bluuebunny/crossref_metadata_2025 huggingface dataset:
pH-Dependence, Isotope Effect and Products of Flavin-sensitized Photodecarboxylation and Photodehydrogenation
Authors: Haas W. , Hemmerich P.
Published: February 2015

The pH-dependence of flavin-sensitized photodehydrogenation and oxidative photodecarboxylation shows a change of reaction rate with an apparent pK of about 5.5. This “photo-pK” cannot be assigned to any known ground state or excited flavin or substrate species, nor is it related to the kind of bond being broken (C-H or C-COO-). Therefore, it is attributed to the pK of a covalent flavin-substrate intermediate. Carboxylates R-COO~ react by decarboxylation, the nature of R determining only the rate of reaction. The acids R -COOH themselves are unreactive, unless functionally substituted at the α-carbon. Hence X-CH(R)-COOH behaves as does X-CH2-R, for X=OH, OR, NH2, NR2. R3N+- CH(R) -COO- is unreactive, while H3N+-CH(R)-COO-is slowly dehydrogenated through its neutral tautomer which is favored in the flavin-substrate exciplex.
Spectrophotometric Studies on Lysine Monooxygenase, a Flavoprotein
Authors: Yamamoto Shozo , Hirata Fusao , Yamauchi Takashi , Nozaki Mitsuhiro , Hyaishi Osamu , Hiromi Keitaro
Published: February 2015

The spectral changes of the enzyme-bound FAD were investigated in the anaerobic and aerobic reactions of lysine monooxygenase, a flavoprotein. Under anaerobic conditions, the enzyme FAD was fully reduced with lysine via a transient intermediate having a broad absorption band in the long wavelength region. This anaerobic species was presumably involved in the dehydrogenation of lysine leading to the formation of an α-keto acid. During the steady state of the aerobic reaction, a separate spectral species with a long wavelength absorption was observed. Both lysine and oxygen were required for its appearance. Kinetic evidence supports the intermediacy of this species in the oxygenation of lysine to an acid amide.
Recent Advances in the Chemistry of Covalently Bound Flavin Coenzymes
Authors: Kenney W. C. , Walker W. H. , Kearney E. B. , Seng R. , Singer T. P. , Cronin J. R. , Hendriks R.
Published: February 2015

Following elucidation of the structures of the flavin components of succinate dehydrogenase (SD) as N (3) -histidyl-8α-FAD and of monoamine oxidase (MAO) as cysteinyl-8α-FAD and determination of the peptide sequences around the flavin sites of these enzymes, attention has been focused on the covalently bound FAD of Chromatium cytochrome c-552. As documented in preliminary communications, the FAD moiety of this enzyme is also substituted at the 8α-position, as judged from ESR hyderfine structure of the free radical cation and the characteristic hypsochromic shift of the second absorption band of the neutral flavoquinone in purified preparations of the flavin. Definite proof has come from the liberation of 8-carbxyriboflavin on performic acid treatment of the enzyme. In regard to ESR and optical spectra and the tendency of the purified flavin (liberated by proteolysis) to undergo autooxidation with a further hypsochromic shift of the second absorption band and increased fluorescence, the flavin resembles the MAO flavin. The fact that fluorescence is >90% quenched at all pH values even at the FMN level and doees not vary with pH between 3.2 and 8 also suggests a thioether linkage as in cysteinyl riboflavin. In many respects, however, the Chromatium flavin differs from cysteinyl riboflavin. Highly purified preparations from tryptic-chymotryptic digests give a positive chloroplatinic test. Electrophoresis clearly shows the presence of carboxyl and amino groups but the peptide gives no characteristic ninhydrin reaction and amino acid analysis of performic acid oxidized samples yields cysteic acid and threonine in amounts less than equimolar to the flavin. The amino acid environment around the flavin may account for these results although a linkage other than a thioether remains a possibility.
Electrochemical Evidence of Specific Action of Indole Acetic Acid on Membranes in Mnium Leaves
Authors: Lüttge U. , Higinbotham N. , Pallaghy C. K.
Published: February 2015

The effect of 5·10-7 and 5·10-6Μ IAA on K+, Cl- and SO4
-- uptake by young and old Mnium gametophytes from 0.2 mM or 10 mM salt solutions has been investigated. These IAA concentrations selectively enhance K+ uptake from 0.2 mM KCl or K2SO4 in old gametophytes. IAA up to 10-5 M does not affect the membrane potential (P.D.). At 0.2 mM KCl the observed P.D. of -200 to - 220 mV is more negative than the calculated Nernst potential of +84 to +107 mV for Cl- and -136 to -157 mV for K+. These results are discussed in relation to a recent model of IAA regulation of cell elongation involving a proton extrusion pump.
Transcription and Degradation of Heavy (pre 28 S) RNA and 4 S RNA during Embryogenesis in Limnaea
Authors: Brahmachary R. L. , Mallik B. , Tapaswi P. K.
Published: February 2015

Short (15 min) and long (1 hour or more) pulses with P32 have been compared at different developmental stages of Limnaea. In short pulses, as opposed to long-pulses, the relative percentage of 4S RNA is at a more or less constant level at all stages of development. Heavy RNA, i. e. heavier than 28S, is traceable with both short and long pulses in the uncleaved and early morula stages. Transcription of heavy RNA seems to decrease significantly immediately before mitosis. No other RNA fraction shows such a marked rhythm associated with mitosis.
Production of Free Radicals from Adamantane by High Energy Irradiation
Authors: Filby W. G. , Günther K.
Published: February 2015

