bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas chromatographic analysis of mercaptans using the ion-selective electrode detector
Authors: Kehr Ján , Králik Peter
Published: September 2010

An electrochemical ion-selective electrode detector in conjunction with the gas chromatograph and the TCD in series is described and its operating characteristics are discussed. Under optimal conditions for resolution, mercaptans are absorbed in 1 . 10-4 mol l-1 AgNO3 absorption solution at a flow rate 1.2 ml min-1 and detected by Ag2S-solid membrane electrode. The detection limit 6 . 10-11 mol S calculated for propyl mercaptan is achieved, however, only in 1 . 10-5 mol l-1 AgNO3, where a poor resolution of mercaptane occurs. Other parameters affecting the separation and sensitivity are flow rate of absorption solution and geometry of the cell and of the absorber.
Cyclization of O-benzoylbenzamidoxime derivatives in water-alcohol media
Authors: Grambal František , Lasovský Jan
Published: September 2010

O-Benzoylated benzamidoximes give 1,2,4-oxadiazoles (yields above 90%) in water-alcoholic media of pH = 2.45 to 6.20. The cyclization rate has been studied with 28 derivatives containing different substituents. The reaction is accelerated by electron-donor substituents at 4-position of benzamidoxime and by electron-acceptor substituents at 4'-position of benzoyl. The dependence of the rate constants vs σ values of the substituents fulfils the two-parameter Hammett equation at a 99% probability level. The activation parameters have been determined, and effects of polarity of medium, kinetic isotopic effect, and the reaction mechanism are discussed.
Oxidation of 19β,28-epoxy-18α-oleanan-3-one and -1-one with peracids
Authors: Sejbal Jan , Klinot Jiří , Hrnčířová Daniela , Vystrčil Alois
Published: September 2010

The reaction of 3-oxo derivative I and 1-oxo derivative XII of 19β,28-epoxy-18α-oleanane with peracids leads to corresponding lactones II or XIII, respectively, which were converted to A-seco acids III, V, and XIV and esters IV, VI, VII, and XV. Under acid catalysis oxidation of ketone I results in the degradation of one methyl group in position 4 and formation of compounds VIII and IX. On reaction with 3-chloroperbenzoic acid the α,β-unsaturated ketone XVI gives epoxyketone XVII.
Preparation of 3-carboxypropanoates of digitoxin and digoxin and their conjugates with L-tyrosine
Authors: Drašar Pavel , Pouzar Vladimír , Černý Ivan , Havel Miroslav , Tureček František , Schmiedová Daniela , Vereš Karel
Published: September 2010

Digitoxin and digoxin 4'''-(3-carboxypropanoates)(4'''-hemisuccinates) III and X were prepared by an indirect method, using dicyclohexylcarbodiimide-induced condensation of the cardioglycoside with 4-(2,2,2-trichloroethoxy)-4-oxobutanoic acid in dichloromethane in the presence of 4-dimethylaminopyridine or pyridine followed by removal of the 2,2,2-trichloroethyl group with zinc in a mixture of tetrahydrofuran, acetic acid and water. The hemisuccinates III and X were condensed with L-tyrosine methyl ester in tetrahydrofuran, using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. Structure of the products was proved by 1H NMR and 13C NMR spectra. The conjugates IV and XI were labelled with [125I] in the L-tyrosine moiety. The obtained radioligands V and XII are designed as a part of the RIA system for cardioglycoside analyses.
Enzymatically catalyzed synthesis of oxytocin fragments 1-6 and 7-9
Authors: Čeřovský Václav , Jošt Karel
Published: September 2010

Papain, α-chymotrypsin, thermolysin and elastase were utilized in the synthesis of peptide bonds of the protected oxytocin nonapeptide, except the S-benzylcysteine-proline bond. Amino groups were protected with benzyloxycarbonyl or tert-butyloxycarbonyl groups, carboxy groups as ethyl ester, phenylhydrazides or amides. The cysteine sulfhydryl group was blocked with the benzyl group whereas the tyrosine hydroxyl was unprotected. Most of the fragments were synthesized in satisfactory yields using an equimolar ratio of both reaction components and minimal (experimentally determined) amount of the given enzyme.
Kinetics of photochemical reactions with excitation by polychromatic radiation
Authors: Hrdina Radim , Čepčiansky Igor , Poskočil Jaroslav
Published: September 2010

