bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial Biosensors for Measuring Availability of Environmental Pollutants
Authors: Tecon Robin , Van der Meer Jan Roelof
Published: August 2008

Traditionally, pollution risk assessment is based on the measurement of a pollutant’s total concentration in a sample. The toxicity of a given pollutant in the environment, however, is tightly linked to its bioavailability, which may differ significantly from the total amount. Physico-chemical and biological parameters strongly influence pollutant fate in terms of leaching, sequestration and biodegradation. Bacterial sensorreporters, which consist of living micro-organisms genetically engineered to produce specific output in response to target chemicals, offer an interesting alternative to monitoring approaches. Bacterial sensor-reporters detect bioavailable and/or bioaccessible compound fractions in samples. Currently, a variety of environmental pollutants can be targeted by specific biosensor-reporters. Although most of such strains are still confined to the lab, several recent reports have demonstrated utility of bacterial sensing-reporting in the field, with method detection limits in the nanomolar range. This review illustrates the general design principles for bacterial sensor-reporters, presents an overview of the existing biosensor-reporter strains with emphasis on organic compound detection. A specific focus throughout is on the concepts of bioavailability and bioaccessibility, and how bacteria-based sensing-reporting systems can help to improve our basic understanding of the different processes at work.
Comparison of Mercury Distribution Between Liver and Muscle – A Biomonitoring of Fish from Lightly and Heavily Contaminated Localities
Authors: Havelková Marcela , Dušek Ladislav , Némethová Danka , Poleszczuk Gorzyslaw , Svobodová Zdeňka
Published: August 2008

Tissue samples from 1,117 fish of 25 species were collected from 1991 through 1996 at 13 locations along the River Elbe. The principal indicator species were perch (Perca fluviatilis) (n=118), chub (Leuciscus cephalus L.) (n=113) and roach (Rutilus rutilus) (n=138). Mercury (Hg) concentrations in muscle and liver were determined by atomic absorption spectrometry. The liver/muscle index in three indicator species from heavily contaminated and lightly contaminated localities were significantly different. In fish from heavily contaminated localities, Hg was deposited preferentially in the liver (the depository for inorganic and organic forms of Hg), while in lightly contaminated areas, it was deposited preferentially in muscle.
Development of Amperometric Hydrogen Peroxide Sensor Based on Horseradish Peroxidase-Immobilized Poly(Thiophene-co-EpoxyThiophene)
Authors: Kim Hwa-Jung , Piao Ming-Hua , Choi Seong-Ho , Shin Chang-Ho , Lee Young-Taeg
Published: August 2008

A modified electrode for hydrogen peroxide (H2O2) sensing was prepared via thiophene (Th) with epoxy group. Thiophene (EpoxyTh) with epoxy group was synthesized by reaction of 3-bromothiophene and glycidyl methacrylate (GMA) in acetonitrile according to Heck Reaction. The electrocopolymerization of Th and EpoxyTh was performed on the surface of indium tin oxide (ITO) electrode by cycling the potential between -1.0 and +2.5 V in mixture of thiophene (Th) and EpoxyTh. Poly(Th-co- EpoxyTh) grown onto the ITO electrode was successfully confirmed by SEM, AFM, and water contact angle analysis, respectively. Finally, the HRP was immobilized on the surface of poly(Th-co-EpoxyTh) electrode by covalent binding. The amperometric response of the HRP-immobilized poly(Th-co-EpoxyTh) electrode for H2O2 was examined by cyclic voltammetry (CV). The HRP-immobilized poly(Th-co-EpoxyTh) electrode showed linearity from 0.1 to 30 mM H2O2, good reproducibility, and long life time.
Determination of Lamotrigine in Pharmaceutical Preparations by Adsorptive Stripping Voltammetry Using Screen Printed Electrodes
Authors: Domínguez-Renedo Olga , Calvo M. Encarnación Burgoa , Arcos-Martínez M. Julia
Published: August 2008

This paper describes a procedure that has been optimized for the determination of lamotrigine by Differential Pulse Adsorptive Stripping Voltammetry (DPAdSV) using carbon screen-printed electrodes (CSPE) and mercury coated carbon screen-printed electrodes. Selection of the experimental parameters was made using experimental design methodology. The detection limit found was 5.0 x 10-6 M and 2.0 x 10-6 M for the non modified and Hg modified CSPE, respectively. In terms of reproducibility, the precision of the above mentioned methods was calculated in %RSD values at 9.83% for CSPE and 2.73% for Hg-CSPE. The Hg-coated CSPEs developed in this work were successfully applied in the determination of lamotrigine in pharmaceutical preparations.
Short-term Influences on Suspended Particulate Matter Distribution in the Northern Gulf of Mexico: Satellite and Model Observations
Authors: D’Sa Eurico J. , Ko Dong S.
Published: August 2008

