bluuebunny/crossref_metadata_2025 huggingface dataset:
A DFT Study on The Two‐Dimensional Second‐Order Nonlinear Optical (NLO) Response of Terpyridine‐Substituted Hexamolybdates: Physical Insight on 2D Inorganic–Organic Hybrid Functional Materials
Authors: Janjua Muhammad Ramzan Saeed Ashraf , Amin Muhammad , Ali Muhammad , Bashir Beenish , Khan Muhammad Usman , Iqbal Muhammad Awais , Guan Wei , Yan Likai , Su Zhong‐Min
Published: December 2011

DFT calculations were carried out in order to study the second‐order nonlinear optical (NLO) response of a series of proposed 2D polyoxometalate‐based terpyridine‐substituted compounds. These compounds can be formulated as [Mo6O17{N4C25H16(X)2}{N4C25H16(X)2}]2– (X = H, F, Cl, Br, I, CF3, or CN), which has a wedge Λ‐shaped acceptor––π‐conjugated bridge––donor––π‐conjugated bridge––acceptor (A‐π‐D‐π‐A) configuration. The calculations showed that these compounds possess significantly large molecular second‐order polarizabilities that range from approximately 1000 × 10–30 to 4300 × 10–30 esu. The combination of trifluoromethyl (CF3) and cyanide (CN) groups at the end of the terpyridine ligand strengthens the bridge conjugation, which is useful for the enhancement of the NLO response. In addition, the greatest contributions to the βvec values are dervied from the charge transfer (CT) from the Mo≡N bond and the organoimido ligand to the terpyridine‐substituted segments. This report demonstrates that various combinations of the acceptor(s) remarkably affect the second‐order NLO response. The electronic transitions to the crucial excited states indicated that the y polarized transition contributed to the off‐diagonal second‐order polarizabiliy tensor (βzyy) and that the z polarized transition accounted for the diagonal second‐order polarizabiliy tensor (βzzz). Thus, itsteered towards in‐plane nonlinear anisotropy (u = βzyy/βzzz) along with a good 2D second‐order NLO response. These compounds can be used as good 2D second‐order NLO materials from the point of view of their large β values.
BRCA1 requirement for the fidelity of plasmid DNA double‐strand break repair in cultured breast epithelial cells
Authors: Thompson Eric G. , Fares Hanna , Dixon Kathleen
Published: December 2011

The tumor suppressor breast cancer susceptibility protein 1 (BRCA1) protects our cells from genomic instability in part by facilitating the efficient repair of DNA double‐strand breaks (DSBs). BRCA1 promotes the error‐free repair of DSBs through homologous recombination and is also implicated in the regulation of nonhomologous end joining (NHEJ) repair fidelity. Here, we investigate the role of BRCA1 in NHEJ repair mutagenesis following a DSB. We examined the frequency of microhomology‐mediated end joining (MMEJ) and the fidelity of DSB repair relative to BRCA1 protein levels in both control and tumorigenic breast epithelial cells. In addition to altered BRCA1 protein levels, we tested the effects of cellular exposure to mirin, an inhibitor of meiotic recombination enzyme 11 (Mre11) 3′–5′‐exonuclease activity. Knockdown or loss of BRCA1 protein resulted in an increased frequency of overall plasmid DNA mutagenesis and MMEJ following a DSB. Inhibition of Mre11‐exonuclease activity with mirin significantly decreased the occurrence of MMEJ, but did not considerably affect the overall mutagenic frequency of plasmid DSB repair. The results suggest that BRCA1 protects DNA from mutagenesis during nonhomologous DSB repair in plasmid‐based assays. The increased frequency of DSB mutagenesis and MMEJ repair in the absence of BRCA1 suggests a potential mechanism for carcinogenesis. Environ. Mol. Mutagen., 2012. © 2011 Wiley Periodicals, Inc.
Polymorphisms in complement system genes and risk of non‐Hodgkin lymphoma
Authors: Bassig Bryan A. , Zheng Tongzhang , Zhang Yawei , Berndt Sonja I. , Holford Theodore R. , Hosgood H.Dean , Hu Wei , Leaderer Brian , Yeager Meredith , Menashe Idan , Boyle Peter , Xu Jun , Zou Kaiyong , Zhu Yong , Chanock Stephen , Rothman Nathaniel , Lan Qing
Published: December 2011

The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non‐Hodgkin lymphoma (NHL) in a population‐based case–control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency‐matched controls. A gene‐based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B‐cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP‐based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR)CT = 0.60, 95% confidence interval (CI) = 0.42–0.87, Ptrend = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (ORCT = 0.39, 95% CI = 0.20–0.73; Ptrend = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings. Environ. Mol. Mutagen., 2012. Published 2011 Wiley‐Liss, Inc.
Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer
Authors: Park Yun‐Yong , Kim Kyounghyun , Kim Sang‐Bae , Hennessy Bryan T. , Kim Soo Mi , Park Eun Sung , Lim Jae Yun , Li Jane , Lu Yiling , Gonzalez‐Angulo Ana Maria , Jeong Woojin , Mills Gordon B. , Safe Stephen , Lee Ju‐Seog
Published: December 2011

