bluuebunny/crossref_metadata_2025 huggingface dataset:
Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding
Authors: Bishop Kathie M. , Garel Sonia , Nakagawa Yasushi , Rubenstein John L.R. , O'Leary Dennis D.M.
Published: October 2004

The homeobox transcription factors Emx1 and Emx2 are expressed in overlapping patterns that include cortical progenitors in the dorsal telencephalic neuroepithelium. We have addressed cooperation of Emx1 and Emx2 in cortical development by comparing phenotypes in Emx1; Emx2 double mutant mice with wild‐type and Emx1 and Emx2 single mutants. Emx double mutant cortex is greatly reduced compared with wild types and Emx single mutants; the hippocampus and dentate gyrus are absent, and growth and lamination of the olfactory bulbs are defective. Cell proliferation and death are relatively normal early in cortical neurogenesis, suggesting that hypoplasia of the double mutant cortex is primarily due to earlier patterning defects. Expression of cortical markers persists in the reduced double mutant neocortex, but the laminar patterns exhibited are less sharp than normal, consistent with deficient cytoarchitecture, probably due in part to reduced numbers of preplate and Reelin‐positive Cajal‐Retzius neurons. Subplate neurons also exhibit abnormal differentiation in double mutants. Cortical efferent axons fail to exit the double mutant cortex, and TCAs pass through the striatum and approach the cortex but do not enter it. This TCA pathfinding defect appears to be non‐cell autonomous and supports the hypothesis that cortical efferents are required scaffolds to guide TCAs into cortex. In double mutants, some TCAs fail to turn into ventral telencephalon and take an aberrant ventral trajectory; this pathfinding defect correlates with an Emx2 expression domain in ventral telencephalon. The more severe phenotypes in Emx double mutants suggest that Emx1 and Emx2 cooperate to regulate multiple features of cortical development. J. Comp. Neurol. 457:345–360, 2003. © 2003 Wiley‐Liss, Inc.
Standardized immune monitoring for the prediction of infections after cardiopulmonary bypass surgery in risk patients
Authors: Strohmeyer Jens‐Christian , Blume Christian , Meisel Christian , Doecke Wolf‐Dietrich , Hummel Manfred , Hoeflich Conny , Thiele Kathi , Unbehaun Axel , Hetzer Roland , Volk Hans‐Dieter
Published: October 2004

Background

Infections are the most common cause of late complications in cardiopulmonary bypass (CPB) surgery patients, and are difficult to predict. Here we studied the diagnostic value of a standardized immune monitoring program based on recent advances in flow cytometry (exact quantification of surface‐marker expression) and cytokine determination (semiautomatic systems).

Methods

CPB patients (56) at risk for complications (age >70 years and/or preoperative left‐ventricular ejection fraction < 25 %) were classified into three groups: without (33), with suspected (14), and with confirmed (9) infection. Applying the Quantibrite™‐system, we daily quantified the expression of CD11b, CD64, CD71, CD86, and HLA‐DR on monocytes/granulocytes. Furthermore, the ex vivo secretion of tumor necrosis factor (TNF)‐α as well as the plasma interleukin (IL)‐10 levels were determined by a semiautomatic system. Ex vivo elastase release was measured by enzyme‐linked immunosorbent assay (ELISA).

Results

All patients showed signs of granulocyte activation and monocyte deactivation. Monocytic HLA‐DR and plasma IL‐10 were the best markers to discriminate patients with infection from those without as early as day 1. Using a cutoff of 5792 HLA‐DR molecules per cell, both sensitivity and negative predictive value for patients who developed microbiologically confirmed infection was 1.0, and the area under the curve (AUC) was 0.85.

Conclusions

Our data suggest that a standardized immune monitoring at day 1 might be useful for early discrimination of patients at elevated risk for infections. Cytometry Part B (Clin. Cytometry) 53B:54–62, 2003. © 2003 Wiley‐Liss, Inc.
Expression and regulation of B7 family molecules on macrophages (MΦ) in preterm and term neonatal cord blood and peripheral blood of adults
Authors: Orlikowsky Thorsten W. , Spring Bärbel , Dannecker Günther E. , Niethammer Dietrich , Poets Christian F. , Hoffmann Michael K.
Published: October 2004

Background

Macrophage (MΦ) receptors of the B7 family (CD80, CD86) play a crucial role in T cell activation: the lack of costimulation leads to anergy or apoptosis of reactive T cells. MΦ may differentiate into different subsets, the balance of which defines MΦ‐dependent T cell reactions. The aim of this study was to examine neonatal and adult T cell response with respect to the costimulatory MΦ‐potential in order to identify molecular predictors for the neonatal immune defense.

Methods

MΦ from peripheral blood (PBMΦ) or cord blood (CBMΦ) were stimulated with interferon‐gamma (IFN‐γ), cyclic adenosine monophosphate (cAMP), CD40 ligand (CD40L), or αCD3.

Results

As compared to PBMΦ, CBMΦ showed a significantly decreased upregulation of CD80 and/or CD86 after stimulation with IFN‐γ, cAMP, CD40L, and αCD3. Accordingly, the proliferative T cell response was impaired in the presence of CBMΦ. The fraction of T cells that underwent cell death was higher, and blast formation was significantly lower than that observed in the presence of PBMΦ.

Conclusions

CBMΦ, as compared to PBMΦ, delivered fewer costimulatory but more cytotoxic signals to T cells. These observations suggest that MΦ are one factor explaining the suboptimal immune defense of neonates and their increased susceptibility to infection. Using the costimulatory MΦ‐potential as a predictor for immune responses requires a separate reference value system in neonatology. Cytometry Part B (Clin. Cytometry) 53B:40–47, 2003. © 2003 Wiley‐Liss, Inc.
Cytomics in predictive medicine
Authors: Valet Günter K. , Tárnok Attila
Published: October 2004

Patient‐specific, disease‐course predictions with >95% or >99% accuracy during therapy would be highly valuable for everyday medicine. If these predictors were available, disease aggravation or progression, frequently accompanied by irreversible tissue damage or therapeutic side effects, could then potentially be avoided by early preventive therapy. The molecular analysis of heterogeneous cellular systems (cytomics) by cytometry in conjunction with pattern‐oriented bioinformatic analysis of the multiparametric cytometric and other data provides a promising approach to individualized or personalized medical treatment or disease management. As a consequence, better patient care and new forms of inductive scientific hypothesis development based on the interpretation of predictive data patterns are at reach. Cytometry Part B (Clin. Cytometry) 53B:1–3, 2003. © 2003 Wiley‐Liss, Inc.
FISH cytogenetics and prognosis in breast and non–small cell lung cancers
Authors: Massoner Anita , Augustin Florian , Duba Hans‐Christoph , Zojer Niklas , Fiegl Michael
Published: October 2004

Background

Interphase cytogenetics by fluorescence in situ hybridization (FISH) has been demonstrated to be a valuable diagnostic tool in effusions from patients with solid tumors. As the next step, we investigated whether certain patterns of numeric aberrations in malignant effusion cells supply prognostic information.