Energetic meteorological events such as frontal passages and hurricanes often impact coastal regions in the northern Gulf of Mexico that influence geochemical processes in the region. Satellite remote sensing data such as winds from QuikSCAT, suspended particulate matter (SPM) concentrations derived from SeaWiFS and the outputs (sea level and surface ocean currents) of a nested navy coastal ocean model (NCOM) were combined to assess the effects of frontal passages between 23-28 March 2005 on the physical properties and the SPM characteristics in the northern Gulf of Mexico. Typical changes in wind speed and direction associated with frontal passages were observed in the latest 12.5 km wind product from QuikSCAT with easterly winds before the frontal passage undergoing systematic shifts in direction and speed and turning northerly, northwesterly during a weak and a strong front on 23 and 27 March, respectively. A quantitative comparison of model sea level results with tide gauge observations suggest better correlations near the delta than in the western part of the Gulf with elevated sea levels along the coast before the frontal passage and a large drop in sea level following the frontal passage on 27 March. Model results of surface currents suggested strong response to wind forcing with westward and onshore currents before the frontal passage reversing into eastward, southeastward direction over a six day period from 23 to 28 March 2005. Surface SPM distribution derived from SeaWiFS ocean color data for two clear days on 23 and 28 March 2005 indicated SPM plumes to be oriented with the current field with increasing concentrations in nearshore waters due to resuspension and discharge from the rivers and bays and its seaward transport following the frontal passage. The backscattering spectral slope γ, a parameter sensitive to particle size distribution also indicated lower γ values (larger particles) in nearshore waters that decreased offshore (smaller particles). The use of both satellite and model results revealed the strong interactions between physical processes and the surface particulate field in response to the frontal passage in a large riverdominated coastal margin.
Detection of Carcinoembryonic Antigens Using a Surface Plasmon Resonance Biosensor
Authors: Su Fengyu , Xu Chunye , Taya Minoru , Murayama Kimie , Shinohara Yasuro , Nishimura Shin-Ichiro
Published: August 2008

Carcinoembryonic antigen (CEA) is an oncofoetal cell-surface glycoprotein that serves as an important tumor marker for colorectal and some other carcinomas. In this work, a CEA immunoassay using a surface plasmon resonance (SPR) biosensor has been developed. SPR could provide label-free, real-time detection with high sensitivity, though its ability to detect CEA in human serum was highly dependent on the analytical conditions employed. We investigated the influences of various analytical conditions including immobilization methods for anti-CEA antibody and composition of sensor surface on the selective and sensitive detection of CEA. The results show that anti-CEA antibody immobilized via Protein A or Protein G caused a large increase in the resonance signal upon injection of human serum due to the interactions with IgGs in serum, while direct covalent immobilization of anti-CEA antibody could substantially reduce it. An optimized protocol based on further kinetic analysis and the use of 2nd and 3rd antibodies for the sandwich assay allowed detecting spiked CEA in human serum as low as 25 ng/mL. Furthermore, a self-assembled monolayer of mixed ethylene-glycol terminated alkanethiols on gold was found to have a comparable ability in detecting CEA as CM5 with thick dextran matrix and C1 with short flat layer on gold.
A Fixed-Threshold Approach to Generate High-Resolution Vegetation Maps for IKONOS Imagery
Authors: Cheng Wen-Chun , Chang Jyh-Chian , Chang Chien-Ping , Su Yu , Tu Te-Ming
Published: August 2008

Vegetation distribution maps from remote sensors play an important role in urban planning, environmental protecting and related policy making. The normalized difference vegetation index (NDVI) is the most popular approach to generate vegetation maps for remote sensing imagery. However, NDVI is usually used to generate lower resolution vegetation maps, and particularly the threshold needs to be chosen manually for extracting required vegetation information. To tackle this threshold selection problem for IKONOS imagery, a fixed-threshold approach is developed in this work, which integrates with an extended Tasseled Cap transformation and a designed image fusion method to generate high-resolution (1-meter) vegetation maps. Our experimental results are promising and show it can generate more accurate and useful vegetation maps for IKONOS imagery.
The Image Transceiver Device: Studies of Improved Physical Design
Authors: David Yitzhak , Efron Uzi
Published: August 2008

The Image Transceiver Device (ITD) design is based on combining LCOS micro-display, image processing tools and back illuminated APS imager in single CMOS chip [1]. The device is under development for Head-Mounted Display applications in augmented and virtual reality systems. The main issues with the present design are a high crosstalk of the backside imager and the need to shield the pixel circuitry from the photocharges generated in the silicon substrate. In this publication we present a modified, “deep p-well” ITD pixel design, which provides a significantly reduced crosstalk level, as well as an effective shielding of photo-charges for the pixel circuitry. The simulation performed using Silvaco software [ATLAS Silicon Device Simulator, Ray Trace and Light Absorption programs, Silvaco International, 1998] shows that the new approach provides high photo response and allows increasing the optimal thickness of the die over and above the 10-15 micrometers commonly used for back illuminated imaging devices, thereby improving its mechanical ruggedness following the thinning process and also providing a more efficient absorption of the long wavelength photons. The proposed deep p-well pixel structure is also a technology solution for the fabrication of high performance back illuminated CMOS image sensors.
Cantilever measurements of surface stress, surface reconstruction, film stress and magnetoelastic stress of monolayers
Authors: Sander Dirk , Tian Zhen , Kirschner Jürgen
Published: August 2008

We review the application of cantilever-based stress measurements in surface science and magnetism. The application of thin (thickness appr. 0.1 mm) single crystalline substrates as cantilevers has been used successfully to measure adsorbate-induced surface stress changes, lattice misfit induced film stress, and magneto-elastic stress of ferromagnetic monolayers. Surface stress changes as small as 0.01 N/m can be readily measured, and this translates into a sensitivity for adsorbate-coverage well below 0.01 of one layer. Stress as large as several GPa, beyond the elasticity limits of high strength materials, is measured, and it is ascribed to the lattice misfit between film and substrate. Our results point at the intimate relation between surface stress and surface reconstruction, stress-induced structural changes in epitaxially strained films, and strain-induced modifications of the magneto-elastic coupling in ferromagnetic monolayers.
Research Themes and Trends in Health Information Systems
Authors: Nerur S. , Raghupathi W.
Published: August 2008

Objectives:
The health information systems (HIS) field is characterized as being associated with health care and information systems. Drawing on several disciplines, a body of knowledge has come together that help define the core internal structure of the field. This study attempts to identify the emerging sub-fields using the bibliometric technique of author-cocitation analysis.

