bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathway specificity of dendritic spine morphology in identified synapses onto rat hippocampal CA1 neurons in organotypic slices
Authors: De Simoni Anna , Edwards Frances A.
Published: October 2006

The output of the hippocampus is largely determined by interaction of the three excitatory pathways that impinge on CA1 pyramidal neurons. These synapses, formed by axons of: (1) CA3 pyramidal neurons; (2) neurons of the entorhinal cortex (EC); and (3) neighboring CA1 neurons, are all potentially plastic. Here, we take advantage of the accessibility of the organotypic slice preparation to identify the type of spines with which each of these pathways forms synapses, at different developmental stages. Recent reports have shown that morphology of dendritic spines is activity‐dependent with large mushroom spines being thought to represent stronger synaptic connections than thin or stubby spines. Although in a wide range of preparations, mushroom spines represent only 15% of spines across the whole dendritic tree, we find that this proportion is highly pathway specific. Thus in organotypic slices, the axons of CA3 neurons form synapses with mushroom spines on CA1 neurons in ∼50% of cases, whereas this spine type is rare (<10%) in either of the other two pathways. This high proportion of mushroom spines only occurs after spontaneous excitatory activity in the CA1 cells increases over the second week in vitro. Previous studies suggest that pathway specificity also occurs in vivo. In tissue fixed in vivo, it is the synapses of distal apical dendrites thought to be formed by axons originating in the EC that are richer in mushroom spines. Hence, contrary to previous suggestions, the proportion of mushroom spines is clearly not an intrinsic property of the pathway but rather a characteristic dependent on the environment. We suggest that this is most likely a result of the previous activity of the synapses. The fact that, despite the large differences in pathway specificity between preparations, the overall proportion of different spine types remains unchanged, suggests a strong influence of homeostasis across the network. © 2006 Wiley‐Liss, Inc.
Discovery of deregulation of zinc homeostasis and its associated genes in esophageal squamous cell carcinoma using cDNA microarray
Authors: Kumar Anupam , Chatopadhyay Tusharkant , Raziuddin Mohamad , Ralhan Ranju
Published: October 2006

Esophageal squamous cell carcinoma (ESCC) in the Indian population is associated with poor nutritional status, low socioeconomic conditions, bidi smoking and consumption of smokeless tobacco products, besides alcohol drinking and cigarette smoking. To determine the impact of these risk factors on molecular pathogenesis of ESCC, we determined global gene expression profiles of 7 paired samples of ESCC and histologically confirmed nonmalignant esophageal tissues using 19.1K cDNA microarrays. The most salient finding was identification of 19 differentially expressed genes encoding zinc binding or modulating proteins associated with transcriptional regulation, ubiquitin–protein degradation and maintenance of zinc homeostasis. Validation of differential expression of a subset of genes by real‐time quantitative RT‐PCR (real‐time QRT‐PCR) in clinical specimens of ESCC, esophageal dysplasia and histologically nonmalignant esophageal tissues and immunohistochemical analysis using tissue microarrays confirmed the microarray data and demonstrated upregulation of zinc finger proteins, cellular modulator of immune recognition (c‐MIR), snail homolog 2 (SLUG), zinc transporter, ZnT7 and downregulation of zinc metabolizing protein, metallothionein MT1G. We also observed upregulation of mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), a kinase anchor protein 13 (AKAP13) and transglutaminase2 (TG2). Interestingly, we found upregulation of ZnT7 transcripts in ESCC cells (TE13) grown in zinc deficient condition. In conclusion, our data suggest deregulation of genes associated with zinc homeostasis in ESCC. © 2006 Wiley‐Liss, Inc.
Aromaticity in linear polyacenes: Generalized population analysis and molecular quantum similarity approach
Authors: Bultinck Patrick , Ponec Robert , Carbó‐Dorca Ramon
Published: October 2006

The relative aromaticity of benzenoid rings in the linear polyacenes is investigated using two novel aromaticity approaches. According to the first, the aromaticity of individual benzene rings was gauged by the values of six‐center bond indices (SCI) calculated within the so‐called Generalized Population Analysis (GPA). In the second approach, the same goal is addressed using the theory of Molecular Quantum Similarity (MQS). Both independent approaches are found to correlate very well, and both point toward decreasing aromaticity in any linear polyacenes upon going from the outer to inner rings. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2007
Bond order and valence indices: A personal account
Authors: Mayer I.
Published: October 2006

The paper accounts for the author's activity in developing bond order and valence indices since the early 80s. These indices represent an important conceptual link between the physical description of molecules as systems of electrons and nuclei and the chemical picture of molecules consisting of atoms kept together by bonds. They are also useful for a systematization and interpretation of the results obtained in the quantum chemical calculations, by permitting to extract from the wave function different pieces of information that may be assigned chemical significance. In some cases they can have some predictive power, too. Historically, the prototypes of such indices were introduced in the semiempirical quantum chemistry; the most important developments were Coulson'scharge–bond order matrixin the simple Hückel theory and the Wiberg index in the CNDO framework. (Valence indices were also introduced in the semiempirical theory.) The definition of theab initiobond order index emerged from the asymptotic term of the exchange energy component of the partitioning performed in the framework of the author's so‐called “chemical Hamiltonian approach” using a “mixed” second quantization formalism for overlapping basis sets. They can also be introduced by studying the exchange part of the two‐particle density (or of the second‐order density matrix). Some properties of the bond order indices are discussed and the author's (until now unpublished) proof is also presented, showing the sufficient conditions under which the bond order index of a homonuclear diatomics is equal to the “chemist's bond order,” i.e., the half of the difference between the number of electrons occupying bonding and antibonding orbitals. Theab initiovalence indices are also introduced and discussed, and it is stressed that for correlated wave function the same “exchange only” definition of the bond order and valence indices should be used, which was introduced for the SCF case. The recent concept of the “atomic decomposition of identity” is also discussed and it is utilized for introducing bond orders and valences in the framework of the “3D analysis,” when atoms are defined not by their basis orbitals but as regions of the three‐dimensional (3D) physical space. Two versions of the 3D analysis are considered—the AIM (atoms in molecules)‐type decomposing the space into disjunct atomic domains and the “fuzzy atoms” scheme in which there are no sharp boundaries between the atoms but they exhibit a continuous transition from one to another. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2007
Gluteal muscle attachment during proximal femoral reconstruction in a canine model
Authors: Pluhar G. Elizabeth , Manley Paul A. , Heiner John P. , Vanderby Ray , Markel Mark D.
Published: October 2006