ESR1 is one of the most important transcription factors and therapeutic targets in breast cancer. By applying systems‐level re‐analysis of publicly available gene expression data, we uncovered a potential regulator of ESR1. We demonstrated that orphan nuclear receptor NR2E3 regulates ESR1 via direct binding to the ESR1 promoter with concomitant recruitment of PIAS3 to the promoter in breast cancer cells, and is essential for physiological cellular activity of ESR1 in estrogen receptor (ER)‐positive breast cancer cells. Moreover, expression of NR2E3 was significantly associated with recurrence‐free survival and a favourable response to tamoxifen treatment in women with ER‐positive breast cancer. Our results provide mechanistic insights on the regulation of ESR1 by NR2E3 and the clinical relevance of NR2E3 in breast cancer.
Topographic predictors of susceptibility to alluvial fan flooding, Southern Apennines
Authors: Santangelo N. , Daunis‐i‐Estadella J. , Di Crescenzo G. , Di Donato V. , Faillace P. I. , Martín‐Fernández J. A. , Romano P. , Santo A. , Scorpio V.
Published: December 2011

The flooding susceptibility of alluvial fans in the Southern Apennines has long been neglected. To partly address this oversight, we focus on the region of Campania which contains highly urbanized piedmont areas particularly vulnerable to flooding. Our findings are based on stratigraphic analysis of the fans and morphometric analysis of the basin‐fan systems. Using geomorphological analysis we recognized active alluvial fans while stratigraphic analysis together with statistical analysis of the morphometric variables was used to classify the fans in terms of the transport process involved. The results indicate that in the geological context examined, the best discrimination between debris flow (Df) and water flood (Wf) processes is achieved by means of two related variables, one for the basin (feeder channel inclination, Cg) and one for the fan (fan length, Fl). The probability that an unclassified fan belongs to group Wf is computed by applying a logistic function in which a P value exceeding 0.5 indicates that a basin/fan system belongs to group Wf. This important result led to the classification of the entire basin/fan system data. As regards process intensity, debris flow‐dominated fans are susceptible to the occurrence of flows with high viscosity and hence subject to more severe events than water flood‐dominated fans. Bearing this in mind, the data gathered in this study allow us to detect where alluvial fan flooding might occur and give information on the different degrees of susceptibility at a regional scale. Regrettably, urban development in recent decades has failed to take the presence of such alluvial fans into account due to the long recurrence time (50–100 years) between floods. This paper outlines the distribution of such susceptibility scenarios throughout the region, thereby constituting an initial step to implementing alluvial fan flooding control and mitigation. Copyright © 2012 John Wiley & Sons, Ltd.
DDTs in rice frogs (Rana limnocharis) from an agricultural site, South China: Tissue distribution, biomagnification, and potential toxic effects assessment
Authors: Wu Jiang-Ping , Zhang Ying , Luo Xiao-Jun , Chen She-Jun , Mai Bi-Xian
Published: December 2011

Contamination with agricultural pesticides such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD), is among several proposed stressors contributing to the global declines in amphibian populations and species biodiversity. These chemicals were examined in insects and in the muscle, liver, and eggs of rice frogs (Rana limnocharis) from the paddy fields of an agricultural site in South China. The ΣDDT (sum of DDT, DDE, and DDD) concentrations ranged from 154 to 915, 195 to 1,400, and 165 to 1,930 ng/g lipid weight in the muscle, liver, and eggs, respectively. All the DDTs (DDT, DDE, and DDD) showed higher affinity for the liver relative to muscle tissue and can be maternally transferred to eggs in female frogs. The average biomagnification factors for DDTs ranged from 1.6 to 1.9 and 1.5 to 2.9 in female and male frogs, respectively, providing clear evidence of their biomagnification from insects to frogs. Compared with the reported DDT levels demonstrated to have toxic effects on frogs, DDTs in the present frogs are unlikely to constitute an immediate health risk. However, the adverse impacts of high DDT residues in eggs on the hatching success and their potential toxicity to the newly metamorphosed larval frogs should be assessed further. Environ. Toxicol. Chem. 2012;31:705–711. © 2011 SETAC
Implications of the solvent vehicles dimethylformamide and dimethylsulfoxide for establishing transcriptomic endpoints in the zebrafish embryo toxicity test
Authors: Turner Catherine , Sawle Ashley , Fenske Martina , Cossins Andrew
Published: December 2011

Current aquatic chemical testing guidelines recognize that solvents can potentially interfere with the organism or environmental conditions of aquatic ecotoxicity tests and therefore recommend concentration limits for their use. These recommendations are based on evidence of adverse solvent effects in apical level tests. The growing importance of subapical and chronic endpoints in future test strategies, however, suggests that the limits may need reassessment. To address this concern, microarrays were used to determine the effects of organic solvents, dimethylformamide (DMF) and dimethylsulfoxide (DMSO), on the transcriptome of zebrafish (Danio rerio) embryos. Embryos were exposed for 48 h to a range of concentrations between 0.025 and 32.0 ml/L. Effects on survival and development after 24 and 48 h were assessed microscopically, with no effects on mortality or morphology up to 2.0 and 16.0 ml/L for DMF and DMSO. However, analysis of 48-h embryonic RNA revealed large numbers of differentially expressed genes at concentrations well below the 0.1 ml/L solvent limit level. The enrichment of differentially expressed genes was found for metabolic, developmental, and other key biological processes, some of which could be linked to observed morphological effects at higher solvent concentrations. These findings emphasize the need to remove or lower as far as possible the concentrations of solvent carriers in ecotoxicology tests. Environ. Toxicol. Chem. 2012;31:593–604. © 2011 SETAC
The exon‐level biomarker SLC39A14 has organ‐confined cancer‐specificity in colorectal cancer
Authors: Sveen Anita , Bakken Anne Cathrine , Ågesen Trude H. , Lind Guro E. , Nesbakken Arild , Nordgård Oddmund , Brackmann Stephan , Rognum Torleiv O. , Lothe Ragnhild A. , Skotheim Rolf I.
Published: December 2011

