bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteolytic Processing and Deubiquitinating Activity of Papain-Like Proteases of Human Coronavirus NL63
Authors: Chen Zhongbin , Wang Yanhua , Ratia Kiira , Mesecar Andrew D. , Wilkinson Keith D. , Baker Susan C.
Published: March 2007

Human coronavirus NL63 (HCoV-NL63), a common human respiratory pathogen, is associated with both upper and lower respiratory tract disease in children and adults. Currently, no antiviral drugs are available to treat CoV infections; thus, potential drug targets need to be identified and characterized. Here, we identify HCoV-NL63 replicase gene products and characterize two viral papain-like proteases (PLPs), PLP1 and PLP2, which process the viral replicase polyprotein. We generated polyclonal antisera directed against two of the predicted replicase nonstructural proteins (nsp3 and nsp4) and detected replicase proteins from HCoV-NL63-infected LLC-MK2 cells by immunofluorescence, immunoprecipitation, and Western blot assays. We found that HCoV-NL63 replicase products can be detected at 24 h postinfection and that these proteins accumulate in perinuclear sites, consistent with membrane-associated replication complexes. To determine which viral proteases are responsible for processing these products, we generated constructs representing the amino-terminal end of the HCoV-NL63 replicase gene and established proteasecis-cleavage assays. We found that PLP1 processes cleavage site 1 to release nsp1, whereas PLP2 is responsible for processing both cleavage sites 2 and 3 to release nsp2 and nsp3. We expressed and purified PLP2 and used a peptide-based assay to identify the cleavage sites recognized by this enzyme. Furthermore, by using K48-linked hexa-ubiquitin substrate and ubiquitin-vinylsulfone inhibitor specific for deubiquitinating enzymes (DUBs), we confirmed that, like severe acute respiratory syndrome (SARS) CoV PLpro, HCoV-NL63 PLP2 has DUB activity. The identification of the replicase products and characterization of HCoV-NL63 PLP DUB activity will facilitate comparative studies of CoV proteases and aid in the development of novel antiviral reagents directed against human pathogens such as HCoV-NL63 and SARS-CoV.
Electrostatic Interactions Drive Membrane Association of the Human Immunodeficiency Virus Type 1 Gag MA Domain
Authors: Dalton Amanda K. , Ako-Adjei Danso , Murray Paul S. , Murray Diana , Vogt Volker M.
Published: March 2007

The assembly of most retroviruses occurs at the plasma membrane. Membrane association is directed by MA, the N-terminal domain of the Gag structural protein. For human immunodeficiency virus type 1 (HIV-1), this association is mediated in part by a myristate fatty acid modification. Conflicting evidence has been presented on the relative importance of myristoylation, of ionic interactions between protein and membrane, and of Gag multimerization in membrane association in vivo. We addressed these questions biochemically by determining the affinity of purified myristoylated HIV-1 MA for liposomes of defined composition, both for monomeric and for dimeric forms of the protein. Myristoylation increases the barely detectable intrinsic affinity of the apo-protein for liposomes by only 10-fold, and the resulting affinity is still weak, similar to that of the naturally nonmyristoylated MA of Rous sarcoma virus. Membrane binding of HIV-1 MA is absolutely dependent on the presence of negatively charged lipid and is abrogated at high ionic strength. Forced dimerization of MA increases its membrane affinity by several orders of magnitude. When green fluorescent protein fusions of monomeric or dimeric MA are expressed in cells, the dimeric but not the monomeric protein becomes strongly membrane associated. Computational modeling supports these results and suggests a molecular mechanism for the modest effect of myristoylation on binding, wherein the membrane provides a hydrophobic environment for the myristate that is energetically similar to that provided by the protein. Overall, the results imply that the driving force for membrane association stems largely from ionic interactions between multimerized Gag and negatively charged phospholipids.
NEURAL NETWORK MODELS FOR EARTHQUAKE MAGNITUDE PREDICTION USING MULTIPLE SEISMICITY INDICATORS
Authors: PANAKKAT ASHIF , ADELI HOJJAT
Published: March 2007

Neural networks are investigated for predicting the magnitude of the largest seismic event in the following month based on the analysis of eight mathematically computed parameters known as seismicity indicators. The indicators are selected based on the Gutenberg-Richter and characteristic earthquake magnitude distribution and also on the conclusions drawn by recent earthquake prediction studies. Since there is no known established mathematical or even empirical relationship between these indicators and the location and magnitude of a succeeding earthquake in a particular time window, the problem is modeled using three different neural networks: a feed-forward Levenberg-Marquardt backpropagation (LMBP) neural network, a recurrent neural network, and a radial basis function (RBF) neural network. Prediction accuracies of the models are evaluated using four different statistical measures: the probability of detection, the false alarm ratio, the frequency bias, and the true skill score or R score. The models are trained and tested using data for two seismically different regions: Southern California and the San Francisco bay region. Overall the recurrent neural network model yields the best prediction accuracies compared with LMBP and RBF networks. While at the present earthquake prediction cannot be made with a high degree of certainty this research provides a scientific approach for evaluating the short-term seismic hazard potential of a region.
NEW CRITERIA ON GLOBAL EXPONENTIAL STABILITY OF BAM NEURAL NETWORKS WITH DISTRIBUTED DELAYS AND REACTION-DIFFUSION TERMS
Authors: LOU XUYANG , CUI BAOTONG
Published: March 2007

