bluuebunny/crossref_metadata_2025 huggingface dataset:
Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptorα and β
Authors: Rossi V. , Bellastella G. , De Rosa C. , Abbondanza C. , Visconti D. , Maione L. , Chieffi P. , Della Ragione F. , Prezioso D. , De Bellis A. , Bellastella A. , Sinisi A.A.
Published: October 2010

Raloxifene (RAL), a selective estrogen receptor (ER) modulator (SERM) seems to induce apoptosis in both androgen‐dependent and ‐independent prostate cell (PC) lines via activation of ERβ and an antagonistic effect on ERα. In this study, we evaluated the effects of RAL on epithelial PC growth using the two following in vitro models: the androgen‐dependent cell line EPN which expressed both ERs; and a stabilized epithelial cell line derived from a prostate cancer specimen (CPEC), which expressed low levels of ERβ and lacked ERα. In EPN cells, there was an increase in the pre‐G1 apoptotic peak and a reduction in the S phase of the cell cycle with G0/G1 arrest after E2 or RAL treatment;bcl‐2mRNA and Bcl‐2 protein levels were significantly reduced, while activated caspase‐3 and Par‐4 levels increased significantly after either E2 or RAL treatment; in addition, c‐myc transcript was inhibited after 10−6 M RAL treatment. A dose‐dependent increase of metallothionein II gene RNA level was also induced by RAL in EPN. In CPEC, there was only a weak apoptotic peak associated with caspase‐3 activation and Par‐4 increase after either E2 or RAL treatment; while c‐myc transcript level increased. RAL induced a rapid but transient phosphorylation of ERK 1/2 in EPN cells but generated a sustained effect in CPEC. These findings suggest that RAL effects on PC growth control in vitro are cell‐specific, depending on ERβ or ERβ/ERα relative expression levels. Moreover, this study demonstrated that RAL affected both transcriptional regulation and non‐genomic signals, which resulted in the modulation of multiple signaling pathways of apoptosis and of cell cycle progression. J. Cell. Physiol. 226: 1334–1339, 2011. © 2010 Wiley‐Liss, Inc.
Urinary 8‐OHdG elevations in a partial lesion rat model of parkinson's disease correlate with behavioral symptoms and nigrostriatal dopaminergic depletion
Authors: Kikuchi Yoichiro , Yasuhara Takao , Agari Takashi , Kondo Akihiko , Kuramoto Satoshi , Kameda Masahiro , Kadota Tomohito , Baba Tanefumi , Tajiri Naoki , Wang Feifei , Tayra Judith T. , Liang Hanbai , Miyoshi Yasuyuki , Borlongan Cesario V. , Date Isao
Published: October 2010

Increased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG) is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8‐OHdG in PD patients. There are few basic laboratory data examining 8‐OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6‐hydroxydopamine (6‐OHDA). The urinary 8‐OHdG level was measured in relation to behavioral and pathological deficits arising from 6‐OHDA‐induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6‐OHDA injection. We collected urine samples with subsequent measurement of 8‐OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8‐OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8‐OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8‐OHdG level provides a good index of severity of parkinsonism. Urinary 8‐OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6‐OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8‐OHdG level closely approximate onset and disease progression in PD. J. Cell. Physiol. 226: 1390–1398, 2011. © 2010 Wiley‐Liss, Inc.
Dicer is required for the formation of white but not brown adipose tissue
Authors: Mudhasani Rajini , Puri Vishwajeet , Hoover Kathleen , Czech Michael P. , Imbalzano Anthony N. , Jones Stephen N.
Published: October 2010

Dicer, an enzyme involved in microRNA maturation, is required for proper embryo gastrulation and tissue morphogenesis during mammalian development. Using primary cultures of fibroblasts and pre‐adipocytes, we have previously shown that Dicer is essential for early stages of adipogenic cell differentiation. In this study, we have utilized Dicer‐conditional mice to explore a role for Dicer and microRNA biogenesis in the terminal differentiation of adipocytes in vivo and in the formation of white and brown adipose tissue. Deletion of Dicer in differentiated adipocytes in Dicer‐conditional, aP2‐Cre transgenic mice reduced the level of various adipogenic‐associated transcripts and inhibited lipogenesis in white adipocytes, resulting in a severe depletion of white adipose tissue in mice. In contrast, Dicer was not required in vivo for lipogenesis in brown adipose or for brown fat formation. However, Dicer deletion in brown adipose did decrease the expression of genes involved in thermoregulation. The results of our study provide genetic evidence of a role for microRNA molecules in regulating adipogenesis and reveal distinct requirements for Dicer in the formation of white and brown adipose tissue. J. Cell. Physiol. 226: 1399–1406, 2011. © 2010 Wiley‐Liss, Inc.
MicroRNA‐24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN
Authors: Luna Coralia , Li Guorong , Qiu Jianming , Epstein David L. , Gonzalez Pedro
Published: October 2010