The nature and properties of radicals produced by the action of electron and γ-radiation on adamantane have been investigated. Radicals produced by irradiation at 77°K are stable to around room temperature, while irradiation at the latter temperature yields well resolved spectra of species stable to about 130°C. The significance of the latter, assigned as the 1-adamantyl radical, in the formation of trapped radicals is discussed.
Zur Strukturchemie ternärer Telluride der Alkali- und Erdalkalimetalle mit den Elementen der 3. Hauptgruppe / On the Structural Chemistry of Ternary Tellurides of Alkali- and Earthalkalimetalls with the Group- (III) -Elements
Authors: Franke Erich R. , Schäfer Herbert
Published: February 2015

The new compounds SrAl2Te4, SrGa2Te4, SrIn2Te4, BaAl2Te4, BaGa2Te4, BaIn2Te4, Ba7Al6Te16, NaInTe2 and KInTe2 have been prepared by melting together stoichiometric amounts of the elements. All compounds crystallize tetragonal in variants of the TlSe- (B 13) -structure.

SrAl2Te4: α = 8.25 Å, c = 6.72 Å ( ± 0.02 Å)

SrGa2Te4: α = 8.21 Å, c = 6.75 Å ( ± 0.02 Å)

SrIn2Te4: α = 8.27 Å, c = 7.22 Å ( ± 0.02 Å)

BaAl2Te4: α = 8.50 Å, c = 6.72 Å ( ± 0.02 Å)

BaGa2Te4: α = 8.42 Å, c = 6.78 Å ( ± 0.02 Å)

BaIn2Te4: α = 8.44 Å, c = 7.20 Å ( ± 0.02 Å)

NaInTe2: α = 8.33 Å, c = 7.27 Å ( ± 0.02 A)

KInTe2: α = 8.52 Å, c = 7.39 Å ( ± 0.02 A)

Ba7Al6Te16: α = 34.24 Å, c = 6.70 Å ( ± 0.02 Å)

(=4 × 8.57 Å),
Complexes of Bismethyl-imido-triphosphoric-acid-pentakis-dimethyl-amide (TRIPA), a New Tridentate Ligand
Authors: De Bolster M. W. G. , Den Heijer J. , Groeneveld W. L.
Published: February 2015

A number of new complexes containing TRIPA, chemical formula [ (CH3) 2N]2 P (O) N (CH3)P (O) [N (CH3) 2] N (CH3) P (O) [N (CH3) 2] 2, is reported The compounds have the general formula M (TRIPA) n (anion) p, where M = Mg, Ca, Mn, Fe, Co, Ni, Cu, Zn, Cd (p = 2) and Al, Fe (p = 3), n=1,2 and anion stands for BF4⁻, [B (C6H5)4]⁻, NO3⁻ and Cl⁻. They are characterized and identified by chemical analysis and physical measurements.

It is shown that the bis-compounds contain octahedrally solvated metal ions, the ligand acting as a tridentate phosphoryl donor. Electron paramagnetic resonance measurements show some distortion of the octahedrons. The mono-compounds with the nitrate anion probably possess a fivecoordinated structure whereas the chloride complexes are probably dimeric.

The occurrence of more than one geometric isomer for the group [M (TRIPA) 2] P* is discussed. It is concluded that the s-facial and u-facial isomers may occur; a possible connection with the size of the metal ions is indicated. The mer form is rejected because of steric requirements.
Liganden- und Isotopenaustausch im System: Serumproteine — Zink — Polyaminopolycarbonsäuren / Ligand and Isotope Exchange in the System: Serum Proteins — Zinc — Polyaminopolycarbonic Acids
Authors: Segewitz G.
Published: February 2015

In vitro-studies show that the Ca-chelates of EDTA and DTPA are equally effective in removing Zn from the proteins and that the Zn-protein pool is composed of several fractions with different stabilities. Only a small fraction of the protein-bound Zn can be labelled by 65Zn in vitro and, as to the mobilization of 65Zn, Ca-DTPA was found to be 20 times more effective than equimolar Ca-EDTA. The isotope exchange between Zn-DTPA and protein-bound 65Zn is an extremely fast reaction whereas in the case of Zn-EDTA a sluggish exchange takes place. The analysis of the results led to conclusion that the ligand and isotope exchange reactions in the case of EDTA proceed via the free Zn2+-ion; with the high-dentate DTPA, however, the formation of ternary and mixed complexes plays an important role. The implications of the findings as related to the toxicity of the Ca-chelates are discussed.
Mesosomen-ähnliche Strukturen im Mycobionten von Lichina pygmaea / Mesosome-like Structures in the Mycobiont of Lichina pygmaea
Authors: Peveling Elisabeth
Published: February 2015

In the mycobiont of the lichen Lichina pygmaea mesosome-like structures are described which mainly occur in the fungi cells close to the algal layer. These structures consist of numerous irregularly arranged tubuli which are most distinct after fixation with glutaraldehyde at pH 7.0. Using different fixatives at varying pH they tend to visiculate.

In the cytoplasm neighboured to the mesosome-like structures zones of very high contrast appear. They consist of a homogenous and a granular substance. Staining the samples with Best Carmin or treating them with amylase it could be shown that at least the granular component of the darkly stained area represents glycogen.