For quantitative studies of photochemical reactions with low quantum yields the paper suggests application of polychromatic radiation sources whose overall intensity is by orders higher than that of currently available monochromatic sources. The more complicated and laborious calculation methods suggested for treatment of the experimental data can be solved by usual numerical procedures.
Aeration of liquids in a vessel equipped with multistage impellers
Authors: Machoň Václav , Vlček Jiří
Published: September 2010

The paper deals with the influence of the number of impellers and the mode of aeration on the mechanical power input in a stirred gas-liquid dispersion using two impellers on the same shaft. Gas has been supplied either under the lower impeller or under both impellers. The power input was measured in the water-air system. A six-blade turbine impeller of the Rushton type and/or impellers with six inclined blades (with downward or upward pumping effect) were used. Experimental results have been obtained for a single impeller in a tank where the depth of liquid was equal to the tank diameter, and for different combinations of two impellers located on a single shaft where the distance between the impellers was equal to the tank diameter and the liquid depth was twice this diameter. It has been found that the power input data for the two-impeller system of two turbines can be correlated adequately by a simple equation. An estimate was made of the amount of gas supplied below the lower impeller which was transported into the region of the upper impeller.
Speckle patterns in small angle light scattering: The spatial autocorrelation function
Authors: Holoubek Jaroslav , Baldrian Josef
Published: September 2010

The study deals with the determination of the spatial autocorrelation function of speckle patterns caused by the small-angle light scattering from polymer films. The autocorrelation function determines the shape, size and anisometry of the speckle. The effect of the inner structure and orientation of samples (polypropylene foil, poly(decamethylene terephthalate) and a sample of polypropylene filaments) is discussed; it is shown that under the usual experimental conditions the spatial autocorrelation function of speckle patterns can be determined on the basis of the van Cittert-Zernike theorem of the classical coherence theory. The good agreement between the theoretical and experimental dependences of anisometry, the angular dependence of speckle size and the dependence of speckle size on the sample thickness confirm the suitability of a uniform description based on the classical theory of coherence. From the standpoint of the theory of speckle effect, the results presented in this study allow us to infer that in the light scattering from polymer films under usual conditions the assumptions of the application of the central limit theorem are fulfilled: in the scattering volume there is a sufficient number of scattering units, and path fluctuations due to the scattering foil exceed the wavelength of light.
Empirical parameters of (E-Z) isomerization
Authors: Hnyk Drahomír , Procházka Miloš , Juška Libor
Published: September 2010

Equilibrium constants of (E-Z) isomerization of compounds A-CH=CH-B can be expressed, on the basis of factor analysis, in the form log K(Z/E)AB = aA1F1B + aA2F2B, where the first term corresponds to electrostatic interactions of substituents in the isomers and the second term expresses the difference in steric interactions.
Effect of sulphur compounds on the heptane pyrolysis kinetics
Authors: Bajus Martin , Baxa Jozef
Published: September 2010

The effect of 1-didecyl sulphide, diethyl disulphide, p,p'-dichlorodiphenyl disulphide, 1-butanethiol, 0,0'-di-1-butyl dithiophosphate zinc, 0,0'-diethyl dithiophosphoric acid and carbon disulphide, respectively, on the kinetics and selectivity of the thermal decomposition of heptane at 700 °C and 100 kPa was studied in a stainless steel flow-through tube reactor. The sulphur substance content was 0.1-1.0 wt.%. 1-Didecyl sulphide, p,p'-dichlorodiphenyl disulphide, 1-butylthiol, 0,0'-di-1-butyl dithiophosphate zinc and carbon disulphide favour the decomposition of heptane by 5-17%. A decrease in the heptane decomposition rate was observed in the presence of diethyl disulphide (2.8%) and 0,0'-diethyl dithiophosphoric acid (13.9%). The selectivity of decomposition to ethylene is increased by diethyl disulphide, p,p'-dichlorodiphenyl disulphide, carbon disulphide and 1-didecyl sulphide and, in the range of short reaction times, also by 0,0'-diethyl dithiophosphoric acid, 0,0'-di-1-butyl dithiophosphate zinc and 1-butanethiol.
INTERACTING COSMIC FLUIDS IN BRANS–DICKE COSMOLOGY
Authors: FARAJOLLAHI HOSSEIN , MOHAMADI NARGES , AMIRI HAMED
Published: September 2010

We provide a detailed description for power-law scaling FRW cosmological models in Brans–Dicke theory dominated by two interacting fluid components during the expansion of the universe.
MONOPOLE-INSTANTON SOLUTIONS FOR THE MASSIVE SU(2) YANG–MILLS–HIGGS THEORY
Authors: TEH ROSY , WONG KHAI-MING , KOH PIN-WAI
Published: September 2010