This paper presents new theoretical results on global exponential stability of bi-directional associative memory neural networks with distributed delays and reaction-diffusion terms based on the inequality technique, Lyapunov functional, and analysis technique. The results remove the usual assumption that the activation functions are of monotonous or differential character. Exponential converging velocity index is estimated, which depends on the delay kernel functions and system parameters. Finally, two numerical examples are given to show the validity and feasibility of our results.
STABILITY OF NEURAL FIELD
Authors: WU JINN-WEN , CHEN KUO-CHIH
Published: March 2007

The main purpose of this paper is to investigate the case that neurons can not be considered as individuals in the system, so they need to be treated as a continuum. In this paper, we have proved that if the interconnection of neural field is symmetric, then every trajectory of the system converges to an equilibrium. For the case that the interconnection is asymmetric, we give a sufficient condition which can guarantee that the equilibria of the neural field is unique and it also a global attractor.
NEURAL NETWORK APPROACH FOR IMAGE CHROMATIC ADAPTATION FOR SKIN COLOR DETECTION
Authors: BOURBAKIS N. , KAKUMANU P. , MAKROGIANNIS S. , BRYLL R. , PANCHANATHAN S.
Published: March 2007

The goal of image chromatic adaptation is to remove the effect of illumination and to obtain color data that reflects precisely the physical contents of the scene. We present in this paper an approach to image chromatic adaptation using Neural Networks (NN) with application for detecting — adapting human skin color. The NN is trained on randomly chosen color images containing human subject under various illuminating conditions, thereby enabling the model to dynamically adapt to the changing illumination conditions. The proposed network predicts directly the illuminant estimate in the image so as to adapt to human skin color. The comparison of our method with Gray World, White Patch and NN on White Patch methods for skin color stabilization is presented. The skin regions in the NN stabilized images are successfully detected using a computationally inexpensive thresholding operation. We also present results on detecting skin regions on a data set of test images. The results are promising and suggest a new approach for adapting human skin color using neural networks.
Finite Density Simulations: Comparison of Various Approaches
Authors: NAKAMURA Atsushi
Published: March 2007

This is a short overview of the lattice QCD simulations of finite density systems. We first describe a brief introduction of the lattice QCD at finite density, including the minimum necessary formulation, where we show why an annoying complex fermion determinant appears, and why in some cases it does not appear. Then we review several approaches of present and past days. We conclude possible directions of lattice QCD simulations at finite density in near future.
Monte Carlo Study of Lattice QCD with Wilson fermions at Finite Temperature and Chemical Potential
Authors: Chen He-Sheng , Luo Xiang-Qian
Published: March 2007

In this paper, we studied the phase diagram of QCD at finite temperature T and chemical potential μ with 4 flavor Wilson quarks. The calculations are performed on a 83 × 4 lattice using the imaginary chemical potential method. This method allows us to do large scale Monte Carlo simulations at imaginary chemical potential μ = iμI with μI < πT/3. By analytic continuation to the real chemical potential, the phase transition line on the (μ, T) plane can be determined.
Recent Results from Nuclear Lattice Simulations
Authors: LEE DEAN
Published: March 2007

We discuss recent progress in the study of nuclear and neutron matter by combining chiral effective field theory with non-perturbative lattice methods. We present results for hot neutron matter at temperatures 20 to 40 MeV and densities below twice nuclear matter density. This proceedings article is a summary of results from work done in collaboration with Bugra Borasoy and Thomas Schaefer1.
MONTE CARLO HAMILTONIAN OF LATTICE GAUGE THEORY
Authors: PARADIS F. , KRÖGER H. , LUO X. Q. , MORIARTY K. J. M.
Published: March 2007

We discuss how the concept of the Monte Carlo Hamiltonian can be applied to lattice gauge theories.
Gluonic excitation of exotic hybrid charmonium from lattice QCD
Authors: Liu Yan , Luo Xiang-Qian
Published: March 2007

We give the prediction for the ground and excited state masses of the charmonium hybrid mesons, 1-+, 0+-, 0--, with exotic quantum numbers. We employ improved gluon and quark actions on anisotropic lattice, which reduce greatly the lattice artifacts, and lead to good signals. The data are extrapolated to the continuum limit, with finite size effects under well control. The ground state masses of 1-+, 0+-, 0-- agree with our earlier results, where the mass of 0-- were shown for the first time. And the excited state masses, reported for the first time here, are 6.450(190)GeV, 6.629(138)GeV and 8.487(201)GeV respectively.
Calculations of Glueball Wavefunction in Lattice QCD
Authors: Soh Dart-yin , Liu Jun , Luo Xiang-Qian
Published: March 2007

We calculate the glueball 〈gg〉 wavefunction and mass in SU (3) Lattice gauge with improved gauge actions on the anisotropic lattice. All simulations are performed on the cluster of our lab. We have measured the scalar and tensor glueball wavefunction. At the same time, we have briefly calculated the glueball mass as for a consistent check.
Dalitz-esque Treatment of Neutralino Pair Production at the LHC
Authors: Bisset M.
Published: March 2007