The function of the mesosome-like structures in glycogen synthesis is discussed.
Über die Reaktion von Thallium(I)-Sulfid mit den Disulfiden von Vanadium, Niob, Tantal und Molybdän / On the Reaction of Thallium(I) Sulfide with the Disulfides of Vanadium, Niobium, Tantalium and Molybdenum
Authors: Schmidt V. , Rüdorff W.
Published: February 2015

Tl2S reacts with VS22 to Τl3VS4 and VS. With NbS2 and TaS2 the analogous thiometallates(V) are obtained. The metallic thallium hereby produced gives with NbS2 and probably with TaS2 an intercalation-phase TlXNb(Ta)S2. There is no reaction between Tl2S and MoS2 up to 500°C. Thallium(I)-thiometallates(IV), Tl2MeS3, described in literature do not exist.
Metalltrifluorphosphin-Komplexe. XXXIX / Metaltrifluorophosphine Complexes. XXXIX
Authors: Kruck Thomas , Knoll Lothar
Published: February 2015

The UV-irradiation of solutions of allyl jodide and allyl bromide, respectively, and Fe (PF3)5 yields π-allyl-tris(trifluorophosphine)-iron halides, π-C3H5Fe(PF3)3X (X = J, Br). Otherwise, the analogous reaction with allyl chloride yields the diene complexe π-hexa-1.3-diene-tris(trifluorophosphine)-iron (O), π-C6H10Fe(PF3)3. The compounds are characterised by their IR-,1H-NMR-and mass spectra.
Über Substituenten-Einflüsse auf die Bindungsverhältnisse der Metall-Komplexe des Cyclobutadiens / The Influence of Substituents on Bonding Properties in Metal Complexes of Cyclobutadiene
Authors: Brune Hans Albert , Horlbeck Gernot , Röttele Herbert , Tanger Udo
Published: February 2015

The syntheses of some p- substituted phenylcyclobutadieneirontricarbonyls are reported. Carbonyl stretching frequencies, 13C-H- and H-Η-coupling constants are discussed with respect to bonding properties. There is apparently no conjugative interaction between the π-electron systems of cyclobutadiene and the phenyl ring.
Kinetics of Thermal Decomposition of Copper Soaps
Authors: Mehrotra K. N. , Mehta V. P. , Nagar T. N.
Published: February 2015

The thermal decomposition of copper soaps has been studied both as a function of temperature and time. The whole range of the isothermal decomposition of copper soaps has been most adequately expressed by the Prout-Tompkins equation using two different rate constants.
Schichteinlagerungsverbindungen des Komplex-Carbids Ta.2S2C / Layer Intercalation Compounds of the Complex Carbide Ta2S2C
Authors: Schöllhorn Robert , Weiss Armin
Published: February 2015

A new series of nonstoichiometric intercalation compounds has been found with the complex carbide Ta2S2C as host lattice. Typical compositions of the new compounds arc Ta2S2C · nY with nY = 0,57 N2H4, 0,26 H3CHNNHCH3, 0,78 n-C8H17NH2, 0,52 C6H11NH2, 0,23 piperidine, 0,26 pyrrolidine, 0,26 dimethylaniline, 0,4, imidazole, 0,39 N-methylimidazole, 0,43 pyrazole, 0,38 pyridine, 0,32 4-methylpyridine, 0,37 2-aminopyridine, 0,40 3-aminopyridine, 0.36 4-aminopyridine, 1,45 HCONH2, 0,41 HCONHCH3, 0,25 (HOCH2)3PO and 0,28(HOCH2)3PO, 0,29 HCONHC2H5,0,26HCON(CH3)2,0,21HCON(C2H5)2,0,70H2NCONH2, 0,19 (H3C)2NCON(CH3)2, 0,46 pyridine-N-oxide, 0,72 2-methylpyridine-N-oxide, 0,39 4-methylpyridine-N-oxide, 0,91 (CH3)2SO, 0,64 (CH3)3PO, 0.23 hexamethylphosphortriamide.

These intercalation compounds resemble those obtained with transition metal dichalcogenides, e.g. TaS2,the basal spacings being about 2,6-2,8 Å higher than in the latter ones. The observed increment of 2,7 Å confirms the proposed structuref or the host lattice with S Ta C Ta S-sandwich layers.
Isomerisierung und Hydrolyse biozider cyclischer Sulfitester-Endosulfan und 10.10-Dihydro-Endosulfan / Isomerisation and Hydrolysis of Biocidal Cyclic Sulfurous Acid Esters-Endosulfan and 10,10-Dihydro-endosulfan
Authors: Schlüter Horst , Ballschmiter Karlheinz
Published: February 2015

Two isomeric 10,10-dihydro-endosulfans are isolated, and their configurations are determined by means of infrared and nuclear magnetic resonance spectra.

The isomerisation of the sulfurous ester ring of 10,10-dihydro-endosulfan yields a 67/33 ratio for the α/β isomers, while the endosulfan gives a 45/55 ratio.

Both the 10,10-dihydro-endosulfans prove to be less easily hydrolised than endosulfan.
Untersuchungen an biologisch wirksamen Ligandensystemen, IX
Authors: Fritz Heinz P. , Stetten Otto von
Published: February 2015

The preparation of a series of metal complexes of N-formyl-N-hydroxyl-glycine (Hadacidin) is reported as well as their IR-. UV- and 1H-XMR spectra. The complex formation is characterized by means of the complex formation constants.
Schwingungsspektren von Kristallen mit Olivin-Struktur / Vibrational Spectra of Crystals with Olivine Structure
Authors: Hohler V. , Funck E.
Published: February 2015