An alternative transcript variant of SLC39A14, caused by pre‐mRNA splicing, was recently suggested as a biomarker for colorectal cancer (CRC). In our study, we have validated the cancer‐specific splicing pattern of the mutually exclusive exons 4A and 4B in altogether 244 colorectal tissue samples. Exon‐specific quantitative RT‐PCR analyses across 136 Stage I–IV CRC samples and 44 normal colonic mucosa samples showed complete cancer‐specificity, as well as 94% sensitivity of SLC39A14‐exon4B relative to SLC39A14‐exon4A expression. However, across 20 samples from a range of healthy tissues, 18 expressed the CRC variant. This was true also for ten benign lymph nodes, demonstrating that the cancer‐specificity is mainly confined to the colon and rectum. Hence, clinical use of SLC39A14‐exon4B as a detection marker for CRC other than in samples taken from the bowel wall is diminished. Prognostic value by detection of metastasis to lymph nodes is also abated, elucidating an important pitfall to biomarker discovery. However, analyses of ten nondysplastic biopsies from patients with active inflammatory bowel disease showed negative results in seven samples and only weakly positive results in three samples, suggesting value of SLC39A14‐exon4B as a marker to distinguish CRC from other pathologic conditions of the colon. In conclusion, the SLC39A14‐exon4B transcript variant is a CRC biomarker with high sensitivity and organ‐confined specificity. Further use of the transcript and its encoded protein isoform should be explored in an organ‐confined context.
Sun exposure may increase risk of prostate cancer in the high UV environment of New South Wales, Australia: A case–control study
Authors: Nair‐Shalliker Visalini , Smith David P. , Egger Sam , Hughes Ann Maree , Kaldor John M. , Clements Mark , Kricker Anne , Armstrong Bruce K.
Published: December 2011

Ultraviolet (UV) radiation in sunlight may influence risk of prostate cancer. In New South Wales (NSW), Australia, we examined the relationship between sun exposure at 30 and 50 years of age and risk of prostate cancer in a case–control study combining the NSW prostate cancer care and outcome study (cases) and the NSW non‐Hodgkin's lymphoma study (controls). Prostate cancer risk increased with increasing estimated sun exposure (adjusted OR for highest vs. lowest quartiles of average weekly sun exposure in the warmer months 2.07 95% CI: 1.36–3.15) and this increase was most evident with weekend sun exposure (adjusted OR = 5.55, 95% CI: 2.94–10.48). High sun sensitivity was also positively associated with risk for prostate cancer (adjusted OR = 1.63, 95% CI: 1.09–2.44). The apparent effects of weekly sun exposure did not vary by disease aggressiveness. Our results suggest that increasing sun exposure in mid‐adult years increases prostate cancer risk in a high ambient solar UV environment. Given that previous studies, conducted mainly in low solar UV environments, have generally found evidence of a negative association, our findings suggest there may be a U‐shaped relationship between solar UV exposure and prostate cancer. Further studies are needed to test the hypothesis that high solar UV exposure is a risk factor for prostate cancer and to explore possible mechanisms for such an association.
Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer
Authors: Chung Fu‐Tsai , Lee Kang‐Yun , Wang Chih‐Wei , Heh Chih‐Chen , Chan Yao‐Fei , Chen Huan‐Wu , Kuo Chih‐Hsi , Feng Po‐Hao , Lin Ting‐Yu , Wang Chun‐Hua , Chou Chun‐Liang , Chen Hao‐Cheng , Lin Shu‐Min , Kuo Han‐Pin
Published: December 2011

Our study investigated whether tumor‐associated macrophages (TAMs) in advanced non‐small cell lung cancer (NSCLC) are related to treatment response to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) and may be a predictor of survival. Of 206 advanced NSCLC patients treated (first‐line) with an EGFR‐TKI at the study hospital from 2006 to 2009, 107 with adequate specimens for assessing CD68 immunohistochemistry as a marker of TAMs were assessed. After EGFR‐TKI treatment, response was observed in 55 (51%) patients, and the median follow‐up period was 13.5 months. Most TAMs were located in the tumor stroma (>95%) and positively costained with the M2 marker CD163. TAM counts were significantly higher in patients with progressive disease than in those without (p < 0.0001), a trend that remained in patients with known EGFR mutation status (n = 59) and those with wild‐type EGFR (n = 20). High TAM counts, among other factors (e.g., wild‐type EGFR), were significantly related to poor progression‐free survival (PFS) and overall survival (OS) (all p < 0.0001 for TAMs). Multivariate Cox analyses showed that high TAM counts and EGFR mutations were both independent factors associated with PFS [odds ratio (OR), 8.0; 95% confidence interval (CI), 2.87–22.4; p = 0.0001 and OR, 0.03; 95% CI, 0.003–0.31; p = 0.003, respectively] and OS (OR, 2.641; 95% CI, 1.08–6.5; p = 0.03 and OR, 0.14; 95% CI, 0.03–0.56; p = 0.006, respectively). TAMs are related to treatment response irrespective of EGFR mutation and can independently predict survival in advanced NSCLC treated with an EGFR‐TKI.
Spectroscopic and histological evaluation of wound healing progression following Low Level Laser Therapy (LLLT)
Authors: Prabhu Vijendra , Rao Satish B. S. , Chandra Subhash , Kumar Pramod , Rao Lakshmi , Guddattu Vasudeva , Satyamoorthy Kapaettu , Mahato Krishna K.
Published: December 2011