Processes of the form [Formula: see text] are studied via a technique that may be viewed as an adaptation of time-honored Dalitz plot analyses. Xi and Xj are new heavy states (with i,j = 1…n), which may be identical or distinct; and [Formula: see text] and [Formula: see text] are necessarily distinct Standard Model (SM) fermion pairs whose invariant masses can be measured. A Dalitz-like plot of said invariant masses, [Formula: see text]vs.[Formula: see text], exhibits a topology connected to the masses and specific decay chains of Xi and Xj. Aside from relatively minor details, observed patterns consist of a collection of box and wedge shapes. This collection is model-dependent: comparison of the observed pattern to the possibilities for a specific model yields information on which new particle pair combinations are actually being produced, information beyond that extractable from conventional one-dimensional invariant mass distributions. The technique is illustrated via application to the Minimal Supersymmetric Standard Model (MSSM) process [Formula: see text]. Here the heavy states are neutralinos [Formula: see text] (i = 2,3,4) — note [Formula: see text] is excluded — which are produced in gluino/squark [Formula: see text] cascade decay chains. Even with fairly modest expectations for the LHC performance during the first few years, this method still provides substantial insight into the neutralino mass spectrum and couplings if gluino/squark masses are relatively low (≃ 400 GeV).
GLUEBALL MASSES FROM ADS6 GRAVITY THEORY
Authors: CAI BENGENG , WEN CONGKAO , YANG HUANXIONG
Published: March 2007

In view of the general holographic principle between gauge theories and gravity, We calculate the mass spectra of several typical QCD4 glueballs in term of AdS 6 AdS -Schwarzschild black hole metric of Einstein gravity theory. The obtained mass spectra are numerically in consistent with those from the AdS 7 × S 4 black hole metric of the 11-dimensional supergravity. Besides, by separating the thermal circle from the extra dimensions, we find a novel exact D p-brane solution of Type IIB supergravity, which might provide a scenario for studying the non-perturbative dynamics of QCD4 from the perspective of Type IIB supergravity.
ON THE ENTANGLED ERGODIC THEOREM
Authors: FIDALEO FRANCESCO
Published: March 2007

Let U be a unitary operator acting on the Hilbert space [Formula: see text], and α: {1, …, m} ↦ {1, …, k} a partition of the set {1, …, m}. We show that the ergodic average [Formula: see text] converges in the weak operator topology if the Aj belong to the algebra of all the compact operators on [Formula: see text]. We write esplicitly the formula for these ergodic averages in the case of pair-partitions. Some results without any restriction on the operators Aj are also presented in the almost periodic case.
INDEPENDENCE AND MARKOVIANITY FOR STATES ON VON NEUMANN ALGEBRAS
Authors: CECCHINI CARLO
Published: March 2007

Several possible generalizations of the classical notion of markovianity are given for states defined on a von Neumann algebras generated on a triple of subalgebras. Their mutual relation is discussed in the particular case in which they mutually commute, and the generalization of the classical; time reversal theorem is proved. A structure theorem for a class of Markov chains is also proved.
Loss of calcineurin homologous protein-1 in chicken B lymphoma DT40 cells destabilizes Na+/H+ exchanger isoform-1 protein
Authors: Matsushita Masafumi , Sano Yoshie , Yokoyama Shunsuke , Takai Tomoyo , Inoue Hiroki , Mitsui Keiji , Todo Kagefumi , Ohmori Hitoshi , Kanazawa Hiroshi
Published: March 2007

NHE1/SLC9A1 is a ubiquitous isoform of vertebrate Na+/H+ exchangers (NHEs) functioning in maintaining intracellular concentrations of Na+ and H+ ions. Calcineurin homologous protein-1 (CHP1) binds to the hydrophilic region of NHE1 and regulates NHE1 activity but reportedly does not play a role in translocating NHE1 from the endoplasmic reticulum to the plasma membrane. However, an antiport function of NHE1 requiring CHP1 remains to be clarified. Here we established CHP1-deficient chicken B lymphoma DT40 cells by gene targeting to address CHP1 function. CHP1-deficient cells showed extensive decreases in Na+/H+ activities in intact cells. Although NHE1 mRNA levels were not affected, NHE1 protein levels were significantly reduced not only in the plasma membrane but in whole cells. The expression of a CHP1 transgene in CHP1-deficient cells rescued NHE1 protein expression. Expression of mutant forms of CHP1 defective in Ca2+ binding or myristoylation also partially decreased NHE1 protein levels. Knockdown of CHP1 also caused a moderate decrease in NHE1 protein in HeLa cells. These data indicate that CHP1 primarily plays an essential role in stabilization of NHE1 for reaching of NHE1 to the plasma membrane and its exchange activity.
Expression and function of COOH-terminal myosin heavy chain isoforms in mouse smooth muscle
Authors: Martin Anne F. , Bhatti Sunita , Pyne-Geithman Gail J. , Farjah Mariam , Manaves Vlasios , Walker Lori , Franks Roberta , Strauch Arthur R. , Paul Richard J.
Published: March 2007

Isoforms of the smooth muscle myosin motor, SM1 and SM2, differ in length at the carboxy terminal tail region. Their proportion changes with development, hormonal status and disease, but their function is unknown. We developed mice carrying the myosin heavy chain (MyHC) transgenes SM1, cMyc-tagged SM1, SM2, and V5-tagged SM2, and all transgenes corresponded to the SMa NH2-terminal isoform. Transgene expression was targeted to smooth muscle by the smooth muscle α-actin promoter. Immunoblot analysis showed substantial expression of the cMyc-tagged SM1 and V5-tagged SM2 MyHC protein in aorta and bladder and transgene mRNA was expressed in mice carrying unlabeled SM1 or SM2 transgenes. Despite significant protein expression of tagged MyHCs we found only small changes in the SM1:SM2 protein ratio. Significant changes in functional phenotype were observed in mice carrying unlabeled SM1 or SM2 transgenes. Force in aorta and bladder was increased (72 ± 14%, 92 ± 11%) in SM1 and decreased to 57 ± 1% and 80 ± 3% in SM2 transgenic mice. SM1 transgenic bladders had faster (1.8 ± 0.3 s) and SM2 slower (7.1 ± 0.5 s) rates of force redevelopment following a rapid step shortening. We hypothesize that small changes in the SM1:SM2 ratio could be amplified if they are associated with changes in thick filament assembly and underlie the altered contractility. These data provide evidence indicating an in vivo function for the COOH-terminal isoforms of smooth muscle myosin and suggest that the SM1:SM2 ratio is tightly regulated in smooth muscle tissues.
Biomechanical signals upregulate myogenic gene induction in the presence or absence of inflammation
Authors: Chandran Ravi , Knobloch Thomas J. , Anghelina Mirela , Agarwal Sudha
Published: March 2007