Methods:
Co-citation data for members of editorial boards of several health information systems journals for the period of 1998-2006 was collected and analyzed (N = 166). We performed numerous multivariate analyses, including cluster analysis, factor analysis and multidimensional scaling to extract the sub-fields.

Results:
Our findings indicate the presence of several strong sub-fields, including HIS evaluation, communication and e-health, and clinical DSS. In addition, we identified other sub-fields that are distinct but still emerging, such as adoption, outcome and policy, and use and impact of HIS. The study also confirms the existence of several historical sub-fields and contrasts technology-oriented sub-fields with managementoriented sub-fields. Topics on the periphery of HIS provide links to other disciplines as well.

Conclusions:
The study provides a unique perspective on the field of HIS, and the results indicate opportunities for further research that explores collaborations and social networks among the sub-fields.
Autosomal dominant isolated question mark ear
Authors: Shkalim Vered , Eliaz Noam , Linder Nehama , Merlob Paul , Basel‐Vanagaite Lina
Published: August 2008

Question mark (Cosman) ear is an auricular abnormality characterized by a cleft between the lobule and the lower part of the helix, sometimes accompanied by a prominent or deficient upper part of the helix, shallow skin dimple on the posterior surface of the ear, or transposition of the ear lobe/antitragus. It can be inherited as an autosomal dominant trait. Only two families with more than one member with Question mark ear have been reported previously. Here we report on a female infant with bilateral isolated Question mark ear. The family history revealed a similar abnormality in her father and paternal grandfather. The similarity of the Question mark ear to the ear abnormalities described in auriculo‐condylar syndrome (ACS) is discussed. © 2008 Wiley‐Liss, Inc.
Deletion (1)(p32.2–p32.3) detected by array‐CGH in a patient with developmental delay/mental retardation, dysmorphic features and low cholesterol: A new microdeletion syndrome?
Authors: Mulatinho Milene , Llerena Juan , Leren Trond P. , Rao P. Nagesh , Quintero‐Rivera Fabiola
Published: August 2008

We report on a 25‐year‐old male with mental retardation and global developmental delay, low levels of total and LDL cholesterol and dysmorphism, which includes macrocephaly, hypertelorism, synophrys, telecanthus, prominent philtrum, low set ears, bilateral cataracts, bilateral cleft lip with cleft palate and widely spaced nipples. While his karyotype and subtelomeric FISH studies were normal, a de novo, 5.4 Mb interstitial deletion at 1p32 [del(1)(p32.2–p32.3)] was identified by oligonucleotide aCGH. The deleted region encompasses a cluster of genes involved in fatty acid oxidation and cholesterol metabolism. One of these genes is PCSK9, a key regulator for a number of cell‐surface LDL receptors. In addition to the loss of the paternal allele, our patient is hemizygous for the A443T weak loss‐of‐function mutation in exon 8 of PCSK9. Loss‐of‐function mutations within PCSK9 have been shown to cause hypocholesterolemia. Another gene also mapped to this region and deleted in this patient is DAB1, reported to be involved in brain development. Based on the findings in the current patient and in the four previously reported individuals with del(1)(p32.2–p32.3), we suggest that these patients may have a new microdeletion syndrome that may have gone undetected because of its location in a G‐negative band. However, the condition can easily be identified by array‐CGH. © 2008 Wiley‐Liss, Inc.
Giving ourselves: The ethics of anatomical donation
Authors: Gunderman Richard B.
Published: August 2008

In some European countries, such as Italy, medical education is threatened by a dearth of anatomical specimens. Such a shortage could spread to other nations, including the United States. This article addresses two ethical questions in body donation. Why might people choose to donate their bodies to education and science? What sorts of ethical appeals might anatomists, physicians, and other health professionals make to patients and family members for anatomical donation? Two models of giving, egoistic and liberal, merit close examination. Anat Sci Ed 1:217–219, 2008. © 2008 American Association of Anatomists.
Asymmetric Catalysis with Metal Complexes in Nanoreactors
Authors: Yang Qihua , Han Difei , Yang Hengquan , Li Can
Published: August 2008

Recently, the field of heterogeneous asymmetric catalysis, generally using chiral solid catalysts, has attracted much attention in the production of single enantiomers. Among versatile chiral solid catalysts, chiral metal complexes confined in nanoreactors often exhibit very unique enantioselectivity and catalytic activity compared to homogeneous catalysts. In this Focus Review, we summarize the recent advances in asymmetric reactions on chiral metal complexes confined in nanoreactors with an emphasis on the confinement effect and cooperative activation effect of the nanoreactor and new strategies for the preparation of chiral solid catalysts, such as the encapsulation of chiral metal complexes in the nanocages of mesoporous silica and incorporation of chiral ligands in the network of mesoporous organosilicas.
Utilization of N,N‐Dialkylcarbamic Acid Derived from Secondary Amines and Supercritical Carbon Dioxide: Stereoselective Synthesis of Z Alkenyl Carbamates with a CO2‐Soluble Ruthenium–P(OC2H5)3 Catalyst
Authors: Kayaki Yoshihito , Suzuki Tomoyuki , Ikariya Takao
Published: August 2008

