bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Evaluation of an Intercalator–Polyamide Hairpin Designed to Target the Inverted CCAAT Box 2 in the Topoisomerase IIα Promoter
Authors: Flores Lloyd V. , Staples Andrew M. , Mackay Hilary , Howard Cameron M. , Uthe Peter B. , Sexton Jim S. , Buchmueller Karen L. , Wilson W. David , O'Hare Caroline , Kluza Jerome , Hochhauser Daniel , Hartley John A. , Lee Moses 
Published: September 2006

AbstractThe synthesis and DNA‐binding properties of a novel naphthalimide–polyamide hairpin (3) designed to target the inverted CCAAT box 2 (ICB2) site on the topoisomerase IIα (topoIIα) promoter are described. The polyamide component of 3 was derived from the minor‐groove binder, 2, and tailored to bind to the 5′‐TTGGT sequence found in and flanking ICB2. The propensity of mitonafide 4 to intercalate between G–C base pairs was exploited by the incorporation of a naphthalimide moiety at the N terminus of 2. Hybrid 3 targeted 5′‐CGATTGGT and covered eight contiguous base pairs, which included the underlined ICB2 site. DNase I footprinting analysis with the topoIIα promoter sequence demonstrated that 3 bound selectively to the ICB2 and ICB3 sites. Thermal‐denaturation studies confirmed these results, and the highest degree of stabilization was found for ICB2 and ‐3 in preference to ICB1 (4.1, 4.6, and 0.6 °C, respectively). CD studies confirmed minor‐groove binding and suggested a 1:1 binding stoichiometry. Emission‐titration experiments established intercalative binding. Surface plasmon resonance results showed strong binding to ICB2 (2.5×107 M−1) with no observable binding to ICB1. Furthermore, the binding constant of 3 to ICB2 was larger than that of the parent polyamide 2. The increased binding affinity was primarily due to a reduction in the dissociation‐rate constant of the polyamide–DNA complex, which can be attributed to the N‐terminal naphthalimide moiety. In addition, the binding site of 3 was larger than that of 2, which innately improved sequence selectivity. We conclude that the polyamide–naphthalimide 3 selectively binds to the ICB2 site by simultaneous intercalation and minor‐groove binding, and warrants further investigation as a model compound for the regulation of topoIIα gene expression.
Molecular Basis for the Enhanced Lipase‐Catalyzed N‐Acylation of 1‐Phenylethanamine with Methoxyacetate
Authors: Cammenberg Maria , Hult Karl , Park Seongsoon 
Published: September 2006

AbstractOne of the commercial methods for preparing enantiopure amines is lipase‐catalyzed kinetic resolution, although lipases catalyze aminolysis with only low activity. Interestingly, in 1997 Balkenhohl et al. used ethyl methoxyacetate instead of ethyl butyrate as an acylation reagent for the aminolysis of 1‐phenylethanamine and increased the reaction rate more than a 100‐fold. This method has been applied to other aminolysis reactions, but the molecular basis for the enhanced rate is not understood. A molecular‐modeling study of the transition‐state analogue for the aminolysis showed that an interaction between the β‐oxygen atom in methoxyacetate and the amine nitrogen atom might be a key factor in the rate enhancement. Other acylation reagents, such as methyl 3‐methoxypropionate and methyl 4‐methoxybutyrate, were chosen to test the influence of this interaction because these molecules can be spatially arranged to have similar interactions. The results were similar to that in the acylation with methoxyacetate. The initial aminolysis rates were improved (11‐fold and sixfold, respectively) compared to that with butyrate. In contrast, alcoholysis with 1‐phenylethanol afforded the same rate with all acyl donors.
Shape‐Controlled Synthesis of Zinc Oxide: A Simple Method for the Preparation of Metal Oxide Nanocrystals in Non‐aqueous Medium
Authors: Zhang Zhihua , Lu Meihua , Xu Hairuo , Chin Wee‐Shong 
Published: September 2006

