bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic and cognitive abnormalities in mouse models of down syndrome: Exploring genotype‐phenotype relationships
Authors: Belichenko Pavel V. , Kleschevnikov Alexander M. , Salehi Ahmad , Epstein Charles J. , Mobley William C.
Published: July 2007

Down syndrome (DS) is caused by trisomy of human chromosome 21. Because Ts65Dn and Ts1Cje mice are segmentally trisomic for a region of mouse chromosome 16, they genetically model DS and are used to study pathogenic mechanisms. Previously, we provided evidence for changes in both the structure and function of pre‐ and postsynaptic elements in the Ts65Dn mouse. Striking changes were evident in the size of the dendritic spines and in the ability to induce long‐term potentiation (LTP) in the fascia dentata (FD). To explore the genetic basis for these changes, we examined Ts1Cje mice, which are trisomic for a completely overlapping but smaller segment of mouse chromosome 16. As in the Ts65Dn mouse, there was a regionally selective decrease in the density of dendritic spines (∼12%), an increase in the size of spine heads (∼26%), a decrease in the length of spine necks (∼26%), and reorganization of inhibitory inputs with a relative decrease in inputs to dendrite shafts and spine heads and a significant increase to the necks of spines (6.4%). Thus, all of the Ts65Dn phenotypes were present, but they were significantly less severe. In contrast, and just as was the case for the Ts65Dn mouse, LTP could not be induced unless the selective γ‐aminobutyric acid (GABA)A receptor antagonist picrotoxin was applied. Therefore, there was conservation of important synaptic phenotypes in the Ts1Cje mice. The analysis of data from this and earlier studies points to genotype‐phenotype linkages in DS whose complexity ranges from relatively simple to quite complex. J. Comp. Neurol. 504:329–345, 2007. © 2007 Wiley‐Liss, Inc.
Nav1.7 and Nav1.3 are the only tetrodotoxin‐sensitive sodium channels expressed by the adult guinea pig enteric nervous system
Authors: Sage D. , Salin P. , Alcaraz G. , Castets F. , Giraud P. , Crest M. , Mazet B. , Clerc N.
Published: July 2007

The types of sodium channels that are expressed by neurons shape the rising phase of action potentials and influence patterns of action potential discharge. With regard to the enteric nervous system (ENS), there is uncertainty about which channels are expressed, and in particular it is unknown whether Nav1.7 is present. We designed specific probes for the guinea pig Nav1.7 α subunit as well as for the other tetrodotoxin (TTX)‐sensitive α subunits (Nav1.1, Nav1.2, Nav1.3, and Nav1.6) in order to perform in situ hybridization (ISH) histochemistry on guinea pig myenteric ganglia. We established that only Nav1.7 mRNA and Nav1.3 mRNA are expressed in these ganglia. The ISH signal for Nav1.7 transcripts was found in seemingly all the myenteric neurons. The expression of the Nav1.3 α subunit was confirmed by immunohistochemistry in a large proportion (62%) of the myenteric neuron population. This population included enteric sensory neurons. Nav1.6 immunoreactivity, absent from myenteric neurons, was detected in glial cells only when a high anti‐Nav1.6 antibody concentration was used. This suggests that the Nav1.6 α subunit and mRNA are present only at low levels, which is consistent with the fact that no Nav1.6 mRNA could be detected in the ENS by ISH. The fact that adult myenteric neurons are endowed with only two TTX‐sensitive α subunits, namely, Nav1.3 and Nav1.7, emphasizes the singularity of the ENS. Both these subunits, known to have slow‐inactivation kinetics, are well adapted for generating action potentials from slow excitatory postsynaptic potentials, a mode of synaptic transmission that applies to all ENS neuron types. J. Comp. Neurol. 504:363–378, 2007. © 2007 Wiley‐Liss, Inc.
Molecular, cellular, and functional characterizations of pituitary adenylate cyclase‐activating polypeptide and its receptors in the cerebellum of New and Old World monkeys
Authors: Aubert Nicolas , Basille Magali , Falluel‐Morel Anthony , Vaudry David , Bucharles Christine , Jolivel Valerie , Fisch Cecile , De Jouffrey Stephane , Le Bigot Jean‐Francois , Fournier Alain , Vaudry Hubert , Gonzalez Bruno J.
Published: July 2007

The neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP) exerts trophic activities during cerebellar development, and a neuroprotective effect of PACAP has been demonstrated in pathological conditions such as stroke. However, all these data have been obtained in rodents, and neuroprotective effects of PACAP in primates remain unknown. Because of their evolutionary relationships with humans, monkeys represent powerful models for validating the therapeutic interest in PACAP. The objective of the present study was to characterize PACAP and its receptors in the cerebellum of two nonhuman primates. RT‐PCR and in situ hybridization experiments revealed that PACAP is expressed in the cerebellum by Purkinje cells. Via immunohistochemistry, PACAP was detected in Purkinje cells and radial glial fibers. With regard to PACAP receptors, PAC1‐R and VPAC1‐R were detected by RT‐PCR. In situ hybridization revealed a strong expression of PAC1‐R and VPAC1‐R in the granule cell layer (GCL), and VPAC1‐R was also expressed in the Purkinje cell layer. A high density of PACAP binding sites was visualized in the GCL and the Purkinje cell layer. Competition studies indicated that, in the GCL, PACAP induced complete displacement of [125I]PACAP27 binding, whereas vasoactive intestinal polypeptide (VIP) was a weak competitor. In contrast, in the Purkinje cell layer, both PACAP and VIP displaced [125I]PACAP27 binding. Measurement of cAMP levels showed that PACAP is a powerful activator of adenylyl cyclase, whereas VIP is about 100‐fold less potent. Altogether, these observations constitute the first demonstration of a functional PACAPergic system in monkey cerebellum. They strongly suggest that neuroprotective effects of PACAP can be transposed to primates, including human. J. Comp. Neurol. 504:427–439, 2007. © 2007 Wiley‐Liss, Inc.
Sodium deprivation and salt intake activate separate neuronal subpopulations in the nucleus of the solitary tract and the parabrachial complex
Authors: Geerling Joel C. , Loewy Arthur D.
Published: July 2007