Polarized Raman (Ra) and IR reflection spectra from single crystals of olivine, forsterite, monticellite and tephroite have been measured and assigned. Comparing the different spectra including those of other substances of the same structure, it could be shown, that the four stretching vibrations of the SiO4 tetrahedra are the only vibrations which may be interpreted as independent group vibrations. Cation typical vibrations are more or less strongly coupled to the deformation vibrations of the SiO4 tetrahedra.
Über eine neue kristalline Kieselsäure der Zusammensetzung H2Si14O29 · 5 H2O mit Schichtstruktur und Befähigung zur Bildung von Intercalationsverbindungen / A Crystalline Silicic Acid H2Si14O29 · 5 H2O with Layer Structure and Capability of Formation of Intercalation Compounds
Authors: Lagaly Gerhard , Beneke Klaus , Weiss Armin
Published: February 2015

A crystalline silicic acid H2Si14O29 · 5H2O has been prepared by topochemical reaction of sodium silicate Na2Si14O29·12H2O with acids. The compound has a layer structure with silicate sheets of about 11.2 Å thickness. The layer structure is clearly established by two dimensional reactions, mainly the formation of intercalation compounds with X-oxides (dimethylsulfoxide, pyridine-N-oxides etc.), acid amides, urea and its derivatives and bases such as hydrazine and pyridine. Typical exemples are 2 (CH3)2SO · H2Si14O29, 2C5H5NO · H2Si14O29, 2, 7 HCONHCH3 · H2Si14O29; 2, 3 HCON (CH3)2 · H2Si14O29; 1, 6 HCONHC2H5 · H2Si14O29; 1, 6 HCON (C2H5)2 · H2Si14O29.
Photo-induzierte Substitution und Isomerisierung in oktaedrischen cis-Dicarben-Komplexen / Photo-induced Substitution and Isomerisation in Octahedral cis-Dicarbene Complexes
Authors: Öfele Karl , Herberhold Max
Published: February 2015

Irradiation of cis-M. (CO) 4L′2 (M = Cr, Mo, W; L′ = 1,3-dimethyl-4-imidazoline-2-ylidene) in solution leads to photoisomerisation to the corresponding trans-M (CO)4L′2 complexes which are reconverted thermally to the thermodynamically more stable cis-isomers. In the presence of pyridine, the photoreaction of cis-Mo (CO) 4L′2 results in the formation of both fac-Mo (CO)3 (py) L′2 and trans-Mo (CO)4L′2.
Monohydrazones of 2-Acetyl-1,3-indandiones: A New Group of Reagents for the Carbonyl Group
Authors: Bachlaus M. K. , Menaria K. L.
Published: February 2015

Monohydrazones of N-(2-acetyl-1,3-indandione) quaternary iodides have been synthesised and used as reagents for carbonyl group. Aldehydes, ketones, keto-acids and cyclic ketones react with these compounds producing a yellow colour. Carbonyl compounds can be identified by the absorption spectrum of their derivatives with these reagents. The IR studies of these reagents have also been carried out.
Metallkomplexe mit Tetrapyroll-Liganden, VII / Metal Complexes of Tetrapyrrole Ligands, VII
Authors: Buchler Johann W. , Schneehage H. Henning
Published: February 2015

Mononuclear octaethylporphin complexes of the type (OÄP)FeX [X = OC6H5, Cl, OCH3, OAc (7-10)*] or (OÄP)ScY [Y = OAc, (acac) (12, 13)] yield μ-oxo complexes (OÄP)MOM(OÄP) [schematic structur; M = Fe (6) or M = Sc (11)] upon hydrolysis and condensation in the presence of alkali or during chromatography on alumina. The compounds 6, 7, 9, 10 and 11 are characterized by electronic, IR, NMR and mass spectra. The stability of the M-O-M moiety in A towards hydrolysis increases in the order Al<Sc<Fe for M. (OÄP)FeOFe(OÄP) is solvolyzed by excess phenol, methanol or acetic acid to yield 7, 9 or 10, respectively, whereas water remains without action.
Synthesis of Phthaleins with a Chiral Carbon Atom
Authors: Gopal R. , Gupta P. C. , Aggarwala V. P. , Garg S. P.
Published: February 2015

Phthaleins (PE) with a chiral carbon atom - phenyl phenol PE, phenyl resorcinol PE, phenyl catechol PE, phenyl quinol PE, phenyl pyrogallol PE, phenyl phloroglucinol PE and phenyl orcinol PE have been obtained by condensing 2-benzoyl benzoic acid with appropriate phenols. The structure of phenyl resorcinol phthalein, which was found to exist in two isomeric forms, based on chemical reactions and spectral data has been discussed. The Amax values for most of the dyes were found higher than their analogous phthaleins.
Untersuchungen an quartären Pyridinium-Salzen, II / Investigation of Quaternary Pyridinium-Salts, II
Authors: Gündel Wolf-Hellmut
Published: February 2015

Four molecules of quaternary salts of nicotinamide (1 and 4) form a chloroform-soluble condensation product of structure 2 and 5 by action of base under elimination of HX.
Zur Darstellung von Jod-(tristrinuormethansulfonat), Nitryl- und Nitrosyltrifluormethansulfonat, III1,2 / Preparation of Iodine tris-Trifluorom ethane Sulfonate, Nitryl- and Nitrosvl-trifluorom ethane Sulfonate, III1,2
Authors: Schmeisser Martin , Sartori Peter , Lippsmeier Bernd
Published: February 2015

J(OSO2CF3)3 coukl bo obtained from CF3SO3H and J(OCOCF3)3, N2O5 and (CF3O2)2O formed CF3SO3NO2 which could be converted to CF3SO3NO by N2O4.
Optogenetic Stimulation of Accumbens Shell or Shell Projections to Lateral Hypothalamus Produce Differential Effects on the Motivation for Cocaine
Authors: Larson Erin B. , Wissman Anne M. , Loriaux Amy L. , Kourrich Saïd , Self David W.
Published: February 2015