AbstractA general and facile approach has been developed to prepare various metal oxide nanocrystals from commercially available metal acetate precursors using an amine‐mediated reaction. The influence of temperature and capping agents on the yield and final morphology of the metal oxides nanocrystals was investigated. The approach was applied in the synthesis of shape‐controlled ZnO nanocrystals. ZnO nanowires, nanorods, bullets and triangular nanocrystals were successfully prepared by tuning the molar ratio between amine to zinc acetate precursor. On the basis of FTIR and NMR spectroscopic studies, we propose that the amine could mediate the breakdown of the metal acetates through a nucleophilic attack mechanism. The results suggest that amine can play dual role as both the attacking agent and capping agent in this new methodology.
Mössbauer Investigation of the Photoexcited Spin States and Crystal Structure Analysis of the Spin‐Crossover Dinuclear Complex [{Fe(bt)(NCS)2}2bpym] (bt=2,2′‐Bithiazoline, bpym=2,2′‐Bipyrimidine)
Authors: Gaspar Ana B. , Ksenofontov Vadim , Reiman Sergey , Gütlich Philipp , Thompson Amber L. , Goeta Andrés E. , Muñoz M. Carmen , Real José A. 
Published: September 2006

AbstractThe crystal structure of the complex [{Fe(bt)(NCS)2}2bpym] (1) (bt=2,2′‐bithiazoline, bpym=2,2′‐bipyrimidine) has been solved at 293, 240, 175 and 30 K. At all four temperatures the crystal remains in the P$\bar 1$ space group with a=8.7601(17), b=9.450(2), c=12.089(3) Å, α=72.77(2), β=79.150(19), γ=66.392(18)°, V=873.1(4) Å3 (data for 293 K structure). The structure consists of centrosymmetric dinuclear units in which each iron(II) atom is coordinated by two NCS− ions in the cis position and two nitrogen atoms of the bridging bpym ligand, with the remaining positions occupied by the peripheral bt ligand. The iron atom is in a severely distorted octahedral FeN6 environment. The average FeN bond length of 2.15(9) Å indicates that compound 1 is in the high‐spin state (HS–HS) at 293 K. Crystal structure determinations at 240, 175 and 30 K gave a cell comparable to that seen at 293 K, but reduced in volume. At 30 K, the average FeN distance is 1.958(4) Å, showing that the structure is clearly low spin (LS–LS). At 175 K the average FeN bond length of 2.052(11) Å suggests that there is an intermediate phase. Mössbauer investigations of the light‐induced excited spin state trapping (LIESST) effect (λ=514 nm, 25 mW cm−2) in 1 (4.2 K, Hext=50 kOe) show that the excited spin states correspond to the HS–HS and HS–LS pairs. The dynamics of the relaxation of the photoexcited states studied at 4.2 K and Hext=50 kOe demonstrate that HS–HS pairs revert with time to both HS–LS and LS–LS configurations. The HS–LS photoexcited pairs relax with time back to the ground LS–LS configuration. Complex [{Fe0.15Zn0.85(bt)(NCS)2}2bpym] (2) exhibits a continuous spin transition centred around 158 K in contrast to the two‐step transition observed for 1. The different spin‐crossover behaviour observed for 2 is due to the decrease of cooperativity (intermolecular interactions) imposed by the matrix of ZnII ions. This clearly demonstrates the role of the intermolecular interactions in the stabilization of the HS–LS intermediate state in 1.
Chiral Oxazolopiperidone Lactams: Versatile Intermediates for the Enantioselective Synthesis of Piperidine‐Containing Natural Products
Authors: Escolano Carmen , Amat Mercedes , Bosch Joan 
Published: September 2006

