bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Films of Fe (III)-5-Amino 1,10 Phenanthroline Deposited on Two Different Carbon Substrates
Authors: Lozano Maria L. , Galicia Laura , Barrera Enrique
Published: December 2010

In this work the formation and morphologycal characteristics of the films formed on two carbon substrates were studied by electrochemical and spectrophotometric techniques. The two carbon substrates were modified with a complex aqueous solution 2.5x10-4M Fe (III) 5-Amino-1,10 phenanthroline (Fe (III)-5-Aphen) with 1:3 stoichiometry] at pH =6. The Poly Fe(III)-5-Aphen films, were characterized using electrochemical techniques like cyclic voltammetery (CV) and spectroscopic techniques.
Electrochemical Behavior of Glassy Carbon Electrode Modified With Copper-ZSM5
Authors: Oliver-Tolentino Miguel A. , Guzmán-Vargas Ariel , Arce-Estrada Elsa M. , Manzo Robledo Arturo
Published: December 2010

The electrochemical response of modified electrode with Cu-ZSM5 deposited on glassy carbon surface has been studied using cyclic voltammetry and open circuit potential (OCP) measurements. The i-E characteristics showed two cathodic processes at c.a. 0.03V and -0.2V/SCE attributed to the formation of Cu+ and Cu0, respectively. The progressive spread of electro active species on the surface of the zeolite was observed by multi sweep cyclic voltammetry experiment. The diffusion of Cu2+ in the ZSM5 layers depends on the cation nature and increases in the order Li+>K+>NH4
+>Na+. The evaluation of reversible behavior indicated that the electrochemical process is affected by adsorption/desorption phenomena at the interface. It was found that the redox processes are proportional to the amount of Cu species in the zeolite structure.
Determination of Trace Concentrations of Co(II) in Electrolyte for Electrowinning of Zn by Differential Pulse Voltammetry
Authors: Valera Jose Adolfo , Zlatev Roumen , Stoytcheva Margarita , Valdez Benjamin
Published: December 2010

A simple and rapid on-line Differential Pulse Polarographic (DPP) method for direct Co2+ determination in Zn plant electrolyte was developed and tested in real solutions. 1-nitroso-2-naphtol was applied as Co2+ to Co3+ oxidizing and chelate forming agent in ammonia buffer (NH4OH/HCl in 8 to 1 ratio) supporting electrolyte. The great DPP difference between Co3+ and Zn2+ peak potentials allows the complete elimination of the Zn2+ interference ensuring reliable results in the linear concentration range from 10 ppb to 20 ppm. Disposable mercury surface electrodes were applied as working electrodes.
Quantum Chemical Calculations in Stepwise Adrenaline Deprotonation
Authors: Cuán María A. , Gámez-García Victoria G. , Cortés-Romero Carlos M. , Ramirez-Silva Maria T. , Romero-Romo Mario R. , Palomar-Pardavé Manuel E.
Published: December 2010

Theoretical calculations of adrenaline structures formed during the in-vacuo deprotonation were performed using the DFT approach. The electronic properties of these chemical structures such as the atomic charge, the HOMO-LUMO electron distribution and its energy associated are presented and discussed. According to our results, the proton loss is more feasible during the deprotonation process of the amino group followed by cathecol aromatic ring deprotonation and then by the hydrogen loss of the aliphatic hydroxyl group. In fact, the results of the energy values of the latter deprotonation process indicate that it is very unlikely that the aliphatic OH group might loss its proton since it yields unstable chemical species. Under biological pH environment, adrenaline is a fully protonated species which avoids the amino group might be modified by oxidation-reduction reactions. This causes, however, that the cathecol aromatic ring be sensitive to chemical modification by the aforementioned reactions since adrenaline electronic properties are modified by the protonated amino group. This indicates that orbital re-distribution of the molecule might occur due to the proton presence.
Electroosmotic Mobility as a Function of pH of Britton-Robinson Buffers for Capillary Zone Electrophoresis
Authors: Rojas-Hernandez Alberto , Ibarra-Escutia Agustin , Medina-Juarez Obdulia , Ramirez-Silva Maria T.
Published: December 2010

The use of pH buffers is frequent to achieve separations or study mobilities in Capillary Zone Electrophoresis (CZE). Nevertheless, when it is necessary to impose several pH values it could be used the same or different buffers. In the first case it could happens to attempt to impose pH values in regions where buffer capacity of the system is low while in the second case the different nature of ions in buffers could have an effect over the mobility of the different species in study. When physico-chemical parameters are obtained by CZE measurements to impose pH values with a good buffer capacity could be crucial but until our knowledge reaches it is not frequent the use of wide pH range buffers, as Britton-Robinson buffer (1, 2). This work deals with electroosmotic mobility of aqueous solutions of Britton-Robinson buffer as a function of pH.
Determination of pKa Values of Diclofenac and Ibuprofen in Aqueous Solutions by Capillary Zone Electrophoresis
Authors: Vicenteno-Vera Alicia G. , Campos-Hernandez Tania , Ramirez-Silva Maria T. , Galano Annia , Rojas-Hernandez Alberto
Published: December 2010