Methods

From a large series of effusions from patients with solid tumors, 55 effusions from breast cancer and 39 effusions from non–small cell lung cancer (NSCLC) were classified as malignant by cytology or FISH. Tumor cells were classified as FISH aneuploid for chromosome 11 and/or 17 or as not aneuploid. Predominant cytogenetic anomalies and patterns of intratumor cytogenetic heterogeneity were brought in relation to overall survival rate.

Results

There was no difference with respect to overall survival rate when effusions with or without aneuploidy for chromosomes 11 and 17 were compared. Likewise, in effusions with aneuploidy, there was no difference in overall survival rate among patients with different modal chromosome copy numbers (e.g., trisomy vs. tetrasomy 11) or among patients with a low or high grade of intratumor complexity (defined by the intratumor heterogeneity of FISH aneuploidy). In breast cancer, aneuploidy with gain of chromosome 11 was associated with a significantly superior survival rate, suggesting that amplification of chromosome 11 DNA is associated with a less aggressive phenotype.

Conclusions

Simple chromosomal changes as determined by FISH, such as gain of chromosome 11 copy numbers in breast cancer, may be prognostic. Prospective studies in primary tumors that classify distinct prognostic groups by FISH cytogenetics are warranted. © 2004 Wiley‐Liss, Inc.
Implication of bax in Xenopus laevis tail regression at metamorphosis
Authors: Sachs Laurent M. , Le Mevel Sébastien , Demeneix Barbara A.
Published: October 2004

Apoptosis is fundamental to normal vertebrate development. A dramatic example of postembryonic development involving apoptosis is tail regression during amphibian metamorphosis. Earlier studies led us to propose a functional role for the pro‐apoptotic protein Bax in tadpole tail regression. However, its physiological relevance has never been analyzed. We have now cloned a cDNA encoding Xenopus laevis bax (xlbax) and used in vivo gene transfer in tail muscle to analyze the effects of xlbax overexpression. Furthermore, by using an antisense strategy in a similar experimental paradigm, xlbax antisense mRNA was shown to block the apoptotic effects of xlbax and protect against apoptosis in metamorphosing tadpoles. Our results suggest that xlbax is a regulator of muscle fiber death in the regressing tail during metamorphosis. Developmental Dynamics 231:671–682, 2004. © 2004 Wiley‐Liss, Inc.
Tissue inhibitor of metalloproteinase‐2 (TIMP‐2) expression during cardiac neural crest cell migration and its role in proMMP‐2 activation
Authors: Cantemir V. , Cai D.H. , Reedy M.V. , Brauer P.R.
Published: October 2004

Matrix metalloproteinases (MMPs) are important mediators of neural crest (NC) cell migration. Here, we examine the distribution of tissue inhibitor of metalloproteinase (TIMP) ‐2 and TIMP‐3 and test whether manipulating TIMP levels alters chicken cardiac NC cell migration. TIMP‐2 mRNA is expressed at stage 11 in the neural epithelium and only in migrating cardiac NC cells. TIMP‐3 mRNA is expressed only in the notochord at stage 8 and later in the outflow tract myocardium. Exogenous TIMP‐2 increases NC motility in vitro at low concentrations but has no effect when concentrations are increased. In vitro, NC cells express membrane type‐1 matrix metalloproteinase (MT1‐MMP) and TIMP‐2 and they secrete and activate proMMP‐2. Antisense TIMP‐2 oligonucleotides block proMMP‐2 activation, decrease NC cell migration from explants, and perturb NC morphogenesis in ovo. Because TIMP‐2 is required for activation of proMMP‐2 by MT1‐MMP, this finding suggests TIMP‐2 expression by cardiac NC cells initiates proMMP‐2 activation important for their migration. Developmental Dynamics 231:709–719, 2004. © 2004 Wiley‐Liss, Inc.
Coexpression of Cux‐1 and notch signaling pathway components during kidney development
Authors: Sharma Madhulika , Fopma Amber , Brantley Jennifer G. , Vanden Heuvel Gregory B.
Published: October 2004

Cux‐1 is the murine homologue of the Drosophila gene cut, which is required for cellular differentiation in several tissues, including the wing margin and Malpighian tubule. Mammalian cut proteins function as cell cycle‐dependent transcriptional repressors in proliferating cells. Targets of Cux‐1 repression include the cyclin kinase inhibitors p21 and p27. However, little is known about the regulation of Cux‐1. In Drosophila, multiple genetic interactions between Cut and the Notch and Wingless signaling pathways occur during wing development. To begin to determine whether Cux‐1 regulation by the Notch signaling pathway is conserved in mammals, we compared the expression patterns of Cux‐1, the murine Notch receptors (Notch 1–4), and the murine ligands (Jagged 1, Jagged 2, and Delta 1) during murine embryogenesis and kidney development. In this report, we demonstrate that Cux‐1 expression overlaps with that of Notch signaling pathway components in multiple tissues during embryonic development. In the developing kidney, Cux‐1 expression overlaps with that of Notch pathway components in the condensing mesenchyme, in pretubular aggregates (comma and S‐shaped bodies), and in the presumptive podocytes of capillary loop stage glomeruli. Furthermore, Cux‐1 was significantly up‐regulated in the rat kidney epithelial cell line RKE expressing a constitutively active Notch 1, and this finding was associated with a reduction of p27. Moreover, Cux‐1 interacts with the Groucho homolog TLE‐4, a corepressor recruited by Notch effector proteins. Taken together, these results suggest that Cux‐1 may function in the context of the Notch signaling pathway in multiple tissues during mammalian embryogenesis. Developmental Dynamics 231:828–838, 2004. © 2004 Wiley‐Liss, Inc.
Hydrogen‐Bonded Network and Layered Supramolecular Structures Assembled from ClO4− Counterions with Unprecedented Monomeric [AgL2]+ and Chain Polymeric [AgL2]nn+ Complex Cations (L = Thioamide or Thiourea‐Like Ligands)
Authors: Sola Joan , López Alexandre , Coxall Robert A. , Clegg William
Published: October 2004