Previous studies suggest that pharmacological or molecular activation of the nucleus accumbens shell (AcbSh) facilitates extinction of cocaine-seeking behavior. However, overexpression of CREB, which increases excitability of AcbSh neurons, enhances cocaine-seeking behavior while producing depression-like behavior in tests of mood. These discrepancies may reflect activity in differential AcbSh outputs, including those to the lateral hypothalamus (LH), a target region known to influence addictive behavior and mood. Presently, it is unknown whether there is a causal link between altered activity in the AcbSh-LH pathway and changes in the motivation for cocaine. In this study, we used an optogenetics approach to either globally stimulate AcbSh neurons or to selectively stimulate AcbSh terminal projections in the LH, in rats self-administering cocaine. We found that stimulation of the AcbSh-LH pathway enhanced the motivation to self-administer cocaine in progressive ratio testing, and led to long-lasting facilitation of cocaine-seeking behavior during extinction tests conducted after withdrawal from cocaine self-administration. In contrast, global AcbSh stimulation reduced extinction responding. We compared these opposing motivational effects with effects on mood using the forced swim test, where both global AcbSh neuron and selective AcbSh-LH terminal stimulation facilitated depression-like behavioral despair. Together, these findings suggest that the AcbSh neurons convey complex, pathway-specific modulation of addiction and depression-like behavior, and that these motivation and mood phenomenon are dissociable.
Reactive Astrogliosis Causes the Development of Spontaneous Seizures
Authors: Robel Stefanie , Buckingham Susan C. , Boni Jessica L. , Campbell Susan L. , Danbolt Niels C. , Riedemann Therese , Sutor Bernd , Sontheimer Harald
Published: February 2015

Epilepsy is one of the most common chronic neurologic diseases, yet approximately one-third of affected patients do not respond to anticonvulsive drugs that target neurons or neuronal circuits. Reactive astrocytes are commonly found in putative epileptic foci and have been hypothesized to be disease contributors because they lose essential homeostatic capabilities. However, since brain pathology induces astrocytes to become reactive, it is difficult to distinguish whether astrogliosis is a cause or a consequence of epileptogenesis. We now present a mouse model of genetically induced, widespread chronic astrogliosis after conditional deletion of β1-integrin (Itgβ1). In these mice, astrogliosis occurs in the absence of other pathologies and without BBB breach or significant inflammation. Electroencephalography with simultaneous video recording revealed that these mice develop spontaneous seizures during the first six postnatal weeks of life and brain slices show neuronal hyperexcitability. This was not observed in mice with neuronal-targeted β1-integrin deletion, supporting the hypothesis that astrogliosis is sufficient to induce epileptic seizures. Whole-cell patch-clamp recordings from astrocytes further suggest that the heightened excitability was associated with impaired astrocytic glutamate uptake. Moreover, the relative expression of the cation-chloride cotransporters (CCC) NKCC1 (Slc12a2) and KCC2 (Slc12a5), which are responsible for establishing the neuronal Cl−gradient that governs GABAergic inhibition were altered and the NKCC1 inhibitor bumetanide eliminated seizures in a subgroup of mice. These data suggest that a shift in the relative expression of neuronal NKCC1 and KCC2, similar to that observed in immature neurons during development, may contribute to astrogliosis-associated seizures.
Microsaccade Control Signals in the Cerebellum
Authors: Arnstein Daniel , Junker Marc , Smilgin Aleksandra , Dicke Peter W. , Thier Peter
Published: February 2015

Microsaccades, the small saccades made when we try to keep the eyes still, were once believed to be inconsequential for vision, but recent studies suggest that they can precisely relocate gaze to tiny visual targets. Because the cerebellum is necessary for motor precision, we investigated whether microsaccades may exploit this neural machinery in monkeys. Almost all vermal Purkinje cells, which provide the eye-related output of the cerebellar cortex, were found to increase or decrease their simple spike firing rate during microsaccades. At both the single-cell and population level, microsaccade-related activity was highly similar to macrosaccade-related activity and we observed a continuous representation of saccade amplitude that spanned both the macrosaccade and microsaccade domains. Our results suggest that the cerebellum's role in fine-tuning eye movements extends even to the oculomotor system's smallest saccades and add to a growing list of observations that call into question the classical categorical distinction between microsaccades and macrosaccades.
Mitochondrial ATP-Mg/Pi Carrier SCaMC-3/Slc25a23 Counteracts PARP-1-Dependent Fall in Mitochondrial ATP Caused by Excitotoxic Insults in Neurons
Authors: Rueda Carlos B. , Traba Javier , Amigo Ignacio , Llorente-Folch Irene , González-Sánchez Paloma , Pardo Beatriz , Esteban José A. , del Arco Araceli , Satrústegui Jorgina
Published: February 2015

