bluuebunny/crossref_metadata_2025 huggingface dataset:
Fezf1 and Fezf2 are required for olfactory development and sensory neuron identity
Authors: Eckler Matthew J. , McKenna William L. , Taghvaei Sahar , McConnell Susan K. , Chen Bin
Published: January 2011

The murine olfactory system consists of main and accessory systems that perform distinct and overlapping functions. The main olfactory epithelium (MOE) is primarily involved in the detection of volatile odorants, while neurons in the vomeronasal organ (VNO), part of the accessory olfactory system, are important for pheromone detection. During development, the MOE and VNO both originate from the olfactory pit; however, the mechanisms regulating development of these anatomically distinct organs from a common olfactory primordium are unknown. Here we report that two closely related zinc‐finger transcription factors, FEZF1 and FEZF2, regulate the identity of MOE sensory neurons and are essential for the survival of VNO neurons respectively. Fezf1 is predominantly expressed in the MOE while Fezf2 expression is restricted to the VNO. In Fezf1‐deficient mice, olfactory neurons fail to mature and also express markers of functional VNO neurons. In Fezf2‐deficient mice, VNO neurons degenerate prior to birth. These results identify Fezf1 and Fezf2 as important regulators of olfactory system development and sensory neuron identity. J. Comp. Neurol. 519:1829–1846, 2011. © 2011 Wiley‐Liss, Inc.
Glutamatergic neuronal populations in the forebrain of the sea lamprey, Petromyzon marinus: An in situ hybridization and immunocytochemical study
Authors: Villar‐Cerviño Verona , Barreiro‐Iglesias Antón , Mazan Sylvie , Rodicio Maria Celina , Anadón Ramón
Published: January 2011

Despite the importance of glutamate as a major excitatory neurotransmitter in the brain, the distribution of glutamatergic populations in the brain of most vertebrates is still unknown. Here, we studied for the first time the distribution of glutamatergic neurons in the forebrain of the sea lamprey (Petromyzon marinus), belonging to the most ancient group of vertebrates (agnathans). For this, we used in situ hybridization with probes for a lamprey vesicular glutamate transporter (VGLUT) in larvae and immunofluorescence with antiglutamate antibodies in both larvae and adults. We also compared glutamate and γ‐aminobutyric acid (GABA) immunoreactivities in sections using double‐immunofluorescence methods. VGLUT‐expressing neurons were observed in the olfactory bulb, pallium, septum, subhippocampal lobe, preoptic region, thalamic eminence, prethalamus, thalamus, epithalamus, pretectum, hypothalamus, posterior tubercle, and nucleus of the medial longitudinal fascicle. Comparison of VGLUT signal and glutamate immunoreactivity in larval forebrain revealed a consistent distribution of positive cells, which were numerous in most regions. Glutamate‐immunoreactive cell populations were also found in similar regions of the adult forebrain. These include mitral‐like cells of the olfactory bulbs and abundant cells in the lateral pallium, septum, and various diencephalic regions, mainly in the prethalamus, thalamus, habenula, pineal complex, and pretectum. Only a small portion of the glutamate‐immunoreactive cells showed colocalization with GABA, which was observed mainly in the olfactory bulb, telencephalon, hypothalamus, ventral thalamus, and pretectum. Comparison with glutamatergic cells observed in rodent forebrains suggests that the regional distribution of glutamatergic cells does not differ greatly in lampreys and mammals. J. Comp. Neurol. 519:1712–1735, 2011. © 2011 Wiley‐Liss, Inc.
Transportin 1 in the mouse brain: Appearance in regions of neurogenesis, cerebrospinal fluid production/sensing, and circadian clock
Authors: Sato Miho , Mizoro Yasutaka , Atobe Yuta , Fujimoto Yoshito , Yamaguchi Yoshiaki , Fustin Jean‐Michel , Doi Masao , Okamura Hitoshi
Published: January 2011

Transportin1 (Tnpo1) is a carrier protein belonging to the importin‐β family, which transports substrates between the cytoplasm and the nucleus. To gain insight into the role of Tnpo1 gene in the brain, we investigated the localization of Tnpo1‐, Tnpo2‐, and Tnpo3‐expressing cells by in situ hybridization histochemistry. Tnpo1 mRNA‐positive cells were distributed throughout the brain from the olfactory bulb to the medulla oblongata. The cells in the subventricular zone of the lateral ventricle, where neurogenesis occurs even in the adult, and its progeny neurons in the granular cells of the olfactory bulb and the islands of Calleja were strongly labeled. It is also noteworthy that cerebrospinal fluid (CSF)‐generating epithelial cells in the choroid plexus and CSF‐contacting and ‐sensing circumventricular organs, including organum vasculosum lamina terminalis, subfornical organ, and subcommissural organ, expressed high amounts of Tnpo1. The strongest signals were found in the suprachiasmatic nucleus (SCN), where the biological clock resides, which prompted us to examine the circadian characteristics of Tnpo1. Under constant‐dark conditions, the circadian expression profiles of Tnpo1 mRNA in the SCN showed a peak in the subjective night and a trough in the subjective day. Tnpo2 and Tnpo3 showed similar patterns of expression, except in the choroids plexus, the subventricular zone, and the SCN, where the expression was notably weaker. These findings suggest that Tnpo1 is involved in a variety of functions in the adult brain, including neurogenesis, CSF production and sensing, and circadian rhythms. J. Comp. Neurol. 519:1770‐1780, 2011. © 2011 Wiley‐Liss, Inc.
Patterned expression of a cocaine‐ and amphetamine‐regulated transcript peptide reveals complex circuit topography in the rodent cerebellar cortex
Authors: Reeber Stacey L. , Sillitoe Roy V.
Published: January 2011