The analysis of drugs as emergent contaminants in waters and wastewaters is growing in the entire world (1) but in Mexico there are only few studies in this field (2). Capillary Zone Electrophoresis (CZE) is a very useful technique to develop chemical analysis in complex mixtures, based in charge and size of species. Although the knowledge of pKa values of the anlaytes in the specific conditions of separation is decisive to optimize the quantification method not always this information is available with accuracy and precision, and is common the citation of the pKa values reported in The Merck Index, that not always cite updated references in this matter. In this work we report the pKa determination of diclofenac and ibuprofen in buffer solutions that will be used to develop CZE analytical methods to determine the degree of pollution with drugs of some Mexican waters and wastewaters.
Leukemia inhibitory factor regulates trafficking of T-type Ca2+ channels
Authors: Dey Deblina , Shepherd Andrew , Pachuau Judith , Martin-Caraballo Miguel
Published: December 2010

Neuropoietic cytokines such as ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) stimulate the functional expression of T-type Ca2+ channels in developing sensory neurons. However, the molecular and cellular mechanisms involved in the cytokine-evoked membrane expression of T-type Ca2+ channels are not fully understood. In this study we investigated the role of LIF in promoting the trafficking of T-type Ca2+ channels in a heterologous expression system. Our results demonstrate that transfection of HEK-293 cells with the rat green fluorescent protein (GFP)-tagged T-type Ca2+ channel α1H-subunit resulted in the generation of transient Ca2+ currents. Overnight treatment of α1H-GFP-transfected cells with LIF caused a significant increase in the functional expression of T-type Ca2+ channels as indicated by changes in current density. LIF also evoked a significant increase in membrane fluorescence compared with untreated cells. Disruption of the Golgi apparatus with brefeldin A inhibited the stimulatory effect of LIF, indicating that protein trafficking regulates the functional expression of T-type Ca2+ channels. Trafficking of α1H-GFP was also disrupted by cotransfection of HEK-293 cells with the dominant-negative form of ADP-ribosylation factor (ARF)1 but not ARF6, suggesting that ARF1 regulates the LIF-evoked membrane trafficking of α1H-GFP subunits. Trafficking of T-type Ca2+ channels required transient activation of the JAK and ERK signaling pathways since stimulation of HEK-293 cells with LIF evoked a considerable increase in the phosphorylation of the downstream JAK targets STAT3 and ERK. Pretreatment of HEK-293 cells with the JAK inhibitor P6 or the ERK inhibitor U0126 blocked ERK phosphorylation. Both P6 and U0126 also inhibited the stimulatory effect of LIF on T-type Ca2+ channel expression. These findings demonstrate that cytokines like LIF promote the trafficking of T-type Ca2+ channels.
Metabolic amplification of insulin secretion by glucose is independent of β-cell microtubules
Authors: Mourad Nizar I. , Nenquin Myriam , Henquin Jean-Claude
Published: December 2010

Glucose-induced insulin secretion (IS) by β-cells is controlled by two pathways. The triggering pathway involves ATP-sensitive potassium (KATP) channel-dependent depolarization, Ca2+ influx, and rise in the cytosolic Ca2+ concentration ([Ca2+]c), which triggers exocytosis of insulin granules. The metabolic amplifying pathway augments IS without further increasing [Ca2+]c. After exclusion of the contribution of actin microfilaments, we here tested whether amplification implicates microtubule-dependent granule mobilization. Mouse islets were treated with nocodazole or taxol, which completely depolymerized and polymerized tubulin. They were then perifused to measure [Ca2+]c and IS. Metabolic amplification was studied during imposed steady elevation of [Ca2+]c by tolbutamide or KCl or by comparing [Ca2+]c and IS responses to glucose and tolbutamide. Nocodazole did not alter [Ca2+]c or IS changes induced by the three secretagogues, whereas taxol caused a small inhibition of IS that is partly ascribed to a decrease in [Ca2+]c. When [Ca2+]c was elevated and controlled by KCl or tolbutamide, the amplifying action of glucose was unaffected by microtubule disruption or stabilization. Both phases of IS were larger in response to glucose than tolbutamide, although triggering [Ca2+]c was lower. This difference, due to amplification, persisted in nocodazole- or taxol-treated islets, even when IS was augmented fourfold by microfilament disruption with cytochalasin B or latrunculin B. In conclusion, metabolic amplification rapidly augments first and second phases of IS independently of insulin granule translocation along microtubules. We therefore extend our previous proposal that it does not implicate the cytoskeleton but corresponds to acceleration of the priming process conferring release competence to insulin granules.
β4-Subunit increases Slo responsiveness to physiological Ca2+ concentrations and together with β1 reduces surface expression of Slo in hair cells
Authors: Bai Jun-Ping , Surguchev Alexei , Navaratnam Dhasakumar
Published: December 2010