Monopole-instanton in topologically massive gauge theories in 2+1 dimensions with a Chern–Simons mass term have been studied by Pisarski some years ago. He investigated the SU(2) Yang–Mills–Higgs model with an additional Chern–Simons mass term in the action. Pisarski argued that there is a monopole-instanton solution that is regular everywhere, but found that it does not possess finite action. There were no exact or numerical solutions being presented by Pisarski. Hence it is our purpose to further investigate this solution in more detail. We obtained numerical regular solutions that smoothly interpolates between the behavior at small and large distances for different values of Chern–Simons term strength and for several fixed values of Higgs field strength. The monopole-instanton's action is real but infinite. The action vanishes for large Chern–Simons term only when the Higgs field expectation value vanishes.
WHAT WE KNOW AND DON'T KNOW ABOUT THE ORIGIN OF THE SPIN OF THE PROTON
Authors: THOMAS ANTHONY W. , CASEY ANDREW , MATEVOSYAN HRAYR H.
Published: September 2010

The origin of the spin of the proton is one of the most fundamental questions in modern hadron physics. Although tremendous progress has been made since the discovery of the "spin crisis" brought the issue to the fore, much remains to be understood. We carefully review what is known and, especially in the case of lattice QCD, what is not known. We also explain the importance of QCD inspired models in providing a physical picture of proton structure and the connection between those models and what is measured experimentally and on the lattice. We specifically apply these ideas to the issue of quark orbital angular momentum in the proton. We show that the Myhrer–Thomas resolution of the proton spin crisis is remarkably consistent with modern information from lattice QCD.
THE ELUSIVE HIGGS BOSON(S)
Authors: GUNION JOHN F.
Published: September 2010

We outline the motivations for having a light Higgs boson with fairly SM-like couplings to WW, ZZ but with unusual decays that elude LEP limits and that will also make its detection at the LHC quite challenging. The Next-to-Minimal Supersymmetric Model provides a very appealing model of this type.
ELECTROMAGNETIC KLEIN–GORDON AND DIRAC EQUATIONS IN SCALE RELATIVITY
Authors: CÉLÉRIER MARIE-NOËLLE , NOTTALE LAURENT
Published: September 2010

We present a new step in the foundation of quantum field theory with the tools of scale relativity. Previously, quantum motion equations (Schrödinger, Klein–Gordon, Dirac, Pauli) have been derived as geodesic equations written with a quantum-covariant derivative operator. Then, the nature of gauge transformations, of gauge fields and of conserved charges have been given a geometric meaning in terms of a scale-covariant derivative tool. Finally, the electromagnetic Klein–Gordon equation has been recovered with a covariant derivative constructed by combining the quantum-covariant velocity operator and the scale-covariant derivative. We show here that if one tries to derive the electromagnetic Dirac equation from the Klein–Gordon one as for the free particle motion, i.e. as a square root of the time part of the Klein–Gordon operator, one obtains an additional term which is the relativistic analog of the spin-magnetic field coupling term of the Pauli equation. However, if one first applies the quantum covariance, then implements the scale covariance through the scale-covariant derivative, one obtains the electromagnetic Dirac equation in its usual form. This method can also be applied successfully to the derivation of the electromagnetic Klein–Gordon equation. This suggests it rests on more profound roots of the theory, since it encompasses naturally the spin–charge coupling.
UV EMISSION OF TETRAGONAL ZrO2 NANOCRYSTALS EMBEDDED IN ZrSiO4 AMORPHOUS MATRIX
Authors: GE ZHONGYANG , ZHOU YUE , YIN JIANG , GONG YOUPIN , LV SHICHENG , XIA YIDONG , LIU ZHIGUO
Published: September 2010

Amorphous films Zr 0.8 Si 0.2 O 2 were deposited on quartz substrates at room temperature, by using pulsed laser deposition technique. After annealing at high temperature, Zr 0.8 Si 0.2 O 2 films suffer a phase separation to precipitate tetragonal ZrO 2 nanocrystals in ZrSiO 4 amorphous matrix. Their crystal structure, microstructure, optical absorbance and photoluminescence have been systematically investigated. Tetragonal ZrO 2 nanocrystals show intense UV emission around 392 nm under photonic excitation with a wavelength of 250 nm. The corresponding models of electronic excitation and transition related to UV emission also have been proposed.
COMPLEMENTARITY IN GENERIC OPEN QUANTUM SYSTEMS
Authors: BANERJEE SUBHASHISH , SRIKANTH R.
Published: September 2010

