bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphometric index of the developing murine kidney
Authors: Cebrián Cristina , Borodo Karolina , Charles Nikki , Herzlinger Doris A.
Published: September 2004

Mammalian kidney morphogenesis begins when the ureteric bud (UB) induces surrounding metanephric mesenchyme to differentiate into nephrons, the functional units of the mature organ. Although several genes required for this process have been identified, the mechanisms that control final nephron number and the localization of distinct tubular segments to cortical and medullary zones of the kidney remain poorly understood. This finding is due, in part, to the lack of quantitative studies describing the acquisition of mature renal structure. We have analyzed the following parameters of the developing murine kidney throughout embryogenesis: nephron and UB tip number, distance between UB branch points and total kidney, and cortical and medullary volume. Results of this morphometric analysis reveal previously unrecognized changes in the pattern of UB growth and rate of nephrogenesis. In addition, this morphometric index provides a much‐needed reference for accurately describing renal paterning defects exhibited by genetically altered mice. Developmental Dynamics 231:601–608, 2004. © 2004 Wiley‐Liss, Inc.
Identification and characterization of a novel transcript down‐regulated in Dlx1/Dlx2 and up‐regulated in Pax6 mutant telencephalon
Authors: Faedo Andrea , Quinn Jane C. , Stoney Patrick , Long Jason E. , Dye Catherine , Zollo Massimo , Rubenstein John L.R. , Price David J. , Bulfone Alessandro
Published: September 2004

By using a custom‐made array containing cDNAs preferentially expressed in the mouse embryonic telencephalon (Porteus et al. [1992] Brain Res Mol Brain Res 12:7–22; and Alessandro Bulfone, unpublished data), we studied the gene expression profile of the Dlx1/Dlx2−/− subpallium and Pax6−/− pallium. We identified a transcript corresponding to Unigene Cluster Mm.94021 and rat Evf‐1, which is down‐regulated in the Dlx1/Dlx2−/− subpallium and up‐regulated in the Pax6−/− pallium. Here, we report the expression pattern of this transcript, designated mouse Evf1 (mEvf1), in the prenatal forebrain of wild‐type, Dlx1/Dlx2−/− and Pax6−/− mice using RNA in situ hybridization and reverse transcriptase‐polymerase chain reaction. In the wild‐type forebrain mEvf1 expression is restricted to the ventral thalamus, hypothalamus, and subpallial telencephalon (caudal, lateral, and medial ganglionic eminences and septal primordia), whereas it is down‐regulated in the Dlx1/Dlx2−/− subpallium (mainly in caudal, lateral, and medial ganglionic eminences), and up‐regulated in the Pax6−/− lateral and ventral pallium at embryonic day 12.5 and in the dorsal, lateral, and ventral pallium at embryonic day 14.5. Developmental Dynamics 231:614–620, 2004. © 2004 Wiley‐Liss, Inc.
Screen for genes differentially expressed during regeneration of the zebrafish caudal fin
Authors: Padhi Bhaja K. , Joly Lucille , Tellis Patricia , Smith Amanda , Nanjappa Purushothama , Chevrette Mario , Ekker Marc , Akimenko Marie‐Andrée
Published: September 2004

The zebrafish caudal fin constitutes an important model for studying the molecular basis of tissue regeneration. The cascade of genes induced after amputation or injury, leading to restoration of the lost fin structures, include those responsible for wound healing, blastema formation, tissue outgrowth, and patterning. We carried out a systematic study to identify genes that are up‐regulated during “initiation” (1 day) and “outgrowth and differentiation” (4 days) of fin regeneration by using two complementary methods, suppression subtraction hybridization (SSH) and differential display reverse transcriptase polymerase chain reaction (DDRT‐PCR). We obtained 298 distinct genes/sequences from SSH libraries and 24 distinct genes/sequences by DDRT‐PCR. We determined the expression of 54 of these genes using in situ hybridization. In parallel, gene expression analyses were done in zebrafish embryos and early larvae. The information gathered from the present study provides resources for further investigations into the molecular mechanisms of fin development and regeneration. Developmental Dynamics 231:527–541, 2004. © 2004 Wiley‐Liss, Inc.
Two DM domain genes, DMY and DMRT1, involved in testicular differentiation and development in the medaka, Oryzias latipes
Authors: Kobayashi Tohru , Matsuda Masaru , Kajiura‐Kobayashi Hiroko , Suzuki Aya , Saito Noriko , Nakamoto Masatoshi , Shibata Naoki , Nagahama Yoshitaka
Published: September 2004

The recent discovery of the DMY gene (DM domain gene on Y chromosome and one of the DMRT1 family genes) as a key determinant of male development in the medaka (Oryzias latipes) has led to its designation as the prime candidate gene for sex‐determination in this species. This study focused on the sites and pattern of expression of DMY and DMRT1 genes during gonadal differentiation of medaka to further determine their roles in testis development. DMY mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express DMY during the early migratory period. Expression of DMY persists in Sertoli cell lineage cells, from PGC‐supporting cells to Sertoli cells, indicating that only DMY‐positive cells enclose PGCs during mitotic arrest after hatching. DMRT1 is expressed in spermatogonium‐supporting cells after testicular differentiation (20–30 days after hatching), and its expression is much higher than that of DMY in mature testes. In XX sex‐reversed testes, DMRT1 is expressed in the Sertoli cell lineage, similar to the expression of DMY in XY testes. These results suggest strongly that DMY regulates PGC proliferation and differentiation sex‐specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation. Developmental Dynamics 231:518–526, 2004. © 2004 Wiley‐Liss, Inc.
Crk‐associated substrate (Cas) family member, NEDD9, is regulated in human neuroblastoma cells and in the embryonic hindbrain by all‐trans retinoic acid
Authors: Merrill Ronald A. , See Angela Wai‐Man , Wertheim Margaret L. , Clagett‐Dame Margaret
Published: September 2004