Reversible transformation of diethylamine (1) and supercritical carbon dioxide (scCO2) into N,N‐diethylcarbamic acid (2) was confirmed by direct acquisition of 1H and 13C{1H} NMR spectra. The equilibrium between 1+CO2 and 2 is strongly influenced by conditions of the supercritical state. Low temperature favors formation of carbamic acid, whereas high temperature causes decarboxylation. On the basis of the spectroscopic results of carbamic acid formation under scCO2 conditions, the ruthenium‐catalyzed formation of alkenyl carbamates from terminal alkynes, 1, and carbon dioxide was investigated to demonstrate the useful transformation of elusive carbamic acids. Selectivity toward the CO2‐fixation products over enynes obtained by dimerization of the alkyne substrates was improved by the use of scCO2 as a reaction medium. In particular, a CO2‐soluble ruthenium complex, trans‐[RuCl2{P(OC2H5)3}4], was found to be effective in affording Z alkenyl carbamates with high stereoselectivity.
Advancing public sector performance analysis
Authors: Heinrich Carolyn J.
Published: August 2008

Recent reforms intended to promote more accountable and responsive government have increased public attention to performance analysis and accelerated the production and use of information on agency performance and public program outcomes. Drawing from cases and empirical studies, this presentation considers questions about what should count as evidence, how it should be communicated, who should judge the quality and reliability of evidence and performance information, and how to achieve a balance between processes that produce rigorous information for decision making and those that foster democratic governance and accountability. Promising directions are suggested for efforts to improve government effectiveness through the use of more rigorous information in decision making, along with acknowledgment of the limitations and risks associated with such efforts. Copyright © 2008 John Wiley & Sons, Ltd.
Design of (Gd‐DO3A)n‐polydiamidopropanoyl‐peptide nucleic acid‐D(Cys‐Ser‐Lys‐Cys) magnetic resonance contrast agents
Authors: Amirkhanov Nariman V. , Dimitrov Ivan , Opitz Armin W. , Zhang Kaijun , Lackey John P. , Cardi Christopher A. , Lai Song , Wagner Norman J. , Thakur Mathew L. , Wickstrom Eric
Published: August 2008

We hypothesized that chelating Gd(III) to 1,4,7‐tris(carboxymethylaza)cyclododecane‐10‐azaacetylamide (DO3A) on peptide nucleic acid (PNA) hybridization probes would provide a magnetic resonance genetic imaging agent capable of hybridization to a specific mRNA. Because of the low sensitivity of Gd(III) as an magnetic resonance imaging (MRI) contrast agent, a single Gd‐DO3A complex per PNA hybridization agent could not provide enough contrast for detection of cancer gene mRNAs, even at thousands of mRNA copies per cell. To increase the Gd(III) shift intensity of MRI genetic imaging agents, we extended a novel DO3An‐polydiamidopropanoyl (PDAPm) dendrimer, up to n = 16, from the N‐terminus of KRAS PNA hybridization agents by solid phase synthesis. A C‐terminal D(Cys‐Ser‐Lys‐Cys) cyclized peptide analog of insulin‐like growth factor 1 (IGF1) was included to enable receptor‐mediated cellular uptake. Molecular dynamic simulation of the (Gd‐DO3A‐AEEA)16‐PDAP4‐AEEA2‐KRAS PNA‐AEEA‐D(Cys‐Ser‐Lys‐Cys) genetic imaging nanoparticles in explicit water yielded a pair correlation function similar to that of PAMAM dendrimers, and a predicted structure in which the PDAP dendron did not sequester the PNA. Thermal melting measurements indicated that the size of the PDAP dendron included in the (DO3A‐AEEA)n‐PDAPm‐AEEA2‐KRAS PNA‐AEEA‐D(Cys‐Ser‐Lys‐Cys) probes (up to 16 Gd(III) cations per PNA) did not depress the melting temperatures (Tm) of the complementary PNA/RNA hybrid duplexes. The Gd(III) dendrimer PNA genetic imaging agents in phantom solutions displayed significantly greater T1 relaxivity per probe (r1 = 30.64 ± 2.68 mM−1 s−1 for n = 2, r1 = 153.84 ± 11.28 mM−1 s−1 for n = 8) than Gd‐DTPA (r1 = 10.35 ± 0.37 mM−1 s−1), but less than that of (Gd‐DO3A)32‐PAMAM dendrimer (r1 = 771.84 ± 20.48 mM−1 s−1) (P < 0.05). Higher generations of PDAP dendrimers with 32 or more Gd‐DO3A residues attached to PNA‐D(Cys‐Ser‐Lys‐Cys) genetic imaging agents might provide greater contrast for more sensitive detection. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 1061–1076, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Molecular dynamics simulations of Factor Xa: Insight into conformational transition of its binding subsites
Authors: Singh Narender , Briggs James M.
Published: August 2008

Protein flexibility and conformational diversity is well known to be a key characteristic of the function of many proteins. Human blood coagulation proteins have multiple substrates, and various protein–protein interactions are required for the smooth functioning of the coagulation cascade to maintain blood hemostasis. To address how a protein may cope with multiple interactions with its structurally diverse substrates and the accompanied structural changes that may drive these changes, we studied human Factor X. We employed 20 ns of molecular dynamics (MD) and steered molecular dynamics (SMD) simulations on two different conformational forms of Factor X, open and closed, and observed an interchangeable conformational transition from one to another. This work also demonstrates the roles of various aromatic residues involved in aromatic–aromatic interactions, which make this dynamic transition possible. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 1104–1113, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Erkältungsviren: Keine Hoffnung auf Immunität
Authors: Höffeler Fritz
Published: August 2008