Cyclic mechanical stress (CMS) leads to alterations of cellular functions in the trabecular meshwork (TM), including the up‐regulation of transforming growth factor beta 1 (TGFβ1), that can potentially contribute to the pathogenesis of glaucoma. Although microRNAs (miRNAs) are known to play important roles in many biological functions, little is known about their potential involvement in the cellular responses elicited by mechanical stress. Here we analyzed changes in miRNA expression induced by CMS, and examined the possible role of miR‐24 in the response of human TM cells to CMS. CMS induced the expression of miR‐24 that led to the down regulation of the subtilisin‐like proprotein convertase FURIN, which is known to play a major role in the processing of TGFβ1. FURIN was confirmed as a novel target of miR‐24 by 3' UTR luciferase assay and western blot. Overexpression of miR‐24 resulted in a significant decrease in activated TGFβ1. This effect was mimicked by down regulation of FURIN by siRNA. Conversely, inhibition of miR‐24 expression with a specific antagomir led to a small but significant increase in TGFβ1. Furthermore, the increase in active TGFβ1 induced by CMS in HTM cells was prevented by miR‐24. Altogether, our results suggest that miRNAs might contribute to the regulation of responses to CMS in TM cells. Specifically, miR‐24 might play an important role in modulating the induction of TGFβ1 mediated by CMS through direct targeting of FURIN. J. Cell. Physiol. 226: 1407–1414, 2011. © 2010 Wiley‐Liss, Inc.
Analysis of dynamic tyrosine phosphoproteome in LFA‐1 triggered migrating t‐cells
Authors: Verma Navin K. , Dempsey Eugene , Freeley Michael , Botting Catherine H. , Long Aideen , Kelleher Dermot , Volkov Yuri
Published: October 2010

The ordered, directional migration of T‐lymphocytes is a key process during immune surveillance and response. This requires cell adhesion to the high endothelial venules or to the extracellular matrix by a series of surface receptor/ligand interactions involving adhesion molecules of the integrin family including lymphocyte function associated molecule‐1 (LFA‐1) and intercellular adhesion molecules (ICAMs). Reversible protein phosphorylation is emerging as a key player in the regulation of biological functions with tyrosine phosphorylation playing a crucial role in signal transduction. Thus, the study of this type of post‐translational modification at the proteomic level has great biological significance. In this work, phospho‐enriched cell lysates from LFA‐1‐triggered migrating human T‐cells were subjected to immunoaffinity purification of tyrosine phosphorylated proteins, mass spectrometric, and bioinformatic analysis. In addition to the identification of several well‐documented proteins, the analysis suggested involvement of a number of new and novel proteins in LFA‐1 induced T‐cell migration. This dataset expands the list of the signaling components of the LFA‐1 induced phosphotyrosine protein complexes in migrating T‐cells that will be extremely useful in the study of their specific roles within LFA‐1 associated signaling pathways. Identification of proteins previously not reported in the context of LFA‐1 stimulated signal transduction might provide new insights into understanding the LFA‐1 signaling networks and aid in the search for new potential therapeutic targets. J. Cell. Physiol. 226: 1489–1498, 2011. © 2010 Wiley‐Liss, Inc.
Control of lung development by latent TGF‐β binding proteins
Authors: Dabovic Branka , Chen Yan , Choi Jiwon , Davis Elaine C. , Sakai Lynn Y. , Todorovic Vesna , Vassallo Melinda , Zilberberg Lior , Singh Amanjot , Rifkin Daniel B.
Published: October 2010

The latent TGF‐β binding proteins (LTBP‐1 ‐3, and ‐4) assist in the secretion and localization of latent TGF‐β molecules. Ltbp3−/−and Ltbp4S−/− mice have distinct phenotypes and only in the lungs does deficiency of either Ltbp‐3 or Ltbp‐4 cause developmental abnormalities. To determine if these two LTBPs have additional common functions, we generated mice deficient for both Ltbp‐3 and Ltbp‐4S. The only novel defect in Ltbp3−/−;Ltbp4S−/− mice was an early lethality compared to mice with single mutations. In addition lung abnormalities were exacerbated and the terminal air sac septation defect was more severe in Ltbp3−/−;Ltbp4S−/− mice than in Ltbp4S−/− mice. Decreased cellularity of Ltbp3−/−;Ltbp4S−/− lungs was correlated with higher rate of apoptosis in newborn lungs of Ltbp3−/−;Ltbp4S−/− animals compared to WT, Ltbp3−/−, and Ltbp4S−/− mice. No differences in the maturation of the major lung cell types were discerned between the single and double mutant mice. However, the distribution of type 2 cells and myofibroblasts was abnormal, and myofibroblast segregation in some areas might be an indication of early fibrosis. We also observed differences in ECM composition between Ltbp3−/−;Ltbp4S−/− and Ltbp4S−/− lungs after birth, reflected in decreased incorporation of fibrillin‐1 and ‐2 in Ltbp3−/−;Ltbp4S−/− matrix. The function of the lungs of Ltbp3−/−;Ltbp4S−/− mice after the first week of life was potentially further compromised by macrophage infiltration, as proteases secreted from macrophages might exacerbate developmental emphysema. Together these data indicate that LTBP‐3 and ‐4 perform partially overlapping functions only in the lungs. J. Cell. Physiol. 226: 1499–1509, 2011. © 2010 Wiley‐Liss, Inc.
Regulation of PIP5K activity by Arf6 and its physiological significance
Authors: Funakoshi Yuji , Hasegawa Hiroshi , Kanaho Yasunori
Published: October 2010

The phospholipid kinase phosphatidylinositol 4‐phosphate 5‐kinase (PIP5K) catalyzes the phosphorylation of the membrane phospholipid phosphatidylinositol 4‐phosphate to generate the pleiotropic phospholipid phosphatidylinositol 4,5‐bisphosphate [PI(4,5)P2]. To date, three mammalian PIP5K isozymes, α, β, and γ, and several splicing variants of the γ isozyme have been identified. These PIP5K isozymes and PIP5Kγ variants play critical roles in various cellular functions through their product PI(4,5)P2. The small GTPase Arf6 is one of the key activators of PIP5K. Increasing evidence suggests that PIP5K functions as a downstream effector of Arf6 to regulate a wide variety of cellular functions, such as exocytosis, endocytosis, endosomal recycling, membrane ruffle formation, immune response, and bacterial invasion. In this review, we place our focus on the recent advances in Arf6/PIP5K signaling and its linkage to cellular functions. J. Cell. Physiol. 226: 888–895, 2011. © 2010 Wiley‐Liss, Inc.
Human embryonic stem cell proliferation and differentiation as parameters to evaluate developmental toxicity
Authors: Pal Rajarshi , Mamidi Murali Krishna , Kumar Das Anjan , Bhonde Ramesh
Published: October 2010