Inflammation of the muscle invariably leads to muscle cell damage and impaired regeneration. Biomechanical signals play a vital role in the regulation of myogenesis in healthy and inflamed muscle. We hypothesized that biomechanical signals counteract the actions of proinflammatory mediators and upregulate the basic helix-loop-helix and MADS box transcription enhancer factor 2 (MEF2) families of transcription factors, leading to increased myogenesis in inflamed muscle cells. For this purpose, C2C12 cells plated on collagenized silastic membranes were subjected to equibiaxial cyclic tensile strain (CTS) in the presence or absence of TNF-α, and the myogenic gene induction was examined over a period of 72 h. Exposure of cells to CTS resulted in a significant upregulation of mRNA expressions and synthesis of myogenic regulatory factors, MYOD1, myogenin (MYOG), MEF2A, and cyclin-dependent kinase inhibitor 1A (CDKN1A; p21) as well as muscle structural proteins like myosin heavy chain (MYHC) isoforms (MYH1, MYH2, and MYH4) and α-tropomyosin (TPM1), eventually leading to an increase in myotube formation. Contrarily, TNF-α suppressed the expression of all of the above differentiation-inducing factors in C2C12 cells. Further results revealed that simultaneous exposure of C2C12 cells to CTS and TNF-α abrogated the TNF-α-mediated downregulation of myogenic differentiation. In fact, the mRNA expression and protein synthesis of all myogenic factors ( Myod1, Myog, Mef2a, Cdkn1a, Myh1, Myh2, Myh4, and Tpm1) were increased in stretched C2C12 cells despite the sustained presence of TNF-α. These results demonstrate that mechanotransduction regulates multiple signaling molecules involved in C2C12 cell differentiation. On one hand, these signals are potent transducers of myotube phenotype in myoblasts; on the other, these signals counteract catabolic actions of proinflammatory cytokines like TNF-α and allow the expression of myogenic genes to upregulate muscle cell differentiation.
Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2
Authors: Sigalet David L. , Wallace Laurie E. , Holst Jens J. , Martin Gary R. , Kaji Tatsuru , Tanaka Hiroaki , Sharkey Keith A.
Published: March 2007

Glucagon-like peptide-2 (GLP-2) is an important regulator of nutritional absorptive capacity with anti-inflammatory actions. We hypothesized that GLP-2 reduces intestinal mucosal inflammation by activation of vasoactive intestinal polypeptide (VIP) neurons of the submucosal plexus. Ileitis or colitis was induced in rats by injection of trinitrobenzene sulfonic acid (TNBS), or colitis was induced by administration of dextran sodium sulfate (DSS) in drinking water. Subsets of animals received (1–33)-GLP-2 (50 μg/kg sc bid) either immediately or 2 days after the establishment of inflammation and were followed for 3–5 days. The involvement of VIP neurons was assessed by concomitant administration of GLP-2 and the VIP antagonist [Lys1-Pro2,5-Arg3,4-Tyr6]VIP and by immunohistochemical labeling of GLP-2-activated neurons. In all models, GLP-2 treatment, whether given immediately or delayed until inflammation was established, resulted in significant improvements in animal weights, mucosal inflammation indices (myeloperoxidase levels, histological mucosal scores), and reduced levels of inflammatory cytokines (IFN-γ, TNF-α, IL-1β) and inducible nitric oxide synthase, with increased levels of IL-10 in TNBS ileitis and DSS colitis. Reduced rates of crypt cell proliferation and of apoptosis within crypts in inflamed tissues were also noted with GLP-2 treatment. These effects were abolished with coadministration of GLP-2 and the VIP antagonist. GLP-2 was shown to activate neurons and to increase the number of cells expressing VIP in the submucosal plexus of the ileum. These findings suggest that GLP-2 acts as an anti-inflammatory agent through activation of enteric VIP neurons, independent of proliferative effects. They support further studies to examine the role of neural signaling in the regulation of intestinal inflammation.
Tidal volume dependency of gas exchange in bronchoconstricted pig lungs
Authors: Kleinsasser Axel , Olfert I. Mark , Loeckinger Alex , Prisk G. Kim , Hopkins Susan R. , Wagner Peter D.
Published: March 2007