Salt intake is an established response to sodium deficiency, but the brain circuits that regulate this behavior remain poorly understood. We studied the activation of neurons in the nucleus of the solitary tract (NTS) and their efferent target nuclei in the pontine parabrachial complex (PB) in rats during sodium deprivation and after salt intake. After 8‐day dietary sodium deprivation, immunoreactivity for c‐Fos (a neuronal activity marker) increased markedly within the aldosterone‐sensitive neurons of the NTS, which express the enzyme 11‐β‐hydroxysteroid dehydrogenase type 2 (HSD2). In the PB, c‐Fos labeling increased specifically within two sites that relay signals from the HSD2 neurons to the forebrain—the pre‐locus coeruleus and the innermost region of the external lateral parabrachial nucleus. Then, 1–2 hours after sodium‐deprived rats ingested salt (a hypertonic 3% solution of NaCl), c‐Fos immunoreactivity within the HSD2 neurons was virtually eliminated, despite a large increase in c‐Fos activation in the surrounding NTS (including the A2 noradrenergic neurons) and area postrema. Also after salt intake, c‐Fos activation increased within pontine nuclei that relay gustatory (caudal medial PB) and viscerosensory (rostral lateral PB) information from the NTS to the forebrain. Thus, sodium deficiency and salt intake stimulate separate subpopulations of neurons in the NTS, which then transmit this information to the forebrain via largely separate relay nuclei in the PB complex. These findings offer new perspectives on the roles of sensory information from the brainstem in the regulation of sodium appetite. J. Comp. Neurol. 504:379–403, 2007. © 2007 Wiley‐Liss, Inc.
Vestibular ganglion neurons survive hair cell defects in jerker, shaker, and varitint‐waddler mutants and downregulate calretinin expression
Authors: Čabraja Mario , Bäurle Jörg
Published: July 2007

Bipolar neurons (BNs) in the vestibular ganglion (VG) connect vestibular hair cells with the central nervous system (CNS). Disturbed function and cell loss in central vestibular target areas or in the vestibular periphery involve BNs either retro‐ or anterogradely. However, the impact of central vestibular disturbances or hair cell defects on the maintenance of BNs is poorly understood. In the present study the volume of the VG, the size and total number of BNs, and the number of BNs expressing the calcium‐binding protein calretinin (Calr) were quantified stereologically in the cerebellar mutants purkinje cell degeneration (pcd/pcd), weaver (wv/wv), and Lurcher (Lc/+), and in the vestibular mutants jerker (je/je), shaker‐1 (sh/sh), and Varitint‐waddler (Va/+). In all the different mutant mice investigated the total number of BNs did not differ from that of wildtypes. In contrast, the number of Calr‐positive BNs was significantly reduced in je/je (23%) and sh/sh (33%) mutants. Reduced cell size was apparent in sh/sh mutants and the volume of the VG significantly decreased in je/je mice. Calr was virtually absent from calyx endings in the vestibular periphery of je/je, sh/sh, and Va/+ mutants, whereas in wildtypes and cerebellar mutants many calyces displayed intense Calr labeling. These results imply that the survival of BNs is apparently unaffected by the peripheral and central target defects found in the mutants investigated. Whether the decrease in Calr expression may reflect biochemical adaptations in response to input disturbances or a specific loss of large BNs is discussed. J. Comp. Neurol. 504:418–426, 2007. © 2007 Wiley‐Liss, Inc.
Convergence of olfactory and vomeronasal projections in the rat basal telencephalon
Authors: Pro‐Sistiaga Palma , Mohedano‐Moriano Alicia , Ubeda‐Bañon Isabel , del mar Arroyo‐Jimenez Maria , Marcos Pilar , Artacho‐Pérula Emilio , Crespo Carlos , Insausti Ricardo , Martinez‐Marcos Alino
Published: July 2007

Olfactory and vomeronasal projections have been traditionally viewed as terminating in contiguous non‐overlapping areas of the basal telencephalon. Original reports, however, described areas such as the anterior medial amygdala where both chemosensory afferents appeared to overlap. We addressed this issue by injecting dextran amines in the main or accessory olfactory bulbs of rats and the results were analyzed with light and electron microscopes. Simultaneous injections of different fluorescent dextran amines in the main and accessory olfactory bulbs were performed and the results were analyzed using confocal microscopy. Similar experiments with dextran amines in the olfactory bulbs plus FluoroGold in the bed nucleus of the stria terminalis indicate that neurons projecting through the stria terminalis could be integrating olfactory and vomeronasal inputs. Retrograde tracing experiments using FluoroGold or dextran amines confirm that areas of the rostral basal telencephalon receive inputs from both the main and accessory olfactory bulbs. While both inputs clearly converge in areas classically considered olfactory‐recipient (nucleus of the lateral olfactory tract, anterior cortical amygdaloid nucleus, and cortex–amygdala transition zone) or vomeronasal‐recipient (ventral anterior amygdala, bed nucleus of the accessory olfactory tract, and anteroventral medial amygdaloid nucleus), segregation is virtually complete at posterior levels such as the posteromedial and posterolateral cortical amygdalae. This provides evidence that areas so far considered receiving a single chemosensory modality are likely sites for convergent direct olfactory and vomeronasal inputs. Therefore, areas of the basal telencephalon should be reclassified as olfactory, vomeronasal, or mixed chemosensory structures, which could facilitate understanding of olfactory–vomeronasal interactions in functional studies. J. Comp. Neurol. 504:346–362, 2007. © 2007 Wiley‐Liss, Inc.
Projection of diffusions on submanifolds: Application to mean force computation
Authors: Ciccotti Giovanni , Lelièvre Tony , Vanden‐Eijnden Eric
Published: July 2007