The present study focuses on the evaluation of the effect of He‐Ne laser on tissue regeneration by monitoring collagen synthesis in wound granulation tissues in Swiss albino mice using analysis of laser induced fluorescence (LIF) and light microscopy techniques. The spectral analyses of the wound granulation tissues have indicated a dose dependent increase in collagen levels during the post‐wounding days. The histological examinations on the other hand have also shown a significant increase in collagen deposition along with the reduced edema, leukocytes, increased granulation tissue, and fibroblast number in the optimal laser dose treated group compared to the non‐illuminated controls. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Upregulation of mTORC2 activation by the selective agonist of EPAC, 8‐CPT‐2Me‐cAMP, in prostate cancer cells: Assembly of a multiprotein signaling complex
Authors: Misra Uma K. , Pizzo Salvatore V.
Published: December 2011

Ligation of cell surface‐associated GRP78 by activated α2‐macroglobulin triggers pro‐proliferative cellular responses. In part, this results from activation of adenylyl cyclase leading to an increase in cAMP. We have previously employed the cAMP analog 8‐CPT‐2Me‐cAMP to probe these responses. Here we show in 1‐LN prostate cancer cells that 8‐CPT‐2Me‐cAMP causes a dose‐dependent increase in Epac1, p‐AktT308, p‐AktS473, but not p‐CREB. By contrast, the PKA activator 6‐Benz‐cAMP caused a dose‐dependent increase in p‐CREB, but not Epac1. We measured mTORC2‐dependent Akt phosphorylation at S473 in immunoprecipitates of mTOR or Rictor from 1‐LN cells. 8‐CPT‐2Me‐cAMP caused a two‐threefold increase in p‐AktS473 and AktS473 kinase activity in Rictor immunoprecipitates. By contrast, there was only a negligible effect on p‐AktT308 in Rictor immunoprecipitates. Silencing Rictor gene expression by RNAi significantly suppressed 8‐CPT‐2Me‐cAMP‐induced phosphorylation of Akt at Ser473. These studies represent the first report that Epac1 mediates mTORC2‐dependent phosphorylation of AktS473. Pretreatment of these cells with the PI 3‐Kinase inhibitor LY294002 significantly suppressed 8‐CPT‐2Me‐cAMP‐dependent p‐AktS473 and p‐AktS473 kinase activities, and both effects were rapamycin insensitive. This treatment caused a two to threefold increase in S6 Kinase and 4EBP1 phosphorylation, indices of mTORC1 activation. Pretreatment of the cells with LY294002 and rapamycin significantly suppressed 8‐CPT‐2Me‐cAMP‐induced phosphorylation of S6 Kinase and 4EBP1. We further demonstrate that in 8‐CPT‐2Me‐cAMP‐treated cells, Epac1 co‐immunoprecipitates with AKAP, Raptor, Rictor, PDE3B, and PDE4D suggesting thereby that during Epac1‐induced activation of mTORC1 and mTORC2, Epac1 may have an additional function as a “scaffold” protein. J. Cell. Biochem. 113: 1488–1500, 2012. © 2011 Wiley Periodicals, Inc.
PA28β regulates cell invasion of gastric cancer via modulating the expression of chloride intracellular channel 1
Authors: Zheng Da‐Li , Huang Qing‐Ling , Zhou Fei , Huang Qiao‐Jia , Lin Jian‐Yin , Lin Xu
Published: December 2011

PA28β is a subunit of proteasome activator PA28. Previous study suggests that PA28β is involved in the invasiveness and metastasis of gastric adenocarcinoma (GA), however, the mechanism is not fully understood. In the present study, we showed that invasive abilities of gastric cancer cells were enhanced when PA28β being down‐regulated, and were inhibited when PA28β being overexpressed. To explore the possible mechanism of PA28β associated elevated invasiveness, the protein profiles of PA28β knock down and parental negative control gastric cancer cells were compared using proteomics approach. The results revealed that there were 43 proteins were differentially expressed, among them, chloride intracellular channel 1 (CLIC1) was significantly up‐regulated and selected for further functional study. Down‐regulation of CLIC1 by RNA interference was able to markedly inhibit cell invasion of PA28β knock down gastric carcinoma cells. In addition, an inverse correlation between PA28β and CLIC1 expressions was also verified in GA tissue samples, suggesting that knockdown of PA28β could enhance tumor invasion and metastasis, at least in part, through up‐regulation of CLIC1. Our results provide novel insight into the mechanisms of PA28β related invasiveness and metastasis of GA, and suggest new alternative approaches for GA treatment. J. Cell. Biochem. 113: 1537–1546, 2012. © 2011 Wiley Periodicals, Inc.
Molecular mechanisms of early growth response protein‐1 (EGR‐1) expression by quercetin in INS‐1 beta‐cells
Authors: Chang Seo‐Yoon , Cho Jae Min , Kim Dong‐Bin , Jang Hyun‐Jong , Ko Seung Hyun , Jo Yang‐Hyeok , Kim Myung‐Jun
Published: December 2011