Über 200 verschiedene Viren aus fünf Gattungen können beim Menschen eine Erkältung auslösen. Nur die wenigsten Infektionen münden in eine starke Erkältung. Ihre Symptome werden nicht durch die Viren selbst ausgelöst, sondern sind größtenteils das Resultat von durch das angeborene Immunsystem ausgelösten Entzündungsreaktionen. Erkältungen können nicht verhindert, aber ihr Verlauf gemildert werden. Da der Mensch pro Erkältung immer nur durch einen, aber meist von Infektion zu Infektion wechselnden Virustyp infiziert wird, ist eine vollständige Immunität gegen alle Viren nahezu unmöglich.
Die Evolution des Fluges und der Echoortung: Fledermäuse
Authors: Habersetzer Jörg , Simmons Nancy B. , Seymour Kevin , Gunnell Gregg F. , Schlosser‐Sturm Evelyn
Published: August 2008

Die lange Kontroverse, ob in der Evolution der Fledermäuse das Fliegen am Anfang stand oder die Echoortung mit für uns unhörbarem Ultraschall (oder ob sich beide simultan entwickelten), wurde aufgrund eines neuen Fundes – Onychonycteris finneyi – zugunsten der “Flight first”‐Hypothese entschieden. Noch im Gestein verborgene Details der Bezahnung, des Flugapparates und der Innenohren werden in Fortführung des Forschungsvorhabens mit speziellen mikrotomografischen Verfahren untersucht und mit denen fossiler und rezenter Fledermäuse verglichen.
Selectivity of Neutral/Weakly Basic P1 Group Inhibitors of Thrombin and Trypsin by a Molecular Dynamics Study
Authors: Wu Emilia L. , Han KeLi , Zhang John Z. H.
Published: August 2008

Molecular dynamics (MD) simulations followed by molecular mechanics generalized Born surface area (MM‐GBSA) analyses have been carried out to study the selectivity of two neutral and weakly basic P1 group inhibitors (177 and CDA) to thrombin and trypsin. Detailed binding free energies between these inhibitors and individual protein residues are calculated by using a per‐residue basis decomposition method. The analysis of the detailed interaction energies provides insight on the protein–inhibitor‐binding mechanism and helps to elucidate the basis for achieving selectivity through interpretation of the structural and energetic results from the simulations. The study shows that the dominant factor of selectivity for both inhibitors is van der Waals energy, which suggests better shape complementarity and packing with thrombin. Nonpolar solvation free energy and total entropy contribution are also in favor of selectivity, but the contributions are much smaller. Binding mode and structural analysis show that 177 binds to thrombin and trypsin in a similar binding mode. In contrast, the CDA binds to thrombin and trypsin in very different modes.
Metallobiological Necklaces: Mass Spectrometric and Molecular Modeling Study of Metallation in Concatenated Domains of Metallothionein
Authors: Chan Jayna , Huang Zuyun , Watt Ian , Kille Peter , Stillman Martin
Published: August 2008

The ubiquitous protein metallothionein (MT) has proven to be a major player not only in the homeostasis of CuI and ZnII, but also binds all the Group 11 and 12 metals. Metallothioneins are characterised by the presence of numerous cys‐x‐cys and cys–cys motifs in the sequence and are found naturally with either one domain or two, linked, metal‐binding domains. The use of chains of these metal–thiolate domains offers the possibility of creating chemically tuneable and, therefore, chemically dependent electrochemical or photochemical surface modifiers or as nanomachinery with nanomechanical properties. In this work, the metal‐binding properties of the Cd4‐containing domain of α‐rhMT1a assembled into chains of two and three concatenated domains, that is, “necklaces”, have been studied by spectrometric techniques, and the interactions within the structures modelled and interpreted by using molecular dynamics. These chains are metallated with 4, 8 or 12 CdII ions to the 11, 22, and 33 cysteinyl sulfur atoms in the α‐rhMT1a, αα‐rhMT1a, and ααα‐rhMT1a proteins, respectively. The effect of pH on the folding of each protein was studied by ESI‐MS and optical spectroscopy. MM3/MD simulations were carried out over a period of up to 500 ps by using force‐field parameters based on the reported structural data. These calculations provide novel information about the motion of the clustered metallated, partially demetallated, and metal‐free peptide chains, with special interest in the region of the metal‐binding site. The MD energy/time trajectory conformations show for the first time the flexibility of the metal–sulfur clusters and the bound amino acid chains. We report unexpected and very different sizes for the metallated and demetallated proteins from the combination of experimental data, with molecular dynamics simulations.
Controllable Cyclization Reactions of 2‐(2′,3′‐Allenyl)acetylacetates Catalyzed by Gold and Palladium Affording Substituted Cyclopentene and 4,5‐Dihydrofuran Derivatives with Distinct Selectivity
Authors: Jiang Xuefeng , Ma Xiaojing , Zheng Zilong , Ma Shengming
Published: August 2008

Efficient room‐temperature syntheses of cyclopentenes and 4,5‐dihydrofurans with different substitution patterns were performed starting from the same materials (i.e., 2‐(2′,3′‐allenyl)acetylacetates). Depending on the choice of metal catalyst, the Au‐catalyzed reaction afforded C‐attack‐5‐endo cyclization products 2, whereas the Pd‐catalyzed one led to the formation of O‐attack‐5‐exo cyclization products 3. The selectivity may be explained by the steric and electronic effects of the substrates and catalysts.
Bonding and Bending in Zirconium(IV) and Hafnium(IV) Hydrazides
Authors: Herrmann Heike , Fillol Julio Lloret , Gehrmann Thorsten , Enders Markus , Wadepohl Hubert , Gade Lutz H.
Published: August 2008