In vitro models based on embryonic stem cells (ESC) are highly promising for improvement of predictive toxicology screening in humans. After the successful validation of embryonic stem cell test (EST) in 2001; concerns have been raised on the usage of mouse ESC and also the morphological evaluation of beating cell clusters. This requires specialized skill‐sets and is highly prone to misjudgement and false positive results. To overcome these limitations, we undertook the present study incorporating improvisations over the conventional EST. Here, we explored the potential of a human ESC (hESC)‐based assay to evaluate the potential toxicity of penicillin‐G, caffeine, and hydroxyurea. Drug treatment inhibited hESC adhesion and substantially altered the morphology and viability (∼50%) of embryoid bodies (EBs). Flow cytometry analysis not only showed a significant increase of apoptotic cells in the highest doses but also induced a diverse pattern in DNA content and cell cycle distribution relative to control. Both semi‐quantitative and quantitative RT‐PCR studies revealed a selective down regulation of markers associated with stemness (Nanog, Rex1, SOX‐2, and hTERT); cardiac mesoderm (Cripto1, MEF‐2C, and Brachyury); hepatic endoderm (AFP, HNF‐3β, HNF‐4α, GATA‐4, and SOX‐17); and neuroectoderm (Nestin, SOX‐1, NURR1, NEFH, Synaptophysin, TH, and Olig2) in a drug as well as dose dependent manner indicating abnormal differentiation. Furthermore, a decrease in the expression of AFP and GFAP proteins followed by a dose‐dependent reduction in the levels of hCG‐β, progesterone‐II, and estradiol hormones was demonstrated by immunocytochemistry and ECLIA, respectively. This new and unique approach comprising of DNA cell cycle analysis, germ layer‐specific marker expression and hormone levels as endpoints might offer a clinically relevant and commercially viable alternative for predicting in vivo developmental toxicity. J. Cell. Physiol. 226: 1583–1595, 2011. © 2010 Wiley‐Liss, Inc.
Divalent metal transporter 1 is a hypoxia‐inducible gene
Authors: Qian Zhong‐Ming , Mei Wu Xiao , Fan Ming , Yang Lin , Du Fang , Yung Wing‐Ho , Ke Ya
Published: October 2010

Our recent study revealed a high correlation between the expression of hypoxia‐inducible factor‐1 (HIF‐1) alpha and divalent metal transporter 1 (DMT1) in HepG2 cells treated with chemical or physical hypoxia. We therefore speculated that DMT1 might be one of the target genes of HIF‐1. Here, we characterized the DMT1 exon1B promoter region and identified a functional hypoxia response element (HRE, 5′‐TCAGTACCTAACGTGGCGCCACGGC‐3′) harboring a binding site for HIF‐1. We demonstrated that hypoxia‐dependent activation of a luciferase reporter gene in transfected HepG2 cells is mediated by a fragment of human DMT1 exon1B promoter containing the putative HRE sequence. We also showed that the HIF‐1 binding site (HBS) is in DMT1 exon1B promoter with the core sequence of HRE (5′‐ACGTG‐3′) at −327 to −323 relative to the transcription start site of the human DMT1 exon1B gene. The mutation of this sequence prevented stimulation of luciferase activity. Electrophoretic mobility shift assays revealed that the HRE sequence found in the DMT1 gene promoter was bound by HIF‐1. In addition, we provide evidence that hypoxia could significantly increase ferrous uptake, while the silencing of total DMT1 by RNA interference down‐regulates DMT1 expression and ferrous uptake in HepG2 cells. We conclude that DMT1 is a hypoxia‐inducible gene. J. Cell. Physiol. 226: 1596–1603, 2011. © 2010 Wiley‐Liss, Inc.
Exhaustive exercise increases inflammatory response via toll like receptor‐4 and NF‐κBp65 pathway in rat adipose tissue
Authors: Rosa José C. , Lira Fábio S. , Eguchi Ricardo , Pimentel Gustavo D. , Venâncio Daniel P. , Cunha Cláudio A. , Oyama Lila M. , De Mello Marco T. , Seelaender Marília , Oller do Nascimento Cláudia M.
Published: October 2010