In this 18 month in vivo canine study we compared three methods of attaching the gluteal muscles to the proximal femur during hip reconstruction with an allograft‐prosthesis composite (APC). All three methods are commonly practiced in human hip revision surgery and data on their effectiveness in dogs is directly relevant to human treatment. The methods compared were host gluteal tendon sutured to allograft tendon, host greater trochanter apposed to allograft using a cable grip system, and host cortical bone shells around the allograft secured with cerclage wires. For each method, we assessed changes in allograft‐host bone fusion, weight bearing, gluteal muscle mass, and structural properties through qualitative radiography, gait analysis, histology, and biomechanical testing. Hip reconstruction using the WRAP method resulted in the greatest limb use with complete resolution of gluteal muscle atrophy 18 months after surgery. This method yielded a stronger, more stable hip joint that allowed for more normal limb function. These hips had the more rapid rate of bony union at the host bone‐allograft junction and little resorption of the graft. The increased limb use and resultant larger gluteal muscle mass conferred to the WRAP hip composites the greatest tensile strength and stiffness when tested 18 months after reconstruction. There was a large amount of new bone formation on the periosteal surface where the WRAP reconstructions had an overlay of live bone that resulted in a more rapid union and increased cortical width at the level of the osteotomy. New bone also penetrated into the allograft a greater distance from the osteotomy in the WRAP group. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:208–220, 2007
Cover Picture: Macromol. Biosci. 10/2006
Authors: Miller Scott A. , Hong Edmund D. , Wright David
Published: October 2006

Cover: The rapid, benchtop method of efficient enzyme immobilization within a silica nanocomposite is reported. Glucose oxidase (cover) and horseradish peroxidase were encapsulated via PAMAM dendrimer mediated silification. This simple and effective methodology for enzyme immobilization has potential applications in biocatalysis, biomaterials, and biomimetics. Further details can be found in the article by S. A. Miller, E. D. Hong, and D. Wright* on page 839.
Use of Nitrogen as a Blowing Agent for the Production of Fine‐Celled High‐Density Polyethylene Foams
Authors: Lee John W. S. , Park Chul B.
Published: October 2006

Summary:While many experiments have been performed to examine the effects of administering CO2as a blowing agent in the foaming process, very few studies have investigated the use of N2for this purpose. In this study, foaming experiments were conducted in extrusion using HDPE as a polymeric material and N2as a blowing agent. Talc was used as a nucleating agent, and three different pressure‐drop rates were applied to study the effects of pressure‐drop rates on HDPE foams. The experimental results revealed that the void fraction of high‐density foams blown with N2was not affected by the die temperature, contrasting the situation in low‐density foams. Surprisingly, it was the cell density which determined the void fraction of high‐density foams. It was also found that the use of talc significantly increased the cell density and the void fraction of the foams and minimized the role played by the pressure‐drop rate in cell nucleation.

Effect of N2content on the cell density of HDPE foams.

magnified image

Effect of N2content on the cell density of HDPE foams.
Terminal latency index in neuropathy with antibodies against myelin‐associated glycoproteins
Authors: Lupu Vitalie D. , Mora Carlos A. , Dambrosia Jim , Meer Jacob , Dalakas Marinos , Floeter Mary Kay
Published: October 2006

Neuropathy with antibodies against myelin‐associated glycoproteins (MAG/SGPG‐N) and hereditary sensorimotor neuropathy type 1 (HMSN1) are characterized by chronic demyelination with little conduction block. Electrodiagnostic studies suggest that in HMSN1 conduction slowing occurs uniformly along the nerve, whereas in MAG/SGPG‐N it is predominantly distal. Some but not all previous reports have shown that the terminal latency index (TLI) was useful to distinguish MAG/SGPG‐N from chronic idiopathic demyelinating polyneuropathy. We compared median TLI from 21 patients with MAG/SGPG‐N with those obtained from 26 patients with HMSN1, 20 with HMSN2, and 12 healthy volunteers. All patients with TLI <0.26 had MAG/SGPG‐N, and all patients with TLI ≥0.32 had HMSN1. In the remaining patients with intermediate TLI values, ulnar distal motor latency (DML) aided in differentiation between MAG/SGPG‐N and HMSN1 with an overall sensitivity of 100% and specificity of 98%. In conclusion, median TLI in combination with ulnar DML can further guide the demyelinating neuropathy evaluation toward hereditary or autoimmune causes. Muscle Nerve, 2006
Sensory conduction study of the infrapatellar branch of the saphenous nerve
Authors: Bademki̇ran Fi̇kret , Obay Basra , Aydogdu Ibrahi̇m , Erteki̇n Cumhur
Published: October 2006