The complexes [Ag(etu)2]ClO4 (1) and [{Ag(py2tH)2}(ClO4)(H2O)0.5]n (2) have been obtained from the reactions of AgClO4 with the corresponding thioamide ligands (etu = imidazolidine‐2‐thione; py2tH = pyridine‐2‐thione). Complex 1, consisting of centrosymmetric monomeric [Ag(etu)2]+ cations and ClO4− counterions, constitutes the first bis[thio(mono‐ or di)amide] complex (M = Cu, Ag) known thus far to possess a linear MS2 mononuclear core. Component ions behave in the crystal structure as complementary partners, with all four N−H groups of each [Ag(etu)2]+ cation and all four oxygen atoms of each ClO4− anion involved in N−H···O−Cl hydrogen bonding associations. This leads to the assembly of a three‐dimensional supramolecular network. Complex 2, whose previously reported structure has been redetermined with higher precision, contains catena‐[Ag(py2tH)2]nn+ polymeric cations consisting of linear chains of linked Ag2(μ‐S)2 rings, with distorted tetrahedral AgS4 centres. Supramolecular association through N−H···O−Cl, N−H···O(water) and Cl−O···H−O−H···O−Cl hydrogen bonding, where all N−H groups and H2O molecules and only one or two oxygen atoms of each ClO4− anion are involved, leads to the formation of a two‐dimensional layered supramolecular structure. A correlation of some stereochemical parameters and a simple qualitative sulfur‐bridge bonding model has been developed for 2 and other related thioamide complexes containing M2(μ‐S)2 rings or M−S−M′ single bridges. For these structural units, suitable ranges of tilt and twist dihedral angles have been estimated and assigned to different bonding types. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Incorporation of a (Cyclopentadienyl)molybdenum Oxo Complex in MCM‐41 and Its Use as a Catalyst for Olefin Epoxidation
Authors: Abrantes Marta , Gago Sandra , Valente Anabela A. , Pillinger Martyn , Gonçalves Isabel S. , Santos Teresa M. , Rocha João , Romão Carlos C.
Published: October 2004

The tricarbonyl complex [(η5‐C5H4‐COOMe)Mo(CO)3Cl] was prepared from the reaction of sodium (methoxycarbonyl)cyclopentadienide, (C5H4‐CO2Me)Na, with (Bu4N)[Mo(CO)5I]. Heating the ester with 3‐(triethoxysilyl)propylamine gave the amide derivative {[η5‐C5H4‐CONH‐C3H6Si(OEt)3]Mo(CO)3Cl}. The functionalised tricarbonyl complex was immobilised in the ordered mesoporous silica MCM‐41 with a loading of 13 wt.‐% Mo (1.4 mmol·g−1) by carrying out a grafting reaction in dichloromethane. Powder X‐ray diffraction and nitrogen adsorption−desorption analysis indicated that the structural integrity of the support was preserved during the grafting and that the channels remained accessible, despite significant reductions in surface area, pore volume and pore size. The success of the coupling reaction was confirmed by 29Si and 13C (CP) MAS NMR spectroscopy. A supported dioxo complex of the type [(η5‐C5H4R)MoO2Cl] was subsequently prepared by oxidative decarbonylation of the tethered tricarbonyl complex using tert‐butyl hydroperoxide (TBHP). The oxidised material is an active catalyst for the liquid phase epoxidation of cyclooctene with TBHP as the oxygen source. Similar catalytic results were obtained using the tethered tricarbonyl complex directly as a pre‐catalyst since fast oxidative decarbonylation occurs under the reaction conditions used. For both systems, the desired epoxide was the only product and the initial activities were about 13 mol·molMo−1·h−1. The solid catalysts were recycled several times. Some activity was lost between the first and second runs but thereafter tended to stabilise. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Mono‐ and Dinuclear Rhenium Polyhydride Complexes Bearing the Chelating Ligand 1,2‐Bis(dicyclohexylphosphanyloxy)ethane
Authors: Bolaño Sandra , Bravo Jorge , García‐Fontán Soledad
Published: October 2004

Variable‐temperature NMR spectroscopic studies of new rhenium polyhydride compounds of the type [ReH7(dcype)] (1), [Re2H8(dcype)2] (3) and [ReH5(dcype)L] (5a−f) [dcype = Cy2PO(CH2)2OPCy2; L = PPhn(OR)3−n, n = 0−2, R = Me, Et] show them to be highly fluxional classical hydride complexes. In the case of the ethoxy compounds 5b, 5d and 5f, three hydride interchange processes were observed in the temperature range 283−173 K and their activation parameters were determined by NMR line‐shape analysis. A mechanism is proposed for each. Protonation of 1 and 5 with HBF4·OMe2 gave the nonclassical hydrides [ReH8(dcype)]BF4 (2) and [ReH6(dcype)L]BF4 (6) which are relatively stable. Compound 2 decomposes at 273 K in solution releasing H2,whereas compound 6 can be stored at room temperature for more than 24 h without decomposition. Protonation of 3 with HBF4·OMe2 gave the classical dinuclear hydride [Re2H9(dcype)2]BF4. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Hydroalumination of Carbon Dioxide, Carbon Disulfide, and Phenyl Isocyanate with an Aluminum Ketiminate Compound
Authors: Kuo Pei‐Cheng , Chen I‐Chun , Chang Jr‐Chiuan , Lee Ming‐Tsung , Hu Chin‐Han , Hung Chen‐Hsiung , Lee Hon Man , Huang Jui‐Hsien
Published: October 2004