AbstractPhenylglycinol‐derived oxazolopiperidone lactams are exceptionally versatile building blocks for the enantioselective construction of structurally diverse piperidine‐containing natural products and bioactive compounds. These lactams are readily available in both enantiomeric series by cyclocondensation of the chiral amino alcohol with a δ‐oxo acid derivative and allow the substituents to be introduced at the different ring positions in a regio‐ and stereocontrolled manner, providing access to enantiopure polysubstituted piperidines bearing virtually any type of substitution pattern, and also quinolizidines, indolizidines, perhydroquinolines, hydroisoquinolines, as well as complex indole alkaloids. Of particular interest are cyclocondensation reactions with racemic or prochiral δ‐oxo (di)acid derivatives in processes involving dynamic kinetic resolution and/or differentiation of enantiotopic or diastereotopic ester groups, as they directly lead to lactams that already incorporate the carbon substituents on the heterocyclic ring. The use of (S)‐3,4‐dimethoxyphenylalaninol or (S)‐tryptophanol in the above cyclocondensation reactions expands the potential and the scope of the methodology, providing a straightforward route to enantiopure benzo[a]‐ and indolo[2,3‐a]quinolizidines.
Highly Regioselective Rhodium‐Catalysed Hydroformylation of Unsaturated Esters: The First Practical Method for Quaternary Selective Carbonylation
Authors: Clarke Matthew L. , Roff Geoffrey J. 
Published: September 2006

AbstractHighly regioselective hydroformylation of unsaturated esters can be achieved when a highly reactive, ligand‐modified, rhodium catalyst is employed near ambient temperatures (15–50 °C) and pressures over 30 bar. The use of 1,3,5,7‐tetramethyl‐2,4,8‐trioxa‐6‐phosphaadamantane shows distinct advantages over other commonly applied phosphanes in terms of reaction rate, and regio‐ and chemoselectivity. Hydroformylation of a range 1,1‐di‐ and 1,1,2‐trisubstituted unsaturated esters yields quaternary aldehydes that are forbidden products according to Keulemans Rule. The aldehydes can be reductively aminated with molecular hydrogen to give β‐amino acid esters in high yield. The overall green chemical process involves converting terminal alkynes into unusual β‐amino acid esters with only water generated as an essential byproduct. This catalytic system has also been applied to the hydroformylation of simple 1,2‐disubstitued unsaturated esters, which have been hydroformylated with excellent α‐selectivity and good chemoselectivity for the first time.
An Efficient Access to Novel Enantiomerically Pure Steroidal δ‐Amino Acids
Authors: Sünnemann Hans Wolf , Hofmeister Anja , Magull Jörg , de Meijere Armin 
Published: September 2006

AbstractA highly chemoselective sequence of Stille and Heck couplings on the heterocyclic bromoenol triflates 2 a–c with the bicycloalkenylstannanes cis‐3 and trans‐3 furnished the intermediate bromobutadienes 4 a–c in good yields ranging from 73–94 %. A modified Heck coupling protocol employing the palladacycle 8 and an additional bidentate ligand such as 1,4‐bis(diphenylphosphinyl)butane allowed a significant reduction in catalyst loading while still obtaining the heterocyclic 1,3,5‐hexatrienes 5 a–c in good yields (71–94 %). The unsymmetrically substituted 1,3,5‐hexatrienes 5 a–c in solution underwent 6π‐electrocyclizations following an optimized microwave‐heating protocol to yield the steroidal tetracycles cis‐7 a–c and trans‐7 b (59–69 %). Tetracycles cis‐7 a–c are the products of a subsequent 1,5‐hydrogen shift to the thermodynamically more stable, more highly substituted diene units. Removal of the tert‐butyl groups provided the novel steroidal δ‐amino acid 9 a and the δ‐amino acid derivatives 9 b, c in good yields (76–86 %).
In utero exposure to diethylstilbestrol (DES) does not increase genomic instability in normal or neoplastic breast epithelium
Authors: Larson Pamela S. , Ungarelli Rosemarie A. , de las Morenas Antonio , Cupples L. Adrienne , Rowlings Kathleen , Palmer Julie R. , Rosenberg Carol L. 
Published: September 2006