Although neuropathies of the infrapatellar nerve (infrapatellar branch of the saphenous nerve, IPBSN) have been reported clinically, no electrophysiological method has been defined to evaluate IPBSN conduction. We therefore studied a total of 60 saphenous nerves and 60 IPBSNs from 36 volunteers. The IPBSN was stimulated medially with a surface electrode 2 cm below the patella. The response was recorded with a needle electrode located close to the nerve 1 cm lateral to the femoral artery in the inguinal region. Sensory nerve action potentials were obtained from each subject; mean latency of the first positive peak was 8.1 ± 0.9 ms, conduction velocity was 54 ± 4.4 m/s, and response amplitude was 1.3 ± 1.1 μV. The method that we describe may be an easy and useful electrophysiological test for neuropathies of the IPBSN. Muscle Nerve, 2006
Challenges in drug development for muscle disease: A stakeholders' meeting
Authors: Mendell Jerry R. , Csimma Cristina , McDonald Craig M. , Escolar Diana M. , Janis Scott , Porter John D. , Hesterlee Sharon E. , Howell R. Rodney
Published: October 2006

Current treatment benefits for patients with muscle disease are limited, but progress in legislative and scientific initiatives have set the stage for the development of new therapies. The MD‐CARE Act (Public Law 107‐84), which allocates federal resources to muscular dystrophy, was approved by Congress and signed into law by the President of the United States in 2001. This has shifted the emphasis toward translational research. To facilitate a push toward therapy for muscle disorders, the Muscular Dystrophy Association (MDA) sponsored a meeting with representatives from industry, the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and other government agencies and academia. Each contributed in different ways. The FDA helped define the necessary data to support investigational new drug (IND) applications including the design of proof‐of‐principle studies, outcome measures for clinical trials, and the pathway for developing surrogate measures for fast‐tracking promising new drugs. The NIH, other government agencies, and the MDA described potential funding sources for translational research. Industry delineated a complementary role with academia, and academic investigators elucidated the current strengths and weaknesses of available clinical endpoints. The meeting provided a format for communication for diverse disciplines that usually have no common meeting ground, helping to lay the foundation for bringing products to market in a timely fashion. Muscle Nerve, 2006
On the mechanics of contact between a flexible transducer diaphragm located at a rigid boundary and an elastic material
Authors: Selvadurai A. P. S. , Labanieh S. , Boulon M. J.
Published: October 2006

In this paper we examine the mechanics of contact between a flexible elastic diaphragm and an isotropic elastic halfspace region where contact is established through the application of a normal stress. It is shown that a convenient solution for the maximum displacement and maximum flexural moment in the flexible diaphragm can be obtained by employing a variational technique. Copyright © 2006 John Wiley & Sons, Ltd.
A second‐order immersed interface technique for an elliptic Neumann problem
Authors: Bouchon François , Peichl Gunther H.
Published: October 2006

A second‐order finite difference scheme for mixed boundary value problems is presented. This scheme does not require the tangential derivative of the Neumann datum. It is designed for applications in which the Neumann condition is available only in discretized form. The second‐order convergence of the scheme is proven and the theory is validated by numerical examples. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 23: 400–420, 2007
Superconvergence of discontinuous Galerkin finite element method for the stationary Navier‐Stokes equations
Authors: Li Jian , He Yinnian
Published: October 2006

This article focuses on discontinuous Galerkin method for the two‐ or three‐dimensional stationary incompressible Navier‐Stokes equations. The velocity field is approximated by discontinuous locally solenoidal finite element, and the pressure is approximated by the standard conforming finite element. Then, superconvergence of nonconforming finite element approximations is applied by using least‐squares surface fitting for the stationary Navier‐Stokes equations. The method ameliorates the two noticeable disadvantages about the given finite element pair. Finally, the superconvergence result is provided under some regular assumptions. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 23: 421–436, 2007
An analysis for a high‐order difference scheme for numerical solution to utt = A(x, t)uxx + F(x, t, u, ut, ux)
Authors: Li Wei‐Dong , Sun Zhi‐Zhong , Zhao Lei
Published: October 2006

This article is concerned with a high‐order implicit difference scheme presented by Mohanty, Jain, and George for the nonlinear hyperbolic equation utt = A(x, t)uxx + F(x, t, u, ut, ux) with Dirichlet boundary conditions. Some prior estimates of the difference solution are obtained by the energy methods. The solvability of the difference scheme is proved by the energy method and Brower's fixed point theorem. Similarly, the uniqueness, the convergence in L∞‐norm and the stability of the difference solution are obtained. A numerical example is provided to demonstrate the validity of the theoretical results. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 23: 484–498, 2007
Photolabile and thermally labile polymers as templates and for surface patterning
Authors: Voit B. , Braun F. , Gernert M. , Sieczkowska B. , Millaruelo M. , Messerschmidt M. , Mertig M. , Opitz J.
Published: October 2006

