bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bimetallic Complexes of Ytterbium and Europium Stabilized by Sterically Demanding Dipyridylamides
Authors: Dietel Anna M. , Döring Christian , Glatz Germund , Butovskii Mikhail V. , Tok Oleg , Schappacher Falko M. , Pöttgen Rainer , Kempe Rhett 
Published: February 2009

AbstractDeprotonation of Ap*pyH {Ap*pyH = (6‐methylpyridin‐2‐yl)‐[6‐(2,4,6‐triisopropylphenyl)‐pyridin‐2‐yl]‐amine} using KH leads to Ap*pyK which undergoes a clean salt metathesis reaction with [YbI2(thf)4] and [EuI2(thf)4] in THF forming[Yb2(Ap*py)3I(thf)] and [Eu2(Ap*py)3I(thf)], respectively. The two YbII centers in [Yb2(Ap*py)3I(thf)] are in close proximity and chemically different. Thus, an f‐block‐element–f‐block‐element coupling pattern was observed. The low‐field 171Yb signal consists of a central singlet and two satellites with integral intensities of about 7 % each. This 14 % approximately corresponds to the natural abundance of the 171Yb isotope and was assigned as a doublet arising from 1J(171Yb, 171Yb) spin‐spin coupling with a magnitude of 76.1 Hz. The 151Eu Mössbauer spectrum of [Eu2(Ap*py)3I(thf)] recorded at 77 K shows an isomer shift (δ) of –11.9(1) mm/s with an experimental line width (Γ) of 6.9(1) mm/s. This line width is extremely large and results from an overlap of the signals from both crystallographically independent europium sites. The reaction of [Yb2(Ap*py)3I(thf)] with Ap*pyK leads to [Yb2(Ap*py)4(thf)2]. In the reactions of [Yb2(Ap*py)3I(thf)] with azidotrimethylsilane and sulfur the rearrangement products [Yb2(Ap*py)3I2] and [Yb2(Ap*py)3I3] were obtained, respectively. Treating [Yb2(Ap*py)3I(thf)] with NaN(SiMe3)2 afforded homoleptic “ate” complex Na2[Yb(Ap*py)4]. A mixed silylamide dipyridylamide complex was obtained in the reaction of NaYb[N(SiMe3)2]3 with Ap*pyH. All complexes – three of which are paramagnetic – were characterized by X‐ray crystal structure analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Highly Chemoselective Synthesis of 6‐Alkoxy‐1‐alkyl(aryl)‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines and 1‐Alkyl(aryl)‐6‐amino‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines
Authors: Zanatta Nilo , da S. Fernandes Liana , Nachtigall Fabiane M. , Coelho Helena S. , Amaral Simone S. , Flores Alex F. C. , Bonacorso Helio G. , P. Martins Marcos A. 
Published: February 2009

AbstractA simple and highly chemoselective method for the synthesis of a large series of novel 6‐alkoxy‐1‐alkyl(aryl)‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines and 1‐alkyl(aryl)‐6‐amino‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridines, from the reaction of 6‐alkoxy‐3‐trifluoroacetyl‐4,5‐dihydro‐6H‐pyrans with primary alkyl and arylamines, in good yields, is reported. Preliminary in vitro antimicrobial activity of the 1‐alkyl(aryl)‐6‐amino‐3‐trifluoroacetyl‐1,4,5,6‐tetrahydropyridine series was assessed against a variety of microorganisms including yeast‐like fungi, bacteria and algae, and some of these compounds exhibit significant antimicrobial activity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Coupling of Site‐Directed Mutagenesis and Immobilization for the Rational Design of More Efficient Biocatalysts: The Case of Immobilized 3G3K PGA from E.coli
Authors: Serra Immacolata , Cecchini Davide A. , Ubiali Daniela , Manazza Elena M. , Albertini Alessandra M. , Terreni Marco 
Published: February 2009