Early growth response‐1 (EGR‐1), one of immediate early response genes, is involved in diverse cellular response. We recently reported that quercetin increased catalytic subunit of γ‐glutamylcysteine ligase (GCLC) via the interaction of EGR‐1 to GCLC promoter in INS‐1 beta‐cells. Therefore, this study investigated molecular mechanisms of quercetin‐induced EGR‐1 expression in INS‐1 cells. Quercetin significantly induced EGR‐1 protein and its mRNA expressions. This induction of EGR‐1 was completely blocked by pretreatment with a PKA inhibitor, H89 and partially blocked by a p38 inhibitor, SB203580. Additionally, the siRNA‐mediated inhibition of PKAα and p38 resulted in significant reduction of quercetin‐induced EGR‐1 promoter activity. Also, quercetin‐induced EGR‐1 protein expression was significantly decreased in the cells transfected with PKAα siRNA. Study using truncated EGR‐1 promoter constructs showed that serum response element (SRE) sites, not cAMP response element site, were essential for EGR‐1 transcription. However, electrophoretic mobility shift assay showed that quercetin did not affect the band intensity of DNA‐protein complex on SRE site of EGR‐1 promoter. Also, immune‐shift assay using serum response factor (SRF) and phospho‐SRF antibodies showed no difference between control and quercetin‐treated groups. Collectively, quercetin‐induced EGR‐1 expression is largely dependent on PKA and partly on p38 MAPK pathway, and SRE sites of EGR‐1 promoter are involved in quercetin‐induced EGR‐1 transcriptional activity. J. Cell. Biochem. 113: 1559–1568, 2012. © 2011 Wiley Periodicals, Inc.
Oxidative stress due to aluminum exposure induces eryptosis which is prevented by erythropoietin
Authors: Vota Daiana M. , Crisp Renée L. , Nesse Alcira B. , Vittori Daniela C.
Published: December 2011

The widespread use of aluminum (Al) provides easy exposure of humans to the metal and its accumulation remains a potential problem. In vivo and in vitro assays have associated Al overload with anemia. To better understand the mechanisms by which Al affects human erythrocytes, morphological and biochemical changes were analyzed after long‐term treatment using an in vitro model. The appearance of erythrocytes with abnormal shapes suggested metal interaction with cell surface, supported by the fact that high amounts of Al attached to cell membrane. Long‐term incubation of human erythrocytes with Al induced signs of premature erythrocyte death (eryptosis), such as phosphatidylserine externalization, increased intracellular calcium, and band 3 degradation. Signs of oxidative stress, such as significant increase in reactive oxygen species in parallel with decrease in the amount of reduced glutathione, were also observed. These oxidative effects were completely prevented by the antioxidant N‐acetylcysteine. Interestingly, erythrocytes were also protected from the prooxidative action of Al by the presence of erythropoietin (EPO). In conclusion, results provide evidence that chronic Al exposure may lead to biochemical and morphological alterations similar to those shown in eryptosis induced by oxidant compounds in human erythrocytes. The antieryptotic effect of EPO may contribute to enhance the knowledge of its physiological role on erythroid cells. Irrespective of the antioxidant mechanism, this property of EPO, shown in this model of Al exposure, let us suggest potential benefits by EPO treatment of patients with anemia associated to altered redox environment. J. Cell. Biochem. 113: 1581–1589, 2012. © 2011 Wiley Periodicals, Inc.
SNX10 is required for osteoclast formation and resorption activity
Authors: Zhu C.H. , Morse L. R. , Battaglino R. A.
Published: December 2011

RANKL‐stimulation of osteoclast precursors results in up‐regulation of genes involved in the process of differentiation and activation. In this report we describe the expression and functional characterization of Sorting Nexin 10 (snx10). Snx10 belongs to the sorting nexin (SNX) family, a diverse group of proteins with a common feature: the PX domain, which is involved in membrane trafficking and cargo sorting in endosomes. Snx10 is strongly up‐regulated during RANKL‐induced osteoclast differentiation in vitro and expressed in osteoclasts in vivo. qPCR analysis confirmed a significant increase in the expression of snx10 in in vitro‐derived osteoclasts, as well as in femur and calvaria. Immunohistochemical analysis of mouse embryo sections showed expression in long bone, calvariae, and developing teeth. The expression was limited to cells that also expressed TRAP, demonstrating osteoclastic localization. Confocal immunofluorescence and subcellular fractionation analysis revealed Snx10 localization in the nucleus and in the endoplasmic reticulum (ER). To study a possible role for snx10 in osteoclast differentiation and function we silenced snx10 expression and found that snx10 silencing inhibited RANKL‐induced osteoclast formation and osteoclast resorption on hydroxyapatite. Silencing also inhibited TRAP secretion. Taken together, these results confirm that snx10 is expressed in osteoclasts and is required for osteoclast differentiation and activity in vitro. Since inhibition of vesicular trafficking is essential for osteoclast formation and activity and SNX10 is involved in intracellular vesicular trafficking, these studies may identify a new candidate gene involved in the development of human bone diseases including osteoporosis. J. Cell. Biochem. 113: 1608–1615, 2012. © 2011 Wiley Periodicals, Inc.
Evaluation of physiological importance of metallothionein protein expressed by Tetrahymena cadmium metallothionein 1 (TMCd1) gene in Escherichia coli
Authors: Suleman Aliya , Shakoori Abdul Rauf
Published: December 2011

TMCd1 is a cadmium inducible metallothionein (MT) gene. In the present study the TMCd1 gene of a ciliate protozoan has been expressed in E. coli and the function of the expressed TMCd1 protein as a metal‐binding protein has been evaluated. The growth of E. coli cells expressing the GST fused TMCd1 proteins in the presence of cadmium metal clearly demonstrated the role of TMCd1 as a metal‐binding protein. The metal accumulation experiments showed that the bacterial cells expressing the functional TMCd1 protein accumulated 19‐fold more cadmium in contrast to control cells that lacked the TMCd1 protein expression. The results clearly demonstrate a physiological role of full length TMCd1 protein of a ciliate, expressed in E. coli, in cadmium metal sequestration and detoxification. J. Cell. Biochem. 113: 1616–1622, 2012. © 2011 Wiley Periodicals, Inc.
Meta‐analysis of time‐to‐event data: a comparison of two‐stage methods
Authors: Simmonds Mark C. , Tierney Jayne , Bowden Jack , Higgins Julian PT
Published: December 2011