Independent of airway pressure, pulmonary resistance is known to fall with increasing tidal volumes, traditionally thought to result from radial traction on the airways. R. C. Anafi and T. A. Wilson ( J Appl Physiol 91: 1185–1192, 2001) recently presented a model of a single terminal airway that explains the tidal volume-associated fall in resistance with an additional mechanism pertinent to narrow airways: a stable, nearly closed airway that is challenged with an increase in tidal volume “pops open” to become a stable, well-opened airway, and thus resistance drops suddenly. To test this model in vivo, the effects of high (24 ml/kg) and low (9 ml/kg) tidal volume in bronchoconstricted lungs were assessed using 1) the multiple inert gas elimination technique (MIGET) and 2) a 15-breath multiple breath inert gas washout (MBW) technique in anesthetized pigs. With high tidal volume, ventilation/perfusion (V̇a/Q̇) mismatch was reduced (log SD Q̇ from 1.30 ± 0.11 to 1.09 ± 0.12, P < 0.05), and blood flow to lung units with V̇a/Q̇ ratios < 0.1 was significantly reduced (37 ± 4% of cardiac output to 7 ± 4%, P < 0.05). Dynamic compliance was twice as high during high-tidal-volume ventilation ( P = 0.002). MBW analysis revealed that, while heterogeneity of ventilation during bronchoconstriction was not significantly different between either low or high tidal volume (log SD V̇mbw = 1.39 ± 0.09 and 1.34 ± 0.02, respectively), preinspiratory lung volume (PILV) decreased by 42% with low-tidal-volume ventilation ( P < 0.05), whereas it did not change with high-tidal-volume ventilation. The higher PILV during high tidal volume is also consistent with Anafi and Wilson's model. In summary, the outcomes from MIGET, and to some extent the MBW, in our anesthetized and mechanically ventilated pigs are consistent with a bistable terminal airway model as proposed by Anafi and Wilson. However, our data do not allow exclusion of other mechanisms that may lead to improved ventilatory distribution when tidal volume is increased.
Direct Inhibition ofIhby Analgesic Loperamide in Rat DRG Neurons
Authors: Vasilyev Dmitry V. , Shan Qin , Lee Yan , Mayer Scott C. , Bowlby Mark R. , Strassle Brian W. , Kaftan Edward J. , Rogers Kathryn E. , Dunlop John
Published: March 2007

Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels are responsible for the functional hyperpolarization-activated current ( Ih) in dorsal root ganglion (DRG) neurons, playing an important role in pain processing. We found that the known analgesic loperamide inhibited Ihchannels in rat DRG neurons. Loperamide blocked Ihin a concentration-dependent manner, with an IC50= 4.9 ± 0.6 and 11.0 ± 0.5 μM for large- and small-diameter neurons, respectively. Loperamide-induced Ihinhibition was unrelated to the activation of opioid receptors and was reversible, voltage-dependent, use-independent, and was associated with a negative shift of V1/2for Ihsteady-state activation. Loperamide block of Ihwas voltage-dependent, gradually decreasing at more hyperpolarized membrane voltages from 89% at –60 mV to 4% at –120 mV in the presence of 3.7 μM loperamide. The voltage sensitivity of block can be explained by a loperamide-induced shift in the steady-state activation of Ih. Inclusion of 10 μM loperamide into the recording pipette did not affect Ihvoltage for half-maximal activation, activation kinetics, and the peak current amplitude, whereas concurrent application of equimolar external loperamide produced a rapid, reversible Ihinhibition. The observed loperamide-induced Ihinhibition was not caused by the activation of peripheral opioid receptors because the broad-spectrum opioid receptor antagonist naloxone did not reverse Ihinhibition. Therefore we suggest that loperamide inhibits Ihby direct binding to the extracellular region of the channel. Because Ihchannels are involved in pain processing, loperamide-induced inhibition of Ihchannels could provide an additional molecular mechanism for its analgesic action.
Dopaminergic Modulation of Local Network Activity in Rat Prefrontal Cortex
Authors: Bandyopadhyay Susanta , Hablitz John J.
Published: March 2007

Dopamine modulates prefrontal cortex excitability in complex ways. Dopamine's net effect on local neuronal networks is therefore difficult to predict based on studies on pharmacologically isolated excitatory or inhibitory connections. In the present work, we have studied the effects of dopamine on evoked activity in acute rat brain slices when both excitation and inhibition are intact. Whole cell recordings from layer II/III pyramidal cells under conditions of normal synaptic transmission showed that bath-applied dopamine (30 μM) increased the outward inhibitory component of composite postsynaptic currents, whereas inward excitatory currents were not significantly affected. Optical imaging with the voltage-sensitive dye N-(3-(triethylammonium)propyl)-4-(4-(p-diethylaminophenyl)buta-dienyl)pyridinium dibromide revealed that bath application of dopamine significantly decreased the amplitude, duration, and lateral spread of activity in local cortical networks. This effect of dopamine was observed both with single and train (5 at 20 Hz) stimuli. The effect was mimicked by the D1-like receptor agonist R(+)-6-chloro-7,8-dihydroxy-1-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (1 μM) and was blocked by R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (10 μM), a selective antagonist for D1-like receptors. The D2-like receptor agonist quinpirole (10 μM) had no significant effect on evoked dye signals. Our results suggest that dopamine's effect on inhibition dominates over that on excitation under conditions of normal synaptic transmission. Such neuromodulation by dopamine may be important for maintenance of stability in local neuronal networks in the prefrontal cortex.
Discrete Place Fields of Hippocampal Formation Interneurons
Authors: Wilent W. Bryan , Nitz Douglas A.
Published: March 2007

The spike discharge of hippocampal excitatory principal cells, also called “place cells,” is highly location specific, but the discharge of local inhibitory interneurons is thought to display relatively low spatial specificity. Whereas in other brain regions, such as sensory neocortex, the activity of interneurons is often exquisitely stimulus selective and directly determines the responses of neighboring excitatory neurons, the activity of hippocampal interneurons typically lacks the requisite specificity needed to shape the defined structure of principal cell fields. Here we show that hippocampal formation interneurons have “on” fields (abrupt increases in activity) and “off” fields (abrupt decreases in activity) that are associated with the same location-specific informational content, spatial resolution, and dependency on context as the “place fields” of CA1 principal cells. This establishes that interneurons have well-defined place fields, thus having important implications for understanding how the hippocampus represents spatial information.
Local Generation of Theta-Frequency EEG Activity in the Parasubiculum
Authors: Glasgow Stephen D. , Chapman C. Andrew
Published: March 2007

