bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental analysis of activin‐like kinase receptor‐4 (ALK4) expression in Xenopus laevis
Authors: Chen Yumei , Whitaker Lisha L. , Ramsdell Ann F. 
Published: December 2004

AbstractThe type I transforming growth factor‐beta (TGFβ) receptor, activin‐like kinase‐4 (ALK4), is an important regulator of vertebrate development, with roles in mesoderm induction, primitive streak formation, gastrulation, dorsoanterior patterning, and left–right axis determination. To complement previous ALK4 functional studies, we have analyzed ALK4 expression in embryos of the frog, Xenopus laevis. Results obtained with reverse transcriptase‐polymerase chain reaction indicate that ALK4 is present in both the animal and vegetal poles of blastula stage embryos and that expression levels are relatively constant amongst embryos examined at blastula, gastrula, neurula, and early tail bud stages. However, the tissue distribution of ALK4 mRNA, as assessed by whole‐mount in situ hybridization, was found to change over this range of developmental stages. In the blastula stage embryo, ALK4 is detected in cells of the animal pole and the marginal zone. During gastrulation, ALK4 is detected in the outer ectoderm, involuting mesoderm, blastocoele roof, dorsal lip, and to a lesser extent, in the endoderm. At the onset of neurulation, ALK4 expression is prominent in the dorsoanterior region of the developing head, the paraxial mesoderm, and midline structures, including the prechordal plate and neural folds. Expression in older neurula stage embryos resolves to the developing brain, somites, notochord, and neural crest; thereafter, additional sites of ALK4 expression in tail bud stage embryos include the spinal cord, otic placode, developing eye, lateral plate mesoderm, branchial arches, and the bilateral heart fields. Together, these results not only reflect the multiple developmental roles that have been proposed for this TGFβ receptor but also define spatiotemporal windows in which ALK4 may function to modulate fundamental embryological events. Developmental Dynamics 232:393–398, 2005. © 2004 Wiley‐Liss, Inc.
Expression of doublecortin (DCX) and doublecortin‐like kinase (DCLK) within the developing chick brain
Authors: Capes‐Davis Amanda , Tolhurst Ornella , Dunn Joanne M. , Jeffrey Peter L. 
Published: December 2004

AbstractDoublecortin (DCX) is a microtubule‐associated protein widely expressed in the developing mammalian nervous system and important for neuronal migration. DCX is known to belong to a novel protein family defined by sequence homology and the presence of a conserved microtubule‐binding domain, but the functions of other members of this family are still undefined. In this study, we describe the cloning of the chick ortholog of doublecortin‐like kinase (DCLK), a member of this family, and assess the expression of DCX and DCLK in the layered regions of the developing chick brain. DCX and DCLK are widely expressed in pallial and subpallial structures, including the telencephalon, optic tectum, and cerebellum, in similar distribution patterns. In addition to their expression in migrating cells, both proteins were also detected in the ventricular zone and in postmigratory Purkinje cells. Finally, DCX and DCLK were found to be coexpressed in all areas examined. In postmigratory Purkinje cells, DCX and DCLK both colocalized to the cell membrane, although DCLK was also distributed more generally throughout the cell soma. These data are consistent with multiple roles for DCX and DCLK in the developing chicken brain and suggest that the chick cerebellum will be an intriguing system to explore the effects of DCX and DCLK on postmigratory neuronal function. Developmental Dynamics 232:457–467, 2005. © 2004 Wiley‐Liss, Inc.
Developmental expression and nutritional regulation of a zebrafish gene homologous to mammalian microsomal triglyceride transfer protein large subunit
Authors: Marza Esther , Barthe Christophe , André Michèle , Villeneuve Laure , Hélou Chantal , Babin Patrick J. 
Published: December 2004