The vitamin A metabolite, all‐trans retinoic acid (atRA), plays an essential role in vertebrate embryogenesis, including development of the nervous system. In the human neuroblastoma cell line, SH‐SY5Y, atRA rapidly induces (within 4 hr) the expression of the Crk‐associated substrate (Cas) family member, neural precursor cell‐expressed, developmentally down‐regulated gene 9 (NEDD9) also called the human enhancer of filamentation (HEF1). NEDD9 is expressed in the developing hindbrain (5‐somite stage) in the presumptive rhombomeres 2, 3, and 5 before the onset of overt segmentation. Exposure of rat embryos to excess atRA at times ranging from E9.25 to E12 leads to altered NEDD9 expression in the developing hindbrain within 6 hr. NEDD9 expression is also perturbed in vitamin A‐deficient embryos. A putative retinoic acid response element in the 5′ region of the NEDD9 promoter binds specifically to a RXR/RAR heterodimer and forms a higher molecular weight complex upon addition of a retinoic acid receptor‐specific antibody. Regulation of NEDD9 may be an important means whereby atRA promotes cell spreading and neurite outgrowth in SH‐SY5Y human neuroblastoma cells, and NEDD9 represents a new downstream target of atRA and its receptors in the developing hindbrain. Developmental Dynamics 231:564–575, 2004. © 2004 Wiley‐Liss, Inc.
Intussusceptive angiogenesis: Its emergence, its characteristics, and its significance
Authors: Burri Peter H. , Hlushchuk Ruslan , Djonov Valentin
Published: September 2004

This review shall familiarize the reader with the various aspects of intussusceptive angiogenesis (IA). The basic event in IA is the formation of transvascular tissue pillars. Depending on location, timing, and frequency of pillar emergence, the IA process has different outcomes. In capillaries, a primary IA function is to expand the capillary bed in size and complexity (intussusceptive microvascular growth). It represents an alternative to capillary sprouting. Highly ordered pillar formation in a developing capillary network leads to the formation of vascular trees (intussusceptive arborization). In small arteries and veins, pillar formation at the vessels' branching angles leads either to remodeling of the branching geometry or even to vascular pruning (intussusceptive branching remodeling). It appears essential that future angiogenic research considers always both phenomena, sprouting and intussusception. Vascularization of tissues, organs, and tumors rely heavily on both mechanisms; neglecting one or the other would obscure our understanding of the angiogenesis process. Developmental Dynamics 231:474–488, 2004. © 2004 Wiley‐Liss, Inc.
Identification of a CD4+CD25+ T cell subset committed in vivo to suppress antigen‐specific T cell responses without additional stimulation
Authors: Nolte‐‘t Hoen Esther N. M. , Wagenaar‐Hilbers Josée P. A. , Boot Elmieke P. J. , Lin Chia‐Huey , Arkesteijn Ger J. A. , van Eden Willem , Taams Leonie S. , Wauben Marca H. M.
Published: September 2004

Naturally occurring CD4+ regulatory T cells can be identified on the basis of expression of CD25 and suppression of T cell responses in vitro after TCR triggering. Here, we demonstrate that a CD134+ subset of CD4+CD25+ T cells in naive rats suppresses antigen‐specific T cell responses in vitro without additional TCR stimulation. In contrast, CD4+CD25+CD134– regulatory T cells and total CD4+CD25+ regulatory T cells have suppressive activity only during simultaneous activation of responder and regulatory T cells or after in vitro pre‐activation. Furthermore CD4+CD25+CD134+ T cells have a more activated phenotype than CD4+CD25+CD134– T cells, as based on the expression of CD62L, CD45RC, and MHC class II. We propose that the CD134+ regulatory T cells contain an in vivo activated and highly suppressive regulatory T cell subset. CD4+CD25+CD134+ T cells can be found in several compartments of the immune system, including spleen, lymph nodes, and blood. Interestingly though, the relative amounts of these cells within the CD4+ population and their CD134 expression levels are highest in mucosa‐draining lymph nodes and lowest in blood. This suggests that the presence of CD4+CD25+CD134+ T cells indicates sites of active immune suppression.
C5a anaphylatoxin as a product of complement activation up‐regulates the complement inhibitory factor H in rat Kupffer cells
Authors: Schlaf Gerald , Nitzki Frauke , Heine Ines , Hardeland Rüdiger , Schieferdecker Henrike L. , Götze Otto
Published: September 2004

The 155‐kDa complement regulator factor H (FH) is the predominant soluble regulatory protein of the complement system. It acts as a cofactor for the factor I‐mediated conversion of the component C3b to iC3b, competes with factor B for a binding site on C3b and C3(H2O) and promotes the dissociation of the C3bBb complex. The primary site of synthesis is the liver, i.e. FH‐specific mRNA and protein were identified in both hepatocytes (HC) and Kupffer cells (KC). Previous studies in rat primary HC and KC had shown that the proinflammatory cytokine IFN‐γ influences the balance between activation and inhibition of the complement system through up‐regulation of the inhibitory FH. In this study we show that C5a, as a product of complement activation, stimulates the expression of FH‐specific mRNA and protein in KC and thus induces a negative feedback. Quantitative‐competitive RT‐PCR showed an approximate threefold C5a‐induced up‐regulation of FH. ELISA analyses revealed a corresponding increase in FH protein in the supernatants of KC. The up‐regulation of FH was completely inhibited by the C5a‐blocking monoclonal antibody 6‐9F. Furthermore, an involvement of LPS and IFN‐γ was excluded, which strongly indicates a direct effect of C5a on the expression of FH in KC.
Mini‐review: Transendothelial migration of leukocytes: through the front door or around the side of the house?
Authors: Engelhardt Britta , Wolburg Hartwig
Published: September 2004