AbstractBACKGROUND.In 1992, the National Cancer Institute (NCI) established the Continuation of Follow‐Up of DES‐Exposed Cohorts to study the long‐term health effects of exposure to diethylstilbestrol (DES). Genetic effects on human breast tissue have not been examined. The authors investigated whether breast tissue of women exposed in utero to DES might exhibit the genetic abnormalities that characterize other DES‐associated tumors.METHODS.Subjects enrolled in the NCI Cohort were queried about breast biopsies or breast cancer diagnoses. Available tissue blocks were obtained for invasive cancers (IC), in situ cancers (CIS), or atypical hyperplasia (AH). Exposure status was blinded, lesions were microdissected, and their DNA was analyzed for microsatellite instability (MI) and loss of heterozygosity (LOH), or allele imbalance (AI), at 20 markers on 9 chromosome arms.RESULTS.From 31 subjects (22 exposed, 9 unexposed), 273 samples were analyzed (167 normal epithelium, 16 AH, 30 CIS, 60 IC). Exposed and unexposed subjects exhibited no differences in breast cancer risk factors or demographic characteristics, except for age at diagnosis (exposed vs. unexposed: 43.2 vs. 48.8 years of age, P = .02). The authors found that MI was rare and that AI was common, with frequencies consistent with previous reports. The global age‐adjusted relative rate (RR) of AI was 1.3, 95% CI = 0.8–2.4. No statistically significant associations were observed after adjustment for risk factors or after stratification by histology or by chromosome arm.CONCLUSIONS.In utero DES exposure does not appear to significantly increase genomic instability in breast epithelium, as measured by MI and AI. Breast tissue may respond differently from that of the reproductive tract to in utero DES exposure. Consequences of in utero DES exposure on the breast may be mediated by proliferative effects of estrogen. Cancer 2006. © 2006 American Cancer Society.
Extrapulmonary small cell cancer
Authors: Haider Kamal , Shahid Rabia K. , Finch Daygen , Sami Amer , Ahmad Imran , Yadav Sunil , Alvi Riaz , Popkin David , Ahmed Shahid 
Published: September 2006

AbstractBACKGROUND.The objective of this study was to determine variables that correlate with the survival of patients with extrapulmonary small cell carcinoma (EPSCC).METHODS.Medical records of 101 eligible patients with EPSCC who were diagnosed in Saskatchewan from 1971 to 2002 were reviewed. Survival was calculated by using the Kaplan–Meier method. A logistic regression analysis with a backward elimination was carried out to determine prognostic variables that predicted mortality.RESULTS.The median patient age was 72 years (range, 24–100 years), and the male‐to‐female ratio was 1.4:1. The primary disease sites were as follows: breast, 9%; gastrointestinal, 20%; genitourinary, 18%; gynecologic, 11%; head and neck, 10%; thymus, 2%; and unknown primary site, 31%. Fifty‐one patients had limited disease (LD), and 50 patients had extensive disease (ED). Patients with LD had a median overall survival of 34 months (range, 0.2–276 months) compared with 2 months (range, 0.1–108 months) in patients with ED (P < .0001). Among different primary sites, patients with gynecologic small cell cancer (SCC) had a median survival of 54.4 months, whereas patients with SCC of an unknown primary site had a survival of 2.5 months. Among various variables that were examined with respect to their prognostic importance, an abnormal white blood cell count (odds ratio [OR], 6.9; 95% confidence interval [95% CI], 3.4–14.1), an Eastern Cooperative Oncology Group performance status >2 (OR, 4.5; 95% CI, 2.1–9.9), and ED (OR, 2.7; 95% CI, 1.4–5.0) were found to be correlated significantly with mortality.CONCLUSIONS.The gastrointestinal and genitourinary tracts were the 2 major sites involved by EPSCC in the current series. Survival varied according to the primary sites, and patients with gynecologic tumors had the best prognosis. An abnormal white blood cell count, a poor performance status, and disease extent were important factors in predicting survival. Cancer 2006. © 2006 American Cancer Society.
Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma
Authors: Brown Elizabeth E. , Whitby Denise , Vitale Francesco , Marshall Vickie , Mbisa Georgina , Gamache Christine , Lauria Carmela , Alberg Anthony J. , Serraino Diego , Cordiali‐Fei Paola , Messina Angelo , Goedert James J. 
Published: September 2006