Changing kinetics of large-conductance potassium (BK) channels in hair cells of nonmammalian vertebrates, including the chick, plays a critical role in electrical tuning, a mechanism used by these cells to discriminate between different frequencies of sound. BK currents are less abundant in low-frequency hair cells and show large openings in response to a rise in intracellular Ca2+ at a hair cell's operating voltage range (spanning −40 to −60 mV). Although the molecular underpinnings of its function in hair cells are poorly understood, it is established that BK channels consist of a pore-forming α-subunit (Slo) and a number of accessory subunits. Currents from the α (Slo)-subunit alone do not show dramatic increases in response to changes in Ca2+ concentrations at −50 mV. We have cloned the chick β4- and β1-subunits and show that these subunits are preferentially expressed in low-frequency hair cells, where they decrease Slo surface expression. The β4-subunit in particular is responsible for the BK channel's increased responsiveness to Ca2+ at a hair cell's operating voltage. In contrast, however, the increases in relaxation times induced by both β-subunits suggest additional mechanisms responsible for BK channel function in hair cells.
Hypoxia. 4. Hypoxia and ion channel function
Authors: Shimoda Larissa A. , Polak Jan
Published: December 2010

The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes.
Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury
Authors: Kannan Kolenkode B. , Colorado Iriana , Reino Diego , Palange David , Lu Qi , Qin Xiaofa , Abungu Billy , Watkins Anthony , Caputo Francis J. , Xu Da-Zhong , Semenza Gregg L. , Deitch Edwin A. , Feinman Rena
Published: December 2010

Gut injury and loss of normal intestinal barrier function are key elements in the paradigm of gut-origin systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome (MODS). As hypoxia-inducible factor (HIF-1) is a critical determinant of the physiological and pathophysiological response to hypoxia and ischemia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Using partially HIF-1α-deficient mice in an isolated superior mesenteric artery occlusion (SMAO) intestinal ischemia reperfusion (I/R) injury model (45 min SMAO followed by 3 h of reperfusion), we showed a direct relationship between HIF-1 activation and intestinal I/R injury. Specifically, partial HIF-1α deficiency attenuated SMAO-induced increases in intestinal permeability, lipid peroxidation, mucosal caspase-3 activity, and IL-1β mRNA levels. Furthermore, partial HIF-1α deficiency prevented the induction of ileal mucosal inducible nitric oxide synthase (iNOS) protein levels after SMAO and iNOS deficiency ameliorated SMAO-induced villus injury. Resistance to SMAO-induced gut injury was also associated with resistance to lung injury, as reflected by decreased levels of myeloperoxidase, IL-6 and IL-10 in the lungs of HIF-1α+/− mice. In contrast, a short duration of SMAO (15 min) followed by 3 h of reperfusion neither induced mucosal HIF-1α protein levels nor caused significant gut and lung injury in wild-type or HIF-1α+/− mice. This study indicates that intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. However, the duration and severity of the gut I/R insult dictate whether HIF-1 plays a gut-protective or deleterious role.
ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good
Authors: Xu Ping , Sriramula Srinivas , Lazartigues Eric
Published: December 2010

The last decade has seen the discovery of several new components of the renin-angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1–7)/Mas axis. Accordingly, the new system is now seen as a balance between a provasoconstrictor, profibrotic, progrowth axis (ACE/ANG-II/AT1receptor) and a provasodilatory, antifibrotic, antigrowth arm (ACE2/ANG-(1–7)/Mas receptor). Already, this simplistic vision is evolving and new components are branching out upstream [ANG-(1–12) and (pro)renin receptor] and downstream (angiotensin-IV and other angiotensin peptides) of the classical cascade. In this review, we will summarize the role of the ACE2/ANG-(1–7)/Mas receptor, focusing on the central nervous system with respect to cardiovascular diseases such as hypertension, chronic heart failure, and stroke, as well as neurological diseases. In addition, we will discuss the new pharmacological (antagonists, agonists, activators) and genomic (knockout and transgenic animals) tools that are currently available. Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor.
Regulation of hepatic cholesterol biosynthesis by berberine during hyperhomocysteinemia
Authors: Wu Nan , Sarna Lindsei K. , Siow Yaw L. , O Karmin
Published: December 2010

Hyperhomocysteinemia, an elevation of blood homocysteine levels, is a metabolic disorder associated with dysfunction of multiple organs. We previously demonstrated that hyperhomocysteinemia stimulated hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase leading to hepatic lipid accumulation and liver injury. The liver plays an important role in cholesterol biosynthesis and overall homeostasis. HMG-CoA reductase catalyzes the rate-limiting step in cholesterol biosynthesis. Hepatic HMG-CoA reductase is a major target for lowering cholesterol levels in patients with hypercholesterolemia. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on hepatic cholesterol biosynthesis in hyperhomocysteinemic rats and to identify the underlying mechanism. Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 4 wk. HMG-CoA reductase activity was markedly elevated in the liver of hyperhomocysteinemic rats, which was accompanied by hepatic lipid accumulation. Activation of HMG-CoA reductase was caused by an increase in its gene expression and a reduction in its phophorylation (an inactive form of the enzyme). Treatment of hyperhomocysteinemic rats with berberine for 5 days inhibited HMG-CoA reductase activity and reduced hepatic cholesterol content. Such an inhibitory effect was mediated by increased phosphorylation of HMG-CoA reductase. Berberine treatment also improved liver function. These results suggest that berberine regulates hepatic cholesterol biosynthesis via increased phosphorylation of HMG-CoA reductase. Berberine may be therapeutically useful for the management of cholesterol homeostasis.
Glycerol-induced fluid shifts attenuate the vestibulosympathetic reflex in humans
Authors: Dyckman Damian J. , Sauder Charity L. , Ray Chester A.
Published: December 2010