AbstractThe microsomal triglyceride transfer protein (MTP) large subunit is required for the assembly and secretion of apolipoprotein B‐containing lipoproteins. We have found a zebrafish mtp homologous gene coding a protein with 54% identity with human MTP large subunit with the most conserved regions distributed in the corresponding predicted α‐helical and C‐ and A‐sheet domains. In situ hybridizations showed that zebrafish mtp transcripts were distributed in the yolk syncytial layer during early embryogenesis and in anterior intestine and liver from 48 hr postfertilization onward. Real‐time quantitative RT‐PCR confirmed the developmental regulation and tissue‐specificity of mtp expression. A significant pretranslational up‐regulation of mtp expression was observed in the anterior intestine after feeding. The nutritional regulation of zebrafish mtp expression observed in the anterior intestine supports the notion that this protein, similar to mammalian MTP large subunit, could be a factor implicated directly or indirectly in large lipid droplets accumulation observed in the fish enterocyte after feeding. Developmental Dynamics 232:506–518, 2005. © 2004 Wiley‐Liss, Inc.
Chalcogenide–Lewis Acid Mediated Tandem Michael Aldol Reaction — an Alternative to the Morita–Baylis–Hillman Reaction and a New Development
Authors: Kataoka Tadashi , Kinoshita Hironori 
Published: December 2004

AbstractA tandem Michael aldol reaction mediated by a chalcogenide and Lewis acid was developed in three different types. Reactions of electron‐deficient alkenes with aldehydes or α‐keto esters in the presence of a sulfide and TiCl4 gave α‐chloromethyl aldols. Reactions of chalcogenide–enones with carbonyl compounds gave α‐(α‐hydroxyalkyl)enones (Mori‐ta–Baylis–Hillman adducts) after the work‐up of the reaction mixture with triethylamine. The intramolecular Michael aldol reactions of N‐enoylthioamides with aldehydes in the presence of BF3Et2O produced tricyclic compounds bearing a bridgehead bound to four heteroatoms and induced four stereocenters in one step, three of which were consecutive. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis and Incorporation of C(5′)‐Ethynylated Uracil‐Derived Phosphoramidites into RNA
Authors: Eppacher Simon , Christen Markus , Vasella Andrea 
Published: December 2004

AbstractThe D‐allo‐ and L‐talo‐hept‐6‐ynofuranosyluracil‐derived phosphoramidites 11A and 11T were prepared in 9–10% yield over eight steps from the previously described propargylic alcohols 1A and 1T, respectively. The corresponding nucleotides were incorporated into rU14 by standard solid‐phase synthesis. While the duplex consisting of rU14 with one L‐talo‐hept‐6‐ynofuranosyluracil in the middle of the strand and rA14 (I⋅V) had the same melting point as the reference duplex rU14⋅rA14 (I⋅II), the duplex with one D‐allo‐hept‐6‐ynofuranosyluracil in the middle of rU14 and rA14 (I⋅III) melted 1.5° lower than the reference duplex. The duplex I⋅VI consisting of rU14 with six L‐talo‐hept‐6‐ynofuranosyluracils distributed over the entire strand and rA14 showed a melting point that is 11° lower than the reference duplex. The corresponding duplex I⋅IV of rU14 possessing six D‐allo‐hept‐6‐ynofuranosyluracils and rA14 showed a melting point which is more than 20° below the one of the reference duplex. These results are in qualitative agreement with the predictions based on the conformational analysis of the nucleosides and the interference of the ethynyl moiety with the hydration of the oligonucleotides.
Redox Properties of the Iron Complexes of Orally Active Iron Chelators CP20, CP502, CP509, and ICL670
Authors: Merkofer Martin , Kissner Reinhard , Hider Robert C. , Koppenol Willem H. 
Published: December 2004

AbstractRedox cycling of iron is a critical aspect of iron toxicity. Reduction of a low‐molecular‐weight iron(III)‐complex followed by oxidation of the iron(II)‐complex by hydrogen peroxide may yield the reactive hydroxyl radical (OH.) or an oxoiron(IV) species (the Fenton reaction). Complexation of iron by a ligand that shifts the electrode potential of the complex to either to far below −350 mV (dioxygen/superoxide, pH=7) or to far above +320 mV (H2O2/HO., H2O pH=7) is essential for limitting Fenton reactivity. The oral chelating agents CP20, CP502, CP509, and ICL670 effectively remove iron from patients suffering from iron overload. We measured the electrode potentials of the iron(III) complexes of these drugs by cyclic voltammetry with a mercury electrode and determined the dependence on concentration, pH, and stoichiometry. The standard electrode potentials measured are −620 mV, −600 mV, −535 mV, and −535 mV with iron bound to CP20, ICL670, CP502, and CP509, respectively, but, at lower chelator concentrations, electrode potentials are significantly higher.
Synthesis of Tetrahydropyridoimidazole‐2‐acetates: Effect of Carboxy and Methoxycarbonyl Groups at C(2) on the Inhibition of Some β‐ and α‐Glycosidases
Authors: Terinek Miroslav , Vasella Andrea 
Published: December 2004