Meta‐analysis is widely used to synthesise results from randomised trials. When the relevant trials collected time‐to‐event data, individual participant data are commonly sought from all trials. Meta‐analyses of time‐to‐event data are typically performed using variants of the log‐rank test, but modern statistical software allows for the use of maximum likelihood methods such as Cox proportional hazards models or interval‐censored logistic regression. In this paper, the different approaches to the analysis of time‐to‐event data are examined and compared with show that log‐rank test approaches are in fact first‐order approximations to the maximum likelihood methods and that some methods assume proportional hazards, whereas others assume proportional odds. A simulation study is performed to compare the different methods, which shows that log‐rank test approaches give biased estimates when the underlying hazard ratio or odds ratio is far from unity. It also shows that proportional hazards methods give biased results when hazards are not proportional, and proportional odds methods give biased results when odds are not proportional. Maximum likelihood models should, therefore, be preferred to log‐rank test based methods for the meta‐analysis of time‐to‐event data and any such meta‐analysis should investigate whether proportional hazards or proportional odds assumptions are valid. Copyright © 2011 John Wiley & Sons, Ltd.
Squalene resources and uses point to the potential of biotechnology
Authors: Naziri Eleni , Mantzouridou Fani , Tsimidou Maria Z.
Published: December 2011

Squalene uses extend from cosmetics to the medical and nutraceutical sectors. International concern for the protection of the deep sea sharks, the major source for this hydrocarbon so far, has engendered research interest in other directions (plant kingdom, microbes). Biotechnology offers an alternative approach with the potential of safety requirements and high‐yield. Saccharomyces cerevisiae appears to be a promising choice for food and nutraceutical applications.
DNA‐Inspired Hierarchical Polymer Design: Electrostatics and Hydrogen Bonding in Concert
Authors: Hemp Sean T. , Long Timothy E.
Published: December 2011

Nucleic acids and proteins, two of nature's biopolymers, assemble into complex structures to achieve desired biological functions and inspire the design of synthetic macromolecules containing a wide variety of noncovalent interactions including electrostatics and hydrogen bonding. Researchers have incorporated DNA nucleobases into a wide variety of synthetic monomers/polymers achieving stimuli‐responsive materials, supramolecular assemblies, and well‐controlled macromolecules. Recently, scientists utilized both electrostatics and complementary hydrogen bonding to orthogonally functionalize a polymer backbone through supramolecular assembly. Diverse macromolecules with noncovalent interactions will create materials with properties necessary for biomedical applications.

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Morphology and Thermal Properties of Compatibilized PA12/PP Blends with Boehmite Alumina Nanofiller Inclusions
Authors: Ogunniran Elijah Soba , Sadiku Rotimi , Sinha Ray Suprakas , Luruli Nyambeni
Published: December 2011

Boehmite alumina nanoparticles are added to PP‐g‐MAH‐compatibilized blends of PA 12 and PP to study the effects of nanoparticle loading in the resulting composites. WAXD and SEM data suggest that the nanoparticles enhanced the coalescence of PP. DSC, DMA, and TGA reveal that the final properties such as crystallization temperature, flexural storage modulus, thermal degradation temperature, etc., improve with increasing nanoparticle loading for blend/based composites. FTIR results show that the nanoparticles interfere with the interfacial activity at 5 wt% nanoparticle loading. All results are compared between the neat polymers and the compatibilized blend and show that despite a slight increase in dispersed‐phase domain size, all other properties improve with the addition of AlO(OH).

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Slowly growing solutions of singular linear functional differential systems
Authors: Pylypenko V. , Ronto A.
Published: December 2011

We obtain new conditions under which a system of linear functional differential equations with singular coefficients has a unique solution possessing a given initial value and satisfying a certain growth restriction.
Critical exponents of a doubly degenerate non‐divergent parabolic equation with interior and boundary sources
Authors: Yin Jingxue , Jin Chunhua
Published: December 2011

This paper is concerned with the following problem

where \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$m\in \mathbb R$\end{document}, p > 1, q1, q2 > 0 and Ω is a bounded domain in \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb R^N$\end{document} with smooth boundary. We will give a rather complete classification of the parameters (m, q1, q2) based on the global existence and blow up features of solutions. In particular, it is shown that there is a threshold mc, such that if m < mc, then there exists a critical Fujita exponent pair (q1, q2) for the nonlinear sources, while if m ≥ mc, such exponent pair does not exist.
Development of Mechanically Tailored Gelatin‐Chondroitin Sulphate Hydrogel Films
Authors: Van Vlierberghe Sandra , Samal Sangram Keshari , Dubruel Peter
Published: December 2011

The aim of the present work was to develop and characterize biohybrid hydrogels containing combinations of gelatin and chondroitin sulphate. Two approaches have been compared. First, physisorption of chondroitin sulphate to gelatin hydrogels was investigated using surface plasmon resonance measurements. Due to the limited interaction between both biopolymers, we developed in a second approach methacrylate‐modified chondroitin sulphate hydrogels as such or in combination with methacrylamide‐modified gelatin. Rheology measurements indicated that following this approach, mechanically stable hydrogel films could be obtained after UV irradiation in the presence of Irgacure 2959 as UV photo‐initiator. When keeping the gelatin concentration and the modification degree constant, an increase in derivatization of the chondroitin sulphate component resulted in a high increase of the storage modulus.
The Influence of Zwitterionic Phospholipid Brushes Grafted via UV‐Initiated or SI‐ATR Polymerization on the Hemocompatibility of Polycarbonateurethane
Authors: Feng Yakai , Yang Dazhi , Behl Marc , Lendlein Andreas , Zhao Haiyang , Guo Jintang
Published: December 2011