The glycerol dehydration test (GDT) has been used to test for the presence of Ménière's disease and elicits acute alterations in vestibular reflexes in both normal and pathological states. Activation of the vestibulosympathetic reflex (VSR) increases muscle sympathetic nerve activity (MSNA) and peripheral vascular resistance. We hypothesized that the GDT would attenuate the VSR through fluid shifts of the inner ear. Sixteen male subjects (26 ± 1 yr) were randomly assigned to be administered either glycerol mixed with cranberry juice (97 ± 3 ml glycerol + equal portion of cranberry juice; n = 9) or a placebo control [water + cranberry juice (100 ml each); n = 7]. Subjects in both groups performed head-down rotation (HDR), which engages the VSR, before and after administration of either the glycerol or placebo. MSNA (microneurography), arterial blood pressure, and leg blood flow (venous occlusion plethysmography) were measured during HDR. Before glycerol administration, HDR significantly increased MSNA burst frequency (Δ8 ± 1 bursts/min; P < 0.01) and total activity (Δ77 ± 18%; P < 0.01) and decreased calf vascular conductance (−Δ20 ± 3%; P < 0.01). However, HDR performed postadministration of glycerol resulted in an attenuated MSNA increase (Δ3 ± 1 bursts/min, Δ22 ± 3% total activity) and decrease in calf vascular conductance (−Δ7 ± 4%). HDR significantly increased MSNA burst frequency (Δ5 ± 1 and Δ5 ± 2 bursts/min) and total activity (Δ58 ± 13% and Δ52 ± 18%) in the placebo group before and after placebo, respectively ( P < 0.01). Likewise, decreases in calf vascular conductance during HDR before and after placebo were not different (−Δ13 ± 4% and −Δ14 ± 2%, respectively; P < 0.01). These results suggest that fluid shifts of the inner ear via glycerol dehydration attenuate the VSR. These data provide support that inner ear fluid dynamics can have a significant impact on blood pressure regulation via the VSR in humans.
ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate
Authors: David Valentin , Martin Aline , Hedge Anne-Marie , Drezner Marc K. , Rowe Peter S. N.
Published: December 2010

Increased acidic serine aspartate-rich MEPE-associated motif (ASARM) peptides cause mineralization defects in X-linked hypophosphatemic rickets mice (HYP) and “directly” inhibit renal phosphate uptake in vitro. However, ASARM peptides also bind to phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and are a physiological substrate for this bone-expressed, phosphate-regulating enzyme. We therefore tested the hypothesis that circulating ASARM peptides also “indirectly” contribute to a bone-renal PHEX-dependent hypophosphatemia in normal mice. Male mice ( n = 5; 12 wk) were fed for 8 wk with a normal phosphorus and vitamin D3diet (1% Pidiet) or a reduced phosphorus and vitamin D3diet (0.1% Pidiet). For the final 4 wk, transplantation of mini-osmotic pumps supplied a continuous infusion of either ASARM peptide (5 mg·day−1·kg−1) or vehicle. HYP, autosomal recessive hypophosphatemic rickets (ARHR), and normal mice (no pumps or ASARM infusion; 0.4% Pidiet) were used in a separate experiment designed to measure and compare circulating ASARM peptides in disease and health. ASARM treatment decreased serum phosphate concentration and renal phosphate cotransporter (NPT2A) mRNA with the 1% Pidiet. This was accompanied by a twofold increase in serum ASARM and 1,25-dihydroxy vitamin D3[1,25 (OH)2D3] levels without changes in parathyroid hormone. For both diets, ASARM-treated mice showed significant increases in serum fibroblast growth factor 23 (FGF23; +50%) and reduced serum osteocalcin (−30%) and osteopontin (−25%). Circulating ASARM peptides showed a significant inverse correlation with serum Piand a significant positive correlation with fractional excretion of phosphate. We conclude that constitutive overexpression of ASARM peptides plays a “component” PHEX-independent part in the HYP and ARHR hypophosphatemia. In contrast, with wild-type mice, ASARM peptides likely play a bone PHEX-dependent role in renal phosphate regulation and FGF23 expression. They may also coordinate FGF23 expression by competitively modulating PHEX/DMP1 interactions and thus bone-renal mineral regulation.
An anatomical and functional model of the human tracheobronchial tree
Authors: Florens M. , Sapoval B. , Filoche M.
Published: December 2010