The cerebellum (Cb) of mammals and birds consists of an evolutionarily conserved map defined by Purkinje cell (PC) protein expression. In mice, ZebrinII/aldolaseC is expressed in a striking array of stripes in lobules I–V (anterior zone; AZ) and VIII–anterior IX (posterior zone; PZ), whereas the small heat shock protein 25 (HSP25) is expressed in stripes in lobules VI–VII (central zone, CZ) and posterior IX–X (nodular zone, NZ). Little is known about whether molecularly defined afferent subsets terminate within specific PC stripes or whether their topography is conserved across species. Using immunohistochemistry, we demonstrate in adult mice and rats that cocaine‐ and amphetamine‐regulated transcript (CART) expression can be used to partition sensory‐motor projections into complex topographic maps. We found that in mice CART was expressed in climbing fiber bands that generally corresponded to the pattern of HSP25‐expressing PCs in the CZ/NZ. In contrast, CART was expressed in climbing fiber bands in all four transverse zones of the rat Cb. Within the rat AZ/PZ, climbing fibers terminated selectively within the dendrites of ZebrinII‐immunoreactive PCs. In additional experiments, we observed CART expression in loose clusters of spinocerebellar mossy fibers in the mouse AZ/PZ, whereas in rat CART immunoreactive mossy fibers terminated predominantly in the CZ/NZ. We conclude that, although the overall topography of CART‐expressing afferents is restricted within a conserved map of PC stripes and transverse zones, their termination patterns also reflect species‐specific compartmental features. J. Comp. Neurol. 519:1781–1796, 2011. © 2011 Wiley‐Liss, Inc.
A Novel Pyrene‐Based Fluorescing Amphiphile with Unusual Bulk and Interfacial Properties
Authors: Salonen Anniina , Knyazev Anton , von Bandel Nicolas , Degrouard Jéril , Langevin Dominique , Drenckhan Wiebke
Published: January 2011

We have synthesised a new, pyrene‐based, low‐molecular‐mass, amphiphilic molecule that displays a wealth of properties of potential interest for aggregation and interfacial applications. In order to elucidate some of the key properties of this molecule, which consists of a pyrene‐containing hydrophobic head and a short PEG‐based hydrophilic tail, we investigate herein some aspects of its concentration‐dependent behaviour in aqueous solutions. We show that the inclusion of the hydrophobic pyrene group not only provides the molecule with intriguing bulk and interfacial properties down to low concentrations, but also with various means of assessing its aggregation behaviour by means of its well‐characterised fluorescence properties. Combining a range of fluorescence techniques with microscopic imaging (optical and Cryo‐TEM), interfacial tension measurements and foaming studies, we have been able to identify and characterise three concentration‐dependant regimes. At low concentrations, the molecule is dissolved in monomeric form. At intermediate concentrations, labile aggregates are formed, which, at higher concentrations, give way to aggregates containing pre‐associated pyrenes. Our measurements strongly imply that the latter aggregates are hexagonally close‐packed tubular micelles. In this latter regime we also find a range of micron‐sized precipitates. Additionally, the molecule displays strong interfacial activity, yet a surprisingly slow dynamics of interfacial adsorption. Finally, we demonstrate the possibility of using it to visualize interfaces and also create reasonably stable (1 hour) and fluorescing foams.
Efficient Conversion of Furfuryl Alcohol into Alkyl Levulinates Catalyzed by an Organic–Inorganic Hybrid Solid Acid Catalyst
Authors: Zhang Zehui , Dong Kun , Zhao Zongbao (Kent)
Published: January 2011

A clean, facile, and environment‐friendly catalytic method has been developed for the conversion of furfuryl alcohol into alkyl levulinates making use of the novel solid catalyst methylimidazolebutylsulfate phosphotungstate ([MIMBS]3PW12O40). The solid catalyst is an organic–inorganic hybrid material, which consists of an organic cation and an inorganic anion. A study for optimizing the reaction conditions such as the reaction time, the temperature and the catalyst loading has been performed. Under optimal conditions, a high n‐butyl levulinate yield of up to 93 % is obtained. Furthermore, the kinetics of the reaction pathways and the mechanism for the alcoholysis of furfuryl alcohol are discussed. This method is environmentally benign and economical for the conversion of biomass‐based derivatives into fine chemicals.
Advances in kidney transplant immunosuppression: Emerging biologics
Authors: Kumar Vineeta , Gaston Robert S.
Published: January 2011

There remains a need in solid‐organ transplantation for an immunosuppressive agent with a novel mechanism of action and fewer adverse consequences to replace current immunosuppressive drugs and improve long‐term patient and graft survival. There are several agents on the horizon, both small molecules and biologics, offering this promise along with ease and consistency of long‐term administration. We discuss three biologic agents currently in advanced stages of clinical trials in kidney transplantation.
The three‐signal hypothesis of lymphocyte activation/targets for immunosuppression
Authors: Goral Simin
Published: January 2011

Kidney transplantation is the preferred mode of renal replacement therapy for most patients with end‐stage renal disease. Despite the increasing success of transplantation over the years, allograft rejection remains a major problem. Recently, there has been considerable improvement in understanding the role of the immune system in rejection. In the setting of transplantation, T cells have proved to be crucial players in the immune response, and their activation has been shown to be a very tightly regulated process involving numerous interactions of receptors including the T‐cell receptor (TCR):CD3 complex, co‐stimulatory receptors, and appropriate signaling molecules, resulting in production of cytokines as well as clonal expansion and differentiation of effector T lymphocytes. In this review, current knowledge of the mechanisms of lymphocyte activation as well as potential targets for various immunosuppressive agents are discussed.
New targets for immunosuppression in kidney transplantation: Focus on recent clinical trials
Authors: Wojciechowski David , Vincenti Flavio
Published: January 2011