We develop a unified, information theoretic interpretation of the number-phase complementarity that is applicable both to finite-dimensional (atomic) and infinite-dimensional (oscillator) systems, with number treated as a discrete Hermitian observable and phase as a continuous positive operator valued measure (POVM). The relevant uncertainty principle is obtained as a lower bound on entropy excess, X, the difference between the entropy of one variable, typically the number, and the knowledge of its complementary variable, typically the phase, where knowledge of a variable is defined as its relative entropy with respect to the uniform distribution. In the case of finite-dimensional systems, a weighting of phase knowledge by a factor μ (> 1) is necessary in order to make the bound tight, essentially on account of the POVM nature of phase as defined here. Numerical and analytical evidence suggests that μ tends to 1 as the system dimension becomes infinite. We study the effect of non-dissipative and dissipative noise on these complementary variables for an oscillator as well as atomic systems.
Terrestrialization in the Late Devonian: a palaeoecological overview of the Red Hill site, Pennsylvania, USA
Authors: Cressler Walter L. , Daeschler Edward B. , Slingerland Rudy , Peterson Daniel A.
Published: September 2010

Alluvial floodplains were a critical setting during the Late Devonian for the evolution of terrestriality among plants, invertebrate and vertebrates. The Red Hill site in Pennsylvania, US, provides a range of information about the physical and biotic setting of a floodplain ecosystem along the southern margin of the Euramerican landmass during the late Famennian age. An avulsion model for floodplain sedimentation is favoured in which a variety of inter-channel depositional settings formed a wide range of aquatic and terrestrial habitats. The Red Hill flora demonstrates ecological partitioning of the floodplain landscape at a high taxonomic level. In addition to progymnosperm forests, lycopsid wetlands and zygopterid fern glades, the flora includes patches of early spermatophytes occupying sites disturbed by fires. The Red Hill fauna illustrates the development of a diverse penecontemporaneous community including terrestrial invertebrates and a wide range of vertebrates that were living within aquatic habitats. Among the vertebrates are several limbed tetrapodomorphs that inhabited the burgeoning shallow water habitats on the floodplain.
Terrestrialization: the early emergence of the concept
Authors: Janvier Philippe
Published: September 2010

The transition from water to land is perhaps the most dramatic event in the history of life after the rise of photosynthesis, sexuality and predation. During the late Neoproterozoic and the early Palaeozoic, some green plants, fungi and animals happened to overcome the constraints that linked them to the primeval aquatic environment of life, became progressively adapted to the terrestrial, aerobic environment and finally contributed to its change through time. We do not know how many taxa initially survived this trial, but we have some indication of the result in extant life: a threefold world of pluricellular terrestrial organisms, all depending on each other to various degrees and surrounded by a cryptic world of bacteria and unicellular eukaryotes. Fossils provide us with acceptable information about the evolutionary history of only two of these worlds: embryophytes and bilateralian animals. The molecules of their living representatives can only begin to tell us how they gained the complexity that allowed them to achieve this remarkable adaptation to life on land and in air.
An organic geochemical perspective on terrestrialization
Authors: Versteegh Gerard J. M. , Riboulleau Armelle
Published: September 2010

The colonization of land required new strategies for safe gamete/diaspore dispersal, and to cope with desiccation, harmful radiation, fire and gravity. Accordingly, the morphology, behaviour and physiology of the organisms changed. Here, we explore to what extent physiological adaptations, reflected in the molecular content of the sediments, add to our understanding of the terrestrialization. Many compounds considered characteristic of land organisms do not provide valuable information from the fossil record since (1) they were not preserved; (2) they occur or correspond to substances that evolved prior to the terrestrialization (e.g. cutan vs. algaenan, cellulose); or (3) they have been changed diagenetically and/or catagenetically. The latter leads to geo(macro)molecules without a chemical fingerprint relating them to their original bio(macro)molecules despite, sometimes, excellent morphological preservation of the organic remains. Nevertheless, some molecular markers and their stable isotopes provide independent information on the terrestrialization process. The odd predominance of
n
-alkane surface waxes is a feature already apparent in early land plants and could, with caution, be used as such. Furthermore, fossil terpenoids and their derivatives are valuable for reconstructing the evolution of major plant groups. The radiation of the phenylpropanoid pathway with for example, sporopollenin and lignin seems to be closely related to the evolution of land plants.
Early seed plant radiation: an ecological hypothesis
Authors: Prestianni C. , Gerrienne P.
Published: September 2010