The human tracheobronchial tree is a complex branched distribution system in charge of renewing the air inside the acini, which are the gas exchange units. We present here a systematic geometrical model of this system described as a self-similar assembly of rigid pipes. It includes the specific geometry of the upper bronchial tree and a self-similar intermediary tree with a systematic branching asymmetry. It ends by the terminal bronchioles whose generations range from 8 to 22. Unlike classical models, it does not rely on a simple scaling law. With a limited number of parameters, this model reproduces the morphometric data from various sources (Horsfield K, Dart G, Olson DE, Filley GF, Cumming G. J Appl Physiol 31: 207–217, 1971; Weibel ER. Morphometry of the Human Lung. New York: Academic Press, 1963) and the main characteristics of the ventilation. Studying various types of random variations of the airway sizes, we show that strong correlations are needed to reproduce the measured distributions. Moreover, the ventilation performances are observed to be robust against anatomical variability. The same methodology applied to the rat also permits building a geometrical model that reproduces the anatomical and ventilation characteristics of this animal. This simple model can be directly used as a common description of the entire tree in analytical or numerical studies such as the computation of air flow distribution or aerosol transport.
Modulation of synaptic transmission from primary afferents to spinal substantia gelatinosa neurons by group III mGluRs in GAD65-EGFP transgenic mice
Authors: Cui Lian , Kim Yoo Rim , Kim Hye Young , Lee Seok Chan , Shin Hee-Sup , Szabó Gábor , Erdélyi Ferenc , Kim Jun , Kim Sang Jeong
Published: December 2010

Group III metabotropic glutamate receptors (mGluRs) are involved in nociceptive transmission in the spinal cord. However, the cellular mechanism underlying the modulation of synaptic transmission from nociceptive primary afferents to dorsal horn neurons by group III mGluRs has yet to be explored. In this study, we used transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the glutamate decarboxylase (GAD) 65 promoter to identify specific subpopulations of GABAergic inhibitory interneurons. By GABA immunolabeling, we confirmed the majority of GAD65-EGFP-expressing neurons were GABAergic. Because GAD65-EGFP-expressing neurons have not been examined in detail before, we first investigated the physiological properties of GAD65-EGFP- and non-EGFP-expressing neurons in substantia gelatinosa (SG) of the spinal dorsal horn. Membrane properties, such as the resting membrane potential, membrane capacitance, action potential threshold, and action potential height, differed significantly between these two groups of neurons. Most EGFP-expressing neurons displayed a tonic firing pattern (73% of recorded neurons) and received monosynaptic Aδ and/or C primary afferent inputs (85% of recorded neurons). In contrast, we observed a delayed firing pattern in 53% of non-EGFP-expressing neurons. After identifying the physiological properties of EGFP-expressing neurons, we tested the effects of group III mGluRs on synaptic transmission pharmacologically. A group III mGluR agonist, L-AP4, attenuated Aδ fiber-evoked synaptic transmission but did not affect C fiber-evoked synaptic transmission to EGFP-expressing neurons. Similar primary afferent-specific inhibition by L-AP4 was also observed in non-EGFP-expressing neurons. Moreover, Aδ fiber-evoked synaptic transmission was suppressed by a selective mGluR7 agonist, AMN082. These results suggest that modulation of the synaptic transmission from primary afferents to SG neurons by group III mGluR agonist is specific to the type of nociceptive primary afferents but not to the type of target neurons.
Reversal of the late phase of spike frequency adaptation in cat spinal motoneurons during fictive locomotion
Authors: Brownstone Robert M. , Krawitz Sherry , Jordan Larry M.
Published: December 2010

In spinal motoneurons, late spike frequency adaptation (SFA) is defined as the slowing of the firing rate over tens of seconds and can be seen during sustained or intermittent current injection. Although the function of late SFA is not known, it may result in a decrease in force production over time, or muscle fatigue. Because locomotion can persist for long periods of time without fatigue, late SFA was studied using intracellular recordings from adult cat motoneurons during fictive locomotion. Of eight lumbar motoneurons studied, all showed late adaptation during control conditions, but none demonstrated late adaptation during locomotor activity. The most consistent properties that correlated with the presence or absence of late SFA were those related to availability of fast, inactivating sodium channels, particularly action potential rate of rise. Evidence of the reversal of late SFA during locomotion was present for several minutes following locomotor trials, consistent with the suggestion that SFA is modulated through slow metabotropic pathways. The abolition of late adaptation in spinal motoneurons during fictive locomotion is an example of a state-dependent change in the “intrinsic” properties of mammalian motoneurons. This change contributes to increased excitability of motoneurons during locomotion and results in robust firing during sustained locomotion.
Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex
Authors: Fricke K. , Seeber A. A. , Thirugnanasambandam N. , Paulus W. , Nitsche M. A. , Rothwell J. C.
Published: December 2010

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent “homeostatic-like” rule governing the response of the human motor cortex to plasticity probing protocols.
Endocannabinoids mediate synaptic plasticity at glutamatergic synapses on spiny neurons within a basal ganglia nucleus necessary for song learning
Authors: Thompson John A. , Perkel David J.
Published: December 2010