Signiﬁcant advances have been made in post‐kidney transplantation immunosuppression. The introduction of calcineurin inhibitors (CNIs) has led to a reduction in acute rejection and improved 1‐year outcomes. However, long‐term allograft survival has not improved. This may in part be due to the chronic nephrotoxicity of CNIs and negative effects on the cardiovascular and metabolic risk proﬁle via worsening hypertension, diabetes, and dyslipidemia. New drug development now focuses on maintaining low rejection rates but maximizing long‐term allograft survival and modulating the cardio‐metabolic side effects seen with CNIs. Two small molecules are currently undergoing Phase 2 investigation. CP‐690550 (tasocitinib) is a JAK 3 inhibitor, and AEB‐071 (sotrastaurin) is a protein kinase C inhibitor. Two biologic agents are also undergoing development. Belatacept is a humanized antibody that blocks the T‐cell co‐stimulation pathway and has had promising results in both Phase 2 and 3 investigation. Alefacept is a humanized antibody that inhibits T‐cell adhesion and is currently undergoing Phase 2 investigation. This article will review the mechanisms of these drugs and outline the available trial data results.
The role of mTOR inhibition in renal transplant immune suppression
Authors: Patel Samir J. , Dawson Kyle L. , Knight Richard J. , Abdellatif Abdul , Achkar Katafan , Gaber Lillian W. , Gaber A. Osama
Published: January 2011

The mammalian target of rapamycin inhibitors (mTOR‐Is) sirolimus and everolimus represent a class of proliferation signal inhibitors with a wide spectrum of activities, including suppression of T‐cell proliferation and reduction of tumor growth. In solid‐organ transplantation, mTOR inhibitors are an option for maintenance immune suppression due to their relative lack of nephrotoxicity compared with the current backbone of most regimens, the calcineurin inhibitors (CNIs). This property, in conjunction with their unique pharmacology, allows mTOR‐Is to be used as an adjunct or alternative to CNIs. Earlier studies of their use in de novo renal transplantation have delineated potential strategies for use of this class of drugs in groups of patients in whom mTOR inhibition may be useful. From recent kidney studies it appears that the time for introduction of mTOR‐I therapy may be prior to the development of proteinuria or signiﬁcant graft deterioration. Consideration should also be given to the use of mTOR‐Is in patients with or at high risk of post‐transplant malignancy. Due to potential toxicities, knowledge of the adverse effects and pharmacokinetic proﬁles of mTOR‐Is is necessary for proper management of patients receiving these agents.
Belatacept in renal transplantation
Authors: Yost Sarah E. , Ranga K. Vinay , Kaplan Bruce
Published: January 2011

Belatacept is a novel agent that prevents CD28 signaling and inhibits T‐cell activation by costimulation blockade. It was developed from abatacept (CTLA‐4 Ig), the ﬁrst recombinant immunoglobulin fusion protein that contains extracellular portion of CTLA‐4, and the Fc domain of IgG. Early studies have shown that belatacept recipients show comparable patient and graft survival, superior renal function and renal biopsy data compared with cyclo‐sporine‐treated patients. Newer biologic agents such as belatacept offer the promise of real change—due to their lack of mechanism‐related toxic effects—and help monitor drug administration, thereby improving compliance. Belatacept is a potential option for maintenance biologic therapy without a calcineurin inhibitor, accompanied by excellent mid‐term results with yet unknown long‐term safety and efﬁcacy. The increased rate of TCMR and possibly central nervous system post‐transplantation lymphoproliferative disorder are worrisome and need to be further elucidated.
A Clean Low‐Temperature ZnO Deposition Method for Multipurpose Applications
Authors: Estruga Marc , Gonzalez‐Valls Irene , Domingo Concepción , Lira‐Cantu Monica , Ayllón José A.
Published: January 2011

Zinc oxide (ZnO) was dissolved in an aqueous solution of ammonia and hydrogen peroxide. According to XRD characterization, this precursor solution yielded crystalline zincoxide after evaporation and thermal treatment at 90 °C for 2 h. The processability of this precursor solution allowed for ZnO deposition on cellulose paper, which is an example of a thermolabile substrate. Cellulose filter paper that was impregnated with this solution and subsequently thermally treated at 90 °C for 2 h had nanostructured crystalline ZnO well adhered to its surface. This composite material was characterized by XRD and scanning electron microscopy (SEM). The described precursor solution also assisted in the preparation of ZnO porous layers for dye‐sensitized solar cells (DSC). For this purpose, it was mixed with ZnO nanopowder dispersed in ethanol. The mixture was then sprayed on transparent conductive oxide substrates. In this way porous films were obtained after heat treatment at 90 °C for 2 h. Under standard testing conditions (AM1.5G, 100 mW cm–2), a device prepared with (Bu4N)2[Ru(dcbpyH)2(NCS)2] (dcbpy = 4,4′‐dicarboxy‐2,2′‐bipyridine) (N‐719) dye and a film thickness of 5 μm exhibited 1.43 % efficiency.
Electron‐Rich Vaska‐Type Complexestrans‐[Ir(CO)Cl(2‐Ph2PC6H4COOMe)2] andtrans‐[Ir(CO)Cl(2‐Ph2PC6H4OMe)2]: Synthesis, Characterisation and Reactivity
Authors: Dutta Dipak Kumar , Deb Biswajit , Sarmah Bhaskar Jyoti , Woollins J. Derek , Slawin Alexandra M. Z. , Fuller Amy L. , Randall Rebecca A. M.
Published: January 2011