Leukocyte adhesion to the endothelial cells lining the vessel wall and the subsequent migration of the leukocytes into the underlying tissue are key elements of both innate and adaptive immunity. Leukocyte extravasation is generally believed to take place through small gaps at intercellular endothelial cell junctions – the paracellular route. This view has, however, been repeatedly challenged by morphological studies demonstrating leukocyte migration through the endothelial cells themselves – the transcellular pathway. On the basis of the current experimental evidence, we propose consideration that both pathways are equally possible for a leukocyte's journey from the apical surface of the endothelium to its basal side.
Reciprocal stimulation of γδ T cells and dendritic cells during the anti‐mycobacterial immune response
Authors: Dieli Francesco , Caccamo Nadia , Meraviglia Serena , Ivanyi Juraj , Sireci Guido , Bonanno Cesira T. , Ferlazzo Viviana , La Mendola Carmela , Salerno Alfredo
Published: September 2004

γδ T cells and dendritic cells (DC) are two distinct cell types of innate immunity that participate in early phases of immune response against Mycobacterium tuberculosis infection. Here we show that a close functional relationship exists between these cell populations. Using an in vitro coculture system, Vγ1 T cells from Tcrb–/– mice were found to be activated by DC infected in vitro with BCG, as indicated by the elevated CD69 expression, IFN‐γ secretion and cytotoxic activity. This activation process was due to a non‐cognate mechanism since it required neither cell to cell contact nor interaction between the TCR and a specific antigen, but was mediated by DC‐derived IL‐12. Reciprocally, Vγ1 T cells provided a key cytokine, IFN‐γ, which increased IL‐12 production by BCG‐infected DC. Moreover, exposure of BCG‐infected DC to Vγ1 T cells conditioned the former to prime a significantly stronger anti‐mycobacterial CD8 T cell response. Consequently, stimulation of γδ T cells and their non‐cognate interaction with DC could be applied as an immune adjuvant strategy to optimize vaccine‐induced CD8 T cell immunity.
Enhanced basal AP‐1 activity and de‐regulation of numerous genes in T cells transgenic for a dominant interfering mutant of FADD/MORT1
Authors: Chaneva Svetla , Schneider Günter , Siegmund Daniela , Wajant Harald , Mages Jörg , Häcker Georg
Published: September 2004

The essential role of FADD/MORT1 and caspase‐8 in ‘death‐receptor’‐induced apoptosis is well characterized. Surprisingly, these proteins also play a critical role in antigen‐ or mitogen‐induced activation and proliferation of T cells. We report the results of gene expression profiling in T cells from mice defective in FADD‐signaling due to transgenic expression of a dominant negative mutant of FADD (FADDdn T cells). Of the tested genes, 159 were differentially expressed in mutant cells prior to or, more often, after mitogenic stimulation for 20 h. No obvious regulator of proliferation was changed in expression. However, a number of T cell effector genes such as IL‐2 and IL‐9 were up‐regulated upon stimulation. Analysis of IL‐2 regulation showed enhanced mRNA induction but normal protein production in activated FADDdn T cells. Activation of the nuclear factor of activated T cells was normal upon stimulation but the activity of the activator protein 1 (AP‐1) family was strongly increased in resting FADDdn T cells. Expression and transcriptional activity of classical AP‐1 family members was unaltered in FADDdn cells, suggesting the involvement of other AP‐1 family members. The constitutive activation of AP‐1 may thus serve to precondition resting T cells for an enhanced expression of many immunologically relevant genes during activation.
B cells are not required for T cell priming in low zone tolerance to contact allergens and contact hypersensitivity
Authors: Seidel‐Guyenot Wolfgang , Alt Ruth , Perschon Sylwia , Knop Jürgen , Steinbrink Kerstin
Published: September 2004

Low zone tolerance (LZT) to contact allergens is induced by epicutaneous exposure to haptens in subsensitizing doses resulting in an inhibition of contact hypersensitivity (CHS), which, in contrast, occurs after sensitization with immunogenic doses of allergens. Performing the protocol of tolerance induction resulted in robust LZT to allergens in B cell‐deficient mice in vivo, indicating that B cells are not required for the induction and effector phase of LZT. However, CHS reactions in vivo were restricted in B cell‐deficient mice as compared to wild‐type (WT) mice. In contrast, analysis of hapten‐specific T cell activation in vitro revealed a strong proliferative response of T cells derived from both WT and B cell‐deficient sensitized mice. Similar to WT animals, T cells obtained from tolerized B cell‐deficient mice produced a Tc2 cytokine pattern of LZT with high levels of IL‐4 and IL‐10, whereas sensitization of B cell‐deficient mice resulted in the typical Tc1 cytokine profile of CHS. Adoptive transfer of CD8+ effector T cells from tolerized or sensitized B cell‐deficient mice induced significant LZT or CHS reactions, respectively, in WT recipients, demonstrating that the development of hapten‐specific effector CD8+ T cells of LZT and CHS is independent of B cells.
The Nature of the M≡E Bond: Theoretical Investigation of the Molecules [(RO)3M≡E] (M = Mo, W; E = N, P, As, Sb, Bi; R = H, Me) and [(Me3CO)3Mo≡P]
Authors: Pandey Krishna K. , Frenking Gernot
Published: September 2004