AbstractThe gluco‐ and manno‐tetrahydropyridoimidazole‐2‐acetates and ‐acetic acids 16 and 17, and 20 and 21, respectively, were synthesized by condensation, in the presence of HgCl2, of the known thionolactam 26 with the β‐amino ester 25 that was obtained by addition of AcOMe to the imine 22, followed by debenzylation. The resulting methyl esters 16 and 20 were hydrolyzed to the acetic acids 17 and 21. The (methoxycarbonyl)‐imidazole 14 and the acid 15 were obtained via the known aldehyde 29. The imidazoles 14–17, 20, and 21 were tested as inhibitors of the β‐glucosidase from Caldocellum saccharolyticum, the α‐glucosidase from brewer's yeast, the β‐mannosidase from snail, and the α‐mannosidase from Jack beans (Tables 1–3). There is a similar dependence of the Ki values on the nature of the C(2)‐substituent in the gluco‐ and manno‐series. With the exception of 19, manno‐imidazoles are weaker inhibitors than the gluco‐analogues. The methyl acetates 16 and 20 are 3–4 times weaker than the methyl propionates 5 and 11, in agreement with the hydrophobic effect. The gluco‐configured (methoxycarbonyl)‐imidazole 14 is 20 times weaker than the methyl acetate 16, reflecting the reduced basicity of 14, while the manno‐configured (methoxycarbonyl)‐imidazole 18 is only 1.2 times weaker than the methyl acetate 20, suggesting a binding interaction of the MeOCO group and the β‐mannosidase. The carboxylic acids 6, 12, 15, 17, 19, and 21 are weaker inhibitors than the esters, with the propionic acids 6 and 12 being the strongest and the carboxy‐imidazoles 15 and 19 the weakest inhibitors. The manno‐acetate 21 inhibits the β‐mannosidase ca. 8 times less strongly than the propionate 12, but only 1.5 times more strongly than the carboxylate 19, suggesting a compensating binding interaction also of the COOH group and the β‐mannosidase. The α/β selectivity for the gluco‐imidazoles ranges between 110 for 15 and 13.4⋅103 for 6; the manno‐imidazoles are less selective. The methyl propionates proved the strongest inhibitors of the α‐glucosidase (IC50 (5)=25 μM) and the α‐mannosidase (Ki(11) =0.60 μM).
Synthesis of 1,4‐Diethynyl‐ and 1,1,4,4‐Tetraethynylbutatrienes
Authors: Auffrant Audrey , Diederich François , Boudon Corinne , Gisselbrecht Jean‐Paul , Gross Maurice 
Published: December 2004