The successful selective metal deposition using a photolabile polymer consisting of a diazosulfonate side chain group has been reported. In addition to 20 mol% diazosulfonate monomer the terpolymer contains 5 mol% of a silane compound, which is necessary for the covalent anchoring of the film onto the substrate. Furthermore, films were prepared using photolabile polymers containing protected amines onto glass and silicon substrates. These films are suitable for imagewise structuring by UV‐light and laser irradiation, and nanoelements like DNA strands could be attached individually in further steps. These polymeric amines with similar structure like the diazosulfonate terpolymers were synthesized by free radical polymerization of three monomer units which are methyl methacrylate (MMA) (spacer), 3‐(trimethoxysilyl)propylmethacrylate (anchoring group) and N‐(N‐nitroveratryloxycarbonyl‐aminopropyl)‐methacrylamide (photolabile compound). The anchoring groups were varied to enable covalent attachment of the polymers, for example, onto gold substrates. Azosulfonates, sulfonate esters, and both protected amines and carboxylic acid groups were used as thermally labile or photolabile functionalities. Selective deprotection using heat or light could be varied. Finally block copolymers based on orthogonally protected hydroxystyrenes could be prepared by controlled radical polymerization. A highly ordered nanostructure could be realized in thin films of these polymers exhibiting strong changes using heat or light treatment. Copyright © 2006 John Wiley & Sons, Ltd.
Cathepsin protease activity modulates amyloid load in extracerebral amyloidosis
Authors: Röcken C , Fändrich M , Stix B , Tannert A , Hortschansky P , Reinheckel T , Saftig P , Kähne T , Menard R , Ancsin JB , Bühling F
Published: October 2006

In cerebral amyloidoses, such as Alzheimer's disease, proteolytic processing of the precursor protein is a fundamental mechanism of the disease, since it generates the amyloid protein. However, the putative significance of proteases in extracerebral amyloidoses is less well defined. In this study, we investigated the biological significance of cathepsin (Cath) B, CathK, and CathL in the pathology and pathogenesis of extracerebral amyloidoses by using the murine model of reactive or secondary AA amyloidosis with three different cathepsin‐deficient mouse strains. Extracerebral AA amyloid was induced by injecting amyloid‐enhancing factor and silver nitrate into CathB−/−, CathK−/−, and CathL−/− mice. Wild‐type mice served as a control. CathK−/− mice deposited over 90% more amyloid and CathL−/− mice 60% less amyloid than the control (p < 0.0001). The amyloid load in CathB−/− mice did not differ from that in wild‐type mice. In vitro degradation experiments with recombinant human and murine serum amyloid A (SAA) 1.1 and CathK and CathL showed that CathL generates a large number of differently sized SAA cleavage products. One of these fragments spans the heparin/heparan sulphate binding site and the neutral cholesterol ester hydrolase activating region of SAA. CathK showed only endoproteolytic activity and did not generate any AA amyloid‐like peptides. This study provides unequivocal evidence that proteases modulate amyloid load in extracerebral amyloidosis. CathL was identified as an amyloid‐promoting and CathK as an amyloid‐retarding cysteine protease. CathB may only modulate the primary structure of the amyloid peptide without affecting amyloid load. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Isolation and antimicrobial evaluation of isomeric hydroxy ketones in leaf cuticular waxes of Annona squamosa
Authors: Shanker K. Shiva , Kanjilal S. , Rao B. V. S. K. , Kishore K. Hara , Misra S. , Prasad R. B. N.
Published: October 2006

A novel natural compound, 11‐hydroxy‐16‐hentriacontanone, has been isolated from the leaf cuticular wax of Annona squamosa along with its known isomer 10‐hydroxy‐16‐hentriacontanone in a ratio of 67:33. This isomeric mixture of hydroxy ketones constituted together 16.5% of the total cuticular waxes. The new compound was characterised using spectral and chromatographic techniques. The major component was found to be 16‐hentriacontanone (palmitone), which constituted up to 48% of the total cuticular wax, together with a homologous series of hydrocarbons, fatty aldehydes, fatty alcohols, fatty acids and sterols as minor components. The antimicrobial activity of the isomeric hydroxy ketones was tested against selected Gram‐positive and Gram‐negative bacterial strains, and also some selected fungal strains, and compared with palmitone. The antibacterial activity of palmitone was significantly higher than that of the isomeric hydroxy ketones, but their antifungal activities were comparable. Copyright © 2006 John Wiley & Sons, Ltd.
Analysis of phenolic acids in honeys of different floral origin by solid‐pase extraction and high‐performance liquid chromatography
Authors: Dimitrova Burya , Gevrenova Reneta , Anklam Elke
Published: October 2006

The determination of 18 aromatic and arylaliphatic carboxylic acids in honey from different floral origin using solid‐phase extraction (SPE) and reversed‐phase high performance liquid chromatography (RP‐HPLC) is reported. The behaviour of the solutes on SPE cartridges was predicted from preliminary calculations involving the pKa constants of the carboxylic groups, the n‐octanol:water partition coefficients and the distribution coefficients at different pH values of the conditioning and washing solvents. The proposed SPE isolation and pre‐concentration of the acids was achieved on reversed‐phase Bond Elut C18 cartridges using an acetonitrile:tetrahydrofuran (1:1, v/v) elution system. RP‐HPLC separations were performed on a Spherisorb ODS‐2 column using linear gradient elution with a mobile phase composed of 20 mm phosphate buffer (pH 2.92) and methanol, and with UV detection. The reported SPE and RP‐HPLC methods were applied to the analysis of 49 authentic honey samples from various floral sources and the results indicate that they may serve with respect to the quantitative control of a number of phenolic acids in plant‐derived foods and medicinal plants. Copyright © 2006 John Wiley & Sons, Ltd.
Homology models of dipeptidyl peptidases 8 and 9 with a focus on loop predictions near the active site
Authors: Rummey Christian , Metz Günther
Published: October 2006