Glutamate excitotoxicity is caused by sustained activation of neuronal NMDA receptors causing a large Ca2+and Na+influx, activation of poly(ADP ribose) polymerase-1 (PARP-1), and delayed Ca2+deregulation. Mitochondria undergo early changes in membrane potential during excitotoxicity, but their precise role in these events is still controversial. Using primary cortical neurons derived from mice, we show that NMDA exposure results in a rapid fall in mitochondrial ATP in neurons deficient in SCaMC-3/Slc25a23, a Ca2+-regulated mitochondrial ATP-Mg/Pi carrier. This fall is associated with blunted increases in respiration and a delayed decrease in cytosolic ATP levels, which are prevented by PARP-1 inhibitors or by SCaMC-3 activity promoting adenine nucleotide uptake into mitochondria. SCaMC-3 KO neurons show an earlier delayed Ca2+deregulation, and SCaMC-3-deficient mitochondria incubated with ADP or ATP-Mg had reduced Ca2+retention capacity, suggesting a failure to maintain matrix adenine nucleotides as a cause for premature delayed Ca2+deregulation. SCaMC-3 KO neurons have higher vulnerability toin vitroexcitotoxicity, and SCaMC-3 KO mice are more susceptible to kainate-induced seizures, showing that early PARP-1-dependent fall in mitochondrial ATP levels, counteracted by SCaMC-3, is an early step in the excitotoxic cascade.
Neural Mechanisms of Human Perceptual Choice Under Focused and Divided Attention
Authors: Wyart Valentin , Myers Nicholas E. , Summerfield Christopher
Published: February 2015

Perceptual decisions occur after the evaluation and integration of momentary sensory inputs, and dividing attention between spatially disparate sources of information impairs decision performance. However, it remains unknown whether dividing attention degrades the precision of sensory signals, precludes their conversion into decision signals, or dampens the integration of decision information toward an appropriate response. Here we recorded human electroencephalographic (EEG) activity while participants categorized one of two simultaneous and independent streams of visual gratings according to their average tilt. By analyzing trial-by-trial correlations between EEG activity and the information offered by each sample, we obtained converging behavioral and neural evidence that dividing attention between left and right visual fields does not dampen the encoding of sensory or decision information. Under divided attention, momentary decision information from both visual streams was encoded in slow parietal signals without interference but was lost downstream during their integration as reflected in motor mu- and beta-band (10–30 Hz) signals, resulting in a “leaky” accumulation process that conferred greater behavioral influence to more recent samples. By contrast, sensory inputs that were explicitly cued as irrelevant were not converted into decision signals. These findings reveal that a late cognitive bottleneck on information integration limits decision performance under divided attention, and places new capacity constraints on decision-theoretic models of information integration under cognitive load.
Anti-Muscarinic Adjunct Therapy Accelerates Functional Human Oligodendrocyte Repair
Authors: Abiraman Kavitha , Pol Suyog U. , O'Bara Melanie A. , Chen Guang-Di , Khaku Zainab M. , Wang Jing , Thorn David , Vedia Bansi H. , Ekwegbalu Ezinne C. , Li Jun-Xu , Salvi Richard J. , Sim Fraser J.
Published: February 2015

Therapeutic repair of myelin disorders may be limited by the relatively slow rate of human oligodendrocyte differentiation. To identify appropriate pharmacological targets with which to accelerate differentiation of human oligodendrocyte progenitors (hOPCs) directly, we used CD140a/O4-based FACS of human forebrain and microarray to hOPC-specific receptors. Among these, we identified CHRM3, a M3R muscarinic acetylcholine receptor, as being restricted to oligodendrocyte-biased CD140a+O4+cells. Muscarinic agonist treatment of hOPCs resulted in a specific and dose-dependent blockade of oligodendrocyte commitment. Conversely, when hOPCs were cocultured with human neurons, M3R antagonist treatment stimulated oligodendrocytic differentiation. Systemic treatment with solifenacin, an FDA-approved muscarinic receptor antagonist, increased oligodendrocyte differentiation of transplanted hOPCs in hypomyelinatedshiverer/rag2brain. Importantly, solifenacin treatment of engrafted animals reduced auditory brainstem response interpeak latency, indicative of increased conduction velocity and thereby enhanced functional repair. Therefore, solifenacin and other selective muscarinic antagonists represent new adjunct approaches to accelerate repair by engrafted human progenitors.
Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe
Authors: Gagnon Louis , Sakadžić Sava , Lesage Frédéric , Musacchia Joseph J. , Lefebvre Joël , Fang Qianqian , Yücel Meryem A. , Evans Karleyton C. , Mandeville Emiri T. , Cohen-Adad Jülien , Polimeni Jon̈athan R. , Yaseen Mohammad A. , Lo Eng H. , Greve Douglas N. , Buxton Richard B. , Dale Anders M. , Devor Anna , Boas David A.
Published: February 2015

The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.
Ly6h Regulates Trafficking of Alpha7 Nicotinic Acetylcholine Receptors and Nicotine-Induced Potentiation of Glutamatergic Signaling
Authors: Puddifoot Clare A. , Wu Meilin , Sung Rou-Jia , Joiner William J.
Published: February 2015

α7 nAChRs are expressed widely throughout the brain, where they are important for synaptic signaling, gene transcription, and plastic changes that regulate sensory processing, cognition, and neural responses to chronic nicotine exposure. However, the mechanisms by which α7 nAChRs are regulated are poorly understood. Here we show that trafficking of α7-subunits is controlled by endogenous membrane-associated prototoxins in the Ly6 family. In particular, we find that Ly6h reduces cell-surface expression and calcium signaling by α7 nAChRs. We detect Ly6h in several rat brain regions, including the hippocampus, where we find it is both necessary and sufficient to limit the magnitude of α7-mediated currents. Consistent with such a regulatory function, knockdown of Ly6h in rat hippocampal pyramidal neurons enhances nicotine-induced potentiation of glutamatergic mEPSC amplitude, which is known to be mediated by α7 signaling. Collectively our data suggest a novel cellular role for Ly6 proteins in regulating nAChRs, which may be relevant to plastic changes in the nervous system including rewiring of glutamatergic circuitry during nicotine addiction.
Effector Specificity in Macaque Frontal and Parietal Cortex
Authors: Premereur Elsie , Janssen Peter , Vanduffel Wim
Published: February 2015