Cytokines (IL‐6, IL‐10, and TNF‐α) are increased after exhaustive exercise in the retroperitoneal adipose tissue (RPAT) and mesenteric adipose tissue (MEAT). An exhaustive acute exercise protocol induces inflammation in adipose tissue that lasts 6 h after the exercise has ended. It is well‐established that this protocol increases circulating plasma levels of non‐esterified fatty acids (NEFAs) and lipopolysaccharides (LPS), compounds that are important in stimulating signaling via toll like receptor‐4 (TLR‐4) in different type cells. In the present study, we investigated the regulation of TLR‐4 and DNA‐binding of nuclear factor‐κBp65 (NF‐κBp65) in different depots of adipose tissue in rats after exhaustive exercise. Rats were killed by decapitation immediately (E0 group, n = 6), 2 (E2 group, n = 6), and 6 h (E6 group, n = 6) after the exhaustive exercise, which consisted of running on a treadmill (approximately 70% VO2max) for 50 min and then running at an elevated rate that increased at 1 m/min, until exhaustion. The control group (C group, n = 6) was not subjected to exercise. In RPAT, TLR‐4, MYD‐88, and IkBα increased in the E2 group after exercise. MYD‐88 and TRAF6 remained increased in the E6 group in comparison with the control group. DNA‐binding of NF‐κBp65 was not altered. In MEAT, TLR‐4, MYD‐88, TRAF6, and DNA‐binding of NF‐κBp65 were increased only in the E6 group. In conclusion, we have shown that increases in pro‐inflammatory cytokines in adipose tissue pads after exhaustive exercise may be mediated via TLR‐4 signaling, leading to increases in NF‐κBp65 binding to DNA in MEAT. J. Cell. Physiol. 226: 1604–1607, 2011. © 2010 Wiley‐Liss, Inc.
Recurrent readmissions in medical patients: A prospective study
Authors: Mudge Alison M , Kasper Karen , Clair Anne , Redfern Helen , Bell Jack J , Barras Michael A , Dip Grad , Pachana Nancy A
Published: October 2010

BACKGROUND:

Hospital readmissions are common and costly. A recent previous hospitalization preceding the index admission is a marker of increased risk of future readmission.

OBJECTIVES:

To identify factors associated with an increased risk of recurrent readmission in medical patients with 2 or more hospitalizations in the past 6 months.

DESIGN:

Prospective cohort study.

SETTING:

Australian teaching hospital acute medical wards, February 2006‐February 2007.

PARTICIPANTS:

142 inpatients aged ≥50 years with a previous hospitalization ≤6 months preceding the index admission. Patients from residential care, with terminal illness, or with serious cognitive or language difficulties were excluded.

VARIABLES OF INTEREST:

Demographics, previous hospitalizations, diagnosis, comorbidities and nutritional status were recorded in hospital. Participants were assessed at home within 2 weeks of hospital discharge using validated questionnaires for cognition, literacy, activities of daily living (ADL)/instrumental activities of daily living (IADL) function, depression, anxiety, alcohol use, medication adherence, social support, and financial status.

MAIN OUTCOME MEASURE:

Unplanned readmission to the study hospital within 6 months.

RESULTS:

A total of 55 participants (38.7%) had a further unplanned hospital admission within 6 months. In multivariate analysis, chronic disease (adjusted odds ratio [OR] 3.4; 95% confidence interval [CI], 1.3‐9.3, P = 0.002), depressive symptoms (adjusted OR, 3.0; 95% CI, 1.3‐6.8, P = 0.01), and underweight (adjusted OR, 12.7; 95% CI, 2.3‐70.7, P = 0.004) were significant predictors of readmission after adjusting for age, length of stay and functional status.

CONCLUSIONS:

In this high‐risk patient group, multiple chronic conditions are common and predict increased risk of readmission. Post‐hospital interventions should consider targeting nutritional and mood status in this population. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer‐guided vs. standard column‐based algorithms
Authors: Newton Christopher A. , Smiley Dawn , Bode Bruce W. , Kitabchi Abbas E. , Davidson Paul C. , Jacobs Sol , Steed R. Dennis , Stentz Frankie , Peng Limin , Mulligan Patrick , Freire Amado X. , Temponi Angel , Umpierrez Guillermo E.
Published: October 2010

PURPOSE:

To compare the safety and efficacy of continuous insulin infusion (CII) via a computer‐guided and a standard paper form protocol in a medical intensive care unit (ICU).

METHODS:

Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n = 77) or a standard paper protocol (n = 76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL.

RESULTS:

The Glucommander resulted in a lower mean BG value (103 ± 8.8 mg/dL vs. 117 ± 16.5 mg/dL, P < 0.001) and in a shorter time to reach BG target (4.8 ± 2.8 vs.7.8 hours ± 9.1 hours, P < 0.01), and once at target resulted in a higher percentage of BG readings within target (71.0 ± 17.0% vs. 51.3 ± 19.7%, P < 0.001) than the standard protocol. Mean insulin infusion rate in the Glucommander was similar to the standard protocol (P = 0.12). The percentages of patients with ≥1 episode of BG <40 mg/dL and <60 mg/dL were 3.9% and 42.9% in the Glucommander and 5.6% and 31.9% in the standard, respectively [P = not significant (NS)]. Repeated measures analyses show that the probabilities of BG reading <40 mg/dL or <60 mg/dL were not significantly different between groups (P = 0.969, P = 0.084) after accounting for within‐patient correlations with or without adjusting for time effect. There were no differences between groups in the length of hospital stay (P = 0.704), ICU stay (P = 0.145), or inhospital mortality (P = 0.561).

CONCLUSION:

Both treatment algorithms resulted in significant improvement in glycemic control in critically ill patients in the medical ICU. The computer‐based algorithm resulted in tighter glycemic control without an increased risk of hypoglycemic events compared to the standard paper protocol. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
Effect of nitrogen fertilization on nitrogen dynamics in oilseed rape using 15N‐labeling field experiment
Authors: Gombert Julie , Le Dily Frédérik , Lothier Jérémy , Etienne Philippe , Rossato Laurence , Allirand Jean‐Michel , Jullien Alexandra , Savin Alexandre , Ourry Alain
Published: October 2010