Dipeptidyl peptidase 4 (DP4) inhibitors are currently under intensive investigation in late‐stage clinical trials as a treatment for type II diabetes. Lack of selectivity toward the related enzymes DP8 and DP9 has recently emerged as a possible source of drug‐induced toxicity. Unlike DP4, X‐ray structures of DP8 and DP9 are not yet available. As an aid to understanding the structural basis for selectivity, the authors have constructed homology models of DP8 and DP9 based on the X‐ray coordinates of DP4. Accurate sequence alignment reveals common structural features indicative for a well‐preserved overall fold comprising two domains, namely, a hydrolase domain and a so‐called β‐propeller, which together form the active site deeply buried within the protein. The conformation of two loops inside this deep cavity is particularly relevant for the active sites. The authors used a published protocol for loop prediction based on conformational sampling and energy analysis to generate plausible solutions for these two loops. The predictive power of the approach was successfully evaluated for the template protein DP4 and two additional known structures from the same protein family, namely, FAP and DPX. The authors also show that inclusion of the covalent ligand NVP‐728 greatly enhances the refinement. Based on the established evaluation protocol, the corresponding loops of DP8 and DP9 were predicted and the resulting active sites were compared with DP4. In particular, the authors conclude that differences in the P2‐pocket are relevant for the design of selective DP4 inhibitors. The loss of key interactions in DP8 and DP9 as predicted from their models is consistent with the selectivity profile of the DP4 clinical candidate MK‐431. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Critical evaluation of methods to incorporate entropy loss upon binding in high‐throughput docking
Authors: Salaniwal Sumeet , Manas Eric S. , Alvarez Juan C. , Unwalla Rayomand J.
Published: October 2006

Proper accounting of the positional/orientational/conformational entropy loss associated with protein–ligand binding is important to obtain reliable predictions of binding affinity. Herein, we critically examine two simplified statistical mechanics‐based approaches, namely a constant penalty per rotor method, and a more rigorous method, referred to here as the partition function‐based scoring (PFS) method, to account for such entropy losses in high‐throughput docking calculations. Our results on the estrogen receptor β and dihydrofolate reductase proteins demonstrate that, while the constant penalty method over‐penalizes molecules for their conformational flexibility, the PFS method behaves in a more “ΔG‐like” manner by penalizing different rotors differently depending on their residual entropy in the bound state. Furthermore, in contrast to no entropic penalty or the constant penalty approximation, the PFS method does not exhibit any bias towards either rigid or flexible molecules in the hit list. Preliminary enrichment studies using a lead‐like random molecular database suggest that an accurate representation of the “true” energy landscape of the protein–ligand complex is critical for reliable predictions of relative binding affinities by the PFS method. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Theoretical studies on farnesyltransferase: The distances paradox explained
Authors: Sousa Sérgio Filipe , Fernandes Pedro Alexandrino , Ramos Maria João
Published: October 2006

In spite of the enormous interest that has been devoted to its study, the mechanism of the enzyme farnesyltransferase (FTase) remains the subject of several crucial doubts. In this article, we shed a new light in one of the most fundamental dilemmas that characterize the mechanism of this puzzling enzyme commonly referred to as the “distances paradox”, which arises from the existence of a large 8‐Å distance between the two reactive atoms in the reaction catalyzed by this enzyme: a Zn‐bound cysteine sulphur atom from a peptidic substrate and the farnesyldiphosphate (FPP) carbon 1. This distance must be overcome for the reaction to occur. In this study, the two possible alternatives were evaluated by combining molecular mechanics (AMBER) and quantum chemical calculations (B3LYP). Basically, our results have shown that an activation of the Zn‐bound cysteine thiolate with subsequent displacement from the zinc coordination sphere towards the FPP carbon 1 is not a realistic hypothesis of overcoming the large distance reported in the crystallographic structures of the ternary complexes between the two reactive atoms, but that a rotation involving the FPP molecule can bring the two atoms closer with moderate energetic cost, coherent with previous experimental data. This conclusion opens the door to an understanding of the chemical step in the farnesylation reaction. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Molecular Surface Features in Modeling the HIV‐1 RT Inhibitory Activity of 2‐(2,6‐Disubstituted phenyl)‐3‐(substituted pyrimidin‐2‐yl)‐thiazolidin‐4‐ones
Authors: Rawal Ravindra K. , Prabhakar Yenamandra S. , Katti Setu B.
Published: October 2006

Inhibitory activity of 2‐(2,6‐disubstituted phenyl)‐3‐(substituted pyrimidin‐2‐yl)‐thiazolidin‐4‐ones the Human Immunodeficiency Virus‐1 Reverse Transcriptase (HIV‐1 RT) have been analyzed using Combinatorial Protocol in Multiple Linear Regression (CP‐MLR) with several electronic and molecular surface area features of the compounds obtained from Molecular Operating Environment (MOE) software. The study has indicated the role of different charged molecular surface areas in modeling the inhibitory activity of the compounds. The derived models collectively suggested that the compounds should be compact without bulky substitutions on its peripheries for better HIV‐1 RT inhibitory activity. It also emphasized the necessity of hydrophobicity and compact structural features for their activity. The scope of the descriptors identified for these analogues have been verified by extending the dataset with different 2‐(disubstituted phenyl)‐3‐(substituted pyridin‐2‐yl)‐thiazolidin‐4‐ones. The joint analysis of extended dataset highlighted the information content of identified descriptors in modeling the HIV‐1 RT inhibitory activity of the compounds.
How Many Free Radicals can be Trapped by (Hydroxylphenylimino)methylphenol in the Free‐Radical‐Induced Peroxidation of Triolein in Micelles?
Authors: Liu Zai‐Qun
Published: October 2006