The in‐situ‐generated dimeric precursor [Ir(CO)2Cl]2reacts with four molar equivalents of the ligands 2‐Ph2PC6H4COOMe (a) and 2‐Ph2PC6H4OMe (b) to afford tetracoordinated complexes of the typetrans‐[Ir(CO)ClL2] (1a,1b), where L =aandb. The IR spectra of1aand1bin CHCl3solution show the terminal υ(CO) bands at around 1957 and 1959 cm–1, respectively, which are significantly lower in frequency compared to Vaska's complex,trans‐[Ir(CO)Cl(PPh3)2] (1965 cm–1) and substantiate the enhanced electron density at the metal centre. The single‐crystal X‐ray structure of1aindicates iridium–oxygen (ester group) distances [Ir···O(2) 3.24 Å, Ir···O(5) 3.29 Å] and angle [O(5)···Ir···O(2) 157.25°] suggesting a long‐range intramolecular “secondary” Ir···O interaction resulting in a pseudo‐hexacoordinated complex. Complex1breacts with O2to generate [Ir(O2)(CO)Cl(2‐Ph2PC6H4OMe)2] (2b), while1aremains unreactive. Complex2bshows a distorted octahedral structure with peroxo O–O linkage (O2–O3 1.47 Å). The kinetic study of the reaction of1band Vaska's complex towards dioxygen addition reveals that the rate of dioxygen addition to1bis about three times faster than Vaska's complex. Complexes1aand1bundergo oxidative addition with small molecules like CH3I and I2to produce IrIIIcarbonyl species of the type [Ir(CO)Cl(CH3)IL2] (3a,3b) and [Ir(CO)ClI2L2] (4a,4b), where L =a,b.
Synthesis, Structure and Electrochemistry of Macrocyclic Tetrametallic Group 6 (Fischer) Carbene Complexes
Authors: López‐Alberca María P. , Mancheño María J. , Fernández Israel , Gómez‐Gallego Mar , Sierra Miguel A. , Hemmert Catherine , Gornitzka Heinz
Published: January 2011

The 1,4‐addition of diamine dinucleophiles to dimetalliccarbene scaffolds 5 yields tetrametallic azamacrocycles 9 and 10 with exocyclic metal–carbene nuclei, in excellent yields and with high stereocontrol. All‐Z stereoisomers are isolated in all cases, with the exception of the tungsten(0) macrocycle 10, which is obtained as a mixture of isomers. This methodology allows the preparation of a new type of homo‐ and heterocyclophane metallomacrocycles in which the geometry and the size of the cavity can be designed as a function of the biscarbene complexes employed and the diamines used as linkers. The X‐ray structure of complex 10a showing the high stability of the Z configuration of these compounds and the electrochemistry of the metallomacrocycles prepared are also reported.
Making and Breaking of P–P Bonds with Low‐Valent Transition‐Metal Complexes
Authors: Gómez‐Ruiz Santiago , Frank René , Gallego Beatriz , Zahn Stefan , Kirchner Barbara , Hey‐Hawkins Evamarie
Published: January 2011

The 1:1 or 1:2 stoichiometric reaction of [Na2(thf)4(P4Mes4)] (1; Mes = 2,4,6‐Me3C6H2) with [{RhCl(cod)}2] (cod = 1,5‐cyclooctadiene) gave a mixture of compounds of which [Na(thf)3][Rh(P3Mes3)(cod)] (2) with a trimesityltriphosphane‐1,3‐diide ligand was structurally characterized. Density functional calculations on 2 confirmed the structural parameters obtained by X‐ray diffraction studies. Shared electron number and natural bond orbital analyses indicated only weak interactions between Na and P, which were found to be even weaker than the Na–Rh interactions with covalent contribution. When an excess of 1 was used (3:1 or 4:1), 2 was also obtained as the major product together with small amounts of the side‐products cyclo‐P6Mes6 (3) and [Na3(Et2O)(P4Mes4)(PHMes)]∞ (4). Compounds 3 and 4 were only characterized by single‐crystal X‐ray diffraction studies. Their formation indicates that the reaction includes the breaking and making of P–P bonds to give (P3Mes3)2–, PHMes–, and cyclo‐P6Mes6, although the mechanism is unclear. Furthermore, the reaction of 1 with 2 equiv. of [AgCl(PPh3)2] gave the tetranuclear compound [Ag4(P6Mes6)2] (5) in which the novel (P6Mes6)2– ion also indicates degradation of the P4 chain followed by P–P bond formation.
An Effective Diels–Alder Reaction of Vinyl Allenols with Dienophiles
Authors: Choi Subin , Hwang Hoon , Lee Phil Ho
Published: January 2011

Vinyl allenols obtained from reaction of aldehydes with vinyl propargyl bromide and indium underwent Diels–Alder reactions with a variety of symmetric and unsymmetric dienophiles in dichloromethane or toluene regioselectively, producing cyclohexenylmethyl alcohols possessing an exo methylene moiety in good to excellent yield.
H3PW12O40‐Catalysed Alkylation of Arenes and Diveratrylmethanes: Convenient Routes to Triarylmethanes and to Symmetrical and Unsymmetrical 9,10‐Diaryl‐2,3,6,7‐tetramethoxyanthracenes
Authors: Mohammadpoor‐Baltork Iraj , Moghadam Majid , Tangestaninejad Shahram , Mirkhani Valiollah , Mohammadiannejad‐Abbasabadi Kazem , Khavasi Hamid R.
Published: January 2011

An efficient method for the synthesis of triarylmethanes and difurylarylmethanes through solventless reactions between aldehydes and arenes in the presence of H3PW12O40 as a reusable catalyst under thermal and microwave irradiation conditions has been developed. H3PW12O40‐catalysed one‐pot consecutive Friedel–Crafts reactions between veratrole and aldehydes were also applied as a convenient protocol for the preparation of symmetrical 9,10‐diaryl‐2,3,6,7‐tetramethoxyanthracenes. The conversion of aldehydes into their corresponding acylals in the presence of H3PW12O40 and the one‐pot reactions of diveratrylmethanes with these acylals were also used for the synthesis of symmetrical and unsymmetrical 9,10‐diaryl‐2,3,6,7‐tetramethoxyanthracenes.
Stereoselective Olefination of N‐Sulfonyl Imines with Stabilized Phosphonium Ylides for the Synthesis of Electron‐Deficient Alkenes
Authors: Fang Fan , Li Yuan , Tian Shi‐Kai
Published: January 2011