The parasubiculum is a major component of the hippocampal formation that receives inputs from the CA1 region, anterior thalamus, and medial septum and that projects primarily to layer II of the entorhinal cortex. Hippocampal theta-frequency (4–12 Hz) electroencephalographic (EEG) activity has been correlated with sensorimotor integration, spatial navigation, and memory functions. The present study was aimed at determining if theta is also generated locally within the parasubiculum versus volume conducted from adjacent structures. In urethan-anesthetized rats, the phase-reversal of theta activity between superficial and deep layers of the parasubiculum was demonstrated using differential recordings from movable bipolar electrodes that eliminate the influence of volume-conducted activity. Parasubicular theta was abolished by atropine, and was in phase with theta in stratum radiatum/lacunosum-moleculare of the CA1 region. Whole cell current-clamp recordings in brain slices were then used to determine if parasubicular theta may be generated in part by membrane potential oscillations in layer II neurons. Membrane potential oscillations occurred in most layer II neurons, including four putative interneurons, when cells were held at near-threshold voltages using current injection. The frequency of oscillations increased from 3.2 to 6.1 Hz when bath temperature was raised from 22 to 32°C, and oscillations persisted in the presence of blockers of fast ionotropic glutamatergic and GABAergic synaptic transmission. Oscillations are therefore likely generated by intrinsic, voltage-dependent ionic conductances. These results indicate that theta field activity is generated locally within the parasubiculum and that intrinsic membrane potential oscillations, synchronized by local inhibitory inputs, may contribute to the generation of this activity.
Environmental Complexity and Social Organization Sculpt the Brain in Lake Tanganyikan Cichlid Fish
Authors: Pollen Alexander A. , Dobberfuhl Adam P. , Scace Justin , Igulu Mathias M. , Renn Susan C.P. , Shumway Caroly A. , Hofmann Hans A.
Published: March 2007

Complex brains and behaviors have occurred repeatedly within vertebrate classes throughout evolution. What adaptive pressures drive such changes? Both environmental and social features have been implicated in the expansion of select brain structures, particularly the telencephalon. East African cichlid fishes provide a superb opportunity to analyze the social and ecological correlates of neural phenotypes and their evolution. As a result of rapid, recent, and repeated radiations, there are hundreds of closely-related species available for study, with an astonishing diversity in habitat preferences and social behaviors. In this study, we present quantitative ecological, social, and neuroanatomical data for closely-related species from the (monophyletic) Ectodini clade of Lake Tanganyikan cichlid fish. The species differed either in habitat preference or social organization. After accounting for phylogeny with independent contrasts, we find that environmental and social factors differentially affect the brain, with environmental factors showing a broader effect on a range of brain structures compared to social factors. Five out of seven of the brain measures show a relationship with habitat measures. Brain size and cerebellar size are positively correlated with species number (which is correlated with habitat complexity); the medulla and olfactory bulb are negatively correlated with habitat measures. The telencephalon shows a trend toward a positive correlation with rock size. In contrast, only two brain structures, the telencephalon and hypothalamus, are correlated with social factors. Telencephalic size is larger in monogamous species compared to polygamous species, as well as with increased numbers of individuals; monogamy is also associated with smaller hypothalamic size. Our results suggest that selection or drift can act independently on different brain regions as the species diverge into different habitats and social systems.
Gonadotropin-Releasing Hormone and Receptor Distributions in the Visual Processing Regions of Four Coral Reef Fishes
Authors: Maruska Karen P. , Tricas Timothy C.
Published: March 2007

Gonadotropin-releasing hormone (GnRH) is widely distributed in the brain of fishes where it may function as a neuromodulator of sensory processing and behavior. Immunocytochemical and neuronal label experiments were conducted on species from four families of coral reef fishes (Chaetodontidae, butterflyfish; Pomacentridae, damselfish; Gobiidae, goby; and Labridae, wrasse) to assess conservation of GnRH targets in the visual processing retina and brain. In all species, GnRH-immunoreactive (-ir) axons from the terminal nerve project principally to the boundary between the inner plexiform (IPL) and inner nuclear (INL) layers of the retina, and are less prominent in the optic nerve, ganglion cell, IPL and INL. However, the density of GnRH innervation within the retina differed among fish species with highest concentrations in the damselfish and butterflyfish and lowest in the goby and wrasse. Experiments also show that GnRH receptors are associated with GnRH-ir axons within the fish retina primarily at the IPL-INL boundary, the region of light-dark adaptation and image processing of contrast, motion or color. GnRH-ir axons overlapped central projections of retinal ganglion cell axons primarily within the stratum album centrale and stratum griseum centrale of the tectum in all species, and were concentrated in several diencephalic visual processing centers. GnRH receptors are also localized to diencephalic visual centers and the stratum griseum periventriculare of the tectum, where motion perception and coordination of motor behavioral responses in three-dimensional space occur. This work demonstrates that the basic neural substrates for peptide-sensory convergence are conserved at multiple processing levels in the visual system of several reef fishes. Species differences in GnRH innervation to the retina and GnRH receptor distributions may be related to phylogeny, their use of vision in natural behaviors, or possibly binding properties of the antibodies. Future studies are needed to characterize the exact GnRH variants and receptor types found in these species so that possible functional consequences of GnRH influence on vision can be defined.
Benign Paroxysmal Vertigo, and Bárány’s Caloric Reactions
Authors: Pearce J.M.S.
Published: March 2007