The electronic and molecular structures of the metal‐pnicogen complexes [(RO)3M≡E] (M = Mo, W; E = N, P, As, Sb, Bi; R = H, Me) and [(Me3CO)3M≡P] have been investigated at the DFT level using the exchange correlation functionals B3LYP and BP86. The nature of the M≡E interactions was analyzed with charge and energy decomposition methods. The bonding analyses show that the metal‐pnicogen bonds are genuine triple bonds containing a σ‐ and a degenerate π‐bond. The M−E σ‐bonds are always polarized towards the pnicogen atom E, particularly for the nitrogen complexes. The M−N π‐bonds are also polarized towards nitrogen, while the π‐bonds of the heavier pnicogens P−Bi show a small polarization towards the metal atom. The M−E σ‐bonds at the pnicogen E are spn‐hybridized; the p character is always > 80% of the total AO contribution. The hybridization of the metal atoms in the nitrido complexes is approximately sd2 and that in the heavier homologues, approximately sd. The ratio of the energy contributions of the σ‐ and π‐orbitals to the covalent bonding in [(HO)3M≡E] is about 50:50 for all pnicogen atoms E. The metal−nitrido bonds in [(HO)3M≡N] are more covalent than electrostatic. The covalent character becomes smaller when the pnicogen atom becomes heavier with the trend N >> P > As > Sb > Bi. The [(HO)3M≡E] tungsten complexes have stronger bonds that are slightly less covalent than the molybdenum complexes, the π‐bonding contribution in the former species is slightly larger than in the latter. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Chiral Gelators Constructed from 11‐Aminoundecanoic (AUDA), Lauric and Amino Acid Units. Synthesis, Gelling Properties and Preferred Gelation of Racemates vs. the Pure Enantiomers
Authors: Čaplar Vesna , Žinić Mladen , Pozzo Jean‐Luc , Fages Frederic , Mieden‐Gundert Gudrun , Vögtle Fritz
Published: September 2004

A new class of efficient low molecular weight gelator molecules has been designed by combining 11‐aminoundecanoic acid (AUDA), lauric acid and aromatic and aliphatic amino acid units in the same molecule. This yields a special class of fatty acid amphiphiles with core chiral centres and hydrogen bonding sites. Some of the compounds with terminal carboxylic acid and sodium carboxylate functions exhibited ambidextrous gelation properties, being able to form gels both with highly polar solvents (water, DMSO) and also with highly lipophilic solvents, including two hydrocarbon fuels. At variance with several recent observations that the enantiomers are generally more efficient gelators than the corresponding racemates, some of the racemic gelators prepared in this work were found to be capable of gelling up to 16 times larger volumes of certain solvents than the pure enantiomers. Temperature‐dependent FTIR and 1H NMR studies of the gels formed by derivatives with terminal carboxylic acid groups and lipophilic solvents revealed that intermolecular hydrogen bonding between amidic and carboxylic acid units was involved in the self‐assembly of gel aggregates. Additional strong stabilization of the aggregates was observed in the gelators possessing terminal sodium carboxylate groups, and this was attributed to the electrostatic and ion‐dipole interactions between the sodium carboxylate groups. This additional stabilization appears to be responsible for considerably higher thermal stability of the latter gels in relation to those formed by gelators with terminal carboxylic acid groups. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Sonogashira Cross‐Couplings of Dehydroamino Acid Derivatives and Phenylacetylenes
Authors: Abreu Ana S. , Ferreira Paula M. T. , Queiroz Maria‐João R. P. , Gatto Emanuela , Venanzi Mariano
Published: September 2004

Several phenylacetylenes were coupled under Sonogashira cross‐coupling conditions with the methyl esters of N‐(tert‐butoxycarbonyl)‐(E)‐β‐bromo‐ or ‐β,β‐dibromodehydroalanine, to give β‐substituted or β,β‐disubstituted dehydroalanines, respectively. The β‐substituted dehydroalanines were obtained in good to high yields (60−90%) under the usual Sonogashira conditions (1 equiv. of the phenylacetylene, 1 mol % of [Pd(PPh3)4], 2 mol % of CuI, 18 equiv. of NEt3 in acetonitrile, 24 h at room temp.), with retention of stereochemistry. The β,β‐disubstituted dehydroalanines were, in turn, obtained in moderate to good yields (44−63%) under modified Sonogashira conditions (4 equiv. of the phenylacetylene,10 mol % of [PdCl2(PPh3)2], 20 mol % of CuI, 1.4 equiv. of Cs2CO3 in acetonitrile, 2 h at reflux). In the latter reactions, some phenylacetylene dimer and the (E) isomer of the monosubstituted coupled products were also isolated to some extent. The Sonogashira products obtained from the 4‐bromophenylacetylene were allowed to react with functionalized benzo[b]thiophenes under C−C or C−N palladium‐catalyzed cross‐coupling conditions. Preliminary fluorescence studies were performed for mono‐ and disubstituted (4‐aminophenyl)acetylenic dehydroamino acids and for the benzo[b]thiophene derivatives. The results showed that some of the dehydroalanines prepared can be used as fluorescent probes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
TAME‐Hex A − A Novel Bifunctional Chelating Agent for Radioimmunoimaging
Authors: Arslantas Enver , Smith‐Jones Peter M. , Ritter Gerd , Schmidt Richard R.
Published: September 2004