In order to optimize nitrogen (N) fertilization and to reduce the environmental impact of oilseed rape without decreasing yield, a clearer understanding of N dynamics inside the plant is crucial. The present investigation therefore aimed to study the effects of different N‐application rates on the dynamics of N uptake, partitioning, and remobilization. The experiment was conducted on winter oilseed rape (Brassica napus L. cv. Capitol) under three levels of N input (0, 100, and 200 kg N ha–1) from stem elongation to maturity using 15N‐labeling technique to distinguish between N uptake and N retranslocation in the plant. Nitrogen fertilization affected the time‐course of N uptake and also the allocation of N taken up from flowering to maturity. Most pod N came from N remobilization, and leaves accounted for the largest source of remobilized N regardless the N‐application rate. However, the contribution of leaves to the remobilized N pool increased with the N dose whereas the one of taproot decreased. Stems were the main sink for remobilized N from stem elongation to flowering. Leaves remained longer on N200 than on N0 and N100 plants, and N concentration in fallen leaves increased with the N treatment and in N100 plants along an axial gradient from the basal to the upper leaves. Overall, these results show that the timing of N supply is more crucial than the N amount to attain a high N efficiency.
Electronic and structural effects on the nonlinear optical behavior in π‐conjugated structure bis(4‐nitrophenyl) carbonate: a vibrational spectroscopic approach
Authors: Ravikumar C. , Ramachandra Miss Pillai Indu , Hubert Joe I.
Published: October 2010

Fourier transform (FT)‐Raman and infrared (IR) spectra of the nonlinear optical (NLO) material bis(4‐nitrophenyl) carbonate were recorded and analyzed. The geometry, first hyperpolarizability and harmonic vibrational wavenumbers were calculated with the help of Becke3–Lee–Yang–Parr density functional theory method. The detailed interpretation of the vibrational spectra was carried out with the aid of normal coordinate analysis following the scaled quantum mechanical force field methodology. The second‐order NLO properties of the molecule were studied by the Kurtz and Perry powder reflection technique. Stability of the molecule arising from hyperconjugative interactions leading to its NLO activity and charge delocalization were analyzed using natural bond orbital analysis. Copyright © 2010 John Wiley & Sons, Ltd.
Simple determination of azasetron in rat plasma by column‐switching high‐performance liquid chromatography
Authors: Um So Young , Chae Song Wha , Park Hyun Joo , Chung Myeon Woo , Choi Sun Ok , Lee Hwa Jeong
Published: October 2010

For the quantification of azasetron in rat plasma samples, a column‐switching HPLC method was developed and validated. Following dilution of plasma samples with mobile phase A (17 mM potassium phosphate buffer (pH 3.0)) and simple protein precipitation by addition of perchloric acid (60%), the mixture was directly injected onto the pre‐column. After endogenous plasma substances were eluted to waste, the analyte was transferred to the trap column by switching the system. Then, the analyte was back‐flushed to the analytical column for separation with mobile phase B (a 22:78 v/v mixture of acetonitrile and 17 mM potassium phosphate buffer (pH 3.0)) and detected at 250 nm using a photodiode array detector. A linear standard curve was obtained in the concentration range of 10–800 ng/mL with the correlation coefficient (r) of 0.9998. The intra‐ and inter‐day precision and accuracy values for azasetron were in the ranges of 0.3−12.9% and 89.7−101.4%, respectively. The method was valid in terms of specificity, precision, and accuracy. In addition, this efficient analytical method was successfully applied to determine plasma concentrations of azasetron following oral administration of azasetron at a dose of 4.0 mg/kg to rats.
Contact‐Active Antimicrobial and Potentially Self‐Polishing Coatings Based on Cellulose
Authors: Bieser Arno M. , Thomann Yi , Tiller Joerg C.
Published: October 2010

A contact‐active antimicrobial coating is described that is only degraded in the presence of cellulase, which is an extracellular enzyme of numerous microbial strains. Antimicrobial DDA was grafted to a cellulose backbone via a polymeric spacer. The antimicrobial activity of the coatings, their biodegradability and their self‐polishing potential were investigated. It was found that all coatings were antimicrobially active against Staphylococcus aureus. Coatings with high DS and long polymeric spacers degraded in water, while coatings with low DS and short spacers were not hydrolyzed even in the presence of cellulase. One coating was found to be selectively degradable by cellulase and recovered most of its antimicrobial activity after overloading and subsequent treatment with cellulase.

magnified image
Thermal, Mechanical, and Surface Properties of Poly(2‐N‐alkyl‐2‐oxazoline)s
Authors: Rettler Erik F.‐J. , Kranenburg Johannes M. , Lambermont‐Thijs Hanneke M.L. , Hoogenboom Richard , Schubert Ulrich S.
Published: October 2010

Thermal, mechanical, and surface properties of a library of poly(2‐oxazoline)s are investigated. These polymers are suitable to study structure/property relationships as their cationic ROP and the relative facile monomer synthesis allow for control over the molecular structure. The number of carbon atoms in the linear side‐chain is systematically varied from methyl to nonyl. Relations between chemical structures, thermal transitions, surface energies, and elastic moduli are discussed. It is shown that the mechanical and thermal properties of the polymers depend on the presence of a crystalline phase in the material. The amorphous polymers reveal a decrease in the reduced moduli along with a decrease in their respective glass transition temperature with increasing length of the side‐chain.

magnified image
Xanthene‐Based Oligothiophene‐Layered Polymers
Authors: Morisaki Yasuhiro , Fernandes Jonas Alves , Chujo Yoshiki
Published: October 2010

We synthesized xanthene‐based oligothiophene‐layered polymers containing bithiophenes, terthiophenes, quaterthiophenes and quinquethiophenes by the Suzuki‐Miyaura coupling reaction. The polymers were characterized by various spectroscopic and electrochemical methods. They were well soluble in common organic solvents and thermally stable. Effective π‐π interactions among the layered oligothiophene units in the polymer backbone were not observed in the ground state as well as in the excited state. A possible application of the polymers in opto‐electronic devices such as hole transporting materials is expected.