We consider the problem of sampling a Boltzmann‐Gibbs probability distribution when this distribution is restricted (in some suitable sense) on a submanifold Σ of ℝn implicitly defined by N constraints q1(x) = ⃛ = qN(x) = 0 (N < n). This problem arises, for example, in systems subject to hard constraints or in the context of free energy calculations. We prove that the constrained stochastic differential equations (i.e., diffusions) proposed in [7, 13] are ergodic with respect to this restricted distribution. We also construct numerical schemes for the integration of the constrained diffusions. Finally, we show how these schemes can be used to compute the gradient of the free energy associated with the constraints. © 2007 Wiley Periodicals, Inc.
On the shielding effect of the Helmholtz equation
Authors: Chen Yu
Published: July 2007

Hadamard‐type instability has been known for over a century as a cause of ill‐posedness of the Cauchy problem for elliptic PDEs. This ill‐posedness manifests itself as evanescent modes growing exponentially when propagated in the reverse direction. Since every oscillating mode of the Laplace equation is evanescent, the ill‐posedness of its Cauchy problem is solely due to Hadamard‐type instability. The presence of the propagating modes and beams for the Helmholtz equation gives rise to an entirely different type of ill‐posedness, hitherto unknown to the practice, and untreated by the theory, of inverse scattering. We will present this fundamental phenomenon of ill‐posedness for the Helmholtz equation. © 2007 Wiley Periodicals, Inc.
A practical method to analyze workflow logic models
Authors: Huang Yu , Wang Hanpin , Zhao Wen , Xu Chunxiang
Published: July 2007

The analysis of workflow is crucial to the correctness of workflow applications. This paper introduces a simple and practical method for analyzing workflow logic models. Firstly, some definitions of the models and some properties, such as throughness, no‐redundant‐transition and boundedness, are presented. Then, we propose an approach based on synchronized reachability graphs (SRGs) to verify these properties. The SRG uses the characteristics of synchronizers in workflow logic models and mitigates the state explosion by constructing synchronized occurrence sequences rather than interleaving occurrence sequences. This paper also proposes some refined and feasible reduction rules which can preserve vital properties of workflow logic models. Using these two techniques, the SRG‐based verification method can achieve higher efficiency. Furthermore, this research also develops a verification tool based on the method, presents the analysis results of some practical cases and compares our method with others. Copyright © 2007 John Wiley & Sons, Ltd.
Magnetic and Structural Investigation of Mn2+‐Doped ZnSe Semiconductor Nanoparticles
Authors: Hofmann Andreas , Graf Christina , Boeglin Christine , Rühl Eckart
Published: July 2007

X‐ray magnetic circular dichroism (XMCD) experiments on diluted magnetic semiconductor nanocrystals were carried out to study the local electronic structure and magnetic properties of Mn2+ embedded in the lattice of ZnSe nanoparticles. It is shown that Mn2+ is exclusively present in the bulk of ZnSe nanoparticles. Neither Mn–Mn coupling nor traces of oxidation to higher Mn oxidation states was observed. This result, which is consistent with EPR spectroscopic data, provides clear proof of the location of Mn2+ in semiconductor nanoparticles. Further, it is shown that the magnetic ions are highly polarised inside the nanocrystals, where they reach about 50 % of the theoretical value of a pure d5 state under identical conditions.
Ab Initio Molecular Dynamics Free‐Energy Study of Microhydration Effects on the Neutral–Zwitterion Equilibrium of Phenylalanine
Authors: Rodziewicz Pawel , Doltsinis Nikos L.
Published: July 2007

The structures and relative energies of the most stable conformers of both naked and microsolvated phenylalanine, Phe⋅(H2O)n (n=0–3), are calculated by density functional theory. For selected structures, coordination‐constrained ab initio molecular dynamics simulations determine the proton‐transfer mechanism connecting neutral and zwitterionic forms of Phe. The associated free‐energy profiles are calculated by thermodynamic integration. While no zwitterionic free‐energy minimum is found for naked Phe, microsolvation is found to stabilize the zwitterionic form. For cluster sizes n≥3, the proton‐transfer equilibrium shifts towards the zwitterionic structure for specific proton‐transfer pathways. The energetically most favourable interconversion path between the neutral and zwitterionic forms is through a H2O bridge with free‐energy barriers as low as 14.4 kJ mol−1 for Phe⋅(H2O)3. The free energy required for breaking a carboxylic OH bond involved in intramolecular hydrogen bonding is typically lower than in the water‐assisted case. However, the resulting zwitterion turns out to be unstable with respect to the backward proton‐transfer reaction.
FeII Bistable Materials with Dissymmetrical Ligands: Synthesis, Crystal Structure, Magnetic and Mössbauer Properties of FeII Complexes Based on N4 Schiff Bases Possessing 2‐Pyridyl and 1‐R‐Imidazol‐2‐yl Rings
Authors: Bréfuel Nicolas , Shova Sergiu , Tuchagues Jean‐Pierre
Published: July 2007