Activation of type 1 cannabinoid receptors (CB1R) in many central nervous system structures induces both short- and long-term changes in synaptic transmission. Within mammalian striatum, endocannabinoids (eCB) are one of several mechanisms that induce synaptic plasticity at glutamatergic terminals onto medium spiny neurons. Striatal synaptic plasticity may contribute a critical component of adaptive motor coordination and procedural learning. Songbirds are advantageous for studying the neural mechanisms of motor learning because they possess a neural pathway necessary for song learning and adult song plasticity that includes a striato-pallidal nucleus, area X (homologous to a portion of mammalian basal ganglia). Recent findings suggest that eCBs contribute to vocal development. For example, dense CB1R expression in song control nuclei peaks around the closure of the sensori-motor integration phase of song development. Also, systemic administration of a CB1R agonist during vocal development impairs song learning. Here we test whether activation of CB1R alters excitatory synaptic input on spiny neurons in area X of adult male zebra finches. Application of the CB1R agonist WIN55212–2 decreased excitatory postsynaptic current (EPSC) amplitude; that decrease was blocked by the CB1R antagonist AM251. Guided by eCB experiments in mammalian striatum, we tested and verified that at least two mechanisms indirectly activate CB1Rs through eCBs in area X. First, activation of group I metabotropic glutamate receptors with the agonist 3,5-dihydroxyphenylglycine (DHPG) induced a CB1R-mediated reduction in EPSC amplitude. Second, we observed that a 10 s postsynaptic depolarization induced a calcium-mediated, eCB-dependent decrease in synaptic strength that resisted rescue with late CB1R blockade. Together, these results show that eCB modulation occurs at inputs to area X spiny neurons and could influence motor learning and production.
Role of the vesicular transporter VGLUT3 in retrograde release of glutamate by cerebellar Purkinje cells
Authors: Crépel Françis , Galante Micaela , Habbas Samia , McLean Heather , Daniel Hervé
Published: December 2010

In the cerebellum, retrograde release of glutamate (Glu) by Purkinje cells (PCs) participates in the control of presynaptic neurotransmitter release responsible for the late component of depolarization-induced suppression of excitation (DSE), as well as for depolarization-induced potentiation of inhibition (DPI). It might also participate in the depolarization-induced slow current (DISC) in PCs, although this contribution was later challenged. We also know that both DPI and DISC are soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent processes, although the molecular nature of the vesicular transporter was not determined. In PCs, VGLUT3 is the only known vesicular glutamate transporter identified and is expressed during the same developmental frame as when DPI, DISC, and the Glu-dependent component of DSE are observed. We therefore tested the hypothesis that all these processes depend on the presence of VGLUT3 by comparing the Glu-dependent component of DSE, DPI, and DISC in nearly mature (2- to 3-wk-old) wild-type and VGLUT3 knockout mice. Our data demonstrate that, in nearly mature mice, the slow component of DSE occurs through vesicular release of Glu that involves VGLUT3. This Glu-dependent component of DSE is no longer present in fully mature mice. This study also establishes that, in nearly mature mice, DPI also depends on the presence of VGLUT3, whereas this is not the case for DISC. Finally, the unusually large basal paired-pulse facilitation observed in nearly mature VGLUT3−/− mice but not in adult ones suggests that some basal retrograde release of Glu occurs during development and contributes to basal concentrations of extracellular Glu.
The extent and strength of electrical coupling between inferior olivary neurons is heterogeneous
Authors: Hoge Gregory J. , Davidson Kimberly G. V. , Yasumura Thomas , Castillo Pablo E. , Rash John E. , Pereda Alberto E.
Published: December 2010

Gap junctions constitute the only form of synaptic communication between neurons in the inferior olive (IO), which gives rise to the climbing fibers innervating the cerebellar cortex. Although its exact functional role remains undetermined, electrical coupling was shown to be necessary for the transient formation of functional compartments of IO neurons and to underlie the precise timing of climbing fibers required for cerebellar learning. So far, most functional considerations assume the existence of a network of permanently and homogeneously coupled IO neurons. Contrasting this notion, our results indicate that coupling within the IO is highly variable. By combining tracer-coupling analysis and paired electrophysiological recordings, we found that individual IO neurons could be coupled to a highly variable number of neighboring neurons. Furthermore, a given neuron could be coupled at remarkably different strengths with each of its partners. Freeze-fracture analysis of IO glomeruli revealed the close proximity of glutamatergic postsynaptic densities to connexin 36-containing gap junctions, at distances comparable to separations between chemical transmitting domains and gap junctions in goldfish mixed contacts, where electrical coupling was shown to be modulated by the activity of glutamatergic synapses. On the basis of structural and molecular similarities with goldfish mixed synapses, we speculate that, rather than being hardwired, variations in coupling could result from glomerulus-specific long-term modulation of gap junctions. This striking heterogeneity of coupling might act to finely influence the synchronization of IO neurons, adding an unexpected degree of complexity to olivary networks.
Somatosensory context alters auditory responses in the cochlear nucleus
Authors: Kanold Patrick O. , Davis Kevin A. , Young Eric D.
Published: December 2010