AbstractIn this paper, we report the synthesis and opto‐electronic properties of differentially substituted 1,4‐diethynyl‐ and 1,1,4,4‐tetraethynylbuta‐1,2,3‐trienes. These novel chromophores greatly extend the series of building modules for oxidative coupling, which includes 1,2‐diethynyl‐ and 1,1,2,2‐tetraethynylethenes and 1,3‐diethynylallenes (Fig. 1). A general synthesis of 1,1,4,4‐tetraethynylbutatrienes, which tolerates a significant number of peripheral substituents, starts from pentadiynols that are oxidized to the corresponding dialkynyl ketones, followed by Corey–Fuchs dibromo‐olefination, and transition metal mediated dimerization (Schemes 2 and 3). A similar protocol, including oxidation of propargyl aldehydes, dibromo‐olefination, and dimerization yields the less stable 1,4‐diethynylbutatrienes (Scheme 4). Attempts to prepare 1,1,4,4‐tetraethynylbutatrienes with four terminal electron‐donor‐substituted aryl groups failed so far, mainly due to difficulties in the dibromoolefination step (Scheme 6). cis‐trans‐Isomerization of differentially substituted 1,1,4,4‐tetraethynylbutatrienes is remarkably facile, with barriers to rotation in the range of those for peptide bond isomerization (ΔG≠≈20 kcal mol−1). Barriers to rotation of 1,4‐diethynylbutatrienes are higher (ΔG≠≈25 kcal mol−1), allowing in some cases the isolation of pure isomers. Both UV/VIS spectroscopy (Figs. 2 and 3) and electrochemical studies (Table) demonstrate that the all‐C‐cores in diethynyl‐ and tetraethynylbutatrienes have strong electron‐acceptor properties that are greatly enhanced with respect to those of diethynyl‐ and tetraethynylethenes with two C(sp)‐atoms less. Substitution with peripheral electron donor groups leads to efficient intramolecular charge‐transfer interactions, as evidenced by intense, bathochromically shifted longest‐wavelength bands in the UV/VIS spectra.
Synthesis of Stable Dolichylphosphomannose Analogues
Authors: Kulesza Anna , Frank Christian G. , Aebi Markus , Vasella Andrea 
Published: December 2004

AbstractFour oleyl or dolichyl thiophosphate esters 16, 17, 21, and 22, analogues of Dol‐P‐Man possessing C(1)S and/or PS bonds, were synthesized as potential inhibitors of mannosyl transferases operating in the endoplasmic reticulum (ER). The β‐mannosyl derivatives were prepared by a Mitsunobu reaction of 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐mannopyranose (1) with the thiophosphate 2 that provided O‐ and S‐glycosides with good‐to‐excellent diastereoselectivity. A second route to β‐mannosyl derivatives is based on the phosphitylation of the β‐D‐mannopyranosyl thiol 3 with the phosphoramidites 4a and 4b. Oxidation of the intermediate oleyl thiophosphite with t‐BuOOH led to mono‐ and dithiophosphates. The thiophospholipids 16, 21, and 22 were inactive as inhibitors of the Man6(GlcNAc)2‐PP‐Dol glycolipid elongation.
Synthesis, Characterization, and DNA Interaction Studies of the Ruthenium(II) Complexes [Ru(bpy)2(ipbp)]2+ and [Ru(ipbp)(phen)2]2+ (ipbp=3‐(1H‐Imidazo[4,5‐f][1,10]phenanthrolin‐2‐yl)‐4H‐1‐benzopyran‐2‐one; bpy=2,2′‐Bipyridine; phen=1,10‐Phenanthroline)
Authors: Liu Yun‐Jun , Chao Hui , Yao Jun‐Hua , Li Hong , Yuan Yi‐Xian , Ji Liang‐Nian 
Published: December 2004

AbstractA novel ligand 3‐(1H‐imidazo[4,5‐f][1,10]phenanthrolin‐2‐yl)‐4H‐1‐benzopyran‐4‐one (ipbp) and its ruthenium(II) complexes [Ru(bpy)2(ipbp)]2+ (1) and [Ru(ipbp)(phen)2]2+ (2) (bpy=2,2′‐bipyridine, phen=1,10‐phenanthroline) were synthesized and characterized by elemental analysis and mass, 1H‐NMR, and electronic‐absorption spectroscopy. The electrochemical behavior of the complexes was studied by cyclic voltammetry. The DNA‐binding behavior of the complexes was investigated by spectroscopic methods and viscosity measurements. The results indicate that complexes 1 and 2 bind with calf‐thymus DNA in an intercalative mode. In addition, 1 and 2 promote cleavage of plasmid pBR 322 DNA from the supercoil form I to the open circular form II upon irradiation.
Synthesis of N‐Substituted (3S,4S)‐ and (3R,4R)‐Pyrrolidine‐3,4‐diols: Search for New Glycosidase Inhibitors
Authors: Łysek Robert , Vogel Pierre 
Published: December 2004