Reaction of the dichloro complexes [M(N2TBSNpy)Cl2] (M=Zr: 1, Hf: 2; TBS: tBuMe2Si; py: pyridine) with one molar equivalent of LiNHNPh2 gave mixtures of the two diastereomeric chlorohydrazido(1−) complexes [M(N2TBSNpy)(NHNPh2)Cl] (M=Zr: 3 a,b, Hf: 4 a,b) in which the diphenylhydrazido(1−) ligand adopts a bent κ1 coordination. This mixture of isomers could be cleanly converted into the deep green diphenylhydrazido(2−) complexes [Zr(N2TBSNpy)(NNPh2)(py)] (5) and [Hf(N2TBSNpy)(NNPh2)(py)] (6), respectively, by dehydrohalogenation with lithium hexamethyldisilazide (LiHMDS) in the presence of one molar equivalent of pyridine. Both complexes contain a linearly coordinated hydrazinediide for which a DFT‐based frontier orbital analysis established bonding through one σ and two π orbitals. A high polarity of the MN bond was found, in accordance with the description of hydrazinediide(2−) acting as a six‐electron donor ligand. The pyridine ligand in [M(N2TBSNpy)(NNPh2)(py)] (M=Zr: 5, Hf: 6) is substitutionally labile as established by line‐shape analysis of the dynamic spectra (ΔG≠=19 kcal mol−1). A change in denticity of the hydrazido unit from κ1 to κ2 was studied by DFT methods. Both forms are calculated to be very close in energy and are only separated by shallow activation barriers, which supports the notion of a rapid κ1 to κ2 interconversion. This process is believed to happen early on in the NN scission in the presence of coupling reagents. Frontier orbital and natural population analyses suggest that a primarily charge‐controlled nucleophilic attack at Nα is unlikely whereas interaction with an electrophile could play an important role. This hypothesis was tested by the reaction of 5 and 6 with one molar equivalent of B(C6F5)3 to give [Zr(N2TBSNpy)(NNPh2){B(C6F5)3}] (7) and [Hf(N2TBSNpy)(NNPh2){B(C6F5)3}] (8). In these products, B(C6F5)3 becomes attached to the Nα atom of the side‐on bound hydrazinediide and there is an additional interaction of an ortho‐F atom of a C6F5 ring with the metal centre.
Synthesis and Preferred All‐syn Conformation of C3‐Symmetrical N‐(Hetero)arylmethyl Triindoles
Authors: García‐Frutos Eva M. , Gómez‐Lor Berta , Monge Ángeles , Gutiérrez‐Puebla Enrique , Alkorta Ibon , Elguero José
Published: August 2008

A new series of C3‐symmetrical N‐(hetero)arylmethyl triindoles has been synthesized in a straightforward procedure. The structure and conformation in the solid state have been determined for three derivatives (3, 4, and 6) by X‐ray crystallographic analysis. In all three cases, the molecules adopt a tripodal conformation with all of the flexible arms directed towards the same side, thereby delimiting an inner cavity. Compound 6 crystallizes and forms C3‐symmetric dimeric cagelike complexes. Guest molecules of chloroform and water are confined within the resulting cavities with stabilization by different intermolecular interactions; this highlights the potential of these compounds in the construction of supramolecular systems. A computational analysis has been performed to predict the most stable conformers. As a general trend, a preference for a conformation with all branches directed to the same side has been predicted. Comparison between theoretical and experimental results indicates that the computational level selected for the present study, B3LYP/6‐31G*, is able to reproduce both the minimum energy conformations and the rotation barriers about the NCH2 bond.
Cell adhesion in zebrafish myogenesis: Distribution of intermediate filaments, microfilaments, intracellular adhesion structures and extracellular matrix
Authors: Costa Manoel L. , Escaleira Roberta C. , Jazenko Fernanda , Mermelstein Claudia S.
Published: August 2008

To overcome the limitations of in vitro studies, we have been studying myogenesis in situ in zebrafish embryos, at a sub‐cellular level. While in previous works we focused on myofibrillogenesis and some aspects of adhesion structures, here we describe in more detail cell adhesion structures and interactions among cytoskeletal components, membrane and extracellular matrix during zebrafish muscle development. We studied the intermediate filaments, and we describe the full range of desmin distribution in zebrafish development, from perinuclear to striated, until its deposition around the intersomite septa of older somites. This adhesion structure, positive for desmin and actin, has not been previously observed in myogenesis in vitro. We also show that actin is initially located in the intersomite septum region whereas it is confined to the myofibrils later on. While actin localization changes during development, the adhesion complex proteins vinculin, paxillin, talin, dystrophin, laminin and fibronectin always appear exclusively at the intersomite septa, and appear to be co‐distributed, even though the extracellular proteins accumulates before the intracellular ones. Contrary to the adhesion proteins, that are continuously distributed, desmin and sarcomeric actin form triangular aggregates among the septa and the cytoskeleton. We studied the cytoskeletal linker plectin as well, and we show that it has a distribution similar to desmin and not to actin. We conclude that the in situ adhesion structures differ from their in vitro counterparts, and that the actual zebrafish embryo myogenesis is quite different than that which occurs in in vitro systems. Cell Motil. Cytoskeleton 65: 801–815, 2008. © 2008 Wiley‐Liss, Inc.
Long‐term outcomes of radical prostatectomy with multimodal adjuvant therapy in men with a preoperative serum prostate‐specific antigen level ≥50 ng/mL
Authors: Inman Brant A. , Davies Judson D. , Rangel Laureano J. , Bergstralh Eric J. , Kwon Eugene D. , Blute Michael L. , Karnes R. Jeffrey , Leibovich Bradley C.
Published: August 2008

BACKGROUND.