Two novel (bifunctional) chelating agents, TAME‐Hex A and B, which are polyaminopolycarboxylic acids based on the tripodal TAME [tris(aminomethyl)ethane] structure, have been designed and synthesized. The chelators show very good stability with gallium(III) ions and thus are highly effective candidates for use in radioimmunoimaging (RII), especially in positron emission tomography (PET). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Connective Synthesis of Spirovetivanes: Total Synthesis of (±)‐Agarospirol, (±)‐Hinesol and (±)‐α‐Vetispirene
Authors: Maulide Nuno , Vanherck Jean‐Christophe , Markó István E.
Published: September 2004

A concise, connective synthesis of naturally occurring spirovetivanes 1 and 3, in racemic form, is presented. This novel approach involves the efficient assembly of the advanced intermediate 12 through a unique spiroannulation protocol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Trends in Asymmetric Michael Reactions Catalysed by Tripeptides in Combination with an Achiral Additive in Different Solvents
Authors: Tsogoeva Svetlana B. , Jagtap Sunil B. , Ardemasova Zoya A. , Kalikhevich Victor N.
Published: September 2004

The potential of tripeptides 3, 6 and 12 as chiral catalysts for asymmetric Michael addition reactions in the presence of an achiral additive has been tested in different solvents (CHCl3, acetone, DMF, DMSO and the room‐temperature ionic liquid [bmim]PF6). The dependence of yields and enantiomeric excesses on the solvent used has been demonstrated. The experiments show that the combination of additive and peptides provides a catalytic system that appears to be better than the sum of its parts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of C3‐Symmetric Nano‐Sized Polyaromatic Compounds by Trimerization and Suzuki−Miyaura Cross‐Coupling Reactions
Authors: Kotha Sambasivarao , Kashinath Dhurke , Lahiri Kakali , Sunoj Raghavan B.
Published: September 2004

Various C3‐symmetric molecules were prepared by trimerization of acetyl aromatic compounds and subsequently coupled with various boronic acids under Pd0 catalysis conditions to generate oligoaryl/‐heteroaryl C3‐symmetric molecules. Several furan‐ and thiophene‐containing star‐shaped molecules were prepared by the use of Suzuki−Miyaura cross‐coupling as a key step. Structural and conformational details were explored by semi‐empirical molecular orbital theory using the AM1 method. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Glycosyl Phosphonates by Michael‐Type Addition to 2‐Nitroglycals
Authors: Pachamuthu Kandasamy , Figueroa‐Perez Ignacio , Ali Ibrahim A. I. , Schmidt Richard R.
Published: September 2004

A new synthetic strategy, which allows to synthesize both α‐ and β‐anomers of 2‐acetylaminoglycosyl phosphonate or exclusively β‐anomer is described. The present strategy is a successful Michael‐type addition of dimethyl hydrogen phosphonate to 2‐nitroglycals. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Superacidic Activation of α,β‐Unsaturated Amides and Their Electrophilic Reactions
Authors: Koltunov Konstantin Yu. , Walspurger Stéphane , Sommer Jean
Published: September 2004

The electrophilic reactivity of α,β‐unsaturated amides towards weak nucleophiles such as arenes and cyclohexane, initiated either with triflic acid (CF3SO3H) or with excess AlCl3, has been studied. The amides generally condense readily with aromatics in the presence of AlCl3 to give 3‐arylpropionamides and related compounds in excellent yields, while some amides also undergo selective ionic hydrogenation with cyclohexane to give saturated amides. The proposed mechanism of these reactions involves dicationic intermediates (superelectrophiles). The direct observation of a dicationic species (by low‐temperature NMR) is reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
On the Role of Water in Amide Hydrolysis
Authors: Zahn Dirk
Published: September 2004

The mechanism of the water‐assisted amide hydrolysis of N‐methylacetamide has been elucidated by Car‐Parrinello simulation and related to prior investigations of the acid‐ and the base‐catalyzed pathways. Each process was investigated in aqueous solution, and the water molecules were found to play a crucial role in the amide hydrolysis, with several reaction steps involving proton‐transfer events in which the water molecules serve as donors or acceptors. This calls for a quantum treatment of all electronic degrees of freedom, including those of the solvent molecules. A detailed analysis of the mechanisms of the amide hydrolysis pathways obtained from our simulations is given. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Theoretical Studies on Cycloaddition Reactions between 1‐Aza‐2‐azoniaallene Cations and Isocyanates
Authors: Wei Mei‐Ju , Fang De‐Cai , Liu Ruo‐Zhuang
Published: September 2004

The mechanisms of the title reactions between 1‐aza‐2‐azoniaallene cations and isocyanic acid or isocyanates have been theoretically explored at the B3LYP/6‐31++G** level. It was found that all of these reactions proceed in asynchronous but concerted pathways. The substituent effects are also obvious; e.g., the presence either of an electron‐withdrawing chlorine substituent on the 1‐aza‐2‐azoniaallene cation or of an electron‐releasing methyl substituent on the isocyanate both favor the cycloaddition reactions. For the [1,2]‐shift reactions, all the substituents lower their activation barrier, especially Cl substituents on the 1‐aza‐2‐azoniaallene cation, but when Cl substituents are present on the 1‐aza‐2‐azoniaallene cation the rearrangement product is not as stable as others. In addition, solvent effects with the PCM model are also reported, and a model reaction has been investigated at the MP2/6‐31+G* and QCISD/6‐31+G* levels as well as by DFT. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Diethyl Cyclopropylidenemalonate: Facile Preparation, Generation in situ, and Various Transformations
Authors: de Meijere Armin , Kostikov Rafael R. , Savchenko Andrei I. , Kozhushkov Sergei I.
Published: September 2004