An unprecedented protocol has been developed for thestereoselective synthesis of structurally diverse electron‐deficient alkenes in moderate to excellent yields from readily accessible N‐sulfonyl imines and stabilized phosphonium ylides. Significantly, the olefination reaction of N‐sulfonylimines with nitrile‐stabilized phosphonium ylides affords an array of α,β‐unsaturated nitriles with high Z selectivity, and the reactions with ester‐, amide‐, and ketone‐stabilized phosphonium ylides afford α,β‐unsaturated esters, amides, and ketones with high E selectivity, respectively. Spectroscopic analysis of the reaction mixtures and trapping of the intermediates allow plausible mechanisms to be proposed. Initialimine/ylide addition leads to the formation of betaines that cyclize to form 1,2‐azaphosphetanes that subsequently eliminate iminophosphoranes to yield alkenes. For the synthesis of electron‐deficient 1,2‐disubstituted alkenes, the presence of an electron‐withdrawing group in the betaine allows rapid interconversion between its two diastereomers through proton transfer. The Z/E selectivity for alkene synthesis is determined by the different rates at which the two betaine diastereomers form the corresponding 1,2‐azaphosphetane diastereomers. In contrast, the Z/E selectivity for the synthesis of electron‐deficient trisubstituted alkenes originates from the diastereoselective addition of stabilized phosphonium ylides to N‐sulfonyl imines.
Synthesis and First Biological Evaluation of an Iron‐Containing HETE Analogue
Authors: Kausch‐Busies Nina , Kater Benjamin , Neudörfl Jörg M. , Prokop Aram , Schmalz Hans‐Günther
Published: January 2011

As previous studies in the field of bioorganometallic chemistry have unveiled, metal‐containing analogues of natural products frequently exhibit surprising biological activities. In this context, a synthetic approach to analogues of the eicosanoids 5‐HETE and 8‐HETE possessing a 1,3‐butadiene–Fe(CO)3 substructure was elaborated. The chosen structures are characterized by a central (2E,4Z)‐hexa‐2,4‐dien‐1‐ol–Fe(CO)3 moiety (as the potential “metal pharmacophore”) and carry a lipophilic ω‐6‐substituent as well as a hydrophilic α‐side chain (carboxylic acid). Using the cationic complex tricarbonyl[η5‐1‐(methoxycarbonyl)pentadienyl]iron hexafluorophosphate (rac‐4) as a starting material, the synthesis of a simplified Fe(CO)3‐complexed HETE analogue (rac‐3) was achieved by exploiting the addition of an alkynyl Cu species to rac‐4. The carbon skeleton was completed through diastereo(Ψ‐exo)selective addition of a titanium–zinc organyl [prepared from ethyl 4‐iodobutyrate, activated Zn powder, and Ti(OiPr)3Cl] as a butyrate D4 synthon to an aldehyde function by using 2‐Me‐THF as the solvent of choice. The (sensitive) target compound rac‐3 was shown to induce apoptosis at moderate concentrations in cancer cells (BJAB and Nalm‐6).
Study of the Structure and Photochemical Decomposition of Azidoadamantanes Entrapped in α‐ and β‐Cyclodextrin
Authors: Brinker Udo H. , Walla Peter , Krois Daniel , Arion Vladimir B.
Published: January 2011

Photolysis of 1‐azidoadamantane (1), either in its neat state or in alkane solution, yields the dimeric product 4. In contrast, amino alcohol 3 is formed as the sole product in high yield when 1 is confined within cyclodextrins (CyDs). To understand the discrepancy in product distribution caused by supramolecular encapsulation, CyD inclusion complexes (ICs) of azidoadamantanes were fully characterized. Indeed, intermolecular selectivity was influenced by reactant orientation and mobility. Both, 1‐ (1) and 2‐azidoadamantane (5) yield 1:1 ICs with β‐CyD and 1:2 ICs with α‐CyD. As inferred from 2‐D ROESY spectra in D2O, 1 is accommodated at the wider rim of β‐CyD with the azido group pointing into the cavity. However, two principal orientations of 5 inside the cavity of β‐CyD were found. Single crystal X‐ray analysis of solid 5 also demonstrates a bimodal orientation within β‐CyD. In addition, the first induced circular dichroism (ICD) study of an alkyl azide entrapped within CyD cavities is reported. From these data, it was concluded that azide 1 is bound more strongly within β‐CyD in H2O/EtOH = 8:2 at 293 K (Ka = 20240 ± 1000 M–1) than is 2‐azidoadamantane (5) (Ka = 7450 ± 400 M–1).
All‐Carbon‐Substituted Quaternary Carbon Atoms in Oxindoles by an Aerobic Palladium(II)‐Catalyzed Ring Closure onto Tri‐ and Tetrasubstituted Double Bonds
Authors: Schiffner Julia A. , Oestreich Martin
Published: January 2011

Oxidative palladium(II)‐catalyzed cyclization of α,β‐unsaturated amides derived from electron‐rich anilines is reported. The aerobic ring closure of tri‐ and tetrasubstituted alkenes yields oxindoles with congested all‐carbon‐substituted quaternary carbon atoms. The ring‐size selectivity is excellent. Selected unsymmetrically substituted arenes cyclize with perfect regioselectivity. Experimental evidence indicates that the mechanism is likely to involve Friedel–Crafts‐type electrophilic substitution rather than direct C–H bond activation.
Nucleophilic Trifluoromethylation of C=N Bonds
Authors: Dilman Alexander D. , Levin Vitalij V.
Published: January 2011

