , Nguyen Tri M. Bui , Rayala Suresh K. , Kumar Rakesh
Published: April 2009

The p21‐activated kinases (PAKs) are signaling nodes that play a crucial role in cellular processes including cell motility, differentiation, survival, gene transcription, and hormone signaling. PAKs are highly conserved family of serine–threonine kinases that act as effector for small GTPases Rac and Cdc42. Most of our knowledge about PAK functions has been derived from genetic approaches in lower organisms and many of these functions are similar to that seen in mammalian cells. In this review, we have summarized the extensive information generated in lower eukaryotes and very briefly discussed the current status of PAKs in humans. J. Cell. Biochem. 107: 579–585, 2009. © 2009 Wiley‐Liss, Inc.
Theoretical prediction regarding structural and thermodynamical characteristics of stable CH3PO2 isomers and unimolecular decomposition mechanisms of species CH3P(O)2, CH3OPO, and CH2P(O)OH
Authors: Kan Wei , Zhong Hua , Yu Hai‐Tao
Published: April 2009

The detailed isomerization and dissociation reaction potential energy profile of the CH3PO2 system was established at the UCCSD(T)/6‐311++G(3df,2p)//UB3LYP/6‐311++G(d,p) level of theory. Seventy minimum isomers were located and connected by 93 optimized interconversion transition states. Furthermore, 32 isomers with high kinetic stability were predicted to be possible candidates for further experimental detection. The bonding nature of the suggested stable isomers was analyzed while their molecular properties including heats of formation, adiabatic ionization potentials, and adiabatic electronic affinities were calculated at the G2, G2(MP2), G3, and CBS‐Q levels. Based on the isomerization and dissociation potential energy surface, possible unimolecular decomposition mechanisms and pathways of the low‐lying molecules CH3P(O)2, CH3OPO, and CH2P(O)OH were discussed. Furthermore, the transition state theory rate constants of the primary unimolecular dissociation channels were also calculated. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009
Activation of Src kinase by protein–tyrosine phosphatase–PEST in osteoclasts: Comparative analysis of the effects of bisphosphonate and protein–tyrosine phosphatase inhibitor on Src activation in vitro
Authors: Chellaiah Meenakshi A. , Schaller Michael D.
Published: April 2009

PTP–PEST is involved in the regulation of sealing ring formation in osteoclasts. In this article, we have shown a regulatory role for PTP–PEST on dephosphorylation of c‐Src at Y527 and phosphorylation at Y418 in the catalytic site. Activation of Src in osteoclasts by over‐expression of PTP–PEST resulted in the phosphorylation of cortactin at Y421 and WASP at Y294. Also enhanced as a result, is the interaction of Src, cortactin, and Arp2 with WASP. Moreover, the number of osteoclasts displaying sealing ring and bone resorbing activity was increased in response to PTP–PEST over‐expression as compared with control osteoclasts. Cells expressing constitutively active‐Src (527YΔF) simulate the effects mediated by PTP–PEST. Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Therefore, Src‐mediated phosphorylation of cortactin and WASP as well as the formation of WASP·cortactin·Arp2 complex and sealing ring were reduced in these osteoclasts. Similar effects were observed in osteoclasts treated with an Src inhibitor PP2. We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP–PEST/Src, in addition to its effect on the inhibition of the post‐translational modification of small GTP‐binding proteins such as Rab, Rho, and Rac as shown by others. The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates. J. Cell. Physiol. 220: 382–393, 2009. © 2009 Wiley‐Liss, Inc.
Effect of vegetable oil addition on bioaccessibility and biodegradation of polycyclic aromatic hydrocarbons in historically contaminated soils
Authors: Scherr Kerstin E , Hasinger Marion , Mayer Philipp , Loibner Andreas P
Published: April 2009

BACKGROUND: Bioaccessibility is often the limiting factor for the biodegradation of polycyclic aromatic hydrocarbons (PAH) in soils. The present study explores the potential of amending canola oil, an economically and ecologically attractive soil additive, for the enhancement of bioaccessibility and, in consequence, biodegradation of PAH in historically contaminated, bioaccessibility limited soils.