magnified image
Supramolecular Thermoresponsive Hyperbranched Polymers Constructed from Poly(N‐Isopropylacrylamide) Containing One Adamantyl and Two β‐Cyclodextrin Terminal Moieties
Authors: Ge Zhishen , Liu Hao , Zhang Yanfeng , Liu Shiyong
Published: October 2010

Poly(N‐isopropylacrylamide) (PNIPAM) oligomer containing one adamantyl (AD) and two β‐cyclodextrin (β‐CD) moieties at the chain terminals, AD‐PNIPAM‐(β‐CD)2, was synthesized by atom transfer radical polymerization (ATRP) and successive click reactions. In aqueous solution, AD‐PNIPAM‐(β‐CD)2 spontaneously forms supramolecular thermoresponsive hyperbranched polymers via molecular recognition between AD and β‐CD moieties. To the best of our knowledge, this work represents the first report of the construction of supramolecular thermoresponsive hyperbranched polymers from well‐defined polymeric AB2 building units.

magnified image
Uniform PEO Star Polymers Synthesized in Water via Free Radical Polymerization or Atom Transfer Radical Polymerization
Authors: Li Wenwen , Matyjaszewski Krzysztof
Published: October 2010

Amphiphilic star shaped polymers with poly(ethylene oxide) (PEO) arms and cross‐linked hydrophobic core were synthesized in water via either conventional free radical polymerization (FRP) or atom transfer radical polymerization (ATRP) techniques using a simple “arm‐first” method. In FRP, PEO based macromonomers (MM) were used as arm precursors, which were then cross‐linked by divinylbenzene (DVB) using 2,2′‐azoisobutyronitrile (AIBN). Uniform star polymers ($\overline {M} _{{\rm w}} /\overline {M} _{{\rm n}} $ < 1.2) were achieved through adjustment of the ratio of PEO MM, DVB, and AIBN. While in case of ATRP, both PEO MM, and PEO based macroinitiator (MI) were used as arm precursors with ethylene glycol diacrylate as cross‐linker. Even more uniform star polymers with less contamination by low MW polymers were obtained, as compared to the products synthesized by FRP.

magnified image
Unveiling the methylation status of CpG dinucleotides in the substituted segment of the human p53 knock‐in (Hupki) mouse genome
Authors: Kim Sang‐In , Hollstein Monica , Pfeifer Gerd P. , Besaratinia Ahmad
Published: October 2010

Methylated cytosines within CpG dinucleotides (mCpGs) along the DNA‐binding domain of the TP53 tumor suppressor gene (exons ∼5–8) are the single most significant mutational target in human cancers. The human p53 knock‐in (Hupki) mouse model was constructed using gene‐targeting technology to create a mouse strain that harbors human wild‐type TP53 DNA sequences spanning exons 4–9 in both copies of the mouse p53 gene. To date, however, the methylation status of cytosines within CpGs in the substituted segment of the Hupki mouse genome has not been determined. This lack of information deserves special attention because DNA methylation in mammals, which occurs almost exclusively within CpG dinucleotides, is a dynamic process throughout developmental stages and may vary among different species. Here, we have investigated the status of CpG methylation in the substituted segment of the Hupki mouse genome, and compared it to the methylation profile of the corresponding segment in the human genome using the combined bisulfite‐restriction analysis and sodium bisulfite genomic sequencing. We found that all cytosines within CpGs of the TP53 DNA‐binding domain, on both the coding and noncoding strands, were heavily methylated in Hupki fibroblasts, as they were in human fibroblasts. This is in keeping with the fully methylated status of TP53 CpGs that is known to prevail in adult human tissues. The remarkably similar patterns of cytosine methylation within CpG dinucleotides in Hupki cells and human cells further validates the suitability of mutagenesis assays in Hupki cells for experimental induction of TP53 mutations that have been observed in human tumors. © 2010 Wiley‐Liss, Inc.
Loss of tyrosine phosphatase‐dependent inhibition promotes activation of tyrosine kinase c‐Src in detached pancreatic cells
Authors: Connelly Sarah F. , Isley Beth A. , Baker Cheryl H. , Gallick Gary E. , Summy Justin M.
Published: October 2010

Despite an intense focus on novel therapeutic strategies, pancreatic adenocarcinoma remains one of the deadliest human malignancies. The frequent and rapid mortality associated with pancreatic cancer may be attributed to several factors, including late diagnosis, rapid tumor invasion into surrounding tissues, and formation of distant metastases. Both local invasion and metastasis require disruption of tumor cell contacts with the extracellular matrix. Detachment of normal cells from the extracellular matrix leads to a form of programmed cell death termed anoikis. Pancreatic cancer cells avert anoikis by activation of signaling pathways that allow for adhesion‐independent survival. In the present studies, cellular signaling pathways activated in detached pancreatic cancer cells were examined. We demonstrate a rapid and robust activation of Src kinase in detached pancreatic cancer cells, relative to adherent. Src autophosphorylation rapidly returned to baseline levels upon reattachment to tissue culture plastic, in the presence or absence of specific extracellular matrix proteins. Treatment of pancreatic cancer cells with tyrosine phosphatase inhibitors increased steady‐state Src autophosphorylation in adherent cells and abrogated the detachment‐induced increase in Src autophosphorylation. Src was found to co‐immunoprecipitate with the Src homology 2 (SH2) domain containing protein tyrosine phosphatase (SHP‐2) in pancreatic cancer cells, suggesting that SHP‐2 may participate in regulation of Src autophosphorylation in adherent cells. Src family kinase (SFK) dependent increases in Akt and Jun N‐terminal kinase (JNK) phosphorylation were observed in detached cells, indicating the potential for Src‐dependent activation of survival and stress pathways in pancreatic cancer cells that have detached from the extracellular matrix. © 2010 Wiley‐Liss, Inc.
Association of angiotensin I converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms with breast cancer prognostic factors in iranian population
Authors: Namazi Soha , Monabati Ahmad , Ardeshir‐Rouhani‐Fard Shirin , Azarpira Negar
Published: October 2010