The review covers nucleophilic addition reactions of the CF3 carbanion to C=N bonds. Trifluoromethylation reactions of imines, nitrones, hydrazones, iminium ions and azomethine ylides are discussed. Various trifluorometylating reagents are considered, among which the major emphasis is placed on reactions using the Ruppert–Prakash reagent.
Direct Voltammetry of Copper, Zinc‐Superoxide Dismutase Immobilized onto Electrodeposited Nickel Oxide Nanoparticles: Fabrication of Amperometric Superoxide Biosensor
Authors: Salimi Abdollah , Noorbakhsh Abdollah , Rafiee‐Pour Hossain‐Ali , Ghourchian Hedayatollah
Published: January 2011

Direct electron transfer of immobilized copper, zinc‐superoxide dismutase (SOD) onto electrodeposited nickel‐oxide (NiOx) nanoparticle modified glassy carbon (GC) electrode displays a well defined redox process with formal potential of −0.03 V in pH 7.4. Cyclic voltammetry was used for deposition of (NiOx) nanoparticles and immobilization of SOD onto GC electrode. The surface coverage (Γ) and heterogeneous electron transfer rate constant (ks) of immobilized SOD are 1.75×10−11 mol cm−2 and 7.5±0.5 s−1, respectively. The biosensor shows a fast amperometric response (3 s) toward superoxide at a wide concentration range from 10 µM to 0.25 mM with sensitivity of 13.40 nA µM−1 cm−2 and 12.40 nA µM−1 cm−2, detection limit of 2.66 and 3.1 µM based on anodically and cathodically detection. This biosensor exhibits excellent stability, reproducibility and long life time.
A Reference Electrode System for Electrochemical Measurements in Pure Water
Authors: Huang Hongliang , Wang Qiang , Cha Chuan‐Sin , Lu Juntao , Zhuang Lin
Published: January 2011

A reference hydrogen electrode systems is constructed by employing a strip of proton‐type Nafion membrane as an ion‐conducting “bridge” to connect a reversible hydrogen electrode (RHE) in an acidic solution to an electrochemical system using pure water as electrolyte, in which the working electrode (WE) is placed. Using such a reference electrode system, the potential at the “WE/pure water” interface is equal to the equilibrium hydrogen electrode potential in pure water when the potential difference between RHE and WE is zero, irrespective of the pH value of the acidic solution in the RHE compartment. The accuracy and reproducibility of the WE potential measurements are within 1–2 mV.
The Voltammetric Responses of High and Low Molecular Weight DNA on a Variety of Carbon Substrates; Demonstrating the Benefits of Graphitic Surfaces
Authors: Gonçalves Luís M. , Batchelor‐McAuley Christopher , Xiong Linhongjia , Barros Aquiles A. , Compton Richard G.
Published: January 2011

This work compares the voltammetric response of high (∼2000 bp) and low (≤300 bp) molecular weight DNA on a variety of carbon based electrodes demonstrating for both species the advantages of using graphitic electrodes. Results suggest that the edge plane defects are kinetically dominant for the electro‐oxidation of nucleobases, whereas the basal plane sites are favoured for adsorption of the DNA to the electrode surface. For the high molecular weight DNA it is shown that although larger currents are obtained through the use of the edge plane electrode, it is beneficial in terms of signal‐to‐noise ratio to use a basal plane electrode.
Experimental study on retrofit of school buildings by adding sandwich columns to partition brick walls
Authors: Chung L. L. , Wu L. Y. , Lien K. H.
Published: January 2011

Thousands of buildings were damaged by the devastating Chi‐Chi earthquake on September 21, 1999. Of all the public buildings, school buildings are the most vulnerable to earthquake damage, and the retrofitting of existing school buildings becomes a stringent issue. In addition to cost effectiveness, the impact of retrofitting methods on the functions of the school buildings needs to be considered. This paper therefore proposes the retrofitting of school buildings by adding sandwich columns onto partition brick walls. The sandwich column is divided into two parts and is added to the two sides of the partition brick wall held with pairs of U‐shaped bars. The retrofit does not require the removal of windows or doors in the longitudinal direction making the proposed method cost effective and minimizes the impact on the function of the school buildings. Five full‐scale specimens without and with retrofitting were designed and fabricated for testing based on the partition brick wall frames of the existing school buildings. The specimens were subjected to cyclic loading in the out‐of‐plane direction through a loading frame so that the columns deformed with double curvatures. The experimental results verified the feasibility of the proposed retrofit method. The data showed that the lateral strength of the retrofitted specimen doubled that which was not and that the residual strength of the retrofitted specimen was just as high as the ultimate strength of the specimen without retrofitting. The analytical results in lateral strength yielded conservative figures compared with experimental measurements. Copyright © 2011 John Wiley & Sons, Ltd.
Shake table tests on clutter levels of typical medicine shelves and contents subjected to earthquakes
Authors: Kuo Keng‐Chang , Suzuki Yoshiyuki , Katsuragi Satoko , Yao George C.
Published: January 2011

Overturned shelves and fallen objects scattered on floors are one of the most frequently observed forms of nonstructural damage after earthquakes. The term ‘clutter’ is adopted in this study to represent this type of damage. Clutter may cause obstructions and thus hinder the use of a room. Making a seismic evaluation of clutter is a daunting task, due to the diversity of the types of shelves and objects and the way the objects are stored. Nonetheless, in order to achieve performance‐based seismic evaluation, especially for critical facilities such as hospitals, it is reasonable to undertake the estimation of clutter when examining the association between the performance of structural and nonstructural elements. Of particular interest in this paper is clutter caused by objects stored on medicine shelves in pharmacies, which are one of the critical departments for delivering post‐earthquake emergency care. Shake table tests were conducted on three conventional types of medicine shelves. Sinusoidal waves and earthquake motions were input uniaxially. The results of the tests using the sinusoidal wave input indicated the relationship between the input excitation intensity and clutter level expressed in scattering distance from the front of the shelf. Tests using earthquake motion input were then conducted and the results were compared with those for sinusoidal waves. Based on a comparison of the results from these tests, criteria for the seismic evaluation of clutter caused by medicine shelves due to earthquakes were proposed. Copyright © 2011 John Wiley & Sons, Ltd.
Causality in the VIX futures market
Authors: Shu Jinghong , Zhang Jin E.
Published: January 2011