AbstractWe have investigated the synthetic performance of the immobilized 3G3K mutant of the Penicillin G acylase (PGA) from E. coli obtained by site‐directed mutagenesis. The 3G3K mutant, characterized by a tag consisting of three lysines alternating with three glycines at the end of the β‐chain, has previously been reported to have a higher ratio for the rate of antibiotic synthesis and the rate of hydrolysis of the acylating agent (the vs/vh1 value) than the wild‐type enzyme. New immobilization studies have been carried out with the 3G3K mutant by using different glyoxyl supports (activated with aldehyde groups). The catalytic properties of the new immobilized preparations were tested in the synthesis of Cefamandole and Cefonicid by kinetically controlled N‐acylation (kcNa). Compared with the commercial wild‐type PGA, the 3G3K acylase immobilized on glyoxyl agarose showed higher synthetic performance (reaction rates and yields) in all the tested reactions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Dicarbonylchloro(pentabenzylcyclopentadienyl)ruthenium as Racemization Catalyst in the Dynamic Kinetic Resolution of Secondary Alcohols
Authors: Mavrynsky Denys , Päiviö Mari , Lundell Katri , Sillanpää Reijo , Kanerva Liisa T. , Leino Reko 
Published: February 2009

AbstractDicarbonylchloro(pentabenzylcyclopentadienyl)ruthenium has been prepared and its structure confirmed by X‐ray analysis. This complex shows excellent catalytic activity and modest stability against air in racemization reactions of secondary alcohols. In Candida antarctica lipase B (CAL‐B) catalyzed dynamic kinetic resolution (DKR) of 1‐phenyl‐ and 1‐(furan‐2‐yl)ethanol compounds, the new complex shows improved performance as an alcohol racemization catalyst in comparison with its well‐known pentaphenylcyclopentadienyl analogue, hitherto considered as the leading catalyst candidate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Increased genomic instability and altered chromosomal protein phosphorylation timing in HRAS‐transformed mouse fibroblasts
Authors: Dunn Katherine L. , He Shihua , Wark Landon , Delcuve Geneviève P. , Sun Jian‐Min , Yu Chen Hou , Mai Sabine , Davie James R. 
Published: February 2009

AbstractThe RAS‐mitogen‐activated protein kinase signaling pathway is often deregulated in cancer cells. In metastatic HRAS‐transformed mouse fibroblasts (Ciras‐3), the RAS‐MAPK pathway is constitutively activated. We show here that Ciras‐3 cells exhibit a higher incidence of chromosomal instability than 10T1/2 cells, including higher levels of clonal and nonclonal chromosomal aberrations. Stimulation of serum starved 10T1/2 and Ciras‐3 cells with phorbol esters (TPA) results in the phosphorylation of histone H3 at serine 10 and serine 28. Regardless of the increased genomic instability in Ciras‐3 cells, TPA‐induced H3 phosphorylated at serine 10 and H3 phosphorylated at serine 28 partitioned into distinct nuclear subdomains as they did in the parental cells. However, the timing of the response of the H3 phosphorylation event to TPA induction was delayed in Ciras‐3 cells. Further Ciras‐3 cells, which have a more open chromatin structure, had increased steady state levels of phosphorylated H3 and HMGN1 relative to parental 10T1/2 cells. TPA‐induced H3 phosphorylated at serine 10 and 28 were colocalized with the transcriptionally initiated form of RNA polymerase II in 10T1/2 and Ciras‐3 cells. Chromatin immunoprecipitation assays demonstrated that TPA‐induced H3 phosphorylation at serine 28 was associated with the immediate early JUN promoter, providing direct evidence that this histone post‐translational modification is associated with transcriptionally active genes. Together our results demonstrate the increased genomic instability and alterations in the epigenetic program in HRAS‐transformed cells. © 2009 Wiley‐Liss, Inc.
Replication of genetic associations as pseudoreplication due to shared genealogy
Authors: Rosenberg Noah A. , VanLiere Jenna M. 
Published: February 2009

AbstractThe genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype‐phenotype associations using linkage disequilibrium between marker loci and disease‐susceptibility loci can be considered as “pseudoreplicates” rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence. Genet. Epidemiol. 33:479–487, 2009. © 2009 Wiley‐Liss, Inc.
Theiler's virus infection induces TLR3‐dependent upregulation of TLR2 critical for proinflammatory cytokine production
Authors: So Eui Young , Kim Byung S. 
Published: February 2009