The earliest steps of seed plant evolution have been extensively studied during the past 25 years. There is a growing body of evidence indicating that the first major spermatophyte radiation occurred during the Late Devonian. At least fourteen Late Devonian species are now recognized, and our knowledge of the diversity of those early seed plants has dramatically increased. Five morphotypes of seeds have been defined, mostly based on cupule morphology and on the number and degree of fusion of the integumentary lobes. In this paper, we critically discuss the abundant environmental information in order to characterize the environment in which this radiation occurred. Sedimentological information indicates that seed plants evolved in disturbed environments. It is suggested that early seed plants thrived in the shade of the dominating
Archaeopteris
, and that their evolution was canalized by this strong biotic pressure. We also confirm the previous suggestion that the variability of seed morphotypes can be explained by the weak abiotic selective pressure that existed in the
Archaeopteris
understory.
The sedimentary environment of the Late Devonian East Greenland tetrapods
Authors: Astin T. R. , Marshall J. E. A. , Blom H. , Berry C. M.
Published: September 2010

The Late Devonian early tetrapods in East Greenland occur in the Celsius Bjerg Group. Key occurrences are located in a detailed stratigraphic section used here to interpret the sedimentary palaeoenvironments. The palaeoenvironment for the Britta Dal Formation (which contains both
Ichthyostega
and
Acanthostega
) is reinterpreted. The Britta Dal Formation channels have flat bases, are poorly channelized, are of low sinuosity and are part of a very major distributory system that periodically experienced extreme flooding. The tetrapod fossils were recovered from an ephemeral system that was not permanently habitable in the immediate area. Plant megafossils are poorly preserved casts and impressions dominated by lycopsids and fern-like plants. The overbank siltstones are dominated by arid soil forming processes and comprise a spectacular sequence of vertisols. The 1174 m
in situ Ichthyostega
locality in Paralleldal was relocated and occurs just below the midpoint of the second megacycle in the Britta Dal Formation.
Biological Functions and Biogenesis of Secreted Bacterial Outer Membrane Vesicles
Authors: Kulp Adam , Kuehn Meta J.
Published: September 2010

Gram-negative bacteria produce outer membrane vesicles (OMVs) that contain biologically active proteins and perform diverse biological processes. Unlike other secretion mechanisms, OMVs enable bacteria to secrete insoluble molecules in addition to and in complex with soluble material. OMVs allow enzymes to reach distant targets in a concentrated, protected, and targeted form. OMVs also play roles in bacterial survival: Their production is a bacterial stress response and important for nutrient acquisition, biofilm development, and pathogenesis. Key characteristics of OMV biogenesis include outward bulging of areas lacking membrane-peptidoglycan bonds, the capacity to upregulate vesicle production without also losing outer membrane integrity, enrichment or exclusion of certain proteins and lipids, and membrane fission without direct energy from ATP/GTP hydrolysis. Comparisons of similar budding mechanisms from diverse biological domains have provided new insight into evaluating mechanisms for outer membrane vesiculation.
Letting SleepingdosLie: Does Dormancy Play a Role in Tuberculosis?
Authors: Chao Michael C. , Rubin Eric J.
Published: September 2010

Mycobacterium tuberculosis, which causes tuberculosis, remains a major human public health threat. This is largely due to a sizeable reservoir of latently infected individuals, who may relapse into active disease decades after first acquiring the infection. Furthermore, patients have a very slow response to treatment of active disease. Latency and antibiotic tolerance are commonly taken as a proxy for dormancy, a stable nonreplicative state. However, latency is a clinical term that is solely defined by a lack of disease indicators. The actual state of the bacterium in human latency is not well understood. Here we evaluate the results of several in vitro models of dormancy and consider the applicability of various animal models for studying aspects of human latency and resistance to killing by antibiotics. Furthermore, we propose a model for the initiation of dormancy and resuscitation during infection.
Bacterial Shape: Two-Dimensional Questions and Possibilities
Authors: Young Kevin D.
Published: September 2010

Events in the past decade have made it both possible and interesting to ask how bacteria create cells of defined length, diameter, and morphology. The current consensus is that bacterial shape is determined by the coordinated activities of cytoskeleton complexes that drive cell elongation and division. Cell length is most easily explained by the timing of cell division, principally by regulating the activity of the FtsZ protein. However, the question of how cells establish and maintain a specific and uniform diameter is, by far, much more difficult to answer. Mutations associated with the elongation complex often alter cell width, though it is not clear how. Some evidence suggests that diameter is strongly influenced by events during cell division. In addition, surprising new observations show that the bacterial cell wall is more highly malleable than previously believed and that cells can alter and restore their shapes by relying only on internal mechanisms.
Mechanosensitive Channels in Microbes
Authors: Kung Ching , Martinac Boris , Sukharev Sergei
Published: September 2010