RESULTS: The amendment of canola oil (1% and 5%, w/w) to contaminated soils increased the bioaccessibility and the subsequent biodegradation of PAH with up to four rings. Residual concentrations of pyrene and fluoranthene in oil‐treated soils were 38–53% lower compared to the unamended tests. The continuous removal of bioaccessible PAH with a passive sampling system confirmed that oil amendment indeed increased bioaccessibility, leading to a lower non‐accessible PAH fraction. Canola oil amendment did, by contrast, not increase the bioaccessibility of high molecular weight PAH, likely due to their strong binding to soil organic carbon compounds.

CONCLUSION: Canola oil can be used efficiently in low concentrations to render PAH up to four rings accessible for biodegradation in historically contaminated soils. Contaminants remaining in soil after treatment may pose a significantly lowered environmental risk, as is indicated by the lack of mobilisation by a solubilising agent such as canola oil. Copyright © 2009 Society of Chemical Industry
Bioenergetic studies on aerobic growth of Pseudomonas aeruginosa in a single‐substrate media
Authors: Mahadevan Surianarayanan , Sivaprakasam Senthilkumar
Published: April 2009

BACKGROUND: The large‐scale development of various bioprocesses has posed a problem because of the inherent complexities of biological systems. This is because of the lack of discretion in the use of conventional chemical reactors to carry out complex bioreactions. Existing scale‐up methods for bioprocesses are formulated employing offline parameters, i.e. growth rate, substrate uptake rate, oxygen transfer rate and stirring rate per unit volume. Metabolic heat generation is an online process variable portraying the instantaneous activity of any living organism and different types of calorimeters are employed to measure the exothermic heat in non‐invasive way.

RESULTS: In this present study an isothermal heat flux biocalorimeter (BioRC1) is employed to monitor the metabolic heat generated due to physiological activity of Pseudomonas aeruginosa cultivated in glucose‐limited growth medium and attempts are made to obtain correlations between metabolic heat and significant process variables.

CONCLUSIONS: The value of specific growth rate is determined from correlation developed based on online metabolic heat data and it is found to corroborate with literature value. This finding substantiates the application of calorimetric results to predict the biokinetics parameters for bacterial growth. Copyright © 2009 Society of Chemical Industry
Activation of lipase by sol–gel coating with hydrophobic alkyl‐substituted silicates in supercritical carbon dioxide
Authors: Kawakami Koei , Urakawa Taiki , Oda Yasuhiro , Iwai Yoshio
Published: April 2009

BACKGROUND: Sol–gel entrapment of lipases is usually performed in an aqueous solution. A novel method of sol–gel coating of lipase in supercritical carbon dioxide (SC‐CO2) is proposed.

RESULTS: Crude lipase powder (Rhizopus oryzae) coated with hydrophobic silicates, derived from dimethyldimethoxysilane and tetramethoxysilane in SC‐CO2 at 35 °C and 15 MPa, exhibited 5–7 times higher esterification activity than that prepared via an aqueous sol–gel route. Lipase immobilized in a methyl‐substituted silica monolith was also highly activated by sol–gel coating using the same silica precursors in SC‐CO2.

CONCLUSION: Sol– gel coating in SC‐CO2, of lipases in powder and immobilized forms with hydrophobic alkyl‐substituted silicates provides an efficient tool for the enhancement of enzymatic activities in non‐aqueous media. Copyright © 2009 Society of Chemical Industry
Morphological filter improve the efficiency of automated tracking of secretory vesicles with various dynamic properties
Authors: Ku Tien‐Chuan , Kao Lung‐Sen , Lin Chung‐Chih , Tsai Yuh‐Show
Published: April 2009