The authors evaluated the long‐term outcomes of men with prostate cancer and very high (≥50 ng/mL) preoperative serum prostate‐specific antigen (PSA) values that were treated with radical prostatectomy.

METHODS.

This study included 236 men with preoperative serum PSA values ≥50ng/mL who underwent radical retropubic prostatectomy between 1987 and 2004. For comparison, the study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL and patients with PSA levels ≥100 ng/mL. Biochemical recurrence was defined as a single postoperative serum PSA value of 0.4 ng/mL or greater. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer‐specific mortality.

RESULTS.

Biochemical recurrence‐free survival rates in the groups of patients with a PSA level 50 to 99 ng/mL and ≥100 ng/mL were 43% and 36% at 10 years, respectively. Systemic progression‐free survival rates in the PSA 50 to 99 ng/mL and PSA ≥100 ng/mL groups were 83% and 74% at 10 years, respectively. Estimated overall cancer‐specific survival was 87% at 10 years.

CONCLUSIONS.

Patients with prostate cancer and a serum PSA level ≥50 ng/mL have very high‐risk prostate cancer that carries a high likelihood of being pathologically advanced. Although the probability of realizing long‐term survival in these high‐risk patients is less than in patients with more favorable disease, 10‐year survival outcomes remain excellent and argue for aggressive management of these cases. Cancer 2008. © 2008 American Cancer Society.
Differential expression of the multidrug resistance‐related proteins ABCb1 and ABCc1 between blood‐brain interfaces
Authors: Gazzin Silvia , Strazielle Nathalie , Schmitt Charlotte , Fevre‐Montange Michelle , Ostrow J. Donald , Tiribelli Claudio , Ghersi‐Egea Jean‐François
Published: August 2008

Cerebral homeostasis results from the presence of the protective blood‐brain and blood‐cerebrospinal fluid barriers located respectively at the brain capillary endothelium and the choroid plexus epithelium. ABCb1 (Pgp) and ABCc1 (Mrp1) transporters are two major proteins of neuroprotection whose localization and functional significance at both barriers remain partly unsettled. We conducted a comparative analysis of their relative protein content between the two blood‐brain interfaces. Microvessels and choroid plexuses located in the fourth and lateral ventricles were isolated from developing and adult rat brains, and whole homogenates were submitted to quantitative Western blot analysis by using standard curves generated from one of the samples. In adult, choroid plexus‐associated Pgp content was less than 0.5% of the level in microvessels, whereas Mrp1 content in microvessels was 4% of that in the fourth ventricle choroid plexus. Pgp but not Mrp1 was enriched in microvessels over parenchyma. In choroid plexuses, Mrp1 displayed a basolateral epithelial localization, and reached its high adult protein level, early during postnatal development. In postnatal as in adult microvessels, Pgp localization appeared luminal. However, by contrast to Mrp1, the level of this transporter increased 4.6‐fold between 9‐day‐old and adult animals. Western blot analysis of human samples confirmed the mirror image of Pgp and Mrp1 expression between the two barriers. We conclude that there are major differences in the mechanisms by which blood‐brain interfaces fulfill their neuroprotective functions. The data also highlight the significance of the neuroprotective function of the choroid plexus during brain maturation, when the microvasculature is still developing. J. Comp. Neurol. 510:497–507, 2008. © 2008 Wiley‐Liss, Inc.
Dual‐Polarization Imaging of a Dual‐Fluorophore Ion Sensor: A Single‐Molecule Study
Authors: Lu Yin , Bowles Richard K. , Paige Matthew F.
Published: August 2008

The fluorescence emission of the dual‐fluorophore Ca2+ ion sensor molecule, calcium‐green 2 (CG‐2), has been characterized using dual‐polarization imaging at the single‐molecule level. By comparing the fluorescence intensity of individual CG‐2 molecules in two mutually orthogonal polarization image channels, information about the relative orientation of the two constituent fluorophores in the molecule is obtained. Experimental results from polarization measurements are compared with those predicted from a geometric model based on coupled‐fluorophores that are randomly distributed in space. The results confirm previous optical spectroscopy‐based predictions of the orientation of CG‐2′s fluorophores, and the general applications of this dual‐polarization imaging approach for characterizing the optical properties of molecules containing multiple fluorophores is discussed.
Analog circuit design by nonconvex polynomial optimization: Two design examples
Authors: Lui Siu‐Hong , Kwan Hing‐Kit , Wong Ngai
Published: August 2008

We present a framework for synthesizing low‐power analog circuits through global optimization over generally nonconvex multivariate polynomial objective function and constraints. Specifically, a nonconvex optimization problem is formed, which is then efficiently solved through convex programming techniques based on linear matrix inequality (LMI) relaxation. The framework allows both polynomial inequality and equality constraints, thereby facilitating more accurate device modelings and parameter tuning. Compared to traditional nonlinear programming (NLP), the proposed methodology exhibits superior computational efficiency, and guarantees convergence to a globally optimal solution. As in other physical design tasks, circuit knowledge and insight are critical for initial problem formulation, while the nonconvex optimization machinery provides a versatile tool and systematic way to locate the optimal parameters meeting design specifications. Two circuit design examples are given, namely, a nested transconductance(Gm)–capacitance compensation (NGCC) amplifier and a delta–sigma (ΔΣ) analog‐to‐digital converter (ADC), both of them being the key components in many electronic systems. Copyright © 2008 John Wiley & Sons, Ltd.
The geochemistry of the volcanic rocks of Canouan, Grenadine islands, Lesser Antilles arc
Authors: Smith T. E. , Holm P. E. , Thirlwall M. F.
Published: August 2008