All cells, including microbes, detect and respond to mechanical forces, of which osmotic pressure is most ancient and universal. Channel proteins have evolved such that they can be directly stretched open when the membrane is under turgor pressure. Osmotic downshock, as in rain, opens bacterial mechanosensitive (MS) channels to jettison osmolytes, relieving pressure and preventing cell lysis. The ion flux through individual channel proteins can be observed directly with a patch clamp. MS channels of large and small conductance (MscL and MscS, respectively) have been cloned, crystallized, and subjected to biophysical and genetic analyses in depth. They are now models to scrutinize how membrane forces direct protein conformational changes. Eukaryotic microbes have homologs from animal sensory channels of the TRP superfamily. The MS channel in yeast is also directly sensitive to membrane stretch. This review examines the key concept that proteins embedded in the lipid bilayer can respond to the changes in the mechanical environment the lipid bilayer provides.
Pharmacological inhibition of TRPM4 hyperpolarizes vascular smooth muscle
Authors: Gonzales Albert L. , Garcia Zarine I. , Amberg Gregory C. , Earley Scott
Published: September 2010

The contractile state of vascular smooth muscle cells is regulated by small changes in membrane potential that gate voltage-dependent calcium channels. The melastatin transient receptor potential (TRP) channel TRPM4 is a critical mediator of pressure-induced membrane depolarization and arterial constriction. A recent study shows that the tricyclic compound 9-phenanthrol inhibits TRPM4, but not the related channel TRPM5. The current study investigated the specificity of 9-phenanthrol and the effects of the compound on pressure-induced smooth muscle depolarization and arterial constriction. Patch-clamp electrophysiology revealed that 9-phenanthrol blocks native TRPM4 currents in freshly isolated smooth muscle cells in a concentration-dependent manner (IC50 = 10.6 μM). 9-Phenanthrol (30 μM) had no effect on maximum evoked currents in human embryonic kidney cells expressing recombinant TRPC3 or TRPC6 channels. Large-conductance Ca2+-activated K+, voltage-dependent K+, inwardly rectifying K+, and voltage-dependent Ca2+ channel activity in native cerebral artery myocytes was not altered by administration of 9-phenanthrol (30 μM). Using intracellular microelectrodes to record smooth muscle membrane potential in isolated cerebral arteries pressurized to 70 mmHg, we found that 9-phenanthrol (30 μM) reversibly hyperpolarized the membrane from ∼−40 mV to ∼−70 mV. In addition, we found that myogenic tone was reversibly abolished when vessels were exposed to 9-phenanthrol. These data demonstrate that 9-phenanthrol is useful for studying the functional significance of TRPM4 in vascular smooth muscle cells and that TRPM4 is an important regulator of smooth muscle cell membrane depolarization and arterial constriction in response to intraluminal pressure.
Functional expression of SGLTs in rat brain
Authors: Yu Amy S. , Hirayama Bruce A. , Timbol Gerald , Liu Jie , Basarah Ernest , Kepe Vladimir , Satyamurthy Nagichettiar , Huang Sung-Cheng , Wright Ernest M. , Barrio Jorge R.
Published: September 2010

This work provides evidence of previously unrecognized uptake of glucose via sodium-coupled glucose transporters (SGLTs) in specific regions of the brain. The current understanding of functional glucose utilization in brain is largely based on studies using positron emission tomography (PET) with the glucose tracer 2-deoxy-2-[F-18]fluoro-d-glucose (2-FDG). However, 2-FDG is only a good substrate for facilitated-glucose transporters (GLUTs), not for SGLTs. Thus, glucose accumulation measured by 2-FDG omits the role of SGLTs. We designed and synthesized two high-affinity tracers: one, α-methyl-4-[F-18]fluoro-4-deoxy-d-glucopyranoside (Me-4FDG), is a highly specific SGLT substrate and not transported by GLUTs; the other one, 4-[F-18]fluoro-4-deoxy-d-glucose (4-FDG), is transported by both SGLTs and GLUTs and will pass through the blood brain barrier (BBB). In vitro Me-4FDG autoradiography was used to map the distribution of uptake by functional SGLTs in brain slices with a comparable result from in vitro 4-FDG autoradiography. Immunohistochemical assays showed that uptake was consistent with the distribution of SGLT protein. Ex vivo 4-FDG autoradiography showed that SGLTs in these areas are functionally active in the normal in vivo brain. The results establish that SGLTs are a normal part of the physiology of specific areas of the brain, including hippocampus, amygdala, hypothalamus, and cerebral cortices. 4-FDG PET imaging also established that this BBB-permeable SGLT tracer now offers a functional imaging approach in humans to assess regulation of SGLT activity in health and disease.
Lack of α8-integrin aggravates podocyte injury in experimental diabetic nephropathy
Authors: Hartner Andrea , Cordasic Nada , Menendez-Castro Carlos , Volkert Gudrun , Yabu Julie M. , Kupraszewicz-Hutzler Miroslava , Rascher Wolfgang , Hilgers Karl F.
Published: September 2010