AbstractTheiler's murine encephalomyelitis virus (TMEV) infection directly induces many proinflammatory genes, including type I interferon (IFN) and a variety of cytokine genes. These virus‐induced cytokines are a critical factor in developing TMEV‐induced demyelinating disease. We have previously reported that the major activation signal for the cytokine genes is mediated via TLR3. In this study, we describe that TLR2 is upregulated via TLR3 signal and cooperatively participates in the expression of IL‐6, IL‐1β, CCL2, and CCL5 genes following TMEV infection. The expression of these genes was significantly impaired in both TLR2‐deficient and TLR3‐deficient primary astrocytes. However, the induction of type I IFNs was not affected by TLR2 deficiency in the primary cells. TMEV infection led to TLR2‐mediated NF‐κB activation, but not IRF3 or IRF7 activation, critical for type I IFN production. More importantly, TLR3 was required for TMEV‐induced early TLR2 upregulation in primary astrocytes leading to the production of TLR2‐dependent cytokines such as IL‐6. Interestingly, soluble factor(s) produced via TLR2/3‐dependent signals appears to be partially associated with the downstream cytokine production. These results indicate that TMEV utilizes TLR3‐induced TLR2 to induce inflammatory cytokines, which are critical to the development of immune‐mediated demyelinating disease. © 2009 Wiley‐Liss, Inc.
The association between climate teleconnection indices and Upper Klamath seasonal streamflow: Trans‐Niño Index
Authors: Kennedy Adam M. , Garen David C. , Koch Roy W. 
Published: February 2009

AbstractThis research investigates large‐scale climate features affecting inter‐annual hydrologic variability of streams flowing into Upper Klamath Lake (UKL), Oregon, USA. UKL is an arid, mountainous basin located in the rain shadow east of the crest of the Cascade Mountains in the northwestern United States. Developing accurate statistical models for predicting spring and summer seasonal streamflow volumes for UKL is difficult because the basin has complex hydrology and a high degree of topographic and climatologic variability. In an effort to reduce streamflow forecast uncertainty, six large‐scale climate indices—the Pacific North American Pattern, Southern Oscillation Index, Pacific Decadal Oscillation (PDO), Multivariate El Niño‐Southern Oscillation Index, Niño 3·4, and a revised Trans‐Niño Index (TNI)—were evaluated for their ability to explain inter‐annual variation of the major hydrologic inputs into UKL.The TNI is the only index to show significant correlations during the current warm phase of the PDO. During the warm PDO phase (1978–present), the averaged October through December TNI is strongly correlated with the subsequent April through September streamflow (r = 0·7) and 1 April snow water equivalent (r = 0·6). Regional analysis shows that this climate signal is not limited to UKL but is found throughout the northwestern United States.Incorporating the TNI variable into statistical streamflow prediction models results in standard errors of forecasts issued on the first of February and earlier that are 7–10% smaller than those for the models without the TNI. This, coupled with other enhancements to the statistical models, offers a significant increment of improvement in forecasts used by water managers. Copyright © 2009 John Wiley & Sons, Ltd.
Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age
Authors: Shi Zumin , Johnstone Daniel , Talseth‐Palmer Bente A. , Evans Tiffany‐Jane , Spigelman Allan D. , Groombridge Claire , Milward Elizabeth A. , Olynyk John K. , Suchy Janina , Kurzawski Grzegorz , Lubinski Jan , Scott Rodney J. 
Published: February 2009

AbstractHereditary nonpolyposis colorectal cancer (HNPCC) is characterized by germline mutations in DNA mismatch repair genes; however, variation in disease expression suggests that there are potential modifying factors. Polymorphisms of the HFE gene, which cause the iron overload disorder hereditary haemochromatosis, have been proposed as potential risk factors for the development of colorectal cancer (CRC). To understand the relationship between HNPCC disease phenotype and polymorphisms of the HFE gene, a total of 362 individuals from Australia and Poland with confirmed causative MMR gene mutations were genotyped for the HFE C282Y and H63D polymorphisms. A significantly increased risk of developing CRC was observed for H63D homozygotes when compared with combined wild‐type homozygotes and heterozygotes (hazard ratio = 2.93, p = 0.007). Evidence for earlier CRC onset was also observed in H63D homozygotes with a median age of onset 6 years earlier than wild type or heterozygous participants (44 vs. 50 years of age). This effect was significant by all tests used (log‐rank test p = 0.026, Wilcoxon p = 0.044, Tarone‐Ware p = 0.035). No association was identified for heterozygosity of either polymorphism and limitations on power‐prevented investigation of C282Y homozygosity or compound C282Y/H63D heterozygosity. In the Australian sample only, women had a significantly reduced risk of developing CRC when compared with men (hazard ratio = 0.58, p = 0.012) independent of HFE genotype for either single nucleotide polymorphisms. In conclusion, homozygosity for the HFE H63D polymorphism seems to be a genetic modifier of disease expression in HNPCC. Understanding the mechanisms by which HFE interrelates with colorectal malignancies could lead to reduction of disease risk in HNPCC. © 2009 UICC
Novel antivascular efficacy of metronomic docetaxel therapy in prostate cancer: hnRNP K as a player
Authors: Benelli Roberto , Monteghirfo Stefano , Balbi Cecilia , Barboro Paola , Ferrari Nicoletta 
Published: February 2009