The reaction of MeC(O)C(H)=C(Me)NHAr (Ar = 2,6‐diisopropylphenyl) (1) with excess LiAlH4 in diethyl ether at −78 °C generates [AlH(OCMeCHCMeNAr)2] (2) in 76% yield. The aluminum formate compound [Al(OCMeCHCMeNAr)2(OCOH)] (3) can be isolated from the reaction of 2 with CO2 in 93% yield. Compound 3 is thermally stable and remains unchanged when heated under vacuum at 100 °C for 24 h. Similarly, a solution of 2 in dichloromethane reacts with carbon disulfide or phenyl isocyanate at room temperature to yield the insertion products [Al(OCMeCHCMeNAr)2(SCHS)] (4) and [Al(OCMeCHCMeNAr)2(OCH=NPh)] (5), respectively, in 80% and 92% yield. Reaction of 2 with 1 equiv. of urethane in toluene at refluxing temperature for 1 h yields the aluminum isocyanate compound [Al(OCMeCHCMeNAr)2(NCO)] (6). The molecular structures of compounds 2−6 have been determined by X‐ray crystallography. Density functional calculations show that the isomer of compound 2 with an N−N trans arrangement is 3.1 kcal·mol−1 lower in energy than the O−O trans isomer. Inserting CO2 into the Al−H bond of compound 2 results in the formation of the formate compound 3; this reaction is predicted to be exothermic by 29.8 kcal·mol−1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Organic Phase PPO Biosensors Prepared by Multilayer Deposition of Enzyme and Alginate Through Avidin‐Biotin Interactions
Authors: Cosnier S. , Mousty C. , de Melo J. , Lepellec A. , Novoa A. , Polyak B. , Marks R. S.
Published: October 2004

Films of electrogenerated polypyrrole and hydrophilic alginate, both functionalized with biotin moieties, were used to allow for the transfer of polyphenol oxidase activity in organic media. Enzyme electrodes, based on multilayered structures, were protected at the molecular level by the affinity binding of alginate as a hydrophilic additive, and were then transferred into chlorobenzene, dichloromethane, chloroform, ethyl acetate or acetonitrile. The biosensor performance for the detection of catechol at −0.2 V was investigated, highlighting the main influence of the hydrophobicity of the solvent and, to a lesser extent, the dielectric constant. The effect of the substrate hydrophobicity on the biosensor response was examined in chlorobenzene.
On the Structure of PHB (=Poly[(R)‐3‐hydroxybutanoic Acid]) in Phospholipid Bilayers: Preparation of Trifluoromethyl‐Labeled Oligo[(R)‐3‐hydroxybutanoic Acid] Derivatives
Authors: Rueping Magnus , Albert Matthias , Seebach Dieter
Published: October 2004

Oligomers of (R)‐3‐hydroxybutanoate (OHB) have previously been shown to transport cations through lipid bilayers. The ion‐transport activity has been attributed to the formation of hydrophobic aggregates or pores, which have been identified by fluorescence‐microscopy measurements of membrane‐incorporated fluorescence‐labeled OHBs. To obtain more information about these aggregates, we describe here the synthesis of the specifically F‐labeled HB oligomers II–IV for structural investigation by means of solid‐state 19F‐NMR spectroscopic techniques.
Synthesis of 9‐Halogenated 9‐Deazaguanine N7‐(2′‐Deoxyribonucleosides)
Authors: Seela Frank , Shaikh Khalil I. , Wiglenda Thomas , Leonard Peter
Published: October 2004

The syntheses of N7‐glycosylated 9‐deazaguanine 1a as well as of its 9‐bromo and 9‐iodo derivatives 1b,c are described. The regioselective 9‐halogenation with N‐bromosuccinimide (NBS) and N‐iodosuccinimide (NIS) was accomplished at the protected nucleobase 4a (2‐{[(dimethylamino)methylidene]amino}‐3,5‐dihydro‐3‐[(pivaloyloxy)methyl]‐4H‐pyrrolo[3,2‐d]pyrimidin‐4‐one). Nucleobase‐anion glycosylation of 4a–c with 2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D‐erythro‐pentofuranosyl chloride (5) furnished the fully protected intermediates 6a–c (Scheme 2). They were deprotected with 0.01M NaOMe yielding the sugar‐deprotected derivatives 8a–c (Scheme 3). At higher concentrations (0.1M NaOMe), also the pivaloyloxymethyl group was removed to give 7a–c, while conc. aq. NH3 solution furnished the nucleosides 1a–c. In D2O, the sugar conformation was always biased towards S (67–61%).
A New 2H‐Azirin‐3‐amine as a Synthon for α‐Methyl Glutamate
Authors: Hilty Florentine M. , Brun Kathrin A. , Heimgartner Heinz
Published: October 2004

The synthesis of a novel 2,2‐disubstituted 2H‐azirin‐3‐amine 10 as a building block for racemic Glu(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 10 with thiobenzoic S‐acid and the amino acid Z‐Val‐OH yielded the racemic monothiodiamide 17 and the dipeptide 18 as a mixture of diastereoisomers, respectively (Scheme 2). From 18, each of the protecting groups was removed selectively (Scheme 3).
Molecular Structure, Vibrational Spectra, and Hydrogen Bonding of the Ionic Liquid 1‐Ethyl‐3‐methyl‐1H‐imidazolium Tetrafluoroborate
Authors: Katsyuba Sergey A. , Dyson Paul J. , Vandyukova Elena E. , Chernova Alla V. , Vidiš Ana
Published: October 2004