This work focused on assessing the antioxidant capacity of two hydroxyl‐substituent Schiff bases, 2‐(o‐hydroxylphenylimino)methylphenol (OsH) and 2‐(p‐hydroxylphenylimino)methylphenol (PsH) used alone or in combination with α‐tocopherol (TocH) and 6‐hydroxyl‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid (Trolox) in 2,2′‐azobis(2‐amidinopropane hydrochloride) (AAPH)‐induced peroxidation of triolein (GtH) dispersed in cetyl trimethyl ammonium Bromide (CTAB, a cationic micelle), sodium dodecyl sulfate (SDS, an anionic micelle), and Triton X‐100 (a neutral micelle), respectively. The present findings indicate that OsH and PsH are not only concentration‐dependent antioxidants, but also protect GtH with Trolox and TocH synergistically. Especially, the reason for the higher antioxidant capacity of OsH than PsH can be ascribed to the fact that OsH contains a hydroxyl group adjacent to the nitrogen atom. Furthermore, the number of trapped peroxyl radicals by Schiff base, n, can be calculated on the basis of chemical kinetic deduction. As a result, n of OsH and PsH increase in SDS micelle but decrease in CTAB, implicating that their antioxidant capacities are not only related to their structures but also to the charge property of micelles, dispersed GtH also affect their antioxidant behavior prominently. In addition, the synergistic antioxidant capacities of OsH and PsH used in conjuction with Trolox and TocH were investigated in the above micelles, and, it was found that PsH+Trolox in Triton X‐100 and CTAB exhibited a mutual promoting effect, whereas OsH+Trolox in SDS plays a mutual demoting effect. Nevertheless, the n of Schiff bases or other antioxidants in the mixed usage are rather different from that used alone, implying that an interaction among these compounds exists in protecting GtH against AAPH‐induced peroxidation.
QSAR Modeling of PeripheralVersusCentral Benzodiazepine Receptor Binding Affinity of 2‐Phenylimidazo[1,2‐a]pyridineacetamides using Optimal Descriptors Calculated with SMILES
Authors: Roy Kunal , Toropov Andrey , Raska Ivan
Published: October 2006

The optimization of correlation weights scheme has been applied to model Peripheral Benzodiazepine Receptor (PBR) binding affinity (ovary and cortex) and PBR binding selectivity (peripheralversuscentral benzodiazepine receptor) of 2‐phenylimidazo[1,2‐a]pyridineacetamides. In the present study, optimal descriptors based on Simplified Molecular Input Line Entry System (SMILES) notation have been used for the modeling purpose. The optimized descriptor formulated based on the data of training set generated statistically acceptable relations (for PBR cortex,q2=0.717,r2=0.756; for PBR ovary,q2=0.836,r2=0.852; for PBR cortex selectivity,q2=0.732,r2=0.784; for PBR ovary selectivity,q2=0.828,r2=0.845). When the relations of PBR binding affinity or selectivity with the optimized molecular descriptor formulated based on the data of the training set was used for the calculation of the corresponding response parameters of the test set,$\rm{ r_{{\rm{Pred}}}^{\rm{2}} }$values were found to be satisfactory (for PBR cortex, 0.692; for PBR ovary, 0.682; for PBR ovary selectivity, 0.772) except in the case of PBR cortex selectivity ($\rm{ r_{{\rm{Pred}}}^{\rm{2}} }$being 0.321). The results indicate promising potential of the optimization of correlation weights based on SMILES notation in modeling studies.
Non‐sequential MIMO QFT control of the X‐29 aircraft using a generalized formulation
Authors: Kerr Murray L. , Lan Chen‐yang , Jayasuriya Suhada
Published: October 2006

This paper presents a generalized formulation for multi‐input multi‐output (MIMO) quantitative feedback theory (QFT) based controller design and analysis, and its application to the control of the X‐29 aircraft. The formulation is based on a more general control structure, where input and output transfer function matrices are included to provide additional degrees of freedom in the decentralized MIMO QFT feedback structure, that facilitates the exploitation of directions in MIMO QFT designs. The formulation captures existing design approaches for fully populated MIMO QFT controller design and provides for a directional design logic involving the plant and controller alignment and the directional properties of their multivariable poles and zeros. Horowitz's Singular‐G design methodology is placed in the context of the generalized formulation and the Singular‐G design for the X‐29 is analysed and redesigned using non‐sequential MIMO QFT and the formulation, demonstrating its utility. The results highlight a fundamental trade‐off between multivariable controller directions for stability and performance in classically formulated design methodologies, elucidate the properties of Singular‐G designed controllers for the X‐29 and validate recent contributions to the theory for non‐sequential MIMO QFT. Copyright © 2006 John Wiley & Sons, Ltd.
Quantity, controls and functions of large woody debris in Midwestern USA streams
Authors: Cordova J. M. , Rosi‐Marshall E. J. , Yamamuro A. M. , Lamberti G. A.
Published: October 2006