Membrane trafficking is a very important physiological process involved in protein transport, endocytosis, and exocytosis. The functions of vesicles are strongly correlated with various spatial dynamic properties of vesicles, including their types of movements and morphology. Several methods are used to quantify such dynamic properties, but most of them are specific to particular populations of vesicles. We previously developed the so‐called PTrack system for quantifying the dynamics of secretory vesicles near the cell surface, which are small and move slowly. To improve the system performance in quantifying large and fast‐moving vesicles, we firstly combined morphological filter with two‐threshold image processing techniques to locate granules of various sizes. Next, Kalman filtering was used to improve the performance in tracking fast‐moving and large granules. Performance evaluation by using simulation image sequences shown that the new system, called PTrack II, yields better tracking accuracy. The tracking system was validated using time‐lapse images of insulin granules in βTC3 cells, which revealed that PTrack II could track better than PTrack, averaged accuracy up to 56%. The overall tracking results indicate that PTrack II is better at tracking vesicles with various dynamic properties, which will facilitate the acquisition of more‐complete information on vesicle dynamics. Microsc. Res. Tech., 2009. © 2009 Wiley‐Liss, Inc.
On the chromatic number of a random 5‐regular graph
Authors: Díaz J. , Kaporis A. C. , Kemkes G. D. , Kirousis L. M. , Pérez X. , Wormald N.
Published: April 2009

It was only recently shown by Shi and Wormald, using the differential equation method to analyze an appropriate algorithm, that a random 5‐regular graph asymptotically almost surely has chromatic number at most 4. Here, we show that the chromatic number of a random 5‐regular graph is asymptotically almost surely equal to 3, provided a certain four‐variable function has a unique maximum at a given point in a bounded domain. We also describe extensive numerical evidence that strongly suggests that the latter condition holds. The proof applies the small subgraph conditioning method to the number of locally rainbow balanced 3‐colorings, where a coloring is balanced if the number of vertices of each color is equal, and locally rainbow if every vertex is adjacent to at least one vertex of each of the other colors. © 2009 Wiley Periodicals, Inc. J Graph Theory 61: 157–191, 2009
Equitable list coloring and treewidth
Authors: Pelsmajer Michael J.
Published: April 2009

Given lists of available colors assigned to the vertices of a graph G, a list coloring is a proper coloring of G such that the color on each vertex is chosen from its list. If the lists all have size k, then a list coloring is equitable if each color appears on at most ⌈|V(G)|/k⌉ vertices. A graph is equitably k ‐choosable if such a coloring exists whenever the lists all have size k. Kostochka, Pelsmajer, and West introduced this notion and conjectured that G is equitably k‐choosable for k>Δ(G). We prove this for graphs of treewidth w≤5 if also k≥3w−1. We also show that if G has treewidth w≥5, then G is equitably k‐choosable for k≥max{Δ(G)+w−4, 3w−1}. As a corollary, if G is chordal, then G is equitably k‐choosable for k≥3Δ(G)−4 when Δ(G)>2. © 2009 Wiley Periodicals, Inc. J Graph Theory
1,2,4‐Triazines, 9. The synthesis of novel 4‐amino‐1,6‐dihydro‐1,2,4‐triazinones
Authors: Mizutani Masato , Sanemitsu Yuzuru
Published: April 2009

3‐Alkylthio‐4‐amino‐1,6‐dihydro‐1,2,4‐triazin‐5(4H)‐ones were synthesized by the reduction of 3‐thio‐4‐amino‐1,2,4‐triazine‐3,5(2.H,4H)‐diones and successive S‐alkylation. The regiospecific alkylation on the N‐1 position or the exo amino group leads to a variety of 1,6‐dihydro‐1,2,4‐triazin‐5(4H)‐one derivatives. An alternative synthesis of 3‐thio‐4‐amino‐1,6‐dihydro‐1,2,4‐triazine‐3,5(2H,4H)‐diones was accomplished through the cyclization of 1‐thiocarbohydrazidoacetamide derivatives.
The behaviour of stereoisomeric ions in the gas‐phase. The case of some new macrocyclic ether‐tetraesters
Authors: Podda Gianni , Maccioni Antonio , Corda Luciana , Vecchi Enrico , Daolio Sergio , Traldi Pietro
Published: April 2009