AbstractBACKGROUNDClassic Kaposi sarcoma (CKS) is an inflammatory‐mediated neoplasm that develops in the presence of KS‐associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age‐matched and sex‐matched KSHV‐seropositive controls without human immunodeficiency virus‐1 infection and markers of viral control, blood counts, CD4‐positive and CD8‐positive lymphocytes, and serum β‐2‐microglobulin and neopterin levels.METHODSViral loads were detected using real‐time amplification of the KSHV‐K6 and EBV‐pol genes, anti‐K8.1 (lytic) titers were detected by enzyme‐linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression adjusted for sex, age, and study site.RESULTSPeripheral blood mononuclear cells (PBMC) KSHV DNA detection (P ≤ .0001) and high KSHV lytic (>1:1745; P ≤ .0001) and latent (>1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P ≤.05). The detection of Epstein‐Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (<37.4%; P = .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/μL; P = .004), including CD4‐positive (+) cells (<457 cells/μL; P = .07) and CD8+ cells (<213cells/μL; P = .04), and with increased monocytes (≥638 cells/μL; P = .009). Nonsignificant elevations of β‐2‐microglobulin and neopterin were observed among cases regardless of disease burden (P ≥ .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95% CI, 1.4–5.3), a high KSHV lytic antibody titer (OR of 3.7; 95% CI, 1.9–7.4), and low lymphocytes, particularly among those patients age <70 years (OR of 8.0; 95% CI, 2.7–23.7).CONCLUSIONSThe findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS. Cancer 2006. Published 2006 by the American Cancer Society.
Characterization of neuropeptide Y2 receptor protein expression in the mouse brain. I. Distribution in cell bodies and nerve terminals
Authors: Stanić Davor , Brumovsky Pablo , Fetissov Sergueï , Shuster Sam , Herzog Herbert , Hökfelt Tomas 
Published: September 2006

AbstractNeuropeptide Y (NPY), a 36‐amino‐acid peptide, mediates biological effects by activating Y1, Y2, Y5, and y6 receptors. NPY neurons innervate many brain regions, including the hypothalamus, where NPY is involved in regulation of a broad range of homeostatic functions. We examined, by immunohistochemistry with tyramide signal amplification, the expression of the NPY Y2 receptor (Y2R) in the mouse brain with a newly developed rabbit polyclonal antibody. Y2R immunoreactivity was specific with its absence in Y2R knockout (KO) mice and in adjacent sections following preadsorption with the immunogenic peptide (10−5M). Y2R‐positive processes were located in many brain regions, including the olfactory bulb, some cortical areas, septum, basal forebrain, nucleus accumbens, amygdala, hippocampus, hypothalamus, substantia nigra compacta, locus coeruleus, and solitary tract nucleus. However, colchicine treatment was needed to detect Y2R‐like immunoreactivity in cell bodies in many, but not all, areas. The densest distributions of cell bodies were located in the septum basal forebrain, including the bed nucleus, and amygdala, with lower density in the anterior olfactory nucleus, nucleus accumbens, caudal striatum, CA1, CA2, and CA3 hippocampal fields, preoptic nuclei lateral hypothalamus, and A13 DA cells. The widespread distribution of Y2R‐positive cell bodies and fibers suggests that NPY signaling through the Y2R is common in the mouse brain. Localization of the Y2R suggests that it is mostly presynaptic, a view supported by its frequent absence in cell bodies in the normal mouse and its dramatic increase in cell bodies of colchicine‐treated mice. J. Comp. Neurol. 499:357–390, 2006. © 2006 Wiley‐Liss, Inc.
Comparative mapping of serotonin‐immunoreactive neurons in the central nervous systems of nudibranch molluscs
Authors: Newcomb James M. , Fickbohm David J. , Katz Paul S. 
Published: September 2006