The cochlear nucleus, the first central auditory structure, performs initial stimulus processing and segregation of information into parallel ascending pathways. It also receives nonauditory inputs. Here we show in vivo that responses of dorsal cochlear nucleus (DCN) principal neurons to sounds can change significantly depending on the presence or absence of inputs from the somatosensory dorsal column nucleus occurring before the onset of auditory stimuli. The effects range from short-term suppression of spikes lasting a few milliseconds at the onset of the stimulus to long-term increases or decreases in spike rate that last throughout the duration of an acoustic stimulus (up to several hundred milliseconds). The long-term effect requires only a single electrical stimulus pulse to initiate and seems to be similar to persistent activity reported in other parts of the brain. Among the DCN inhibitory interneurons, only the cartwheel cells show a long-term rate decrease that could account for the rate increases (but not the decreases) of DCN principal cells. Thus even at the earliest stages of auditory processing, the represented information is dependent on nonauditory context, in this case somatosensory events.
Alterations of action potentials and the localization of Nav1.6 sodium channels in spared axons after hemisection injury of the spinal cord in adult rats
Authors: Hunanyan Arsen S. , Alessi Valentina , Patel Samik , Pearse Damien D. , Matthews Gary , Arvanian Victor L.
Published: December 2010

Previously, we reported a pronounced reduction in transmission through surviving axons contralateral to chronic hemisection (HX) of adult rat spinal cord. To examine the cellular and molecular mechanisms responsible for this diminished transmission, we recorded intracellularly from lumbar lateral white matter axons in deeply anesthetized adult rats in vivo and measured the propagation of action potentials (APs) through rubrospinal/reticulospinal tract (RST/RtST) axons contralateral to chronic HX at T10. We found decreased excitability in these axons, manifested by an increased rheobase to trigger APs and longer latency for AP propagation passing the injury level, without significant differences in axonal resting membrane potential and input resistance. These electrophysiological changes were associated with altered spatial localization of Nav1.6 sodium channels along axons: a subset of axons contralateral to the injury exhibited a diffuse localization (>10 μm spread) of Nav1.6 channels, a pattern characteristic of demyelinated axons (Craner MJ, Newcombe J, Black JA, Hartle C, Cuzner ML, Waxman SG. Proc Natl Acad Sci USA 101: 8168–8173, 2004b). This result was substantiated by ultrastructural changes seen with electron microscopy, in which an increased number of large-caliber, demyelinated RST axons were found contralateral to the chronic HX. Therefore, an increased rheobase, pathological changes in the distribution of Nav1.6 sodium channels, and the demyelination of contralateral RST axons are likely responsible for their decreased conduction chronically after HX and thus may provide novel targets for strategies to improve function following incomplete spinal cord injury.
The Role of Polyphenols, -Carotene, and Lycopene in the Antioxidative Action of the Extracts of Dried, Edible Mushrooms
Authors: Robaszkiewicz A. , Bartosz G. , Ławrynowicz M. , Soszyński M.
Published: December 2010

One of the nutritional benefits of mushrooms is the presence of bioactive secondary metabolites which have been reported to exert various beneficial effectsin vivo. Therefore, we selected thirteen frequently consumed species of Polish mushrooms and determined the concentration of polyphenols, flavonoids, -carotene, and lycopene in aqueous and methanolic extracts of dried fruiting bodies as well as their reducing power and ability to scavenge ABTS cation radical. We found that the concentration of antioxidants is different in different species and in various parts of the fruiting body of mushrooms. We observed a strong correlation () between the concentration of total phenolics and reducing power/scavenging effects in both aqueous and methanolic extracts, while this correlation was moderate for flavonoids. Beta-carotene did not contribute discernibly to the antioxidative properties of the extracts, while lycopene had a significant contribution to the scavenging activity of methanolic mushroom extracts.
Mirror Prescription Regression: A Differential Interferometric Technique
Authors: Robinson Brian M. , Reardon Patrick J. , Geary Joseph M.
Published: December 2010

We present a remote, differential method for measuring the prescription of aspheric mirrors using null interferometry in the center-of-curvature configuration. The method requires no equipment beyond that used in a basic interferometery setup (i.e., there are no shearing elements or absolute distance meters). We chose this configuration because of its widespread use. However, the method is generalizable to other configurations with an adjustment of the governing equation. The method involves taking a series of interferograms before and after small, known misalignments are applied to the mirror in the interferometry setup and calculating the prescription (e.g., radius of curvature and conic constant) of the mirror, based on these differential measurements, using a nonlinear regression. We apply this method successfully to the testing of a Space Optics Research Lab off-axis parabola with a known focal length of 152.4 mm, a diameter of 76.2 mm, and an off-axis angle of 12°.
Theoretical Modeling Techniques and Their Impact on Tumor Immunology
Authors: Woelke Anna Lena , Murgueitio Manuela S. , Preissner Robert
Published: December 2010