AbstractN‐Substituted (3S,4S)‐ and (3R,4R)‐pyrrolidine‐3,4‐diols 9 and 10, respectively, were derived from (+)‐L‐ and (−)‐D‐tartaric acid, respectively. Compounds 9k, 9l, and 9m with the N‐substituents, BnNH(CH2)2, 4‐PhC6H4CH2NH(CH2)2 and 4‐ClC6H4CH2NH(CH2)2, respectively, showed modest inhibitory activities toward α‐D‐amyloglucosidases from Aspergillus niger and from Rhizopus mold (Table 1). Unexpectedly, several (3R,4R)‐pyrrolidine‐3,4‐diols 10 showed inhibitory activities toward α‐D‐mannosidases from almonds and from jack bean (Table 3). N‐Substitution by the NH2(CH2)2 group, i.e., 10g, led to the highest potency.
Prenatal sonographic features of esophageal and ileal duplications at 18 weeks of gestation
Authors: Gul Ahmet , Tekoglu Gungor , Aslan Halil , Cebeci Altan , Erol Onur , Unal Murat , Ceylan Yavuz 
Published: December 2004

AbstractWe present a case of esophageal and ileal duplications at 18 weeks of gestation. Transabdominal ultrasonography of the fetus showed multiple cystic masses of 12 to 17 mm in diameter and continuity with each other in the abdomen and a unilocular cystic mass of 15 mm in diameter in the posterior mediastinum. The cystic mass filled the abdominal cavity with signs of intestinal obstruction. The thoracic cystic mass was tubular, sausage‐shaped and behind the heart, which was displaced to the antero‐lateral wall of the chest. Amniocentesis revealed a normal fetal karyotype 46,XY. Peristaltic movements in the abdominal cystic structure at 30 weeks of gestation suggested dilated intestinal loops. Follow‐up ultrasound examinations showed polyhydramnios with amniotic fluid index of 30 cm and gradual enlargement of the cystic structures to 50 mm in the abdomen and 30 mm in the posterior mediastinum at 38 weeks of gestation. A male infant weighing 3900 g was delivered. Postnatal ultrasonographic examination and the findings of magnetic resonance imaging also suggested enteric duplication cysts. Prenatal diagnosis allowed prompt neonatal evaluation and surgical treatment of the esophageal and the ileal duplications, which was confirmed by pathological examination. Copyright © 2004 John Wiley & Sons, Ltd.
Fetal echocardiography: are we getting it right?
Authors: Shub A. , Ward C. , Lee‐Tannock A. , Justo R. , Cincotta R. 
Published: December 2004

AbstractObjectiveTo determine the diagnostic accuracy of prenatal fetal echocardiography.MethodsThe study was a retrospective chart review of 190 consecutive patients over a 3‐year period from November 1998 to February 2002 of all women referred to the Maternal Fetal Medicine unit, Mater Mothers Hospital, for fetal echocardiography. The prenatal diagnosis was compared with the postnatal diagnosis made by postnatal echocardiography, surgical findings or post‐mortem. The accuracy of prenatal diagnosis was described on a predetermined 4‐point scale.ResultsOf the 89 patients, for whom complete diagnostic follow‐up was available, there was complete agreement between the prenatal and postnatal diagnosis in 63 cases, minor discrepancies in 25 cases and major disagreement in 1 case.ConclusionsIn experienced hands, fetal echocardiography is accurate and allows medical staff and patients information in order manage a pregnancy appropriately. Copyright © 2004 John Wiley & Sons, Ltd.
Preimplantation genetic diagnosis for Niemann‐Pick disease type B
Authors: Hellani Ali , Schuchman Edward H. , Al‐Odaib Ali , Al Aqueel Aida , Jaroudi Kamal , Ozand Pinar , Coskun Serdar 
Published: December 2004