This study examines the price‐discovery function and information efficiency of a fast growing volatility futures market: the Chicago Board of Option Exchange VIX futures market. A linear Engle–Granger cointegration test with an error correction mechanism (ECM) shows that during the full sample period, VIX futures prices lead spot VIX index, which implies that the VIX futures market has some price‐discovery function. But a modified Baek and Brock nonlinear Granger test detects bi‐directional causality between VIX and VIX futures prices, suggesting that both spot and futures prices react simultaneously to new information. Quarter‐by‐quarter investigations show that, on average, the estimated parameters are not significantly different from zero, thus providing further evidence supporting information efficiency in the VIX futures market. © 2011 Wiley Periodicals, Inc. Jrl Fut Mark
A note on utility‐based futures hedging performance measure
Authors: Lien Donald
Published: January 2011

This note considers the estimator for the utility‐based hedging performance. It shows that the estimator incurs a downward bias, regardless of whether the conventional mean‐variance expected utility function or the more general risk‐averse utility function is adopted. Consequently, the usefulness of the futures contract is under‐estimated. © 2011 Wiley Periodicals, Inc. Jrl Fut Mark
Nuclear Receptors in Liver Disease Δ
Authors: Wagner Martin , Zollner Gernot , Trauner Michael
Published: January 2011

Nuclear receptors are ligand-activated transcriptional regulators of several key aspects of hepatic physiology and pathophysiology. As such, nuclear receptors control a large variety of metabolic processes including hepatic lipid metabolism, drug disposition, bile acid homeostasis, as well as liver regeneration, inflammation, fibrosis, cell differentiation, and tumor formation. Derangements of nuclear receptor regulation and genetic variants may contribute to the pathogenesis and progression of liver diseases. This places nuclear receptors into the frontline for novel therapeutic approaches for a broad range of hepatic disorders and diseases including cholestatic and fatty liver disease, drug hepatotoxicity, viral hepatitis, liver fibrosis, and cancer. (Hepatology 2011;.)
IL28B Genetic Variation and Treatment Response in Patients with Hepatitis C Virus Genotype 3 Infection σ
Authors: Moghaddam Amir , Melum Espen , Reinton Nils , Ring-Larsen Helmer , Verbaan Hans , Bjφro Kristian , Dalgard Olav
Published: January 2011

Polymorphisms near the

IL28B

gene, which code for interferon (IFN)-λ3, predict response to pegylated interferon-α (PEG-IFN) and ribavirin treatment in hepatitis C virus (HCV) genotype 1 infected patients. Follow-up studies of the effect of

IL28B

gene in HCV non–genotype 1 infected patients have almost always used predominantly HCV genotype 2–infected or mixed genotype 2/3–infected cohorts with results partly conflicting with HCV genotype 1. We performed a retrospective analysis of 281 patients infected with HCV genotype 3 for association of response to therapy with

IL28B

polymorphisms. We found that the HCV genotype 1 responder genotypes at rs12979860 and rs8099917 did not associate with sustained virological response to PEG-IFN/ribavirin therapy. However, the responder genotypes of both SNPs showed association with rapid viral response measured at 4 weeks (rs12979860,

P

= 3 × 10−5; rs8099917,

P

= 3 × 10−4). In multivariate analysis, age (<40 years), baseline viral load (<4 × 105 IU/mL) and the responder genotypes of SNPs rs12979860 or rs8099917 remained significant independent predictors of rapid viral response to therapy. Furthermore, we show that

IL28B

polymorphisms are associated with relapse in patients who achieve rapid viral response to PEG-IFN/ribavirin therapy. The responder genotypes also showed association with markers of stage and activity of liver disease, namely high aspartate aminotransferase platelet ratio index (APRI, rs12979860,

P

= 0.018; rs8099917, not significant) and high alanine aminotransferase (ALT, rs12979860,

P

= 0.002; rs8099917,

P

= 0.001), in addition to a high baseline viral load (rs12979860,

P

= 1.4 × 10−5; rs8099917,

P

= 7.3 × 10−6).

Conclusion:

Polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/ribavirin therapy in HCV genotype 3-infected patients. (Hepatology 2011;)
Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresia
Authors: Omenetti Alessia , Bass Lee M. , Anders Robert A. , Clemente Maria G. , Francis Heather , D. Guy Cynthia , McCall Shannon , Choi Steve S. , Alpini Gianfranco , Schwarz Kathleen B. , Diehl Anna Mae , Whitington Peter F.
Published: January 2011

Biliary atresia (BA) is notable for marked ductular reaction and rapid development of fibrosis. Activation of the Hedgehog (Hh) pathway promotes the expansion of populations of immature epithelial cells that coexpress mesenchymal markers and may be profibrogenic. We examined the hypothesis that in BA excessive Hh activation impedes ductular morphogenesis and enhances fibrogenesis by promoting accumulation of immature ductular cells with a mesenchymal phenotype. Livers and remnant extrahepatic ducts from BA patients were evaluated by quantitative reverse-transcription polymerase chain reaction (QRT-PCR) and immunostaining for Hh ligands, target genes, and markers of mesenchymal cells or ductular progenitors. Findings were compared to children with genetic cholestatic disease, age-matched deceased donor controls, and adult controls. Ductular cells isolated from adult rats with and without bile duct ligation were incubated with Hh ligand-enriched medium ± Hh-neutralizing antibody to determine direct effects of Hh ligands on epithelial to mesenchymal transition (EMT) marker expression. Livers from pediatric controls showed greater innate Hh activation than adult controls. In children with BA, both intra- and extrahepatic ductular cells demonstrated striking up-regulation of Hh ligand production and increased expression of Hh target genes. Excessive accumulation of Hh-producing cells and Hh-responsive cells also occurred in other infantile cholestatic diseases. Further analysis of the BA samples demonstrated that immature ductular cells with a mesenchymal phenotype were Hh-responsive. Treating immature ductular cells with Hh ligand-enriched medium induced mesenchymal genes; neutralizing Hh ligands inhibited this.