The synthesis and characterization of two symmetrical FeII complexes, [FeLB4(NCS)2], 1, and [FeLB5(NCS)2], 2 {LBx =N,N′‐bis[(2‐N‐R‐imidazol‐1‐yl)methylene]‐2,2‐dimethylpropane‐1,3‐diamine ligands; 1: x = 4, R = H; 2: x = 5, R = Me} are reported. Whereas the tetradentate ligand LB4 is planar in 1, the X‐ray structure of 2 illustrates the folded conformation of LB5. Ferrous [FeLEx(NCS)2] complexes were synthesized {LEx = N‐[(1‐N‐R2‐imidazol‐2‐yl)methylene]‐N′‐(1‐pyridin‐2‐yl‐ethylidene)‐2,2‐R1‐propane‐1,3‐diamine; 3: x = 1, R1 = H, R2 = H; 4: x = 2, R1 = H, R2 = Me; 5: x = 3, R1 = Me, R2 = H; 6: x = 4, R1 = Me, R2 = Me}. These dissymmetrical Schiff bases, possessing pyridine and imidazole rings, are obtained through the reaction of 2‐methyl‐2‐pyridin‐2‐yl‐hexahydropyrimidine (R1 = H; 3, 4) or 2,5,5‐trimethyl‐2‐pyridin‐2‐yl‐hexahydropyrimidine (R1 = Me; 5, 6) aminals with imidazole‐2‐carboxaldehyde (R2 = H: 3, 5) or 1‐N‐methylimidazole‐2‐carboxaldehyde (R2 = Me: 4, 6) and iron(II) thiocyanate.Single‐crystal X‐ray structures were determined for [FeLE1(NCS)2] 3 [FeLE3(NCS)2] 5 and [FeLE4(NCS)2] 6; these complexes are in the low‐spin state at 180 K. Magnetic susceptibility and Mössbauer measurements showed a smooth and incomplete spin crossover involving ca. 50 % of the iron centres between 200 and 400 K for 5 and 6; 3 and 4 remain low spin up to 350 K; the slight χMT increase between 350 and 400 K results from the onset of spin crossover for 3 and 4. The spin crossover properties in the [FeLEx(NCS)2] series may thus be tuned by the ligand substituents: by changing R1 from H (for 3, 4) to Me (for 5, 6) the spin crossover is lowered from above 400 K to ca. 350 K; the effect of the imidazolyl substituent is weaker: by changing R2 from H (for 5) to Me (for 6) the spin crossover temperature is lowered by ca. 35 K. The electronic effect of the highly conjugated Fe–N=C–C=N– imidazolyl fragment overpasses and qualitatively and quantitatively modifies the effects of R1 and R2. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Recent Developments in Phosphole‐Containing Oligo‐ and Polythiophene Materials (Eur. J. Inorg. Chem. 23/2007)
Authors: Hobbs Matthew G. , Baumgartner Thomas
Published: July 2007

The cover picture shows the schematic structures of a 2,5‐dithienylphosphole and a dithieno[3,2‐b:2′,3′‐d]phosphole, as well as the fluorescence properties of materials based on the latter system. These scaffolds are two of the most promising organophosphorus‐based building blocks for organic electronics to date. Extensive investigations of their structure–property relationships has laid ground for a variety of applications such as sensing or as an active component in electronic devices. Details on the syntheses, their systematic modifications, as well as the resulting (opto)electronic properties of the materials are presented in the Microreview by M. G. Hobbs and T. Baumgartner on p. 3611 ff.
Synthesis of Methyleneisoxazolidine Nucleoside Analogues by Microwave‐Assisted Nitrone Cycloaddition
Authors: Chiacchio Ugo , Corsaro Antonino , Iannazzo Daniela , Piperno Anna , Romeo Giovanni , Romeo Roberto , Saita Maria G. , Rescifina Antonio
Published: July 2007

A new series of conformationally locked N,O‐nucleoside analogues was synthesized by exploiting allenic nucleobases as dipolarophiles in 1,3‐dipolar nitrone cycloadditions. The regio‐ and sitoselectivity of the reaction were rationalized according to the frontier orbital treatment of the nitrone cycloaddition by AM1 calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
DFT Study on the SnII‐Catalyzed Diastereoselective Synthesis of Tetrahydrofuran from D–A Cyclopropane and Benzaldehyde
Authors: Zhang Jinsheng , Shen Wei , Li Ming
Published: July 2007

By means of density functional theory (DFT), the regio‐ and diastereoselective mechanism for the synthesis of 2,5‐disubstituted tetrahydrofuran from a donor–acceptor (D–A) cyclopropane cycloaddition reaction with benzaldehyde catalyzed by Sn(OTf)2 was investigated. As demonstrated, the overall reaction includes the activation of the D–A cyclopropane (S)‐1, an unusual SN2 attack on the activated cyclopropane, the formation of the tetrahydrofuran coordination complex and the regeneration of the catalyst. The D–A cyclopropane is activated by its combination with Sn(OTf)2, which leads to a decrease in the natural bond orbital (NBO) energy ofσ*(C1–C2) and an increase in the dipole moment and angular deviation of the bent bond σ(C1–C2). Two nucleophilic reactions generates two chiral carbon centres, and the first one is rate controlling. In the SN2 reaction, one molecule of trifluoromethane sulfonate forms a hydrogen‐bond H(CHO)···O(OTf), which can control the stretching direction of the benzaldehyde. On the whole, the solvation energies of the species increase with increases in the molecular dipole moments, and the solvent effects increase the reaction barriers. The theoretically predicted dominant product is cis‐(2R,5R)‐tetrahydrofuran. So these can satisfactorily account for the experimental observations.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Ring Expansion Induced by DAST: Synthesis of Substituted 3‐Fluoropiperidines from Prolinols and 3‐Fluoroazepanes from 2‐Hydroxymethylpiperidines
Authors: Déchamps Ingrid , Gomez Pardo Domingo , Cossy Janine
Published: July 2007