AbstractThe serotonergic systems in nudibranch molluscs were compared by mapping the locations of serotonin‐immunoreactive (5‐HT‐ir) neurons in 11 species representing all four suborders of the nudibranch clade: Dendronotoidea (Tritonia diomedea, Tochuina tetraquetra, Dendronotus iris, Dendronotus frondosus, and Melibe leonina), Aeolidoidea (Hermissenda crassicornis and Flabellina trophina), Arminoidea (Dirona albolineata, Janolus fuscus, and Armina californica), and Doridoidea (Triopha catalinae). A nomenclature is proposed to standardize reports of cell location in species with differing brain morphologies. Certain patterns of 5‐HT immunoreactivity were found to be consistent for all species, such as the presence of 5‐HT‐ir neurons in the pedal and cerebral ganglia. Also, particular clusters of 5‐HT‐ir neurons in the anterior and posterior regions of the dorsal surface of the cerebral ganglion were always present. However, there were interspecies differences in the number of 5‐HT‐ir neurons in each cluster, and some clusters even exhibited strong intraspecies variability that was only weakly correlated with brain size. Phylogenetic analysis suggests that the presence of particular classes of 5‐HT‐ir neurons exhibits a great deal of homoplasy. The conserved features of the nudibranch serotonergic system presumably represent the shared ancestral structure, whereas the derived characters suggest substantial independent evolutionary changes in the number and presence of serotonergic neurons. Although a number of studies have demonstrated phylogenetic variability of peptidergic systems, this study suggests that serotonergic systems may also exhibit a high degree of homoplasy in some groups of organisms. J. Comp. Neurol. 499:485–505, 2006. © 2006 Wiley‐Liss, Inc.
Electrical coupling, receptive fields, and relative rod/cone inputs of horizontal cells in the tiger salamander retina
Authors: Zhang Ai‐Jun , Zhang Jian , Wu Samuel M. 
Published: September 2006

AbstractLight responses, dendritic/axonal morphology, receptive field diameters, patterns of dye coupling, and relative rod/cone inputs of various types of horizontal cells (HCs) were studied using intracellular recording and Lucifer yellow/neurobiotin dye injection methods in the flatmount tiger salamander retina. Three physiologically and morphologically distinct types of HC entities were identified. 1) The A‐type HCs are somas that do not bear axons, with average (±SE) soma diameters of 20.01 ± 0.59 μm, relatively sparse and thick dendrites, and they resemble the A‐type HC in mammals. The average receptive field diameter of these cells is 529.6 ± 10.87 μm and they receive inputs predominantly from cones. 2) The B‐type HCs are broad‐field somas that bear thin and long axons, with average soma diameters of 17.67 ± 0.38 μm, thinner dendrites of higher density, and they resemble the B‐type HC in mammals. The average receptive field diameter of these cells is 1,633.55 ± 37.34 μm and they receive mixed inputs from rods and cones. 3) The B‐type HC axon terminals are broad‐field, coarse axon terminal processes and they resemble the B‐type HC axon terminal in rabbits. The average receptive field diameter of these axon terminals is 1,291.67 ± 24.02 μm and they receive mixed inputs from rods and cones. All these types of HC are dye‐coupled with adjacent HCs of the same type. Additionally, B‐type HCs and axon terminals are dye‐coupled with subpopulations of bipolar cells whose axon terminals ramify in the proximal half of the inner plexiform layer, raising the possibility that these HCs may send feedforward antagonistic surround responses to depolarizing bipolar cells through electrical synapses. J. Comp. Neurol. 499:422–431, 2006. © 2006 Wiley‐Liss, Inc.