Reductive cyclopropanation of triethyl methanetricarboxylate (4a) with ethylmagnesium bromide in the presence of titanium tetraisopropoxide furnished diethyl 2‐(1′‐hydroxycyclopropyl)malonate (5a) in 50% yield. Dehydromesylation of the mesylate of cyclopropanol 5a, generated in situ, by treatment with an excess of triethylamine gave diethyl cyclopropylidenemalonate 3‐Et as a highly reactive, unstable compound, which could be isolated as an oil in 39% yield, but more favorably could also be generated in situ from the mesylate or the acetate 11 (prepared from 5a in 90% yield) and trapped without isolation with various N‐, O‐, S‐, and C‐nucleophiles. Thus, ammonia, dimethylamine, isopropylamine, diethylamine, dibenzylamine, morpholine, N‐methylpiperazine, piperazine, aniline, p‐cresol, 1‐thionaphthol, and cyanide anion easily add to the double bond of the diester 3‐Et generated in situ at ambient temperature, forming 1′‐substituted cyclopropylmalonates 10a−i in 18−95% yields. The α,β‐unsaturated diester 3‐Et also easily enters into 1,3‐dipolar and Diels−Alder cycloadditions with nitrones, ethyl diazoacetate, azide anion, and dienes to give the corresponding cycloadducts in 12−83% yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cover Picture: Synthesis and Biological Evaluation of Macrosphelide Cores (Eur. J. Org. Chem. 19/2004)
Authors: Ishihara Kentaro , Kawaguchi Takanori , Matsuya Yuji , Sakurai Hiroaki , Saiki Ikuo , Nemoto Hideo
Published: September 2004

The cover picture shows the structures of the bioactive natural macrolide, macrosphelide A (third structure from left) and its artificial analogues. The other structures exhibit different oxidation states at the allylic positions on the common 16‐membered ring skeleton. The antitumor activity increases from left to right. This image reflects the importance of the oxygen functionalities for the bioactivity of naturally occurring macrosphelides, as discussed in the article by H. Nemoto et al. on p. 3973 ff.
Field assessments on the accuracy of spherical gauges in rainfall measurements
Authors: Chang Mingteh , Harrison Lee
Published: September 2004

In an effort to reduce wind effect on rainfall catch to a minimum level, Chang and Flannery (2001. Hydrological Processes 15: 643–654) designed two spherical orifices to modify the standard gauge and other gauges in use today. Because of the spherical shape, the two orifices will catch rain with an effective diameter always equal to the actual diameter, regardless of wind speed and direction. This report covers the testing of spherical gauges at two different locations, one at the City Landfill, Nacogdoches, TX, and the other at the NWS Forecast Office, Shreveport, LA. Based on 131 storms at Nacogdoches and 94 storms at Shreveport, observed between May 1998 and February 2001, the results showed: (1) spherical gauges recorded an average 6–9% greater than standard gauge and 3–4% less than pit gauge, only 1–2% less than reported in the original study; (2) the catch of spherical gauges was not significantly affected by three gauge heights at 0·91, 1·83, and 2·74 m above the ground, but catch by the standard gauge decreased with increasing gauge height; (3) improvements of the spherical gauges were most significant for larger storms and for winds at higher speeds; (4) the spherical gauge with cylinders recorded 1–2% more rainfall than the spherical gauge with vanes; and (5) correlation coefficients between catch deficiencies and wind speed were low and weak because of the distance and height of the existing wind sensor.

Owing to greater surface wetting and evaporation loss, the spherical gauges may underestimate rainfall catch by standard gauge for small storms (generally less than 5·0 mm), especially on hot summer afternoons and for smaller storms. However, the underestimates do not overshadow the merits of spherical gauges, because the differences are too small to be of hydrologic significance. Using polyethylene or other synthesized materials to construct spherical orifices may improve the catch for small storms. The results of the study agreed with the previous claims that spherical gauges are effective in reducing wind effects on rainfall measurements. The spherical gauges could greatly improve the accuracy of hydrologic simulations and the efficiency on the designs and management of water resources. They are suitable for large‐scale applications. Copyright © 2004 John Wiley & Sons, Ltd.
Effects of suspended sediment characteristics and bed sediment transport on streambed clogging
Authors: Rehg Kristin J. , Packman Aaron I. , Ren Jianhong
Published: September 2004

Fine sediment deposition in streambeds can reduce pore water fluxes and the overall rate of hyporheic exchange, producing deleterious effects on benthic and hyporheic ecological communities. To increase understanding of the factors that control the reduction of hyporheic exchange by fine sediment deposition, we conducted experiments in a laboratory flume to observe changes in the rates of solute exchange and kaolinite clay deposition as substantial amounts of kaolinite accumulated in the streambed. Two long‐term experiments were conducted, with durations of 14 days and 29 days. Use of a laboratory flume system allowed steady stream flow conditions to be maintained throughout both experiments, and alternating injections of known quantities of kaolinite and a sodium chloride tracer were used to assess the effect of clay accumulation on hyporheic exchange directly. In the first experiment, there was no bed sediment transport and kaolinite deposition formed a highly clogged near‐surface layer that greatly reduced hyporheic exchange. Application of a fundamental model for advective hyporheic exchange indicated that the effective permeability and porosity of the streambed decreased substantially during the course of the experiment. In the second experiment, the kaolinite was prepared with different surface properties to be more mobile, and the experiment was conducted with a small degree of bed sediment transport. As a result, no distinct clogged layer developed, and the rate of hyporheic exchange was found to remain approximately constant throughout the experiment (29 days). These results indicate that increasing fine sediment loads, e.g. those that occur from changes in land use, can have substantially different impacts on hyporheic exchange and associated ecological processes depending on the stream flow conditions, the rate and frequency of bed sediment transport, and the extent of interaction of the introduced fines with bed sediments. Copyright © 2004 John Wiley & Sons, Ltd.
Dynamics in land cover and its effect on stream flow in the Chemoga watershed, Blue Nile basin, Ethiopia
Authors: Bewket Woldeamlak , Sterk Geert
Published: September 2004