Biomimetic phosphorylcholine (PC) groups were introduced onto material surfaces in order to improve the hydrophilicity and in this way the hemocompatibility of polycarbonateurethanes (PCUs). Surface‐initiated atom transfer radical polymerization (SI‐ATRP) of 2‐methacryloyloxyethyl phosphorylcholine (MPC) initiated by irradiation with ultraviolet (UV) light created polymer brushes having PC side groups. Fourier transform infrared (FTIR), X‐ray photoelectron spectroscopy (XPS), scanning electrical microscopy (SEM) and water contact angle were used to characterize the chemical and physical properties of the modified PCU surfaces. The PC‐grafted PCU surfaces showed a significantly higher hydrophilicity as indicated by low water contact angles when compared with original PCU. The in vitro hemocompatibility of the PC‐grafted PCU surfaces was evaluated by platelet adhesion tests. The PCU surfaces modified with phosphorylcholine zwitterionic brushes showed effective resistance for platelet adhesion and high hemocompatibility. These PC‐grafted PCU materials might be potentially applied in blood‐contacting materials or devices due to their good mechanical and hemocompatible properties.
Selective Immobilization of Biomolecules on PTMC Network Surfaces Using Micro Contact Printing
Authors: Teixeira Sandra , González‐Campo Arancha , Cabanas‐Danés Jordi , Huskens Jurriaan , Jonkheijm Pascal , Grijpma Dirk W.
Published: December 2011

Using poly(trimethylene carbonate) (PTMC) network surfaces containing unreacted macromer methacrylate groups, thiol‐functionalized biotin (SH‐undecyl‐biotin) can be bound to the surface. With micro contact printing techniques and making use of the biotin‐streptavidin (SAv) binding system patterned surfaces with biological functionality can be prepared in a very straightforward manner. This method has high potential in numerous biomedical applications.
Functional Polymer Scaffolds for Blood Vessel Tissue Engineering
Authors: Diban Nazely , Stamatialis Dimitrios F.
Published: December 2011

Scaffold pore size plays a critical role in the infiltration of the cells into the structure. For engineered blood vessels, co‐cultures of endothelial (EC) on the lumen, and smooth muscle cells (SMC) on the external surface of tubular scaffolds are performed. The more adequate pore sizes for EC are, in general, smaller than for SMC. In the present work, poly(ε‐caprolactone) (PCL) flat film and hollow fibers are prepared by phase inversion. The influence of polymer and coagulation solution compositions on pore morphology of the films is analysed and the results are applied to obtain, in a one step process, PCL hollow fibers with suitable pore size for both EC and SMC.
Enhanced Collagen Type IV Based Differentiation of Embryonic Stem Cells Towards Flk‐1 Expressing Vascular Progenitors by the Wnt/β‐Catenin Synergist QS11
Authors: Poels Mark W. J. , Golbach Lieke A. , Poot André A. , Feijen Jan , Grijpma Dirk W. , Kruijer Wiebe
Published: December 2011

Mouse embryonic stem (mES) cells when plated onto collagen type IV in the presence of serum‐containing medium differentiate into a mixed cell population that contains low levels of Flk‐1 expressing vascular progenitor cells. When isolated and re‐plated onto collagen type IV, Flk‐1+ cells further differentiate into PECAM1+ endothelial and SMA+ mural cells. However, the low abundance and transient nature by which Flk‐1+ cells are generated during embryonic stem (ES) cell differentiation presents limitations in case large numbers of Flk‐1+ cells or its derivates are to be obtained. To optimize Flk‐1 progenitor induction from undifferentiated mES cells, the effects of QS11, a small organic molecule that synergistically activates canonical Wnt signalling, were investigated. In the presence of QS11 the percentage of Flk‐1+ cells in differentiating cultures of mES cells increases 1.5 fold. Furthermore, QS11 enhances cell proliferation in differentiating mES cells that results in a 2 fold increase in cell numbers when Flk‐1 induction is maximal. The combined effects of QS11 on differentiation and proliferation increase the efficiency by which Flk‐1 progenitors can be generated by approximately 300%, thereby providing a novel tool for vascular progenitor cell production for use in fundamental research and applications such as tissue engineering.
Novel Amphiphilic Mikto‐Arm Star‐Shaped Copolymers for the Preparation of PLA‐Based Nanocarriers
Authors: Cajot Sébastien , Riva Raphaël , Billiet Leen , Du Prez Filip , Alexandre Michaël , Lecomte Philippe , Jérôme Christine
Published: December 2011

Three‐arm (A2B) and four‐arm (A2B2) star‐shaped copolymers based on biocompatible and biodegradable hydrophobic poly(ε‐caprolactone) (PCL) (A arms) and biocompatible and bioeliminable hydrophilic poly(ethylene oxide) (PEO) (B arms) were synthesized by the coupling of an ω‐azide terminated PEO chains with PCL chain bearing one (A2B) or two (A2B2) alkyne functions at the middle of the chain by the copper mediated azide‐alkyne cycloaddition (CuAAC). The amphiphilic behavior of these different stars was confirmed by micellization experiments in water followed by dynamic light scattering and transmission electron microscopy analyses. The efficiency to stabilize PLA nanoparticles was investigated in function of the stars structure.
Preparation and In Vivo Imaging of Lucifer Yellow Tagged Hydrogels
Authors: Möller Lena , Krause Andreas , Bartsch Ivonne , Kirschning Andreas , Witte Frank , Dräger Gerald
Published: December 2011