Currently, cancer is one of the leading causes of death in industrial nations. While conventional cancer treatment usually results in the patient suffering from severe side effects, immunotherapy is a promising alternative. Nevertheless, some questions remain unanswered with regard to using immunotherapy to treat cancer hindering it from being widely established. To help rectify this deficit in knowledge, experimental data, accumulated from a huge number of different studies, can be integrated into theoretical models of the tumor‐immune system interaction. Many complex mechanisms in immunology and oncology cannot be measured in experiments, but can be analyzed by mathematical simulations. Using theoretical modeling techniques, general principles of tumor‐immune system interactions can be explored and clinical treatment schedules optimized to lower both tumor burden and side effects. In this paper, we aim to explain the main mathematical and computational modeling techniques used in tumor immunology to experimental researchers and clinicians. In addition, we review relevant published work and provide an overview of its impact to the field.
A Decimal Floating-Point Accurate Scalar Product Unit with a Parallel Fixed-Point Multiplier on a Virtex-5 FPGA
Authors: Baesler Malte , Voigt Sven-Ole , Teufel Thomas
Published: December 2010

Decimal Floating Point operations are important for applications that cannot tolerate errors from conversions between binary and decimal formats, for instance, commercial, financial, and insurance applications. In this paper, we present a parallel decimal fixed-point multiplier designed to exploit the features of Virtex-5 FPGAs. Our multiplier is based on BCD recoding schemes, fast partial product generation, and a BCD-4221 carry save adder reduction tree. Pipeline stages can be added to target low latency. Furthermore, we extend the multiplier with an accurate scalar product unit for IEEE 754-2008decimal64data format in order to provide an important operation with least possible rounding error. Compared to a previously published work, in this paper, we improve the architecture of the accurate scalar product unit and migrate to Virtex-5 FPGAs. This decreases the fixed-point multiplier's latency by a factor of two and the accurate scalar product unit's latency even by a factor of five.
Partial Reconfigurable FIR Filtering System Using Distributed Arithmetic
Authors: Llamocca Daniel , Pattichis Marios , Vera G. Alonzo
Published: December 2010

Dynamic partial reconfiguration (DPR) allows us to adapt hardware resources to meet time-varying requirements in power, resources, or performance. In this paper, we present two new DPR systems that allow for efficient implementations of 1D FIR filters on modern FPGA devices. To minimize the required partial reconfiguration region (PRR), both implementations are based on distributed arithmetic. For a smaller required PRR, the first system only allows changes to the filter coefficient values while keeping the rest of the architecture fixed. The second DPR system allows full FIR-filter reconfiguration while requiring a larger PR region. We investigate the proposed system performance in terms of the dynamic reconfiguration rates. At low reconfiguration rates, the DPR systems can maintain much higher throughputs. We also present an example that demonstrates that the system can maintain a throughput of 10 Mega-samples per second while fully reconfiguring about seventy times per second.
Measurement and Optimization of Metal‐Nanoparticle‐Induced Luminescence Enhancement Factors in a Crossed‐Optical Fiber Configuration
Authors: Rigo Maria Veronica , Geissinger Peter
Published: December 2010

A crossed‐optical‐fiber configuration comprised of silver nanoparticles covalently attached to the core of an optical fiber and labeled with luminescent ruthenium molecules is reported. A second optical fiber was placed at right angle of the fiber containing the nanoparticle/ruthenium, to form a fiber‐fiber junction, and it was used to detect the luminescence from the ruthenium molecules bound to the first fiber. To employ the effect of metal‐enhanced luminescence, the ruthenium complex was kept at an appropriate distance from the nanoparticles by polyelectrolyte spacer layers. For silver nanospheres, nanotriangles and nanorods and for spacer‐layer thicknesses from 2–14 nm luminescence‐enhancement factors were determined. A 27‐fold luminescence enhancement was found when the ruthenium complex was placed 4 nm from silver nanotriangles. Finally, a calibration curve for the oxygen dependence of luminescence intensities and lifetimes of ruthenium complex is presented suggesting that the oxygen sensing capabilities of the nanoengineered‐ruthenium complex are maintained.
The Effect of Race, Sex, and Insurance Status on Time-to-Listing Decisions for Liver Transplantation
Authors: Bryce Cindy L. , Chang Chung-Chou Ho , Angus Derek C. , Arnold Robert M. , Farrell Maxwell , Roberts Mark S.
Published: December 2010

Fair allocation of organs to candidates listed for transplantation is fundamental to organ-donation policies. Processes leading to listing decisions are neither regulated nor understood. We explored whether patient characteristics affected timeliness of listing using population-based data on 144,507 adults hospitalized with liver-related disease in Pennsylvania. We linked hospitalizations to other secondary data and found 3,071 listed for transplants, 1,537 received transplants, and 57,020 died. Among candidates, 61% (n=1,879) and 85.5% (n=2,626) were listed within 1 and 3 years of diagnosis; 26.7% (n=1,130) and 95% (n=1,468) of recipients were transplanted within 1 and 3 years of listing. Using competing-risks models, we found few overall differences by sex, but both black patients and those insured by Medicare and Medicaid (combined) waited longer before being listed. Patients with combined Medicare and Medicaid insurance, as well as those with Medicaid alone, were also more likely to die without ever being listed. Once listed, the time to transplant was slightly longer for women, but it did not differ by race/ethnicity or insurance. The early time period from diagnosis to listing for liver transplantation reveals unwanted variation related to demographics that jeopardizes overall fairness of organ allocation and needs to be further explored.