AbstractTumor growth requires a competent vascular supply and angiogenesis is now considered a potential target for cancer treatment. Chemotherapeutic drugs, and docetaxel in particular, chronically administered using a frequent schedule at low dose (metronomic dosing), can cause potent antiangiogenic effects by targeting the endothelial cells of newly growing blood vessels. Because the exposure to cytotoxic drugs could target both endothelial and tumor cells, we investigated the effects of “metronomic docetaxel” on hormone refractory prostate carcinoma cells. In vitro, metronomic therapy lowered tumor cell viability, inducing apoptosis and reducing the invasive potential at 10‐ to100‐fold lower concentrations as compared with the maximum tolerated dose. Metronomic regimens resulted in a significant reduction of vascular endothelial cell growth factor expression and up‐regulation of endogenous angiogenesis inhibitors. Our studies suggest that heterogeneous nuclear ribonucleoprotein K is a mediator of the effects we observed. Targeting heterogeneous nuclear ribonucleoprotein K may serve as a specific antimetastasis and antiangiogenic therapy and could be a potential predictive marker to determine the optimal dose and schedule for metronomic chemotherapy regimens. These findings highlight the multiple effects that may characterize antiangiogenic metronomic chemotherapy and suggest that docetaxel might act as antitumor compound by affecting both cancer and endothelial cells at the same drug concentration. Careful optimization of drug scheduling and dosages will be required to maximize antitumor responses with metronomic approaches. © 2009 UICC
CD133+ and nestin+ tumor‐initiating cells dominate in N29 and N32 experimental gliomas
Authors: Bexell Daniel , Gunnarsson Salina , Siesjö Peter , Bengzon Johan , Darabi Anna 
Published: February 2009

AbstractThe current study was designed to critically evaluate the notion that cancer stem cell (CSC)‐like cells constitute a subpopulation of cells within experimental gliomas. Virtually all cells within the N29 and N32 rat glioma models homogenously expressed CD133, the stem/progenitor marker nestin as well as the neural lineage markers glial fibrillary acidic protein, βIII‐tubulin, and CNPase in vitro. The phenotype was largely retained on exposure to conditions promoting differentiation in vitro and after intracranial implantation of tumor cells into syngeneic hosts. Unsorted adherently grown cells displayed very high clonogenicity in vitro and robust tumorigenicity in vivo. Single N29 and N32 tumor cells invariably formed clones in vitro, and intracerebral inoculation of as few as 10 adherently growing N29 and N32 tumor cells, respectively, gave rise to a tumor. These results provide an alternative view on CSC‐like cells in glioma models: sphere‐formation is not a prerequisite for accumulation of tumorigenic cells, and CSC‐like cells do not reside within a rare subpopulation of cells in these glioma models. N29 and N32 gliomas may accordingly be used for the development of treatment strategies directed specifically against a practically pure population of brain tumor‐initiating CSC‐like cells. © 2009 UICC
Effects of interferon alpha treatment on recurrence and survival after complete resection or ablation of hepatocellular carcinoma: A meta‐analysis of randomized controlled trials
Authors: Zhang Chuan‐Hai , Xu Ge‐Liang , Jia Wei‐Dong , Ge Yong‐Sheng 
Published: February 2009