Development of diabetic nephropathy is accompanied by changes in integrin-mediated cell-matrix interactions. The α8-integrin chain is specifically expressed in mesangial cells of the glomerulus. During experimental hypertension, α8-integrin plays a protective role in the glomerulus. We hypothesized that α8-integrin is involved in maintaining the integrity of the glomerulus in diabetic nephropathy. Experimental streptozotocin (STZ) diabetes led to an increased expression and glomerular deposition of α8-integrin. To test the functional role of α8-integrin, STZ diabetes was induced in mice with a homozygous (α8−/−) or heterozygous (α8+/−) deletion of the α8-integrin gene and in wild-type litters (α8+/+). Blood glucose and mean arterial blood pressure were not different in α8−/− and α8+/+ mice after 6 wk of diabetes. However, diabetic α8−/− mice developed significantly higher albuminuria and more glomerulosclerosis than diabetic α8+/+ mice. Moreover, in diabetic α8−/− mice, the number of glomerular cells staining positive for the podocyte markers WT-1 and vimentin were reduced more prominently than in diabetic α8+/+. The filtration barrier protein nephrin was downregulated in diabetic glomeruli with the strongest reduction observed in α8−/− mice. Taken together, α8−/− mice developed more severe glomerular lesions and podocyte damage after onset of STZ diabetes than α8+/+ mice, indicating that α8-integrin is protective for the structure and function of the glomerulus and maintains podocyte integrity during the development of diabetic nephropathy.
Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for hypertension?
Authors: Bankir Lise , Bichet Daniel G. , Bouby Nadine
Published: September 2010

Excessive sodium reabsorption by the kidney has long been known to participate in the pathogenesis of some forms of hypertension. In the kidney, the final control of NaCl reabsorption takes place in the distal nephron through the amiloride-sensitive epithelial sodium channel (ENaC). Liddle's syndrome, an inherited form of hypertension due to gain-of-function mutations in the genes coding for ENaC subunits, has demonstrated the key role of this channel in the sodium balance. Although aldosterone is classically thought to be the main hormone regulating ENaC activity, several studies in animal models and in humans highlight the important effect of vasopressin on ENaC regulation and sodium transport. This review summarizes the effect of vasopressin V2 receptor stimulation on ENaC activity and sodium excretion in vivo. Moreover, we report the experimental and clinical data demonstrating the role of renal ENaC in water conservation at the expense of a reduced ability to excrete sodium. Acute administration of the selective V2 receptor agonist dDAVP not only increases urine osmolality and reduces urine flow rate but also reduces sodium excretion in rats and humans. Chronic V2 receptor stimulation increases blood pressure in rats, and a significant correlation was found between blood pressure and urine concentration in healthy humans. This led us to discuss how excessive vasopressin-dependent ENaC stimulation could be a risk factor for sodium retention and resulting increase in blood pressure.
Voluntary wheel running exercise and dietary lactose concomitantly reduce proportion of secondary bile acids in rat feces
Authors: Hagio Masahito , Matsumoto Megumi , Yajima Takaji , Hara Hiroshi , Ishizuka Satoshi
Published: September 2010