Conclusion

: BA is characterized by excessive Hh pathway activity, which stimulates biliary EMT and may contribute to biliary dysmorphogenesis. Other cholestatic diseases show similar activation, suggesting that this is a common response to cholestatic injury in infancy. (HEPATOLOGY 2011;)
Constitutional telomerase mutations are genetic risk factors for cirrhosis
Authors: Calado Rodrigo T. , Brudno Jennifer , Mehta Paulomi , Kovacs Joseph J. , Wu Colin , Zago Marco A. , Chanock Stephen J. , Boyer Thomas D. , Young Neal S.
Published: January 2011

Some patients with liver disease progress to cirrhosis, but the risk factors for cirrhosis development are unknown. Dyskeratosis congenita, an inherited bone marrow failure syndrome associated with mucocutaneous anomalies, pulmonary fibrosis, and cirrhosis, is caused by germline mutations of genes in the telomerase complex. We examined whether telomerase mutations also occurred in sporadic cirrhosis. In all, 134 patients with cirrhosis of common etiologies treated at the Liver Research Institute, University of Arizona, between May 2008 and July 2009, and 528 healthy subjects were screened for variation in the

TERT

and

TERC

genes by direct sequencing; an additional 1,472 controls were examined for the most common genetic variation observed in patients. Telomere length of leukocytes was measured by quantitative polymerase chain reaction. Functional effects of genetic changes were assessed by transfection of mutation-containing vectors into telomerase-deficient cell lines, and telomerase activity was measured in cell lysates. Nine of the 134 patients with cirrhosis (7%) carried a missense variant in

TERT

, resulting in a cumulative carrier frequency significantly higher than in controls (

P

= 0.0009). One patient was homozygous and eight were heterozygous. The allele frequency for the most common missense

TERT

variant was significantly higher in patients with cirrhosis (2.6%) than in 2,000 controls (0.7%;

P

= 0.0011). One additional patient carried a

TERC

mutation. The mean telomere length of leukocytes in patients with cirrhosis, including six mutant cases, was shorter than in age-matched controls (

P

= 0.0004).

Conclusion:

Most

TERT

gene variants reduced telomerase enzymatic activity

in vitro

. Loss-of-function telomerase gene variants associated with short telomeres are risk factors for sporadic cirrhosis. (Hepatology 2011;)
Activation of v-Myb avian myeloblastosis viral oncogene homolog-like2 (MYBL2)-LIN9 complex contributes to human hepatocarcinogenesis and identifies a subset of hepatocellular carcinoma with mutant p53
Authors: Calvisi Diego F. , Simile Maria M. , Ladu Sara , Frau Maddalena , Evert Matthias , Tomasi Maria L. , Demartis Maria I. , Daino Lucia , Seddaiu Maria A. , Brozzetti Stefania , Feo Francesco , Pascale Rosa M.
Published: January 2011

Up-regulation of the v-Myb avian myeloblastosis viral oncogene homolog-like2 B-Myb (

MYBL2

) gene occurs in human hepatocellular carcinoma (HCC) and is associated with faster progression of rodent hepatocarcinogenesis. We evaluated, in distinct human HCC prognostic subtypes (as defined by patient survival length), activation of

MYBL2

and

MYBL2

-related genes, and relationships of p53 status with MYBL2 activity. Highest total and phosphorylated protein levels of MYBL2, E2F1-DP1, inactivated retinoblastoma protein (pRB), and cyclin B1 occurred in HCC with poorer outcome (HCCP), compared to HCC with better outcome (HCCB). In HCCP, highest LIN9-MYBL2 complex (LINC) and lowest inactive LIN9-p130 complex levels occurred. MYBL2 positively correlated with HCC genomic instability, proliferation, and microvessel density, and negatively with apoptosis. Higher MYBL2/LINC activation in HCC with mutated p53 was in contrast with LINC inactivation in HCC harboring wildtype p53. Small interfering RNA (siRNA)-mediated MYBL2/LINC silencing reduced proliferation, induced apoptosis, and DNA damage at similar levels in HCC cell lines, irrespective of p53 status. However, association of MYBL2/LINC silencing with doxorubicin-induced DNA damage caused stronger growth restraint in p53-/- Huh7 and Hep3B cells than in p53+/+ Huh6 and HepG2 cells. Doxorubicin triggered LIN9 dissociation from MYBL2 in p53+/+ cell lines and increased MYBL2-LIN9 complexes in p53-/- cells. Doxorubicin-induced MYBL2 dissociation from LIN9 led to p21WAF1 up-regulation in p53+/+ but not in p53-/- cell lines. Suppression of

p53

or

p21WAF1

genes abolished DNA damage response, enhanced apoptosis, and inhibited growth in doxorubicin-treated cells harboring p53+/+.

Conclusion:

We show that MYBL2 activation is crucial for human HCC progression. In particular, our data indicate that MYBL2-LIN9 complex integrity contributes to survival of DNA damaged p53-/- cells. Thus, MYBL2 inhibition could represent a valuable adjuvant for treatments against human HCC with mutated p53. (HEPATOLOGY 2011;)