Large woody debris (LWD) can increase stream habitat heterogeneity by providing structure, altering flow patterns, enhancing sediment deposition, forming pools and retaining organic matter. In North America, the role of LWD has been studied extensively in streams of mature forests (e.g. Pacific Northwest), but few studies have assessed LWD in streams of younger forests (e.g. Midwestern USA). Our objectives were to: (1) quantify the volume and abundance of LWD in a set of Midwestern streams; (2) evaluate possible factors influencing LWD quantity; (3) identify the functional roles of LWD; and (4) compare LWD levels in the upper Midwest to those elsewhere in North America. In 2002 and 2003, we measured LWD and geomorphological variables in 15 low‐gradient streams draining previously logged watersheds in the Upper Peninsula of Michigan. Mean (±SE) LWD volume (0.77 ± 0.12 m3 100 m−2) and abundance (33 ± 3 pieces 100 m−1) were 71% and 10% lesser, respectively, than in streams of similar gradient elsewhere in North America. Channel shape (width:depth ratio) explained 30% of the variation in LWD volume (multiple stepwise regression, P = 0.015) while LWD length and length:channel width combined, explained 72% of the variation in LWD density (multiple stepwise regression, P < 0.0001). About 50% of the LWD either stored sediment or stabilized banks and 14% of the LWD formed pools, although pool density was not significantly related to LWD volume or density. LWD levels, overall, were low in upper Midwestern streams, but the relative importance of that LWD to ecosystem function may be magnified in these wood‐poor systems. Copyright © 2006 John Wiley & Sons, Ltd.
Suspended sediment concentration in relation to forestry operations in Catamaran Brook and its tributaries (Canada)
Authors: Jolicoeur Serge , Caissie Daniel , Frenette Isabelle , Hardie Peter , Bouchard Mireille
Published: October 2006

The Catamaran Brook Habitat Research Project is a 15‐year investigation of river processes and potential impacts of forestry activities on Atlantic salmon (Salmo salar) and its freshwater lotic habitats. Suspended sediments have been sampled in Catamaran Brook and its tributaries from 1990 to 1997. Data on total event precipitation and hourly peak discharge were related to suspended sediment concentration (SSC) under different catchment conditions (dry vs. wet) and treatment (absence or occurrence of timber harvesting). Although SSC generally showed a good correlation to total event precipitation and hourly peak discharge, there was no clear evidence that forestry operations were an important factor within the main Catamaran Brook during the timber harvesting year and the year that followed. Such was not the case for SSC in small tributaries draining directly from cut blocks during logging. In fact, the highest concentrations of suspended sediment were measured in small tributaries draining cut blocks during timber harvesting (with a maximum SSC of 404 mg L−1in Tributary 1). Within the main Catamaran Brook, a dilution effect rapidly decreased these values downstream of affected tributaries. Processes related to the transfer of sediment to the streams are discussed. Potential improvements in river management and operational timing with respect to the timing of harvesting activities as it relates to precipitation, discharge, catchment conditions (dry vs. wet), freezing/thawing, and salmon migration are also discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Morphological and functional effects of altered cysteine string protein at the Drosophila larval neuromuscular junction
Authors: Dawson‐Scully Ken , Lin Yongqi , Imad Mays , Zhang Jinhui , Marin Leo , Horne Jane A. , Meinertzhagen Ian A. , Karunanithi Shanker , Zinsmaier Konrad E. , Atwood Harold L.
Published: October 2006

The synaptic vesicle‐associated cysteine string protein (CSP) is critical for neurotransmitter release at the neuromuscular junction (NMJ) of Drosophila, where the ∼4% of mutant flies lacking CSP that survive to adulthood exhibit spastic jumping and shaking, temperature‐sensitive paralysis, and premature death. Previously, it has been shown that CSP is also required for nerve terminal growth and the prevention of neurodegeneration in Drosophila and mice. At larval csp null mutant NMJs of Drosophila, intracellular recordings from the muscle showed that evoked release is significantly reduced at room temperature. However, it remained unclear whether the reduction in evoked release might be due to a loss of synaptic boutons, loss of synapses, and alterations in trafficking of vesicles to synapses. To resolve these issues, we have examined synaptic structure and function of csp null mutant NMJs at the level of single boutons. csp null mutations proportionally reduce the number of synaptic boutons of both motor neurons (1s and 1b) innervating larval muscles 6 and 7, while the number of synapses per bouton remains normal. However, focal recordings from individual synaptic boutons show that nerve‐evoked neurotransmitter release is also impaired in both 1s and 1b boutons. Further, our ultrastructural analyses show that the reduction in evoked release at low stimulation frequencies is not due to a loss of synapses or to alterations in docked vesicles at synapses. Together, these data suggest that CSP promotes synaptic growth and evoked neurotransmitter release by mechanistically independent signaling pathways. Synapse 61:1–16, 2007. © 2006 Wiley‐Liss, Inc.
Phosphorylation of CREB and DARPP‐32 during late LTP at hippocampal to prefrontal cortex synapses in vivo
Authors: Hotte Maïté , Thuault Sébastien , Dineley Kelly T. , Hemmings Hugh C. , Nairn Angus C. , Jay Thérèse M.
Published: October 2006