Optically active prolinols can be converted into optically active 3‐fluoropiperidines by treatment with DAST. The reaction often produces 2‐fluoromethylpyrrolidines as byproducts. The ring expansion was also applied to 2‐hydroxypiperidines to produce 3‐fluoroazepanes. The rearrangement proceeds via an aziridinium intermediate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Chlorodifluorothioacetic Acid, CF2ClC(O)SH: Synthesis, Characterization, X‐ray Structure and Conformational Properties
Authors: Erben Mauricio F. , Boese Roland , Willner Helge , Della Védova Carlos O.
Published: July 2007

Chlorodifluoroacetic anhydride, [CF2ClC(O)]2O, and chlorodifluoroacetyl chloride, CF2ClC(O)Cl, react with hydrogen sulfide to yield chlorodifluorothioacetic acid, CF2ClC(O)SH. This novel thiocarboxylic acid has been obtained in pure form and characterized by NMR, IR and Raman spectroscopy. By extrapolation of the vapour pressure curve, log p = 6.102–2068/T (p [bar], T [K]), the boiling point was determined to be 66(1) °C. The melting point of the pure substance is –83(2) °C. The conformational properties of the gas‐phase molecule have been studied by vibrational spectroscopy [IR (vapour), Raman (liquid)] and quantum chemical calculations [B3LYP and MP2 methods with 6‐311++G(d,p) and 6‐311++G(3df,2p) basis sets]. The most stable form has C1 symmetry with a synperiplanar (syn) orientation of the C=O double bond with respect to the S–H single bond whereas in the chlorodifluoroacetyl group the gauche orientation of the ClC–C=O moiety is preferred (gauche‐syn form). The analysis of the IR spectrum of gaseous CF2ClC(O)SH suggests the presence of two other conformations in equilibrium at room temperature. These forms have been fully characterized by high‐level quantum chemical calculations. The structure of a single crystal, grown by a miniature zone‐melting procedure using focused infrared laser radiation, was determined by X‐ray diffraction analysis at low temperature. The crystalline solid [monoclinic, space group C2/c, a = 17.6165(14), b = 5.8848(5), c = 11.0877(9) Å, β = 113.5330(11)°] consists exclusively of molecules adopting the gauche‐syn conformation. These molecules associate, forming pairs of cyclic dimers in the crystal through S–H···O=C hydrogen bonds.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of Positional Thiol Analogs of β‐D‐Galactopyranose
Authors: Pei Zhichao , Dong Hai , Caraballo Rémi , Ramström Olof
Published: July 2007

Approaches toward the synthesis of thio‐β‐D‐galactose derivatives are described. These compounds were prepared from the parent carbohydrates: D‐galactose, methyl β‐D‐galactoside and methyl β‐D‐glucoside, respectively. It was found that not only the strategies of protecting group introduction and selective deprotection, but also the choices of solvent and nucleophilic reagent concentration were crucial to allow the efficient introduction of sulfur at different positions of the galactose ring. The effects from the solvent, the nucleophilic reagent concentration, and the protecting group patterns have been investigated. The results clearly show that ester protecting groups play highly important roles for the synthesis of thio‐containing carbohydrates, requiring nonpolar solvents to suppress the neighboring group participation. For the Lattrell–Dax (nitrite‐mediated) inversion reaction, employed in the synthetic route to the 2‐thio‐β‐D‐galactoside, intramolecular nucleophilic attack, as well as strongerstereospecific ester activation, are necessary to overcome hindrance from 4,6‐O‐benzylidene protection.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Ferrocenyliminophosphites as Easy‐to‐Modify Ligands for Asymmetric Catalysis
Authors: Gavrilov Konstantin N. , Maksimova Marina G. , Zheglov Sergey V. , Bondarev Oleg G. , Benetsky Eduard B. , Lyubimov Sergey E. , Petrovskii Pavel V. , Kabro Anzhelika A. , Hey‐Hawkins Evamarie , Moiseev Sergey K. , Kalinin Valery N. , Davankov Vadim A.
Published: July 2007

Several N,P bidentate phosphite‐type ligands derived from readily available ferrocene‐based iminoalcohols were successfully used in Rh‐catalysed hydrogenations and Pd‐catalysed allylic substitutions of a variety of substrates. Moderate‐to‐high catalytic activities under standard conditions were observed, and the enantiomeric excess of the products were up to 97 %. Results obtained under systematic variation of the ligand parameters indicate that the enantioselectivity is largely determined by the nature of the phosphocentre and also by the substituent in the C*HN‐fragment. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
tert‐Butyl‐calix[4]arenes Substituted at the Narrow Rim with Cobalt Bis(dicarbollide)(1–) and CMPO Groups – New and Efficient Extractants for Lanthanides and Actinides
Authors: Mikulášek Libor , Grüner Bohumír , Dordea Crenguta , Rudzevich Valentyn , Böhmer Volker , Haddaoui Jaouad , Hubscher‐Bruder Véronique , Arnaud‐Neu Françoise , Čáslavský Josef , Selucký Pavel
Published: July 2007