AbstractBackgroundAcid sphingomyelinase (ASM) deficient Niemann‐Pick disease (NPD) is an autosomal recessive disorder caused by mutations in the ASM gene (SMPD1). More than 70 different mutations have been reported in this gene. NPD type B is the most common type in Saudi Arabia with a frequency of 1:40 000 to 1:100 000. The phenotype of Saudi Type B patients is more severe than patients reported from the West. Two mutations specific to Saudi patients have been inherited in the SMPD1 gene. Given the difficult management of the disease, we opted for a preventive approach to the suffering families by screening the whole SMPD1 gene for mutations followed by Preimplantation Genetic Diagnosis (PGD).MethodsThe family suffering from NPD‐B underwent mutation screening for the entire SMPD1 gene followed by PGD using nested PCR and sequencing.ResultsA novel mutation in a family suffering from the same severe NPD‐B phenotype is described in this report (W533R). After PGD, a singleton pregnancy ensued after transfer of one heterozygous and one normal embryo. Postnatal DNA testing of the newborn showed a normal homozygous genotype.ConclusionsThis report reveals a new SMPD1 mutation responsible for similar Saudi severe phenotype, and the prevention of this disorder by PGD. Copyright © 2004 John Wiley & Sons, Ltd.
Screening for aneuploidies of ten different chromosomes in two rounds of FISH: a short and reliable protocol
Authors: Baart E. B. , Martini E. , Van Opstal D. 
Published: December 2004

AbstractObjectiveTo develop a DNA labelling protocol for the simultaneous detection of five different fluorescent chromosomal DNA probes within one round of hybridisation. In combination with a commercial five‐colour probemix for the second round of hybridisation, this results in a fast and reliable Fluorescence in situ Hybridization (FISH) protocol, enabling the detection of 10 chromosomes within a working day. This is especially of use for Preimplantation Genetic Screening (PGS), when only single interphase nuclei are available for analysis and when time is restricted.MethodDNA probes were labelled with four different fluorochromes (Pacific Blue, Alexa Fluor 350, Alexa Fluor 594 and Alexa Fluor 488) using an ARES labelling kit, based on a two‐step method. Aminoallyl‐dUTPs were incorporated by nick translation, followed by chemical linking of the amino‐modified fluorescent dye. The fifth colour was achieved by using two fluorescent dyes in the chemical reaction, resulting in dual labelling of the DNA probe and a fluorescence detectable with a specific filter set. These five probes were simultaneously hybridised in a first FISH round, followed by a second hybridisation with a commercial five‐colour probemix, thus allowing the detection of chromosomes 1, 7, 13, 15, 16, 18, 21, 22, X and Y. The fixation and pre‐treatment procedures of the blastomere nuclei were further optimised.ResultsUsing this labelling and FISH protocol, probe hybridisation efficiency, when tested on lymphocyte nuclei, is 95 to 99%. With the fixation protocol, blastomere nuclei maintain good morphology and show condensed and clear signals even after the second round of hybridisation.ConclusionThis labelling method in combination with specific epifluorescence filters, enables an independent detection of five different chromosomes in one round of FISH. The whole process of biopsy, fixation and two rounds of hybridisation with the analysis of ten chromosomes can be completed within a day. Copyright © 2004 John Wiley & Sons, Ltd.
Segregation analysis in cystic fibrosis at‐risk family demonstrates that the M348K CFTR mutation is a rare innocuous polymorphism
Authors: D'Apice Maria Rosaria , Gambardella Stefano , Russo Silvia , Lucidi Vincenzina , Nardone Anna Maria , Pietropolli Adalgisa , Novelli Giuseppe 
Published: December 2004

AbstractObjectiveCystic fibrosis (CF; OMIM# 219700) is caused by mutation in the CF transmembrane regulator (CFTR) gene. We investigate whether the (paternal) M348K mutation is a benign polymorphism or a disease‐causing mutation in a patient clinically affected with CF, with the second (maternal) CFTR allele identified as N1303K.MethodsThe patient and his father were studied for the presence of mutations in the CFTR gene using the DHPLC system to analyze all CFTR exons. Amplicons showing an abnormal elution profile were sequenced.ResultsThe CFTR gene from the healthy father has two mutations, M348K and G1244E. The affected son inherited only the G1244E paternal mutation from his father, and hence the two paternal mutations are trans and do not occur in the same CFTR gene. The patient's genotype is G1244E(paternal)/N1303K(maternal). This information was used to study an ongoing pregnancy of the couple, where the fetus inherited the same genotype as the affected proband and therefore is affected.ConclusionM348K in the CFTR gene is not a mutation causing CF, but a rare polymorphism. These data are important for genetic counseling and prenatal diagnosis and illustrate the importance of full sequence data when studying rare mutations. Copyright © 2004 John Wiley & Sons, Ltd.