The synthesis of new Lucifer Yellow labeled hyaluronic acid‐ and alginate hydrogels that are covalently cross‐linked is reported. Biocompatibility and biodegradation of the fluorescent tagged hydrogel is investigated using an in vivo fluorescence imaging system.
Preparation of Three‐Dimensional Scaffolds from Degradable Poly(ether)esterurethane by Thermally‐Induced Phase Separation
Authors: Luetzow Karola , Weigel Thomas , Schossig Michael , Kratz Karl , Lendlein Andreas
Published: December 2011

Highly porous scaffolds with an overall volume up to 30 cm3 and porosities in the range from 80% to 93% were prepared from degradable poly(ether)esterurethane by thermally‐induced phase separation (TIPS) and subsequent solvent sublimation. The variation of the polymer concentration when applying a fixed TIPS cooling protocol led to an adjustment in pore size as well as in pore size distribution. While polymer concentrations of 5, 7.5 and 10 wt% resulted in averaged pore sizes ranging from 70 to 90 µm with a broad pore size distribution (according to µ‐CT analysis) for polymer concentrations of 15 wt% a significant lower averaged pore size of 50 µm with a narrow pore size distribution was obtained.
Synthesis and Characterization of Polyetherimides with 3‐Methoxy‐1,2‐propanediol Moieties
Authors: Lange Maik , Luetzow Karola , Neffe Axel T. , Lendlein Andreas
Published: December 2011

Polyetherimides have been evaluated as non‐toxic and steam‐sterilizable and are therefore potentially suited for biomedical applications. To enable a broader range of potential applications, polyetherimides with lower Tg, higher elasticity at room temperature and better processability are required. Our concept was to explore, whether the incorporation of 3‐methoxy‐1,2‐propanediol moieties in the main chain lead to a reduction of Tg and increase the elastic properties of the polymer compared to commercially available polyetherimides from 4,4′‐(4,4′‐isopropylidenediphenoxy)bis(phthalic anhydride) and 1,3‐diaminobenzene. Two different monomers were synthesized and co‐condensated with each other or using 4,4,4′‐(4,4′‐isopropylidenediphenoxy)bis(phthalic anhydride), respectively. The results proofed the successful synthesis and polymerization leading to polymers with molecular weights up to Mn = 6,400 g/mol. The polymers showed lowered Tg, resistance to heat up to 400 °C, tendencies to reduced contact angles and partially reduced E‐moduli in comparison to the commercial polyetherimide ULTEM 1000.
Synthesis and Characterization of Gelatin Fragments Obtained by Controlled Degradation
Authors: Piluso Susanna , Weigel Thomas , Lendlein Andreas , Neffe Axel T.
Published: December 2011

Telechelic oligomers are attractive starting materials for the preparation of materials with tailorable properties. Here, peptide chains with defined molecular weight were obtained by controlled degradation of gelatin with hydroxylamine, which resulted in the cleavage of asparaginyl‐glycine bonds and formation of new aspartyl hydroxamates and amino endgroups. The reaction of gelatin with hydroxylamine resulted in fragments with molecular weights of 15, 25, 37, and 50 kDa (determined by SDS‐PAGE) independently of the reaction time and conditions. The fragment mixture showed typical single and triple helical organization in WAXS spectra, but rheological studies showed lower G′ and G″ values for gels from the fragment mixture than from gelatin, and lower gel‐sol transitions temperatures. A more narrow distribution was found for the fragment mixture (Mn = 25 kDa, PDI = 1.4) than for commercial gelatin.
Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery
Authors: Capelle Hans‐Holger , Blahak Christian , Schrader Christoph , Baezner Hansjörg , Hariz Marwan I. , Bergenheim Tommy , Krauss Joachim K.
Published: December 2011

Background:

There are no data available concerning whether patients with cervical dystonia who have recurrent or new symptoms after peripheral denervation surgery benefit similarly from pallidal deep brain stimulation compared with patients who receive primarily pallidal stimulation.

Methods:

Data on 7 cervical dystonia patients with recurrent or progressive dystonia after peripheral denervation who underwent pallidal stimulation were prospectively collected. Deep brain stimulation was performed in Mannheim/Hannover, Germany, or in Umea, Sweden. To the subgroup from Mannheim/Hannover, a second group of patients without previous peripheral surgery was matched. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale and the Burke‐Fahn‐Marsden dystonia rating scale, as well as the Tsui scale in the Swedish patients.

Results:

The 4 patients from Mannheim/Hannover experienced sustained improvement from pallidal stimulation by a mean of 57.5% according to the Toronto Western Spasmodic Torticollis Rating Scale (P < .05) and by a mean of 69.5% according to the Burke‐Fahn‐Marsden dystonia rating scale (P < .05) at long‐term follow‐up of 40.5 months. The patients from Umea had a mean Tsui score of 7 prior to surgery and a mean score of 3 at the mean follow‐up of 8 months (62.5%). In the matched group the Toronto Western Spasmodic Torticollis Rating Scale improved by 58.8% and the Burke‐Fahn‐Marsden dystonia rating scale by 67% (P < .05) at long‐term follow‐up (mean, 41.5 months).

Conclusions:

Patients who had prior peripheral surgery for cervical dystonia experience improvement from subsequent pallidal stimulation that is comparable to that of de novo patients. © 2011 Movement Disorder Society