The IR and Raman spectra and conformations of the ionic liquid 1‐ethyl‐3‐methyl‐1H‐imidazolium tetrafluoroborate, [EMIM] [BF4] (6), were analyzed within the framework of scaled quantum mechanics (SQM). It was shown that SQM successfully reproduced the spectra of the ionic liquid. The computations revealed that normal modes of the EMIM+⋅BF$\rm{_{4}^{-}}$ ion pair closely resemble those of the isolated ions EMIM+ and BF$\rm{_{4}^{-}}$, except for the antisymmetric BF stretching vibrations of the anion, and the out‐of‐plane and stretching vibrations of the HC(2) moiety of the cation. The most plausible explanation for the pronounced changes of the latter vibrations upon ion‐pair formation is the H‐bonding between HC(2) and BF$\rm{_{4}^{-}}$. However, these weak H‐bonds are of minor importance compared with the Coulomb interactions between the ions that keep them closely associated even in dilute CD2Cl2 solutions. According to the ‘gas‐phase’ computations, in these associates, the BF$\rm{_{4}^{-}}$ anion is positioned over the imidazolium ring of the EMIM+ cation and has short contacts not only with the HC(2) of the latter, but also with a proton of the MeN(3) group.
Synthesis, Structure, and Spectroscopic and Electrochemical Properties of Heteroleptic Bis(phthalocyaninato) Rare Earth Complexes with a C4 Symmetry
Authors: Bian Yongzhong , Wang Rongming , Wang Daqi , Zhu Pehua , Li Renjie , Dou Jianmin , Liu Wei , Choi Chi‐Fung , Chan Hoi‐Shan , Ma Changqin , Ng Dennis K. P. , Jiang Jianzhuang
Published: October 2004

A series of eleven heteroleptic bis(phthalocyaninato) rare earth double‐deckers [MIII(pc){pc(α‐OC5H11)4}] 1–11 (M=Y, SmLu; pc=phthalocyaninato; pc(α‐OC5H11)4=1,8,15,22‐tetrakis(1‐ethylpropoxy)phthalocyaninato) were prepared as racemic mixtures by [MIII(pc)(acac)]‐induced (acac=acetylacetonato) cyclic tetramerization of 3‐(1‐ethylpropoxy)phthalonitrile in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in refluxing pentanol. These compounds could also be prepared by treating [MIII(pc)(acac)] with the metal‐free phthalocyanine H2{pc(α‐OC5H11)4} in refluxing octanol. The whole series of double‐decker complexes 1–11 were characterized by elemental analysis and various spectroscopic methods. The molecular structures of the Sm, Eu, and Er complexes 1, 2, and 8, respectively, were also determined by single‐crystal X‐ray diffraction analysis. The effects of the rare earth ion size on the reaction yield, molecular structure, and spectroscopic and electrochemical properties of these complexes were systematically examined.
Improved Protocol for the Three‐Component Biginelli Reactions and Biginelli‐Like Mannich Reactions of Carbamates, Aldehydes, and Ketones
Authors: Xu Li‐Wen , Wang Zong‐Ting , Xia Chun‐Gu , Li Lyi , Zhao Pei‐Qing
Published: October 2004

A mild, convenient, and improved method for the direct three‐component Biginelli and Biginelli‐like Mannich‐type reactions of carbonyl compounds in the presence of inexpensive FeCl3⋅6 H2O and Me3SiCl as catalysts is described. Reactions performed with carbamates can be used to directly access N‐protected β‐amino carbonyl compounds in a single step.
Amber‐Woody Scent: Alcohols with Divergent Structure Present Common Olfactory Characteristics and Sharp Enantiomer Differentiation
Authors: Margot Christian , Simmons Dana P. , Reichlin Daniel , Skuy David
Published: October 2004

Only one out of the four possible trans isomers of the important perfumery alcohol Norlimbanol® (1) possesses a very strong amber‐woody smell, the isomer 1A with (1′R,3S,6′S) absolute configuration. Its enantiomer 1B is almost odorless and devoid of amber‐woody character, whereas the diastereoisomers 1C and 1D are considerably weaker and perceptible only by the most‐sensitive persons. The same is true for a whole series of perceptual analogs of 1, including β‐alkoxy alcohols. These ethers belong to two structural classes: [(2,2,6‐trimethylcyclohexyl)oxy]‐ (see 3, 4, and 16) or {[2‐(tert‐butyl)cyclohexyl]oxy}alkan‐2‐ol derivatives (see 19 and 20; Table). A superimposition model allowing for good overlap of the respective hydroxylated side chains offers a tentative explanation for the shared perceptual characteristics of the two classes (Fig. 5). The lipophilic cyclohexane moieties present only a minimal overlap in this model, suggesting that quite larger molecules might possess the same smell. (S)‐Configured β‐alkoxy alcohols can conveniently be obtained on a larger scale by enantioselective reduction of the corresponding ketones (Scheme 9).
Microbial Transformation of Sesquiterpenes, (−)‐Ambrox® and (+)‐Sclareolide
Authors: Choudhary M. Iqbal , Musharraf Syed Ghulam , Sami Amtul , Atta‐ur‐Rahman
Published: October 2004

The microbial transformation of (−)‐Ambrox® (1), a perfumery sesquiterpene, by a number of fungi, by means of standard two‐stage‐fermentation technique, afforded ambrox‐1α‐ol (2), ambrox‐1α,11α‐diol (3), ambrox‐1α,6α‐diol (4), ambrox‐1α,6α,11α‐triol (5), ambrox‐3‐one (6), ambrox‐3β‐ol (7), ambrox‐3β,6β‐diol (8), 13,14,15,16‐tetranorlabdane‐3,8,12‐triol (9), and sclareolide (10) (Schemes 1 and 2). Further incubation of compound 10 with Cunninghamella elegans afforded 3‐oxosclareolide (11), 3β‐hydroxysclareolide (12), 2α‐hydroxysclareolide (13), 2α,3β‐dihydroxysclareolide (14), 1α,3β‐dihydroxysclareolide (15), and 3β‐hydroxy‐8‐episclareolide (16) (Scheme 3). Metabolites 2–5, 12, 13, and 16 were found to be new compounds. The major transformations include a reaction path involving hydroxylation, ether‐bond cleavage and inversion of configuration. Metabolites 11–16 of sclareolide showed significant phytotoxicity (Table 1). The structures of the metabolites were characterized on the basis of spectroscopic techniques.
Holo‐ and Hemidirected Coordination Spheres in a Novel Three‐Dimensional Polymeric KIPbII Heteropolynuclear Complex: X‐Ray Crystal Structure of [KPb(AcO)2(SCN)]n
Authors: Morsali Ali , Mahjoub Ali Reza
Published: October 2004