Specific patterns of stimulation applied in the ventral hippocampus produce long‐term potentiation (LTP) of postsynaptic synapses in the prefrontal cortex in vivo. The induction of LTP is dependent on NMDA receptors and cAMP‐dependant kinase (PKA) activation. Yet little is known concerning the cellular mechanisms underlying the expression of this neocortical form of LTP. In the present study, we tested whether LTP at hippocampal to prefrontal cortex synapses leads to activation of DARPP‐32 and CREB as well as defined the temporal regulation of the phosphorylation states of both proteins. Our data indicate a peak in CREB and DARPP‐32 phosphorylation during the late phase of prefrontal LTP (2 h posttetanus). These findings support the hypothesis that prolonged expression of hippocampal‐prefrontal cortex LTP depends on a synergistic mechanism involving phosphorylation of both CREB and DARPP‐32 via activation of the cAMP/PKA‐dependent pathway. Synapse 61:24–28, 2007. © 2006 Wiley‐Liss, Inc.
Effects of acute “binge” cocaine on mRNA levels of μ opioid receptor and neuropeptides in dopamine D1 or D3 receptor knockout mice
Authors: Zhou Yan , Adomako‐Mensah Johannes , Yuferov Vadim , Ho Ann , Zhang Jianhua , Xu Ming , Kreek Mary Jeanne
Published: October 2006

In humans, elevations of mu opioid receptor (MOP‐r) binding potential (BP) in the frontal cortex (FC) are associated with cocaine craving during early abstinence. In rats, decreases in dopaminergic (DAergic) transmission in the medial FC are associated with increased cocaine‐seeking behavior. DA D1 or D3 receptor homozygous knockout (D1−/− or D3−/−) mice offer the opportunity to test the roles of these specific receptors in regulating MOP‐r gene expression in response to cocaine. In the present studies, we found an increase in basal MOP‐r mRNA levels in the FC of both D1−/− and D3−/− mice compared to wild type controls, with no change in the nucleus accumbens (NAc) core or caudate–putamen (CPu). Acute “binge” cocaine (3 × 15 mg/kg for 2.5 h) returned FC MOP‐r mRNA levels in D1−/− or D3−/− mice to those in wild type controls. In the NAc core, the MOP‐r mRNA levels after acute “binge” cocaine were decreased in D1−/− mice while increased in D3−/− mice. In the CPu, however, the MOP‐r mRNA levels after acute “binge” cocaine were increased in D1−/− mice while decreased in D3−/− mice. We also found a decrease in basal orexin mRNA levels in the lateral hypothalamus of the D3−/− mice, which was unaltered by acute “binge” cocaine. Together, our findings suggest that: (1) both D1 and D3 receptors are involved in FC MOP‐r gene regulation; and (2) D1 and D3 receptors play opposite roles in the effects of cocaine on MOP‐r gene regulation differentially in the NAc core or CPu. Synapse 61:50–59, 2007. © 2006 Wiley‐Liss, Inc.
Sustainable management of grassland ecosystems for controlling Asian dusts and desertification in Asian continent and a suggestion of Eco‐Village study in China
Authors: Kim Eun‐Shik , Park Dong Kyun , Zhao Xueyong , Hong Sun Kee , Koh Kang Suk , Suh Min Hwan , Kim Young Sun
Published: October 2006

Asian dusts, yellow sand, or dust and sand storms (DSS) in Asian continent are the end products of desertification, which became a regional environmental problem being aggravated by time. It is closely related to an issue of sustainability in the region. As the desertification is caused not only by natural factors, such as the climate change, strong wind, and low precipitation, but also by rapidly increasing human activities, such as overgrazing, misuse of water resources, and irrational land use, it is urgent to make efforts to combat desertification in Asian continent including China. In this regard, it is necessary to consider socio‐economic aspects as well as ecological aspects and, consequently, the project for the construction of a Demonstration Model Village for eco‐environmental rehabilitation should be paid to a special attention. The authors deal with this regional issue in consideration of three Es, which are represented by ecology, economy, and environment in providing the perspectives in sound approach to the issue. As an approach to the issue of Asian dusts and desertification in Asian continent, this Eco‐Village study provides one way forward.
A solution blending route to ethylene propylene diene terpolymer/layered double hydroxide nanocomposites
Authors: Acharya H. , Srivastava S. K. , Bhowmick Anil K.
Published: October 2006

Ethylene propylene diene terpolymer (EPDM)/MgAl layered double hydroxide (LDH) nanocomposites have been synthesized by solution intercalation using organically modified LDH (DS-LDH). The molecular level dispersion of LDH nanolayers has been verified by the disappearance of basal XRD peak of DS-LDH in the composites. The internal structures, of the nanocomposite with the dispersion nature of LDH particles in EPDM matrix have been studied by TEM and AFM. Thermogravimetric analysis (TGA) shows thermal stability of nanocomposites improved by ≈40 °C when 10% weight loss was selected as point of comparison. The degradation for pure EPDM is faster above 380 °C while in case of its nanocomposites, it is much slower.
Synthesis and characterization of Nb2O5@C core-shell nanorods and Nb2O5nanorods by reacting Nb(OEt)5via RAPET (reaction under autogenic pressure at elevated temperatures) technique
Authors: George P. P. , Pol V. G. , Gedanken A.
Published: October 2006

The reaction of pentaethoxy niobate, Nb(OEt)5, at elevated temperature (800 °C) under autogenic pressure provides a chemical route to niobium oxide nanorods coated with amorphous carbon. This synthetic approach yielded nanocrystalline particles of Nb2O5@C. As prepared Nb2O5@C core-shell nanorods is annealed under air at 500 °C for 3 h (removing the carbon coating) results in neat Nb2O5nanorods. According to the TEM measurements, the Nb2O5crystals exhibit particle sizes between 25 nm and 100 nm, and the Nb2O5crystals display rod-like shapes without any indication of an amorphous character. The optical band gap of the Nb2O5nanorods was determined by diffuse reflectance spectroscopy (DRS) and was found to be 3.8 eV.