In late Oligocene or early Miocene, a series of basalts and basaltic andesites erupted on the island of Canouan and formed the Old Volcanic Massif (OVM). In a second eruptive phase a series of basalts, basaltic andesites and andesites formed the upper part of the Canouan Formation (CF; lower Middle Miocene; post‐16 Ma) and the Upper Volcanic System (UVS; end‐Miocene; 6.8 Ma). These two eruptive phases are characterized by systematic differences in isotope ratios and chemical composition. The OVM rocks have 87Sr/86Sr and 143Nd/144Nd ratios ranging from 0.70512 to 0.70657 and 0.512415 to 0.512414, whereas in the CF/UVS rocks the ratios range from 0.70454 to 0.70493 and 0.512924 to 0.512843. In addition, the rocks of OVM also have lower ΣFe2O3 and Co contents, and higher La/Yb ratios than those of the CF/UVS. The isotopic and chemical data suggest that both suites were formed from similar partial melts of a subduction‐modified, depleted spinel‐lherzolite source. These data also show that the OVM melts assimilated relatively large amounts of highly radiogenic crustal material, whereas the CF/UVS melts assimilated relatively small amounts of highly radiogenic crustal material. The chemical and isotopic variations of the OVM rocks are consistent with the removal of mixtures of clinopyroxene, plagioclase and magnetite during assimilation‐fractional‐crystallization. Within the CF/UVS, the chemical and isotopic variations can be explained in terms of minor crustal assimilation; the removal of olivine, clinopyroxene, plagioclase and magnetite to form the basalts and basaltic andesites; and the removal of clinopyroxene, plagioclase, magnetite and amphibole to form the andesites. Copyright © 2008 John Wiley & Sons, Ltd.
Phosphatase and tensin homolog (PTEN) regulates hepatic lipogenesis, microsomal triglyceride transfer protein, and the secretion of apolipoprotein B–containing lipoproteins
Authors: Qiu Wei , Federico Lisa , Naples Mark , Avramoglu Rita Kohen , Meshkani Reza , Zhang Jing , Tsai Julie , Hussain Mahmood , Dai Kezhi , Iqbal Jahangir , Kontos Christopher D. , Horie Yasuo , Suzuki Akira , Adeli Khosrow
Published: August 2008

Hepatic apolipoprotein B (apoB) lipoprotein production is metabolically regulated

via

the phosphoinositide 3-kinase cascade; however, the role of the key negative regulator of this pathway, the tumor suppressor phosphatase with tensin homology (PTEN), is unknown. Here, we demonstrate that hepatic protein levels of apoB100 and microsomal triglyceride transfer protein (MTP) are significantly down-regulated (73% and 36%, respectively) in the liver of PTEN liver-specific knockout (KO) mice, and this is accompanied by increased triglyceride (TG) accumulation and lipogenic gene expression, and reduced hepatic apoB secretion in freshly isolated hepatocytes. MTP protein mass and lipid transfer activity were also significantly reduced in liver of PTEN KO mice. Overexpression of the dominant negative mutant PTEN C/S124 (adenovirus expressing PTEN C/S mutant [AdPTENC/S]) possessing constitutive phospoinositide 3-kinase activity in HepG2 cells led to significant reductions in both secreted apoB100 and cellular MTP mass (76% and 34%, respectively), and increased messenger RNA (mRNA) levels of sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Reduced apoB100 secretion induced by AdPTENC/S was associated with increased degradation of newly-synthesized cellular apoB100, in a lactacystin-sensitive manner, suggesting enhanced proteasomal degradation. AdPTENC/S also reduced apoB-lipoprotein production in McA-RH7777 and primary hamster hepatocytes. Our findings suggest a link between PTEN expression and hepatic production of apoB-containing lipoproteins. We postulate that perturbations in PTEN not only may influence hepatic insulin signaling and hepatic lipogenesis, but also may alter hepatic apoB-lipoprotein production and the MTP stability. On loss of PTEN activity, increased lipid substrate availability in the face of reduced hepatic lipoprotein production capacity can rapidly lead to hepatosteatosis and fatty liver. (Hepatology 2008;48:1799–1809.)
Single neuron binding properties and the magical number 7
Authors: Migliore Michele , Novara Gaspare , Tegolo Domenico
Published: August 2008

When we observe a scene, we can almost instantly recognize a familiar object or can quickly distinguish among objects differing by apparently minor details. Individual neurons in the medial temporal lobe of humans have been shown to be crucial for the recognition process, and they are selectively activated by different views of known individuals or objects. However, how single neurons could implement such a sparse and explicit code is unknown and almost impossible to investigate experimentally. Hippocampal CA1 pyramidal neurons could be instrumental in this process. Here, in an extensive series of simulations with realistic morphologies and active properties, we demonstrate how n radial (oblique) dendrites of these neurons may be used to bind n inputs to generate an output signal. The results suggest a possible neural code as the most effective n‐ple of dendrites that can be used for short‐term memory recollection of persons, objects, or places. Our analysis predicts a straightforward physiological explanation for the observed puzzling limit of about 7 short‐term memory items that can be stored by humans. © 2008 Wiley‐Liss, Inc.