It has been indicated that renin‐angiotensin system (RAS) has role in various steps of cancer progression. The presence of RAS components has been shown in normal and breast cancer tissue. Insertion/Deletion (I/D) is one of angiotensin I converting enzyme (ACE) polymorphisms and A1166C is one of Angiotensin II type‐1 receptor (AT1R) polymorphisms which have been associated with various diseases such as cardiovascular diseases. In the present study, we aimed to substantiate the putative significance of ACE and AT1R on breast cancer biology by investigating the influence of their gene polymorphisms on breast cancer progression. The I/D and A1166C polymorphisms were evaluated by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), respectively in 70 breast cancer patients diagnosed with invasive breast cancer and 70 healthy women. Breast cancer prognostic factors were obtained from medical and pathology reports of patients. There was no significant difference between cases and controls for ACE (I/D) (P = 0.15) and AT1R (A1166C) genotypes (P = 0.86). In breast cancer patients, when DD genotype was used as reference group, the combination of II and ID genotypes was associated with increased HER‐2 expression (P = 0.020; OR, 4.58; 95% CI, 1.26–16.60). Also, when AA genotype was used as reference group, the AC genotype was associated with higher tumor TNM stage (P = 0.024; OR, 4.66; 95% CI, 1.18–18.35). This is the first study indicating that ACE (I/D) polymorphism is associated with HER‐2 expression and AT1R (A1166C) polymorphism is associated with tumor TNM stage in breast cancer patients. © 2010 Wiley‐Liss, Inc.
Instability of syllable repetition as a marker of disease progression in Parkinson's disease: A longitudinal study
Authors: Skodda Sabine , Flasskamp Andrea , Schlegel Uwe
Published: October 2010

Parkinsonian speakers show a tendency to articulatory acceleration and have difficulties to keep the steady pace of repeated syllables. The aim of this study was to analyse the stability of motor speech performance based upon a syllable repetition paradigm during the course of disease to find a potential marker of disease progression in Parkinson's disease (PD). 58 patients withPD and 35 controls were tested and re‐tested after at least 12 months (mean: 33.40/range: 12–88). In the PD group, motor impairment was similar at first and second visit. Participants had to repeat the syllable /pa/ in a self chosen steady pace. Percental coefficient of variance (COV) of interval length was measured for description of pace stability throughout the performance. Percental pace acceleration (%PA) was based upon a comparison of the speed of syllable repetition in the first and second half of the task. Patients with PD showed a significant elevation of COV and %PA indicating an instability of syllable repetition and a tendency to pace acceleration in the course of performing. Furthermore, in the PD group, COV and %PA showed a significant deterioration from first to second examination. Instability of steady syllable repetition in PD shows characteristic changes during the course of the disease, but no correlation with general motor impairment. Therefore, the underlying mechanism may be independent from dopaminergic deficits. The potential role of impaired syllable repetition as a marker of non‐dopaminergic disease progression in PD needs validation by further studies. © 2010 Movement Disorder Society
Differential genetic susceptibility in diphasic and peak‐dose dyskinesias in Parkinson's disease
Authors: Lee Jee‐Young , Cho Jinwhan , Lee Eun‐Kyung , Park Sung‐Sup , Jeon Beom S.
Published: October 2010

To examine whether there is a differential genetic susceptibility in the diphasic and peak‐dose forms of levodopa‐induced dyskinesias (LID) in patients with Parkinson's disease (PD). The study cohort comprised 503 unrelated Korean PD patients who were treated with levodopa and had a disease duration of at least 5 years. The presence of LID was identified during a routine follow‐up and special care was taken to separate the two distinct forms of LID into diphasic and peak‐dose dyskinesias (PDSK). Genotyping was performed in the 503 patients and in 559 healthy controls to search for polymorphisms of DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.2664C>T, c.366C>G, c.‐200T>G, and the promoter region of SLC6A4. A total of 229 patients expressed LID (peak‐dose in 205, diphasic in 57, and both in 33). The presence of diphasic dyskinesia (DDSK) was exclusively associated with the DRD3 p.S9G variant after adjusting for gender, age at PD onset, Hoehn & Yahr stage, and duration of levodopa treatment. Carrying the AA genotype was likely to shorten the onset of DDSK according to the duration of levodopa therapy (P = 0.02). The presence of PDSK was not significantly associated with any of the six genetic variants studied. There may be a genetic susceptibility in the development of DDSK in PD patients on chronic levodopa therapy, and its underlying pathophysiological mechanism might be distinct from that of PDSK. © 2010 Movement Disorder Society
Laser induced defects in laser doped solar cells
Authors: Hameiri Z. , Puzzer T. , Mai L. , Sproul A. B. , Wenham S. R.
Published: October 2010