Calix[4]arene derivatives bearing two residues A(–) derived from cobalt bis(dicarbollide)(1–) (1) and two CMPO groups B at their narrow rim were synthesized from tBu‐calix[4]arene in four steps. The first step involved the preparation of tBu‐calix[4]arene diether derivatives with appropriate precursors for amino groups (mostly nitriles 3). These were O‐alkylated through ring‐opening reactions with the zwitterionic dioxane derivative [(8‐O(CH2CH2)2O‐1,2‐C2B9H10)‐(1′,2′‐C2B9H11)‐3,3′‐Co]0 (10) to produce ionic nitrile derivatives 4. Reduction of the nitrile groups with BH3·SMe2 (or deprotection in the case of the corresponding phthalimido or Boc derivatives 8) led to a series of diamines 5a–f, which were subsequently converted into the corresponding CMPO derivatives 6a–f by acylation with p‐nitrophenyl(diphenylphosphoryl) acetate. Pure cone conformers were isolated in moderate to excellent yields after the second or third reaction step, although the presence of other conformers in the reaction mixtures was sometimes observed by NMR spectroscopy and HPLC, and in one case a di‐A(–)‐di‐B derivative 6c* in the 1,3‐alternate conformation was prepared. The novel ionic ligands 6a–f showed dramatically enhanced extraction abilities for trivalent actinides and lanthanides in relation to the previously reported simple covalent combination of one A(–) with one B group or to various synergistic mixtures of calixarenes substituted exclusively with two A(–) or two B moieties. A 1:1 mixture of calix[4]arenes containing four A(–) anions (13) and four CMPO functions (14), however, showed similarly high extraction efficiency, comparable to that of the best calixarenes 6b–d with mixed substitution. Complexation studies with 6c for La3+, Eu3+ and Yb3+ in methanol carried out by UV spectrophotometry and microcalorimetry revealed the formation of 1:1 and 1:2 metal‐to‐ligand complexes with log β values ranging from 9.6 to 11.7.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
First Total Synthesis of (+)‐Adenophorine, a Naturally Occurring Inhibitor of Glycosidases
Authors: Pearson Morwenna S. M. , Evain Michel , Mathé‐Allainmat Monique , Lebreton Jacques
Published: July 2007

The first total synthesis of a naturally occurring iminosugar, (+)‐adenophorine, in 14 steps from the (+)‐enantiomer ofGarner's aldehyde, is reported. The strategy is based onthe preparation and functionalization of enantiomericallypure trans‐6‐ethyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Silyl‐Substituted Tetrathia[7]helicenes: Synthesis, X‐ray Characterization and Reactivity
Authors: Bossi Alberto , Maiorana Stefano , Graiff Claudia , Tiripicchio Antonio , Licandro Emanuela
Published: July 2007

We describe the synthesis of trialkylsilyl‐substituted trans‐1,2‐bis(thieno[3,2‐e]benzothiophene‐2‐yl)ethenes as suitable soluble precursors for the preparation of the corresponding silylated tetrathia[7]helicenes, which, in turn, can be desilylated or transformed into dihalogen‐substituted derivatives through electrophilic substitution of silyl substituents. X‐ray structural studies showed that the presence of the two triisopropylsilyl groups on the terminal thiophene rings accounts for the high solubility of the alkene and for the very large dihedral angle in the helicene. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Electrophoretic screening of ligands under suppressed EOF with an inert phospholipid coating
Authors: White Christian M. , Luo Ruijuan , Archer‐Hartmann Stephanie A. , Holland Lisa A.
Published: July 2007

The applicability of dual injection CE for affinity selection of biopolymers that contain multiple binding sites is demonstrated. The efficient analysis of biomolecules such as carbohydrates and proteins, as well as pharmaceuticals by CE requires the reduction or elimination of nonspecific interactions with the capillary surface. Phospholipids are integral components of cell membranes and aqueous phospholipid liquid crystals adopt a bilayer structure on fused‐silica. This phospholipid surface does not interact significantly with the following biomolecules: serum albumin, the 96–110 heparin binding domain of amyloid precursor protein (APP), polydisperse glycosaminoglycans, and variable chain‐length oligosaccharides. Pharmaceuticals including five anionic nonsteroidal anti‐inflammatory drugs, three cationic analgesics, and two cationic β‐blockers, also show minimal interaction with the surface. In addition, the use of a phospholipid coating suppresses EOF, which enables reversed‐polarity separations, dual opposite injection CE, affinity screening via CE by dual opposite injection, and serial target‐ligand injections.
A selective and sensitive approach to characterize odour‐active and volatile constituents in small‐scale human milk samples
Authors: Buettner Andrea
Published: July 2007

A sensitive and selective analytical approach was developed for the characterization of trace volatile and odorous substances in body fluids. The methodology was successfully applied for identification of more than 40 characteristic odorants in human milk. The technique comprises a modified stir bar sorptive extraction system in combination with two‐dimensional gas chromatographic separation and parallel mass spectrometric and olfactometric characterization of the analytes. The present study shows that the technique can be used for both direct extractive sampling and headspace analysis, and that it is applicable for small sample volumes. Copyright © 2007 John Wiley & Sons, Ltd.
Protumorigenic overexpression of stathmin/Op18 by gain-of-function mutation in p53 in human hepatocarcinogenesis
Authors: Singer Stephan , Ehemann Volker , Brauckhoff Antje , Keith Martina , Vreden Sebastian , Schirmacher Peter , Breuhahn Kai
Published: July 2007

The microtubule (MT)-destabilizing protein stathmin/Op18 has previously been described to be negatively regulated by p53 and to be highly expressed in several tumor entities. However, little is known about its expression profile, functional or therapeutic relevance, and regulation in human hepatocarcinogenesis. Here we demonstrate cytoplasmic overexpression of stathmin in premalignant lesions (dysplastic nodules; DNs) and hepatocellular carcinomas (HCCs), which significantly correlated with tumor progression, proliferation, and activation of other protumorigenic factors (e.g., nuclear p53). Inhibition of stathmin expression by gene-specific short interfering RNA (siRNA) was associated with a significant reduction of MT-dependent cellular functions such as tumor cell viability, proliferation, migration, and increased apoptosis in HCC cells. Loss of stathmin expression increased responsiveness of tumor cells to the treatment with cytostatic drugs targeting MT-stability (paclitaxel, vinblastine) and to DNA cross-linking agents (cisplatin). Surprisingly, inducible expression of p53wt in p53-negative HCC cells as well as a reduction of p53wt by siRNA in p53wt-positive cells did not alter stathmin expression. However, stathmin was down-regulated after siRNA-based reduction of p53mut/Y220C and p53mut/R213Q expression in different tumor cell types.