The objective of this study was to analyse changes in stream flow patterns with reference to dynamics in land cover/use in a typical watershed, the Chemoga, in northwestern highland Ethiopia. The results show that, between 1960 and 1999, total annual stream flow decreased at a rate of 1 · 7 mm year−1, whereas the annual rainfall decreased only at a rate of 0 · 29 mm year−1. The decrease in the stream flow was more pronounced during the dry season (October to May), for which a statistically significant decline (0 · 6 mm year−1) was observed while the corresponding rainfall showed no discernible trend. The wet season (June to September) rainfall and stream flow did not show any trends. Extreme low flows analysed at monthly and daily time steps reconfirmed that low flows declined with time, the changes being highly significant statistically. Between 1960 and 1999, the monthly rainfall and stream flow amounts of February (month of lowest long‐term mean flow) declined by 55% and 94% respectively. Similarly, minimum daily flows recorded during the three driest months (December to February) showed statistically highly significant declines over the same period. It declined from 0 · 6 m3 s−1 to 0 · 2 m3 s−1 in December, from 0 · 4 m3 s−1 to 0 · 1 m3 s−1 in January and from 0 · 4 m3 s−1 to 0 · 02 m3 s−1 in February (1 · 0 m3 s−1 = 0 · 24 mm day−1 in the Chemoga watershed). In contrast, extreme high flows analysed at monthly (for August) and daily (July to September) time steps did not reveal discernible trends. The observed adverse changes in the stream flow have partly resulted from changes in land cover/use and/or degradation of the watershed that involved destruction of natural vegetative covers, expansion of croplands, overgrazing and increased area under eucalypt plantations. The other contributory factor has been the increased dry‐season water abstraction to be expected from the increased human and livestock populations in the area. Given the significance of the stream flow as the only source of water to the local people, a set of measures aimed at reducing magnitudes of surface runoff generation and increasing groundwater recharge are required to sustain the water resource and maintain a balanced dry‐season flow in the watershed. Generally, an integrated watershed management approach, whereby the whole of the watershed can be holistically viewed and managed, would be desirable. Copyright © 2004 John Wiley & Sons, Ltd.
Statistical probability distribution of snow depth at the model sub‐grid cell spatial scale
Authors: Marchand Wolf‐Dietrich , Killingtveit Ånund
Published: September 2004

Comprehensive snow depth data, collected using georadar and hand probing, were used for statistical analyses of snow depths inside 1 km grid cells. The sub‐grid cell spatial scale was 100 m. Statistical distribution functions were found to have varying parameters, and an attempt was made to connect these statistical parameters to different terrain variables. The results showed that the two parameters mean and standard deviation of snow depth were significantly related to the sub‐grid terrain characteristics. Linear regression models could explain up to 50% of the variation for both of the snowcover parameters mentioned. Copyright © 2004 John Wiley & Sons, Ltd.
Observations of urban snow properties in Calgary, Canada
Authors: Ho C. L. I. , Valeo C.
Published: September 2004

Urban winter hydrology has garnered very little attention owing to the general notion that high‐intensity rainfalls are the major flood‐generating events in urban areas. As a result, few efforts have been made to research urban snow and its melt characteristics. This study investigates the characteristics of urban snow that differentiate it from rural snow, and makes recommendations for incorporating these characteristics into an urban snowmelt model. A field study was conducted from the fall of 2001 to the spring of 2002 in the city of Calgary, Canada. Snow depths and densities, soil moisture, soil temperature, snow albedo, net radiation, snow evaporation, and surface temperature were measured at several locations throughout the winter period. The combination of urban snow removal practices and the physical elements that exist in urban areas were found to influence the energy balance of the snowpack profoundly. Shortwave radiation was found to be the main source of energy for urban snow; as a consequence, the albedo of urban snow is a very important factor in urban snowmelt modelling. General observations lead to the classification of snow as one of four types: snow piles, snow on road shoulders, snow on sidewalk edges, and snow in open areas. This resulted in the development of four separate functions for the changing snow albedo values. A study of the frozen ground conditions revealed that antecedent soil moisture conditions had very little impact on frozen ground, and thus frozen ground very nearly always acts as a near impervious area. Improved flood forecasting for urban catchments in cold regions can only be achieved with accurate modelling of urban winter runoff that involves the energy balance method, incorporating snow redistribution and urban snow‐cover characteristics, and using small time steps. Copyright © 2004 John Wiley & Sons, Ltd.
Estimation of source water to cedar elm in a central Texas riparian ecosystem
Authors: Muttiah Ranjan S. , White Joseph D. , Duke Jacquelyn R. , Allen Peter M.
Published: September 2004