The electron impact mass spectrometric behaviour of some new diastereoisomeric macrocycles containing diglycolyl moiety as subcyclic unit is reported and discussed in detail with the aid of linked scans, exact mass measurements and collisionally activated decomposition mass analyzed ion kinetic energy spectra.
Nouvelles synthèses de systèmes bicycliques hétéroaromatiques. I. Cycloaddition [4 + 2]π de la diméthyl‐2,7 diméthylthio‐3,5 triazépine‐1,2,4
Authors: Hasnaoui Aissa , El Messaoudi Malika , Lavergne Jean‐Pierre
Published: April 2009

Nous décrivons les réactions de cycloaddition de la diméthylthic‐3,5 triazépine‐1,2,4 1 avec différents diènophiles. La phényl‐4 triazoline‐1,2,4 dione‐3,5, le diméthylacétylène dicarboxylate, l'anhydride maléïque réagissent avec 1 selon une réaction [4 + 2]π. Excepté le premier, ces adduits subissent un réarrangement sigmatropique‐1,3 pour conduire aux hétérocycles.
Synthèse et structure de benzopyranno‐1 triazines‐1,2,4
Authors: Vinot Nicole , Maitte Pierre
Published: April 2009

En milieu basique, la monosemicarbazone de la triméthyl‐2,2,6 chromannedione‐3,4 se cyclise en benzopy‐ranno‐1‐[4,3‐e]‐2,2,6‐triazinone‐3. En milieu acétique, le chlorhydrate de semicarbazide et la dicétone donnent un mélange des benzopyranno‐1‐[4,3‐e]triazinones et [3,4‐e]triazinones‐3. Par contre, dans les měmes conditions, le thiosemicarbazide conduit uniquement à la benzopyranno‐1‐[4,3‐e]triazinethione‐3. La structure des composés préparés est en accord avec les spectres rmn 13C.
Synthesis of 4‐(4‐iodophenyl)piperazine and the 1‐carboxamidino derivative
Authors: Hanson Robert N. , Hariharan Shankar , Astik Ramesh
Published: April 2009

The previously unreported 4‐(4‐iodophenyl)piperazine (2) was synthesized in a 70% yield and characterized. The reaction of 2 with S‐methylthiouronium sulfate gave the corresponding carboxamidino derivative 4 in a 61% yield. The tlc properties of 4 were identical with those of the radioiodinated material that had been prepared and evaluated as a potential myocardial imaging radiopharmaceutical.
Synthesis and reactions of heterocyclic methyl 2‐propenoates and 2,3‐epoxypropanoates with nucleophiles
Authors: Agarwal Kamlesh C. , Knaus Edward E.
Published: April 2009

Reaction of 2‐(3‐,4‐)pyridinecarboxaldehydes5with carbomethoxymethylene triphenylphosphorane afforded predominantlyE‐methyl‐3‐(pyridinyl)‐2‐propenoates7.Oxidation of7a‐cwithm‐chloroperbenzoic acid gave methylE‐3‐(1‐oxidopyridinyl)‐2‐propenoates8a‐cin high yield. The Darzen's reaction of5a‐cwith methyl bromoacetate yielded a mixture of stereoisomerscis‐9a‐cand methyltrans‐3‐(pyridinyl)‐2,3‐epoxy‐propanoates10a‐cin a ratio of 2:1. Oxidation ofcis‐9a‐candtrans‐10a‐cafforded the correspondingcis‐11a‐cand methyltrans‐3‐(1‐oxidopyridinyl)‐2,3‐epoxypropanoates12a‐cin good yield. The reaction of11aand12awith cyclic amines as piperidine gave the respectivethreo‐13and methylerythro‐2‐(1‐piperidino)‐3‐hydroxy‐3‐(1‐oxido‐2‐pyridino)propanoate14.The sodium borohydride reduction of theN‐alkoxylcarbonyl pyridinium salts of9cand10cafforded the correspondingN‐alkoxycarbonyl‐1,2‐dihydropyridyl derivatives15and16.A number of selected compounds (7a‐c,9a‐c,10a,10c,11a‐cand12a,12c) were found to be inactive in the P388 Lymphocytic screen. Compounds9‐12did not react with the model nucleophile ethanethiol in phosphate buffer at 37°.