Conclusion:

Our results demonstrate that overexpression of stathmin is an early protumorigenic event in human hepatocarcinogenesis, and its up-regulation can be mediated by gain-of-function mutations in p53. Thus, stathmin represents a potential therapeutic target, for example, by increasing responsiveness of tumor cells to treatment with chemotherapeutic agents after reduction of stathmin bioactivity. (Hepatology 2007.)
Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry
Authors: Bioulac-Sage Paulette , Rebouissou Sandra , Thomas Cristel , Blanc Jean-Frédéric , Saric Jean , Sa Cunha Antonio , Rullier Anne , Cubel Gaëlle , Couchy Gabrielle , Imbeaud Sandrine , Balabaud Charles , Zucman-Rossi Jessica
Published: July 2007

Hepatocellular adenomas (HCA) with activated β-catenin present a high risk of malignant transformation. To permit robust routine diagnosis to allow for HCA subtype classification, we searched new useful markers. We analyzed the expression of candidate genes by quantitative reverse transcription polymerase chain reaction QRT-PCR followed by immunohistochemistry to validate their specificity and sensitivity according to hepatocyte nuclear factor 1 alpha (HNF1α) and β-catenin mutations as well as inflammatory phenotype. Quantitative RT-PCR showed thatFABP1(liver fatty acid binding protein) andUGT2B7were downregulated in HNF1α-inactivated HCA (P≤ 0.0002);GLUL(glutamine synthetase) andGPR49overexpression were associated with β-catenin–activating mutations (P≤ 0.0005), andSAA2(serum amyloid A2) andCRP(C-reactive protein) were upregulated in inflammatory HCA (P= 0.0001). Immunohistochemistry validation confirmed that the absence of liver-fatty acid binding protein (L-FABP) expression rightly indicated HNF1α mutation (100% sensitivity and specificity), the combination of glutamine synthetase overexpression and nuclear β-catenin staining were excellent predictors of β-catenin–activating mutation (85% sensitivity, 100% specificity), and SAA hepatocytic staining was ideal to classify inflammatory HCA (91% sensitivity and specificity). Finally, a series of 93 HCA was unambiguously classified using our 4 validated immunohistochemical markers. Importantly, new associations were revealed for inflammatory HCA defined by SAA staining with frequent hemorrhages (P= 0.003), telangiectatic phenotype (P< 0.001), high body mass index, and alcohol intake (P≤ 0.04). Previously described associations were confirmed and in particular the significant association between β-catenin–activated HCA and hepatocellular carcinomas (HCC) at diagnosis or during follow-up (P< 10−5).Conclusion:We refined HCA classification and its phenotypic correlations, providing a routine test to classify hepatocellular adenomas using simple and robust immunohistochemistry. (Hepatology 2007.)
Hippocampal theta sequences
Authors: Foster David J. , Wilson Matthew A.
Published: July 2007

The activity of individual hippocampal principal neurons is spatially localized such that each neuron is active only when the animal occupies an area of the environment known as the cell's place field. Additionally, the activity of hippocampal neurons exhibits a particular temporal relationship to the hippocampal EEG, such that spikes fired by the neuron occur at progressively earlier phases of the co‐occurring theta rhythm in the EEG as the animal traverses the place field. This relationship is known as theta precession. A long‐standing prediction following the observation of theta precession has been that among a collection of hippocampal neurons recorded simultaneously, the neurons will fire in sequences reflecting the behavioral order of the place fields. Here we examine this prediction. We show that clear, ordered sequences occur during theta, which we name theta sequences, in which a portion of the animal's spatial experience is played out in forwards order. We further investigate the relationship of theta sequences to phase precession by shuffling spike phases in such a way as to preserve the relationship between spike phase and position. This jitter significantly reduces the prevalence of theta sequences while leaving theta phase precession intact, suggesting that the presence of theta phase precession is not trivially predictive of theta sequences. Finally, we discuss the relationship between theta sequences and individual place fields, and the possible functional role of theta sequences in navigational learning. © 2007 Wiley‐Liss, Inc.
Contribution to the study of thermal waters in Greece: chemical patterns and origin of thermal water in the thermal springs of Lesvos
Authors: Lambrakis N. J. , Stamatis G. N.
Published: July 2007

The occurrence of thermal/spa waters on Lesvos Island is related to the presence of a major faulting system. Thermal waters are the result of mixing of meteoric and infiltrating seawater at great depth, and their total salinity depends on the percentage of seawater in their composition. According to the diagrams of main elements, trace elements and environmental isotopes, most of the components that determine the chemical composition of thermal waters such as sodium, chloride and sulphates originate from seawaters. On the other hand, the concentration of calcium, magnesium, boron, lithium, etc., was affected by water–rock interaction under high temperature conditions. Moving towards the surface, thermal waters may become polluted by influx of recent seawater, allowing their chemical composition to become similar to that of seawater. The thermal waters of Lesvos Island present relatively high concentrations of ammonia and redox sensitive metals because they are hosted in a reducing environment. They also exhibit low nitrate concentrations due to their mixture with recent fresh water. Finally, they show increased radon concentrations, ranging from 20 to 60 kBq m−3 in the eastern and southern parts of the island, and about 230 kBq m−3 in the north, in the area of Eftalou–Argenos. Copyright © 2007 John Wiley & Sons, Ltd.
Statistical approach to determine the salinized ground water flow path and hydrogeochemical features around the underground LPG cavern, Korea
Authors: Lee Jeongho , Kim Ji‐Hoon , Kim Hun‐Mi , Chang Ho‐Wan
Published: July 2007