A riparian ecosystem downstream of a small dam in central Texas was instrumented for sap flow, soil moisture content, and stream level from 2001. Stable isotopes in water (D and 18O) were analysed from rainfall, stream, lake, and cored sapwood cellulose from cedar elm (Ulmus crassifolia). The isotope signature of water source to cedar elm was identified by back calculation starting with the water isotopes in cellulose, and accounting for leaf‐water evaporation and biological fractionation during cellulose synthesis. The estimated mean isotope of the source water to cedar elm was enriched above rainfall in similarity to stream water during 2002. Flow paths that may have contributed to estimated variability from regional base flow and recharge water were identified using the variably saturated HYDRUS‐2D model. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of agricultural drought in Iiuni, Eastern Kenya: application of a Markov model
Authors: Biamah E. K. , Sterk G. , Sharma T. C.
Published: September 2004

In semi‐arid Kenya, episodes of agricultural droughts of varying severity and duration occur. The occurrence of these agricultural droughts is associated with seasonal rainfall variability and can be reflected by seasonal soil moisture deficits that significantly affect crop performance and yield. The objective of this study was to stochastically simulate the behaviour of dry and wet spells and rainfall amounts in Iiuni watershed, Kenya. The stochastic behaviour of the longest dry and wet spells (runs) and largest rainfall amounts were simulated using a Markov (order 1) model. There were eight raingauge stations within the watershed. The entire analysis was carried out using probability parameters, i.e. mean, variance, simple and conditional probabilities of dry and rain days. An analysis of variance test (ANOVA) was used to establish significant differences in rainfall characteristics between the eight stations. An analysis of the number of rain days and rainfall amount per rain day was done on a monthly basis to establish the distribution and reliability of seasonal rainfall. The graphic comparison of simulated cumulative distribution functions (Cdfs) of the longest spells and largest rainfall amounts showed Markovian dependence or persistence. The longest dry spells could extend to 24 days in the long rainy season and 12 in the short rainy season. At 50% (median) probability level, the largest rainfall amounts were 91 mm for the long rainy season and 136 mm for the short rainy season. The short rains were more reliable for crop production than the long rains. The Markov model performed well and gave adequate simulations of the spells and rainfall amounts under semi‐arid conditions. Copyright © 2004 John Wiley & Sons, Ltd.
Peptide‐modified alginate surfaces as a growth permissive substrate for neurite outgrowth
Authors: Dhoot Nikhil O. , Tobias Chris A. , Fischer Itzhak , Wheatley Margaret A.
Published: September 2004

Different strategies are being investigated for treatment of spinal cord injuries, one of the most promising being application of neurotrophic factors, which have been shown to prevent neuronal death and stimulate regeneration of injured axons. Ex vivo gene therapy has emerged as the leading delivery method at the site of the injury, and we have shown previously that encapsulating genetically engineered fibroblasts in an immunoprotective alginate capsule can permit implantation of the factor‐secreting cells without need for immunosuppression. This strategy could be greatly enhanced by providing the sprouting neurons with a permissive substrate upon which to attach and grow. We report here studies on the modification of an alginate gel surface by either coating it with laminin or by covalent attachment of YIGSR peptide. Using NB2a neuroblastoma cells, we found that native alginate elicited minimal cell attachment (∼1.5%); however, YIGSR‐alginate conjugate elicited a fivefold increase in numbers of cells attached using peptide ratios of 0.5 and 1 mg/g alginate, ranging from 9.5% of the cells at the lower ratio, to about 44% at the higher. Only a further 19% increase was obtained at an increased peptide density of 2 mg/g alginate (∼63% over control). Laminin‐coated gels showed ∼60% cell attachment. However, laminin coating did not stimulate differentiation and neurite growth, whereas both numbers and lengths of outgrowths increased with increasing peptide density on peptide‐modified alginate. We demonstrate here the ability of the peptide‐modified alginate gels to allow adhesion of NB2a neuroblastoma cells and to promote neurite outgrowth from these cells when attached to the peptide‐modified alginate surface. Also, we show that the adhesion of NB2a neuroblastoma cells and neurite outgrowth from the attached cells is a function of the peptide density on the gel surface. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 191–200, 2004
Site‐specific delivery of acidic fibroblast growth factor stimulates angiogenic and osteogenic responses in vivo
Authors: Kelpke S. S. , Zinn K. R. , Rue L. W. , Thompson J. A.
Published: September 2004

A major clinical problem in orthopedics is the healing of nonunion fractures. Limitations of this bone repair process include insufficient angiogenesis and mineralization. Integrating appropriate biomaterials with site‐specific neovascularization and osteogenesis at the wound site has been the focus of several clinically relevant therapeutic strategies. As an extracellular protein, acidic fibroblast growth factor (FGF‐1) induces, coordinates, and sustains site‐specific molecular responses associated with angiogenesis and osteogenesis. To establish the ability of this growth factor to coordinate bone regenerative process in vivo, site‐specific delivery of FGF‐1, entrapped in a fibrin/hydroxyapatite composite, was evaluated. Kinetic analysis in vivo revealed the biocomposite was capable of delivering biologically active FGF‐1. Release kinetics revealed an initial delivery of 87.5 ng/h of active FGF‐1 in the first 20 h, followed by a reduced delivery of 28 ng/h during the next 20 h. In situ immunohistological analyses demonstrated that FGF‐1–containing implants induced increased angiogenesis and infiltration of cells expressing osteogenic related markers (i.e., osteopontin, osteocalcin). Collectively, these efforts support that site‐specific delivery of active FGF‐1 in a fibrin/hydroxyapatite composite is competent to induce not only angiogenesis but also osteogenic cellular responses. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 316–325, 2004