The Nobel Prize winner Robert Bárány described benign positional vertigo and related it to the otoliths in 1921. Dix and Hallpike further elucidated this clinically distinctive, common disorder in 1952. The displacement of otoliths from the utricle or saccule into one of the semicircular canals later proved to be the underlying mechanism, described by Schuknecht and utilised therapeutically by Semont and Epley.
Regional Cerebral Perfusion Differences between Periventricular Grey, Thalamic and Dual Target Deep Brain Stimulation for Chronic Neuropathic Pain
Authors: Pereira Erlick A.C. , Green Alexander L. , Bradley Kevin M. , Soper Nigel , Moir Liz , Stein John F. , Aziz Tipu Z.
Published: March 2007

Regional cerebral blood flow changes were evaluated in different subcortical brain targets following deep brain stimulation (DBS) for chronic pain. Three patients with intractable neuropathic pain were assessed; one had stimulating electrodes in the ventroposterolateral thalamic nucleus (VPL), one in the periventricular grey (PVG) area, and one had electrodes in both targets. Pain relief was achieved in all patients. Cerebral perfusion was measured by single-photon emission computed tomography to determine the effects of DBS. Comparison was made between individual scans using subtraction analysis. DBS consistently increased perfusion in the posterior subcortical region between VPL and PVG, regardless of the site of stimulation. Furthermore, thalamic and dual target DBS increased thalamic perfusion, yet PVG DBS decreased perfusion in the PVG-containing midbrain region and thalamus. Dual target stimulation decreased anterior cingulate and insular cortex perfusion. The study demonstrates regional differences in cerebral perfusion between three accepted and efficacious targets for analgesic DBS.
Prediction of Volumetric Data Errors in Patients Treated with Gamma Knife Radiosurgery
Authors: Pan Hung-Chuan , Cheng Fu-Chou , Sun Ming-Hsi , Chen Chi-Chang Clayton , Sheehan Jason
Published: March 2007

Purpose: Volumetry is the most commonly used method to measure tumor response in patients who receive Gamma Knife radiosurgery. We calculated the data errors in measurement made by different methods based on the stereotactic fiducials (Gamma Knife workstation), surface area multiplied by thickness (PACS), and product of maximum diameter in x, y, and z dimensions (geometric method) to more precisely evaluate tumor response in patients treated with Gamma Knife radiosurgery. Materials and Methods: From 2003 to 2006, 210 tumors were enrolled in this study. MRIs obtained from these patients were transferred to Gamma Knife and PACS workstations. Data errors were defined as the difference between the volume calculated by various methods and the Gamma Knife workstation divided by the volume obtained from the Gamma Knife workstation. Linear regression was used for data analysis. Results: There were 27 lesions with volume <0.5 cm3, 97 lesions between 0.5 and 4 cm3, 68 lesions between 4 and 14 cm3, and 18 lesions larger than 14 cm3. A strong linear correlation was found between the volume measurement by Gamma Knife workstation and PACS and the geometric method (r = 0.993, 0.967, respectively). Poor correlation between the Gamma Knife and PACS workstation volume measurement was observed in tumors less than 0.5 cm3 (r = 0.763), but better correlation was found between the Gamma Knife workstation and geometric method (r = 0.871). Fewer data errors were observed in the PACS than in the geometric method (p < 0.001) in tumors with volumes of 0.5–4 cm3 and 4–14 cm3; whereas in tumors less than 0.5 cm3, fewer data errors were observed in the geometric method (p = 0.01). The data error in the whole series was 6 ± 15% in the PACS system and was relatively correlated with the volume (p = 0.03) and the number of slices (p = 0.021), but not with the Pearsonian coefficient of skewness (p = 0.81). Conclusion: The different methods of measurement of tumor volume (>0.5 cm3) demonstrated strong linear correlation. In tumors with volume less than 0.5 cm3, the most reliable method was the geometric method. When using the PACS system in the evaluation of tumor response, a data error as high as 21% should be considered.
The Relationship between Nocturnal Urinary Leptin and Gonadotrophins as Children Progress towards Puberty
Authors: Maqsood Arfa R. , Trueman Julie A. , Whatmore Andrew J. , Westwood Melissa , Price David A. , Hall Catherine M. , Clayton Peter E.
Published: March 2007

Background/Aims: Leptin is necessary for normal human pubertal development but its exact role in the period leading up to the onset of puberty has not been defined. This study has assessed the relationship between leptin and gonadotrophin secretion over time as children progress into puberty. Subjects and Methods: Twenty children (13 boys and 7 girls) judged to be close to the initiation of puberty were recruited. Three consecutive first morning urine samples were collected from each subject each month over 6 months. At the end of the study, the children were classified into those who remained physically prepubertal (n = 7) and those that had advanced in puberty (n = 13). Leptin and gonadotrophins were measured by immunoradiometric and immunofluorometric assay, respectively. Results: Total urinary leptin excreted over 6 months was higher in girls than in boys, both prepubertally and in early puberty, and in both sexes, was higher in those advancing into puberty than in those remaining prepubertal (girls 8.0 vs. 3.4 ng/l and boys 3.6 vs. 1.7 ng/l; both p < 0.05). In the whole group, when controlling for gender, there was a significant correlation between both leptin and luteinizing hormone (LH; r = 0.43, p < 0.001) and leptin and follicle-stimulating hormone (FSH; r = 0.32, p = 0.001). The possibility of a lead relationship was explored by pairing leptin values with the gonadotrophin values in the following month. Leptin was significantly correlated with FSH but not LH in both pre- and peripubertal children (prepubertal r = 0.45, p = 0.01; peripubertal r = 0.32, p = 0.01). Conclusions: This study has shown that in children approaching and progressing into puberty, leptin is associated with LH and FSH over the same time frame, and with FSH when leptin is acting as the lead hormone. These data imply that leptin is an important facilitator of the early phases of human puberty.
Corticosteroids and Ciclosporin A in Idiopathic Membranous Nephropathy: Higher Remission Rates of Nephrotic Syndrome and Less Adverse Reactions than after Traditional Treatment with Cytotoxic Drugs
Authors: Goumenos Dimitrios S. , Katopodis Konstantinos P. , Passadakis Ploumis , Vardaki Eleftheria , Liakopoulos Vasilios , Dafnis Eugenios , Stefanidis Ioannis , Vargemezis Vasilios , Vlachojannis Jannis G. , Siamopoulos Kostas C.
Published: March 2007