A novel three‐dimensional polymeric KIPbII heteropolynuclear complex, [KPb(AcO)2(SCN)]n, with mixed acetate and thiocyanate ligands, has been synthesized and characterized. Its single‐crystal X‐ray structure (Fig. 1) shows three types of K+ ions with coordination numbers of seven, and three types of Pb2+ ions with coordination numbers of eight, eight, and nine, respectively. The Pb centers (Pb(1) and Pb(3); Fig. 1) with coordination numbers of nine and eight, respectively, possess stereochemically ‘inactive’ electron lone pairs, and the coordination sphere is holodirected. However, the arrangement of O‐, N‐, and S‐atoms for the eight‐coordinated Pb(2) suggests a gap or hole in the coordination geometry around this atom. This ‘hole’ is possibly occupied by a stereochemically ‘active’ electron lone pair of Pb(2), and its coordination sphere is, thus, hemidirected.
Modelling two‐dimensional steady‐state groundwater flow and flow sensitivity to boundary conditions in blanket peat complexes
Authors: Lapen D. R. , Price J. S. , Gilbert R.
Published: October 2004

This study used a two‐dimensional steady‐state finite‐element groundwater flow model to simulate groundwater flow in two Newfoundland blanket peat complexes and to examine flow system sensitivity to changes in water table recharge and aquifer properties. The modelling results were examined within the context of peat‐forming processes in the two complexes. Modelled flow compared favourably with observed flow. The sensitivity analyses suggested that more highly decomposed bog peat along bog margins probably has/had a positive impact on net peat accumulation within bog interiors. Peat with lower hydraulic conductivity along bog margins effectively impedes lateral drainage, localizes water table drawdown to extreme bog margins, and elevates water tables along bog interiors. Peat formation and elevated water tables in adjacent poor fens/laggs currently rely on placic and ortstein horizons impeding vertical drainage and water flow inputs from adjacent bogs. Modest reductions in atmospheric recharge were found to govern bog‐flow‐system geometries in a way that would adversely affect paludification processes in adjacent fens/laggs. Copyright © 2004 John Wiley & Sons, Ltd.
Dosing and scheduling influence the antitumor efficacy of a phosphinic peptide inhibitor of matrix metalloproteinases
Authors: Dive Vincent , Andarawewa Kumari L. , Boulay Anne , Matziari Magdalini , Beau Fabrice , Guerin Eric , Rousseau Bernard , Yiotakis Athanasios , Rio Marie‐Christine
Published: October 2004

The in vivo disposition and antitumor efficacy of a newly developed phosphinic matrix metalloproteinase inhibitor (RXP03) were examined. RXP03 potently inhibits MMP‐11, MMP‐8 and MMP‐13, but not MMP‐1 and MMP‐7. Twenty‐four hours after i.p. injection into mice, most of the RXP03 was recovered intact in plasma, feces (biliary excretion) and tumor tissue. Pharmacokinetic parameters indicated that, after an i.p. dose of 100 μg/day, the plasma concentration of RXP03 over 24 hr remained higher than the Ki values determined for MMP‐11, MMP‐8 and MMP‐13. Efficacy of RXP03 on the growth of primary tumors induced by s.c. injection of C26 colon carcinoma cells in mice was observed to depend both on RXP03 doses and treatment schedules. Tumor volumes in mice treated for 18 days with 50, 100 and 150 μg/day of RXP03 were decreased compared with control tumor volumes, 100 μg/day being the most effective dose. Treatment at higher dose (600 μg/day) did not significantly reduce the tumor size as compared to control. Short treatments with RXP03 100 μg/day, 3 to 7 days after C26 inoculation, were more effective on tumor growth than continuous treatment over 18 days. Strikingly, RXP03 treatment started 6 days after the C26 injection and continued until day 18 led to stimulation of tumor growth, as compared to control. These paradoxical effects, depending on the RXP03 treatment schedule, underline the need to define carefully the spatiotemporal function of each MMP at various stages of tumor growth to achieve optimal therapeutic effects by MMP inhibitor treatment.
Folate intake and colorectal cancer risk: A meta‐analytical approach
Authors: Sanjoaquin Miguel A. , Allen Naomi , Couto Elisabeth , Roddam Andrew W. , Key Timothy J.
Published: October 2004

Adequate consumption of folate may reduce the risk of colorectal cancer. We performed a meta‐analysis of 7 cohort and 9 case‐control studies that examined the association between folate consumption and colorectal cancer risk. In cohort studies, the association between folate consumption and colorectal cancer risk was stronger for dietary folate (folate from foods alone; relative risk for high vs. low intake = 0.75; 95% CI = 0.64–0.89) than for total folate (folate from foods and supplements; relative risk for high vs. low intake = 0.95; 95% CI = 0.81–1.11) and there was no significant heterogeneity between studies. There was significant heterogeneity between case‐control studies. These results offer some support for the hypothesis that folate has a small protective effect against colorectal cancer but confounding by other dietary factors cannot be ruled out. © 2004 Wiley‐Liss, Inc.
Ultraviolet radiation modulates nuclear factor kappa B activation in human lens epithelial cells
Authors: Boileau Thomas W.‐M. , Bray Tammy M. , Bomser Joshua A.
Published: October 2004