Single neurons in the frontal eye fields (FEFs) and lateral intraparietal area (LIP) of macaques are preferentially activated by saccade- versus reach-related processes. fMRI studies focusing on saccade- and reach-specific activity in human cortex, however, provided conflicting evidence for effector specificity. To gain further insights into effector preferences throughout monkey cortex using the same technique as in humans, we performed a mixed block/event-related fMRI experiment in macaques. Within single fMRI runs, monkeys alternated between a visually guided saccade task, a visually guided arm movement task, and a fixation-only task requiring no saccades or arm movements. The detection of a peripheral pop-out go cue initiating the required operant behavior and the identification of a target among distractors was identical in the arm and saccade tasks. We found saccade-related activity in parietal areas V6, V6A, LIP, and caudal intraparietal area and frontal areas FEF, 45a, 45b, and 46. Areas 45 and FEF even showed markedly decreased fMRI activity during arm movements relative to fixation only. Conversely, medial and anterior intraparietal areas (MIP and AIP), and parietal area PEip; somatosensory areas S1 and S2; and (pre)motor areas F1, F3, F5, and F6 showed increased arm movement-related activity. F1, F5, PEip, and somatosensory cortex also showed deactivations during saccades relative to fixation only. Control experiments showed that such deactivations in both operant-specific functional networks did not depend on training history or rapid task switching requiring active suppression of the unpreferred operant behavior. Therefore, although both tasks required divided attention to detect a pop-out go cue and target, two largely segregated and mainly effector-driven cortical networks were activated.
Fast Gamma Oscillations Are Generated Intrinsically in CA1 without the Involvement of Fast-Spiking Basket Cells
Authors: Craig Michael T. , McBain Chris J.
Published: February 2015

Information processing in neuronal networks relies on the precise synchronization of ensembles of neurons, coordinated by the diverse family of inhibitory interneurons. Cortical interneurons can be usefully parsed by embryonic origin, with the vast majority arising from either the caudal or medial ganglionic eminences (CGE and MGE). Here, we examine the activity of hippocampal interneurons during gamma oscillations in mouse CA1, using anin vitromodel where brief epochs of rhythmic activity were evoked by local application of kainate. We found that this CA1 KA-evoked gamma oscillation was faster than that in CA3 and, crucially, did not appear to require the involvement of fast-spiking basket cells. In contrast to CA3, we also found that optogenetic inhibition of pyramidal cells in CA1 did not significantly affect the power of the oscillation, suggesting that excitation may not be essential for gamma genesis in this region. We found that MGE-derived interneurons were generally more active than CGE interneurons during CA1 gamma, although a group of CGE-derived interneurons, putative trilaminar cells, were strongly phase-locked with gamma oscillations and, together with MGE-derived axo-axonic and bistratified cells, provide attractive candidates for being the driver of this locally generated, predominantly interneuron-driven model of gamma oscillations.
Dopamine Directly Modulates GABAAReceptors
Authors: Hoerbelt Paul , Lindsley Tara A. , Fleck Mark W.
Published: February 2015

Dopamine is a critical neuromodulator that activates GPCRs in mammals or ligand-gated ion channels in invertebrates. The present study demonstrates that dopamine (0.1–10 mm) exerts novel, opposing effects on different populations of mammalian (rat) GABAAreceptors. Using whole-cell patch-clamp electrophysiology, we observed direct dopamine-mediated inhibition of tonic-level (1 μm) GABA-evoked currents in untransfected striatal neurons that could be recapitulated in HEK293 cells containing α1β3 or α1β2γ2 subunits. Surprisingly, direct activation by dopamine was seen in the absence of GABA with α1β2γ2, α5β3γ2, or α1β3γ2 transfections. This activity was also present in α1β3γ2 receptors containing a mutant β3 subunit (H267A [Zβ3]) insensitive to trace levels of inhibitory Zn2+. Dopamine activation required β and γ subunits but not α subunits (Zβ3γ2 EC50value, 660 μm). Dopamine activity was fully blocked by picrotoxin but not GABAAcompetitive antagonists, and was strongly correlated with spontaneous receptor activity. We also report opposing effects of bicuculline and gabazine, such that bicuculline surprisingly activated non-α-containing (β3γ2) GABAAreceptors, whereas gabazine suppressed spontaneous activity in these receptors. Our results suggest that dopamine may directly inhibit GABAAreceptors that are both immediately adjacent to dopamine release sites in the striatum and activated by tonic GABA. Furthermore, synaptic/phasic release of dopamine may directly enhance signaling at some spontaneously active noncanonical GABAAreceptors that lack α subunits.
Use-Dependent Activation of Neuronal Kv1.2 Channel Complexes
Authors: Baronas Victoria A. , McGuinness Brandon R. , Brigidi G. Stefano , Gomm Kolisko Rachel N. , Vilin Yury Y. , Kim Robin Y. , Lynn Francis C. , Bamji Shernaz X. , Yang Runying , Kurata Harley T.
Published: February 2015