Background/Aim: Idiopathic membranous nephropathy, the most common cause of nephrotic syndrome in adults, has been traditionally treated with corticosteroids and cytotoxic drugs. Ciclosporin A (CsA) is used in resistant cases, but also as a first-line treatment, due to the serious side effects of cytotoxic drugs. In this study, the remission rates of nephrotic syndrome and the incidence of side effects of corticosteroids and low CsA doses are compared with those after treatment with cytotoxic drugs. Methods: Seventy-seven nephrotic patients with well-preserved renal function who were treated with methylprednisolone and CsA (n = 46) or cytotoxic drugs (n = 31) were studied. The effects of treatments were estimated on the basis of remission rates of nephrotic syndrome and preservation of the renal function. Results: Remission (complete or partial) of nephrotic syndrome was observed in 85% of the patients treated with CsA and in 55% of the patients treated with cytotoxic drugs (p < 0.01). Deterioration of the renal function, more common in patients with multiple relapses and interstitial fibrosis, was observed in 26 and 23% of the patients, respectively (p = NS). Serious side effects and discontinuation of treatment were more frequent in patients treated with cytotoxic drugs (10 vs. 4%). Conclusion: The combination of corticosteroids with CsA represents a better regimen for patients having idiopathic membranous nephropathy, since it is associated with higher remission rates of nephrotic syndrome and less severe side effects than corticosteroids and cytotoxic drugs.
Renal Dopaminergic System Activity in Uninephrectomized Rats up to 26 Weeks after Surgery
Authors: Moreira-Rodrigues M. , Sampaio-Maia B. , Moura M. , Pestana M.
Published: March 2007

Background: Dopamine of renal origin exerts natriuretic and diuretic effects by activating D1-like receptors located at various regions in the nephron. Two weeks after uninephrectomy the renal dopaminergic system was suggested to be involved in the adaptative increase of sodium excretion. Aim: The aim of the present study was to evaluate the renal adaptations in sodium handling and renal dopaminergic system activity in uninephrectomized (Unx) rats up to 26 weeks after the surgery. Results: A time-dependent increase in both systolic and diastolic blood pressure was observed in Unx rats up to 26 weeks after uninephrectomy. This was accompanied by a compensatory increase in aromatic L-amino acid decarboxylase at 2 weeks but not 10 and 26 weeks after uninephrectomy. In contrast to what has been found 2 weeks after uninephrectomy, at 10 and 26 weeks after surgery the natriuretic response to volume expansion was reduced in Unx rats and this was accompanied by insensitivity of natriuresis to dopamine D1 receptor selective antagonist (Sch23390). Conclusion: A time-dependent decrease in dopamine sensitive natriuresis is observed in Unx rats throughout the 26 weeks after uninephectomy. It is suggested that this may contribute to compromise sodium excretion and increase blood pressure.
Pulse Wave Reflection Is Amplified in Normotensive Patients with Autosomal-Dominant Polycystic Kidney Disease and Normal Renal Function
Authors: Borresen Malene L. , Wang Dan , Strandgaard Svend
Published: March 2007

Background: In young ADPKD patients, we have previously found an impaired endothelium-dependent relaxation in small resistance vessels but a normal flow-mediated dilatation of the brachial artery. The present study investigated arterial stiffness in early ADPKD by pulse-wave analysis (PWA) and measurement of pulse-wave velocity (PWV). Methods: 18 young normotensive ADPKD patients with normal renal function and 18 controls were studied by applanation tonometry with the SphygmoCor® equipment. Parameters included an estimate of aortic blood pressure, augmentation index (AIx), AIx standardized to heart rate 75 (AIx(HR75)) and PWV. Glomerular filtration rate (GFR) was measured by the 51Cr-EDTA plasma clearance method. Statistical comparisons were made with t tests and multiple linear regression analysis. Results: GFR was the same in the two groups. Brachial diastolic blood pressure was slightly but significantly higher in ADPKD patients than in controls (81 ± 9 vs. 73 ± 9 mm Hg, p < 0.05). No significant difference was present in brachial systolic blood pressure. AIx was significantly higher in ADPKD than in controls: 21.6 ± 11.3 vs. 11.4 ± 11.2%, p < 0.02. AIx(HR75) and estimated aortic systolic and diastolic blood pressure was likewise significantly higher in ADPKD than in controls. Multiple linear regression analysis showed AIx and AIx(HR75) to be independently correlated to group (ADPKD/control), p < 0.02 and p < 0.05, respectively. No difference was found between PWV in the two groups. Conclusion: Reflection of the pulse wave was amplified in young normotensive ADPKD patients, demonstrating early pathology in the arterial system.