AbstractAvailable literature on the benefit of interferon alpha (IFN‐α) as adjuvant postsurgical or ablative treatment of hepatocellular carcinoma reports discordant results. By meta‐analysis of the available data, we evaluated the effects of IFN‐α on recurrence and survival after complete resection or ablation of hepatocellular carcinoma. All randomized controlled trials comparing IFN‐α with placebo or no treatment after tumor resection or ablation were selected. Finally, 6 studies published in 2001 or later with a total of 600 patients were included in this meta‐analysis. Data on postsurgical or ablative early recurrence and 1 year survival of hepatocellular carcinoma in IFN‐α treated and untreated patients were extracted from each study. Proportions were combined, and the odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Analysis results show that IFN‐α significantly decreased postsurgical or ablative overall early recurrence (OR = 0.62; 95% CI = 0.42–0.93; p = 0.02) and improved overall 1 year survival (OR = 3.14; 95% CI = 1.79–5.52; p < 0.0001). Subgroup analyses show that IFN‐α decreased postsurgical early recurrence (OR = 0.58; 95% CI = 0.37–0.91; p = 0.02) and improved 1 year survival (OR = 3.19; 95% CI = 1.80–5.67; p < 0.0001) evidently. Subgroup analyses also show that IFN‐α reduced early recurrence after resection without pre‐resection ablation therapy (OR = 0.58; 95% CI = 0.37–0.91; p = 0.02) and improved 1 year survival (OR = 3.83; 95% CI = 2.01–7.27; p < 0.0001). These results suggest that IFN‐α treatment could significantly decrease early recurrence and improve 1 year survival of patients with hepatocellular carcinoma after complete resection or ablation. The use of IFN‐α as adjuvant postsurgical or ablative treatment seems promising but requires further study. © 2009 UICC
BAMBI gene is epigenetically silenced in subset of high‐grade bladder cancer
Authors: Khin Sann Sanda , Kitazawa Riko , Win Ne , Aye Than Than , Mori Kiyoshi , Kondo Takeshi , Kitazawa Sohei 
Published: February 2009

AbstractThe bone morphogenetic protein (BMP) and activin membrane‐bound inhibitor (BAMBI) is a transmembrane TGFRI/BMPRI‐related pseudoreceptor, antagonizes transforming growth factor (TGF)‐β/BMP signaling by inhibiting the formation of functional authentic receptor complexes (TGFRI/BMPRI and TGFRII/BMPRII). On the assumption that BAMBI gene expression is epigenetically altered during human bladder cancer progression, we screened the expression of BAMBI protein by immunohistochemistry and the methylation status of the BAMBI promoter. In the normal or reactive urothelium, BAMBI expression was mostly overlapped with that of BMPRI, and a similar colocalization pattern was noted in low‐grade papillary cancers. In high‐grade and invasive cancers, however, mainly two reciprocal immunohistochemical expression patterns were observed: BAMBI‐low/BMPRI‐high, and BAMBI‐high/BMPRI‐low, indicating that BAMBI expression is controlled such that it does not interfere with the responsiveness of high‐grade cancer cells to TGF‐β/BMP signaling. Moreover, methylation of the BAMBI gene correlated significantly with negative BAMBI expression in bladder tumors. Although BAMBI overexpression significantly increased the number of apoptotic cells in T24 line, knock‐down small interfering RNA showed no remarkable change. Cell motility assay revealed that on treatment with either TGF‐β1 or BMP2, T24 and HTB9 lines showed a marked increase in the number of migrated cells which, however, decreased significantly through the forced expression of BAMBI. Since certain subsets of aggressive tumors often promote cell motility, invasion and survival by inducing epithelial‐to‐mesenchymal transition through TGF‐β/BMP in an autocrine and paracrine manner, hypermethylation of the BAMBI gene promoter that leads to BAMBI gene suppression may be one of the epigenetic events affecting the invasiveness or aggressiveness of bladder cancers. © 2009 UICC
Molecular variants of HPV‐16 associated with cervical cancer in Indian population
Authors: Pillai M.R. , Hariharan R. , Babu Janki Mohan , Lakshmi S. , Chiplunkar S.V. , Patkar M. , Tongaonkar H. , Dinshaw K. , Jayshree R.S. , Reddy B.K.M. , Siddiqui M. , Roychoudury Soma , Saha Baisakhi , Abraham P. , Gnanamony M. , Peedicayil A. , Subhashini J. , Ram T.S. , Dey Bindu , Sharma C. , Jain S.K. , Singh N. 
Published: February 2009

AbstractHuman papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV‐16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV‐16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78Y (12.1%). Twenty‐nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development of HPV diagnostics, vaccine, and for therapeutic purpose. © 2009 UICC