Laser doping offers a promising method to define selective emitters for solar cells. Its main advantage is the localised nature of the laser beam, which allows melting of the surface area without heating the bulk. The ability to perform this process over a dielectric film offers further benefits, such as the possibility of creating self‐aligned metallisation patterns simultaneously with the selective emitter formation. However, laser induced defects, contaminations and discontinuities in the selective emitter can reduce solar cell performance. In this work the influence of different dielectric films on defect formation is investigated. It was found that a thin oxide beneath the SiNximproves the implied open circuit voltage of the solar cells for a wide range of laser output powers. Fewer defects were observed when using this SiO2/SiNxstack compared to the standard single SiNxanti‐reflection coating layer. It was also found that the recrystallised silicon layer grows epitaxially according the substrate orientation. No dislocation or stacking faults were observed in deeper areas using transmission electron microscopy, although some defects were observed near the surface. Electron beam induced current images revealed discontinuities in junctions formed with high laser powers. We conclude that micro‐cracks create these discontinuities, which can potentially induce shunts. Finally, laser doped solar cells with a standard SiNxand with a double SiO2/SiNxstack layer as anti‐reflection coating were compared. An efficiency of 18.4% on a large area commercial grade p‐type CZ substrate was achieved. Copyright © 2010 John Wiley & Sons, Ltd.
One‐pot preparation of ABA‐type block‐graft copolymers via a combination of “click” chemistry with atom transfer nitroxide radical coupling reaction
Authors: Jing Rongkuan , Wang Guowei , Huang Junlian
Published: October 2010

A new strategy for the one‐pot preparation of ABA‐type block‐graft copolymers via a combination of Cu‐catalyzed azide‐alkyne cycloaddition (CuAAC) “click” chemistry with atom transfer nitroxide radical coupling (ATNRC) reaction was reported. First, sequential ring‐opening polymerization of 4‐glycidyloxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (GTEMPO) and 1‐ethoxyethyl glycidyl ether provided a backbone with pendant TEMPO and ethoxyethyl‐protected hydroxyl groups, the hydroxyl groups could be recovered by hydrolysis and then esterified with 2‐bromoisobutyryl bromide, the bromide groups were converted into azide groups via treatment with NaN3. Subsequently, bromine‐containing poly(tert‐butyl acrylate) (PtBA‐Br) was synthesized by atom transfer radical polymerization. Alkyne‐containing polystyrene (PS‐alkyne) was prepared by capping polystyryl‐lithium with ethylene oxide and subsequent modification by propargyl bromide. Finally, the CuAAC and ATNRC reaction proceeded simultaneously between backbone and PtBA‐Br, PS‐alkyne. The effects of catalyst systems on one‐pot reaction were discussed. The block‐graft copolymers and intermediates were characterized by size‐exclusion chromatography, 1H NMR, and FT‐IR in detail. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010
A novel fluorine‐containing graft copolymer bearing perfluorocyclobutyl aryl ether‐based backbone and poly(methyl methacrylate) side chains
Authors: Liu Hao , Li Yongjun , Zhang Sen , Yang Dong , Hu Jianhua , Huang Xiaoyu
Published: October 2010

A series of novel graft copolymers consisting of perfluorocyclobutyl aryl ether‐based backbone and poly(methyl methacrylate) side chains were synthesized by the combination of thermal [2π + 2π] step‐growth cycloaddition polymerization of aryl bistrifluorovinyl ether monomer and atom transfer radical polymerization (ATRP) of methyl methacrylate. A new aryl bistrifluorovinyl ether monomer, 2‐methyl‐1,4‐bistrifluorovinyloxybenzene, was first synthesized in two steps from commercially available reagents, and this monomer was homopolymerized in diphenyl ether to provide the corresponding perfluorocyclobutyl aryl ether‐based homopolymer with methoxyl end groups. The fluoropolymer was then converted to ATRP macroinitiator by the monobromination of the pendant methyls with N‐bromosuccinimide and benzoyl peroxide. The grafting‐from strategy was finally used to obtain the novel poly(2‐methyl‐1,4‐bistrifluorovinyloxybenzene)‐g‐poly(methyl methacrylate) graft copolymers with relatively narrow molecular weight distributions (Mw/Mn ≤ 1.46) via ATRP of methyl methacrylate at 50 °C in anisole initiated by the Br‐containing macroinitiator using CuBr/dHbpy as catalytic system. These fluorine‐containing graft copolymers can dissolve in most organic solvents. This is the first example of the graft copolymer possessing perfluorocyclobutyl aryl ether‐based backbone. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010
Surface morphology and amide concentration depth profile of aminolyzed poly(ethylene terephthalate) films
Authors: Avadanei Mihaela , Drobota Mioara , Stoica Iuliana , Rusu Elena , Barboiu Virgil
Published: October 2010

Surface of biaxially oriented poly(ethylene terephthalate) films was chemically modified by exposure to ethylenediamine (EDA), triethylenetetramine (TETA), and tetraethylenepentamine (TEPA) for different treatment times. Variable angle attenuated total reflection Fourier transform infrared (ATR‐FTIR) spectroscopy was used in conjunction with weight loss measurements, scanning electron microscopy (SEM), and atomic force microscopy to establish the surface modification and to draw the depth profile of the newly created species, with emphasis on amide group. A clear differentiation was found between the effects of the three amines studied: EDA produces the highest amidation degree but, because of its deep penetration into the film, leads to delamination of rather thick layers, TETA reacts at and near surface and develops surface cracks without delamination, and TEPA is the mildest reactant, generating amide groups on the surface without visible deterioration of the sample. It was proved that the amide II absorption band became weaker with increasing analyzed depth, with a pronounced heterogeneity near the surface. SEM micrographs showed the development of cracks onto the surface at longer aminolysis time, which allowed a better understanding of ATR‐FTIR observations. Assuming an exponential decay for the depth profile spectrally obtained, the surface concentration of amide groups and the decay constant were determined for the amines and reaction times used. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010