The ground water flow path of the coastal area in the Yellow Sea, Korea, was interpreted using both the cross‐correlation analysis of hydraulic properties and the principal component analysis (PCA) of ground water chemistry. Data was obtained from observation wells in the underground liquefied petroleum gas (LPG) cavern constructed in the coastal area of Pyeongtaek. Cross‐correlation results showed that the operating pressure became more influenced on artificial factors for the variation of the groundwater level of the study area (45–66% of correlation coefficient) even though its affecting area was limited to the region with fractures or faults, and also showed that the delay time from the variation of operating pressure to the fluctuation of ground water level were relatively long periods (28–31 days). Three hydrogeochemical events (encrusted cement dissolution, host rock dissolution, and seawater intrusion), which were dominantly influenced on ground water quality, could be induced from the result of PCA. Quantitative evaluation for these events using the mixed equation with principal component scores suggest that the dissolution of encrusted cement materials was the predominant factor (39·0% of the total mixed proportion) to change the chemical composition of the seepage water during the ground water flow from the observation wells to the cavern. Integration of the statistical results also imply that ground water flow and hydrogeochemistry were predominantly affected by artificial factors such as cavern operation pressure and dissolution of encrusted cement materials, which were interdependent factors on the observation wells with high cross‐correlation coefficients and pH. Copyright © 2007 John Wiley & Sons, Ltd.
Modified hydrograph method for arid regions
Authors: Şen Zekai
Published: July 2007

There is a real need for more research on regionalization of flood estimation methods in arid zones. Such estimations are important because reliable long‐term storm rainfall and corresponding runoff measurements are commonly unavailable. This is the situation in many parts of the Kingdom of Saudi Arabia. Hence, it is necessary to develop a new approach, one that suits the conditions found in the Kingdom, which depend on available, but incomplete measurements and catchment morphological features.

In this paper, a modified methodology based on the classical Snyder approach is proposed and it is referred to as the Saudi Geological Survey (SGS) approach in order to reflect works of this kind within the Survey. The basis of the methodology has two phases, namely, logical and empirical. The former phase is valid for any part of the world whether humid or arid, but the latter phase is location specific, which in the case of this paper, is the Arabian Peninsula. The application of the methodology is presented for Wadi Baysh, a major wadi in the south‐western part of the Kingdom. Furthermore, a synthetic unit hydrograph (UH) methodology based on a Gamma distribution function is also presented with applications to some of the Wadi Baysh sub‐basins. For this purpose, a dimensionless UH has been obtained, which is special for the area. Copyright © 2007 John Wiley & Sons, Ltd.
Impact of septic tank systems on local groundwater quality and water supply in the Pearl River Delta, China: case study
Authors: Lu Yintao , Tang Changyuan , Chen Jianyao , Sakura Yasuo
Published: July 2007

Located at southern coast of China, the Pearl River Delta (PRD) is facing serious water problems in both quantity and quality after its rapid urbanization in the last decade. Most remarkably, the local groundwater, that was used to be the source of drinking water before the urbanization was polluted due to poor management of the septic tanks. In order to study the effects of suburban development on local groundwater flow and water quality in the PRD region, Fengcun of Guangzhou has been chosen as the study area. In Fengcun, drinking water was groundwater before the 1990s, but now piped reservoir water is used by each family because the groundwater has been polluted. This study clarifies the source and process of the groundwater pollution from septic tanks using isotopic and geochemical characteristics, especially nitrate (NO3−) concentrations. Water samples were collected from the wells and ponds in Fengcun in March and July 2005 and in July 2006. Based on the pe–pH diagram, NO3− and ammonium of groundwater are from the effect of human activities, rather than from nitrification and ammonification of N2. NO3− pollution of groundwater is from point sources, and NO3− concentrations decrease from northeast to southwest. Groundwater is polluted rapidly by the leakage of septic tanks. NO3− concentrations of pollution sources were lower than 20 mg l−1 in March 2005, but had increased to about 120 mg l−1 in July 2006. This implies that groundwater protection should be strengthened in rural areas of the PRD. Copyright © 2007 John Wiley & Sons, Ltd.
Basin‐scale stream‐flow forecasting using the information of large‐scale atmospheric circulation phenomena
Authors: Maity Rajib , Nagesh Kumar D.
Published: July 2007

It is well recognized that the time series of hydrologic variables, such as rainfall and streamflow are significantly influenced by various large‐scale atmospheric circulation patterns. The influence of El Niño‐southern oscillation (ENSO) on hydrologic variables, through hydroclimatic teleconnection, is recognized throughout the world. Indian summer monsoon rainfall (ISMR) has been proved to be significantly influenced by ENSO. Recently, it was established that the relationship between ISMR and ENSO is modulated by the influence of atmospheric circulation patterns over the Indian Ocean region. The influences of Indian Ocean dipole (IOD) mode and equatorial Indian Ocean oscillation (EQUINOO) on ISMR have been established in recent research. Thus, for the Indian subcontinent, hydrologic time series are significantly influenced by ENSO along with EQUINOO. Though the influence of these large‐scale atmospheric circulations on large‐scale rainfall patterns was investigated, their influence on basin‐scale stream‐flow is yet to be investigated. In this paper, information of ENSO from the tropical Pacific Ocean and EQUINOO from the tropical Indian Ocean is used in terms of their corresponding indices for stream‐flow forecasting of the Mahanadi River in the state of Orissa, India. To model the complex non‐linear relationship between basin‐scale stream‐flow and such large‐scale atmospheric circulation information, artificial neural network (ANN) methodology has been opted for the present study. Efficient optimization of ANN architecture is obtained by using an evolutionary optimizer based on a genetic algorithm. This study proves that use of such large‐scale atmospheric circulation information potentially improves the performance of monthly basin‐scale stream‐flow prediction which, in turn, helps in better management of water resources. Copyright © 2007 John Wiley & Sons, Ltd.