In excitable cells, ion channels are frequently challenged by repetitive stimuli, and their responses shape cellular behavior by regulating the duration and termination of bursts of action potentials. We have investigated the behavior ofShakerfamily voltage-gated potassium (Kv) channels subjected to repetitive stimuli, with a particular focus on Kv1.2. Genetic deletion of this subunit results in complete mortality within 2 weeks of birth in mice, highlighting a critical physiological role for Kv1.2. Kv1.2 channels exhibit a unique property described previously as “prepulse potentiation,” in which activation by a depolarizing step facilitates activation in a subsequent pulse. In this study, we demonstrate that this property enables Kv1.2 channels to exhibit use-dependent activation during trains of very brief depolarizations. Also, Kv subunits usually assemble into heteromeric channels in the central nervous system, generating diversity of function and sensitivity to signaling mechanisms. We demonstrate that other Kv1 channel types do not exhibit use-dependent activation, but this property is conferred in heteromeric channel complexes containing even a single Kv1.2 subunit. This regulatory mechanism is observed in mammalian cell lines as well as primary cultures of hippocampal neurons. Our findings illustrate that use-dependent activation is a unique property of Kv1.2 that persists in heteromeric channel complexes and may influence function of hippocampal neurons.
Norepinephrine Activates Dopamine D4Receptors in the Rat Lateral Habenula
Authors: Root David H. , Hoffman Alexander F. , Good Cameron H. , Zhang Shiliang , Gigante Eduardo , Lupica Carl R. , Morales Marisela
Published: February 2015

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4receptors. Therefore, NE may be an important regulator of LHb function.
Mouse Model ofOPRM1(A118G) Polymorphism Increases Sociability and Dominance and Confers Resilience to Social Defeat
Authors: Briand Lisa A. , Hilario Monica , Dow Holly C. , Brodkin Edward S. , Blendy Julie A. , Berton Olivier
Published: February 2015

A single nucleotide polymorphism (SNP) in the human μ-opioid receptor gene (OPRM1A118G) has been widely studied for its association in drug addiction, pain sensitivity, and, more recently, social behavior. The endogenous opioid system has been shown to regulate social distress and reward in a variety of animal models. However, mechanisms underlying the associations between theOPRM1A118G SNP and these behaviors have not been clarified. We used a mouse model possessing the human equivalent nucleotide/amino acid substitution to study social affiliation and social defeat behaviors. In mice with theOprm1A112G SNP, we demonstrate that the G allele is associated with an increase in home-cage dominance and increased motivation for nonaggressive social interactions, similar to what is reported in human populations. When challenged by a resident aggressor, G-allele carriers expressed less submissive behavior and exhibited resilience to social defeat, demonstrated by a lack of subsequent social avoidance and reductions in anhedonia as measured by intracranial self-stimulation. Protection from social defeat in G-allele carriers was associated with a greater induction of c-fos in a resilience circuit comprising the nucleus accumbens and periaqueductal gray. These findings led us to test the role of endogenous opioids in the A112G mice. We demonstrate that the increase in social affiliation in G carriers is blocked by pretreatment with naloxone. Together, these data suggest a mechanism involving altered hedonic state and neural activation as well as altered endogenous opioid tone in the differential response to aversive and rewarding social stimuli in G-allele carriers.
A high‐resolution genomic analysis of multidrug‐resistant hospital outbreaks of Klebsiella pneumoniae
Authors: Chung The Hao , Karkey Abhilasha , Pham Thanh Duy , Boinett Christine J , Cain Amy K , Ellington Matthew , Baker Kate S , Dongol Sabina , Thompson Corinne , Harris Simon R , Jombart Thibaut , Le Thi Phuong Tu , Tran Do Hoang Nhu , Ha Thanh Tuyen , Shretha Shrijana , Joshi Suchita , Basnyat Buddha , Thwaites Guy , Thomson Nicholas R , Rabaa Maia A , Baker Stephen
Published: February 2015

Multidrug‐resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource‐poor hospital settings. Through whole‐genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high‐dependency wards in a hospital in Kathmandu during 2012 with a case‐fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage‐specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward‐specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM‐1 containing lineage in 2011 would have alerted the high‐dependency ward staff to intervene. We argue that some form of real‐time genetic characterisation, alongside clade‐specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high‐ and low‐income settings.
The water deprivation test and a potential role for the arginine vasopressin precursor copeptin to differentiate diabetes insipidus from primary polydipsia
Authors: de Fost M , Oussaada S M , Endert E , Linthorst G E , Serlie M J , Soeters M R , DeVries J H , Bisschop P H , Fliers E
Published: February 2015

The water deprivation test is the gold standard test to differentiate central or nephrogenic diabetes insipidus (DI) from primary polydipsia (PP) in patients with polyuria and polydipsia. Few studies have addressed the diagnostic performance of this test. The aim of this retrospective cohort study was to evaluate the diagnostic performance of the standard water deprivation test, including plasma arginine vasopressin (AVP) measurements, in 40 consecutive patients with polyuria. We compared initial test results with the final clinical diagnosis, i.e., no DI, central DI, or nephrogenic DI. The median length of follow-up was 8 years. In a subset of ten patients, the novel marker copeptin (CP) was measured in plasma. Using the final diagnosis as a gold standard, a threshold for urine osmolality of >800 mOsmol/kg after water deprivation yielded a sensitivity and specificity of 96 and 100%, respectively, for diagnosing PP. Sensitivity increased to 100% if the cut-off value for urine osmolality was set at 680 mOsmol/kg. Plasma AVP levels did not differ between patient groups and did not differentiate among central DI, nephrogenic DI, or PP. In all three patients with central DI, plasma CP was <2.5 pmol/l with plasma osmolality >290 mOsmol/kg, and >2.5 pmol/l in patients without DI. The optimal cut-off value for differentiating PP from DI during a water deprivation test was urine osmolality >680 mOsmol/kg. Differentiating between central and nephrogenic DI should be based on clinical judgment as AVP levels did not discriminate.