bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractWhen 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

AbstractThis 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

Abstract
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

AbstractThe 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

AbstractChemokines 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

AbstractParathyroid 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

AbstractThe 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

AbstractA 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

AbstractAnti‐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

AbstractConstitutive 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

AbstractParents' 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

AbstractEstrogen 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

AbstractTranscription 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

AbstractThe 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.