Exposure to ultraviolet radiation (UVR) is a known risk factor for cataract, but the molecular mechanisms involved have not been elucidated. We hypothesized that exposure to UVR would modulate the activation of nuclear factor kappa‐B (NF‐κB) within the human lens epithelium, since NF‐κB is a key regulator of cellular responses to UVR stress in other cell types. Human lens epithelial (HLE) cells were exposed to acute physiological doses of ultraviolet A (UVAR), B (UVBR), C (UVCR) radiation, or interleukin‐1β (IL‐1β) and NF‐κB activation was measured by electrophoretic shift assay (EMSA). Phosphorylation of IκB in response to UVAR was measured by Western blotting. Irradiation of HLE cells with UVAR (0–1100 J/m2) did not reduce cell survival, while UVBR (400–1600 J/m2) and UVCR (300–900 J/m2) significantly reduced HLE cell survival. EMSA analysis of HLE nuclear proteins indicated activation of NF‐κB, but not activator protein‐1 (AP‐1), by UVAR. The effects of UVBR and UVCR were less pronounced. Exposure of HLE cells to UVAR (0–900 J/m2) followed by a 30‐min incubation resulted in a dose‐dependent activation of NF‐κB. UVAR‐induced NF‐κB activation in HLE cells was evident 10 min postirradiation, maximal at 60 min and returned to control levels by 120 min. Western blot analysis of phosphorylation of the NF‐κB inhibitory protein, IκB, revealed that UVAR activates NF‐κB via a mechanism involving the phosphorylation of IκB‐α; this effect was dose‐dependent. Supershift analysis demonstrated that UVAR and IL‐1β activate the transcriptionally active p65/p50 NF‐κB dimer. These studies demonstrate that UVAR activates NF‐κB in HLE cells in a time‐ and dose‐dependent manner via signaling through IκB‐α. The activation of NF‐κB in HLE cells by UVAR may have implications for the development and progression of cataract and other related ocular disorders.© 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:108–113, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10067
Signal transduction events in lung injury induced by 2‐chloroethyl ethyl sulfide, a mustard analog
Authors: Chatterjee Diptendu , Mukherjee Shyamali , Smith Milton G. , Das Salil K.
Published: October 2004

Sulfur mustard has been used as a vesicant chemical warfare agent. To understand the mechanism by which mustard gas exposure causes respiratory damage, we have used 2‐chloroethyl ethyl sulfide (CEES) as a mustard analog. Our initial studies have shown that guinea pigs exposed to CEES intratracheally accumulate high levels of TNF‐α. Accumulation of TNF‐α leads to activation of both acid and neutral sphingomyelinases, resulting in high accumulation of ceramides, a second messenger involved in cell apoptosis. In addition, NF‐κB was activated for a short period (1–2 h after exposure) as determined by mobility shift assay. Supershift assays indicated that both p50 and p65 of NF‐κB were activated due to CEES exposure. However, NF‐κB rapidly disappeared after 2 h. It is possible that the initial activation of NF‐κB was an adaptive response to protect the cells from damage since NF‐κB is known to inhibit TNF‐α/ceramide‐induced cell apoptosis. Since NF‐κB disappeared after 2 h, the cells continued being damaged owing to accumulation of ceramides and activation of several caspases, leading to apoptosis. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:114–121, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10068
A serotonin receptor antagonist induces oocyte maturation in both frogs and mice: Evidence that the same G protein‐coupled receptor is responsible for maintaining meiosis arrest in both species
Authors: Sheng Yinglun , Wang Ling , Liu X. Shawn , Montplaisir Véronique , Tiberi Mario , Baltz Jay M. , Liu X. Johné
Published: October 2004

Accumulating evidence has indicated that vertebrate oocytes are arrested at late prophase (G2 arrest) by a G protein coupled receptor (GpCR) that activates adenylyl cyclases. However, the identity of this GpCR or its regulation in G2 oocytes is unknown. We demonstrated that ritanserin (RIT), a potent antagonist of serotonin receptors 5‐HT2R and 5‐HT7R, released G2 arrest in denuded frog oocytes, as well as in follicle‐enclosed mouse oocytes. In contrast to RIT, several other serotonin receptor antagonists (mesulergine, methiothepine, and risperidone) had no effect on oocyte maturation. The unique ability of RIT, among serotonergic antagonists, to induce GVBD did not match the antagonist profile of any known serotonin receptors including Xenopus 5‐HT7R, the only known Gs‐coupled serotonin receptor cloned so far in this species. Unexpectedly, injection of x5‐HT7R mRNA in frog oocytes resulted in hormone‐independent frog oocyte maturation. The addition of exogenous serotonin abolished x5‐HT7R‐induced oocyte maturation. Furthermore, the combination of x5‐HT7R and exogenous serotonin potently inhibited progesterone‐induced oocyte maturation. These results provide the first evidence that a G‐protein coupled receptor related to 5‐HT7R may play a pivotal role in maintaining G2 arrest in vertebrate oocytes. © 2004 Wiley‐Liss, Inc.
Expression, location, and interactions of ErbB2 and its intramembrane ligand Muc4 (sialomucin complex) in rat mammary gland during pregnancy
Authors: Price‐Schiavi Shari A. , Andrechek Eran , Idris Nebila , Li Peter , Rong Min , Zhang Jin , Carraway Coralie A. Carothers , Muller William J. , Carraway Kermit L.
Published: October 2004

Muc4 (also called Sialomucin complex) is a heterodimeric glycoprotein complex consisting of a peripheral O‐glycosylated subunit ASGP‐1 (ascites sialoglycoprotein‐1) tightly but non‐covalently bound to an N‐glycosylated transmembrane subunit ASGP‐2. Muc4/SMC can act as an intramembrane ligand for ErbB2 via an EGF‐like domain present in the transmembrane subunit. The complex is developmentally regulated in normal rat mammary gland and overexpressed in a number of mammary tumors. Overexpression of Muc4/SMC has been shown to block cell–cell and cell–matrix interactions, protect tumor cells from immune surveillance, promote metastasis, and protect from apoptosis. We have investigated whether Muc4/SMC and ErbB2 are co‐expressed and co‐localized in normal rat mammary gland and whether Muc4/SMC–ErbB2 complex formation is developmentally regulated in this tissue. Muc4/SMC and ErbB2 have different expression patterns and regulatory mechanisms in the developing rat mammary gland, but both are maximally expressed during late pregnancy and lactation. The two proteins form a complex in lactating mammary gland which is not detected in the virgin gland. Moreover, this complex does not contain ErbB3. ErbB2 is co‐localized with Muc4/SMC at the apical surfaces of ductal and alveolar cells in lactating gland; however, another form of ErbB2, recognized by a different antibody, localizes to the basolateral surfaces of these cells. ErbB2 phosphorylated on Tyr 1248 co‐localized with Muc4/SMC at the apical surface but not at the basolateral surfaces of these cells. To investigate the function of Muc4 in the mammary gland, transgenic mice were derived using an MMTV‐Muc4 construct. Interestingly, mammary gland development in the transgenic mice was aberrant, exhibiting a bifurcated pattern, including invasion down the blood vessel, similar to that exhibited by transgenic mice inappropriately expressing activated ErbB2 in the mammary gland. These data provide further evidence of the ability of Muc4/SMC to interact with ErbB2 and influence its behavior in normal epithelia. © 2004 Wiley‐Liss, Inc.
Internalization and trafficking of the human and rat growth hormone‐releasing hormone receptor
Authors: Veyrat‐Durebex Christelle , Pomerleau Luc , Langlois Daniel , Gaudreau Pierrette
Published: October 2004

Internalization and intracellular trafficking of the growth hormone‐releasing hormone receptor (GHRH‐R) were studied in rat anterior pituitary and human (h) and rat (r) GHRH‐R‐transfected BHK cells, with the GHRH agonist, [Nα‐5‐carboxyfluoresceinyl‐D‐Ala2, Ala8, Ala15, Lys22]hGHRH(1‐29)NH2 (Fluo‐GHRH). Time‐ and temperature‐dependent internalization of stimulated GHRH‐R was blocked by phenyl arsine oxide (PAO) in both cell types. In anterior pituitary and rGHRH‐R‐transfected BHK cells, only filipin III and cerulenin blocked receptor‐mediated internalization of Fluo‐GHRH while in hGHRH‐R‐transfected BHK cells, only hyperosmolar sucrose inhibited this process. These results suggest that hGHRH‐R internalization is clathrin‐dependent, while fatty acid acylation of rGHRH‐R appears to be a prerequisite to caveolin‐dependent internalization. Experiments in anterior pituitary using Bodipy‐FL‐C5 ganglioside GM1, a specific marker of lipid rafts such as caveolae, confirmed this latter pathway. Co‐localization of Fluo‐GHRH with LysoTracker indicated that Fluo‐GHRH was directed to acidic organelles in both cell types. Finally, studies using cycloheximide and monensin showed that upon stimulation with GHRH, an optimal concentration of functional GHRH‐R was maintained at the plasma membrane due to de novo synthesis and recycling in pituitary cells and to de novo synthesis solely in hGHRH‐R‐transfected BHK cells. This first study on the dynamics of the GHRH/GHRH‐R complexes using fluorescence imaging in a native environment compared to cell system models, revealed that both receptor primary structure and concentration at the plasma membrane play important roles in internalization and trafficking of specific G‐protein‐coupled receptors (GPCR). © 2004 Wiley‐Liss, Inc.
Endogenous recovery of injured spinal cord: Longitudinal in vivo magnetic resonance imaging
Authors: Narayana Ponnada A. , Grill Raymond J. , Chacko Tessy , Vang Russell
Published: October 2004

Pathological changes were followed longitudinally with in vivo magnetic resonance imaging (MRI) and behavioral studies in experimental spinal cord injury (SCI). MRI‐observed pathology was correlated with histology. On MRI, the cavitated regions of the injured cord were gradually filled with viable tissue between two and 8 weeks postinjury, and a concomitant improvement was observed in the neurobehavioral scores. By weeks 3–6, on MRI, the gray matter (GM) returned in the segments caudal, but not rostral, to the injury site. The corresponding histological sections revealed motor neurons as well as other nuclei in the gray matter immediately caudal to the epicenter, but not at the site of injury, suggesting neuronal recovery in perilesioned areas. The neuronal and neurological recovery appeared to occur about the same time as neovasculature that was reported on the contrast‐enhanced MRI, suggesting a role for angiogenesis in recovery from SCI. The role of angiogenesis in neuronal recovery is further supported by the immunohistochemical observation of greater bromodeoxyuridine uptake by blood vessels near the lesion site compared with uninjured cords. © 2004 Wiley‐Liss, Inc.
Differential gene expression in neural stem cells and oligodendrocyte precursor cells: A cDNA microarray analysis
Authors: Hu Jian‐Guo , Fu Sai‐Li , Zhang Kai‐Hua , Li Ying , Yin Lan , Lu Pei‐Hua , Xu Xiao‐Ming
Published: October 2004

The use of neural stem cells (NSCs) or their progeny oligodendrocyte precursor cells (OPCs) represents a promising repair strategy for many neurological disorders. However, the molecular events and biological features during the transition from NSCs to OPCs remain unclear. In the present study, we isolated NSCs from the embryonic rat forebrain and induced them into OPCs by using B104 conditioned medium (B104CM) in vitro. We then employed cDNA array technology to compare changes in gene expression between the two cell populations. Among 1,176 genes examined, 40 were differentially expressed, and some of them may be involved in OPC differentiation from NSCs. Our findings thus provide new insights into the molecular basis of differentiation of OPCs from NSCs. © 2004 Wiley‐Liss, Inc.
High mobility group box protein‐1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity
Authors: Takata Kazuyuki , Kitamura Yoshihisa , Tsuchiya Daiju , Kawasaki Toshiyuki , Taniguchi Takashi , Shimohama Shun
Published: October 2004

One pathogenic characteristic of Alzheimer's disease (AD) is the formation of extracellular senile plaques with accumulated microglia. According to the amyloid hypothesis, the increase or accumulation of amyloid‐β (Aβ) peptides in the brain parenchyma is the primary event that influences AD pathology. Although the role of microglia in AD pathology has not been clarified, their involvement in Aβ clearance has been noted. High mobility group box protein‐1 (HMGB1) is an abundant nonhistone chromosomal protein. We reported recently that HMGB1 was associated with senile plaques and the total protein level significantly increased in AD brain. In this study, diffuse HMGB1 immunoreactivity was observed around dying neurons in the kainic acid‐ and Aβ1–42 (Aβ42)‐injected rat hippocampi. HMGB1 also colocalized with Aβ in the Aβ42‐injected rats but not in transgenic mice, which show massive Aβ production without neuronal loss in their brains. Furthermore, coinjection of HMGB1 delayed the clearance of Aβ42 and accelerated neurodegeneration in Aβ42‐injected rats. These results suggest that HMGB1 released from dying neurons may inhibit microglial Aβ42 clearance and enhance the neurotoxicity of Aβ42. HMGB1 may thus be another target in the investigation of a therapeutic strategy for AD. © 2004 Wiley‐Liss, Inc.