According to epidemiologic studies, a negative correlation exists between exercise amount and subsequent cancer development risk in the large intestine. The proportion of secondary bile acids (SBA) in the large intestine is related to subsequent risk for colorectal carcinogenesis. The aim of this study was to investigate the effects of voluntary wheel running exercise and dietary intervention on bile acid (BA) metabolism in the large intestine. Wistar/ST rats (6 wk old) were divided into two groups, exercise and sedentary, after acclimation. Four days after the animals were assigned to a group, rats in each group were fed diets supplemented with different carbohydrate sources including dextrin, sucrose, and lactose. The wheel running period was 4 wk in the exercise group, whereas rats in the sedentary group remained in individual cages during this period. BA composition in collected feces was analyzed with ultraperformance liquid chromatography-electrospray ionization mass spectrometry. We found that wheel running exercise decreased plasma concentrations of cholesterol, triglyceride, and free fatty acids. These decreases were accompanied by a reduction in the proportion of SBA to primary BA (PBA) in feces; however, daily excretion of BA was comparable regardless of wheel running exercise. In addition, ingestion of lactose decreased the SBA-to-PBA ratio and suppressed production of hyodeoxycholic acid in feces. In conclusion, voluntary wheel running exercise, in combination with dietary intervention, could independently reduce the SBA-to-PBA ratio within the large intestine without changing BA excretion. These changes may contribute to the prevention of colorectal carcinogenesis.
Prostacyclin and milrinone by aerosolization improve pulmonary hemodynamics in newborn lambs with experimental pulmonary hypertension
Authors: Kumar Vasanth H. , Swartz Daniel D. , Rashid Nasir , Lakshminrusimha Satyan , Ma Changxing , Ryan Rita M. , Morin Frederick C.
Published: September 2010

Aerosolized prostacyclin (PGI2) produces selective pulmonary vasodilation in patients with pulmonary hypertension (PH). The response to PGI2may be increased by phosphodiesterase type 3 inhibitors such as milrinone. We studied the dose response effects of aerosolized PGI2and aerosolized milrinone both alone and in combination on pulmonary and systemic hemodynamics in newborn lambs with Nω-nitro-l-arginine methyl ester (l-NAME)-induced PH. We hypothesized that coaerosolization of PGI2with milrinone would additively decrease pulmonary vascular resistance (PVR), prolong the duration of action of PGI2, and selectively dilate the pulmonary vasculature. Near-term lambs were delivered by C-section and instrumented and PH was induced by l-NAME (bolus 25 mg/kg; infusion 10 mg·kg−1·h−1) and indomethacin. In the first set of experiments, PGI2was aerosolized at random doses of 2, 20, 100, 200, 500, and 1,000 ng·kg−1·min−1followed by milrinone at doses of 0.1, 1, and 10 μg·kg−1·min−1over 10 min. In the second set of experiments, milrinone at 1 μg·kg−1·min−1was aerosolized in combination with PGI2at doses of 20, 100, and 200 ng·kg−1·min−1over 10 min. Pulmonary arterial pressures (PAP) and PVR decreased significantly with increasing doses of aerosolized PGI2and milrinone. The combination of PGI2and milrinone significantly reduced PAP and PVR more than either of the drugs aerosolized alone. Addition of milrinone significantly increased the duration of action of PGI2. When aerosolized independently, PGI2and milrinone selectively dilated the pulmonary vasculature but the combination did not. Milrinone enhances the vasodilatory effects of PGI2on the pulmonary vasculature but caution must be exercised regarding systemic hypotension.
Endocannabinoid-Dependent LTD in a Nociceptive Synapse Requires Activation of a Presynaptic TRPV-Like Receptor
Authors: Yuan Sharleen , Burrell Brian D.
Published: September 2010

Recent studies have found that some forms of endocannabinoid-dependent synaptic plasticity in the hippocampus are mediated through activation of transient potential receptor vanilloid (TRPV) receptors instead of cannabinoid receptors CB1 or CB2. The potential role for synaptic localization of TRPV receptors during endocannabinoid modulation of nociceptive synapses was examined in the leech CNS where it is possible to record from the same pair of neurons from one preparation to the next. Long-term depression (LTD) in the monosynaptic connection between the nociceptive (N) sensory neuron and the longitudinal (L) motor neuron was found to be endocannabinoid-dependent given that this depression was blocked by RHC-80267, an inhibitor of DAG lipase that is required for 2-arachidonoyl glycerol (2AG) synthesis. Intracellular injection of a second DAG lipase inhibitor, tetrahyrdolipstatin (THL) was also able to block this endocannabinoid-dependent LTD (ecLTD) when injected postsynaptically but not presynaptically. N-to-L ecLTD was also inhibited by the TRPV1 antagonists capsazepine and SB 366791. Bath application of 2AG or the TRPV1 agonists capsaicin and resiniferatoxin mimicked LTD and both capsaicin- and 2AG-induced depression were blocked by capsazepine. In addition, pretreatment with 2AG or capsaicin occluded subsequent expression of LTD induced by repetitive activity. Presynaptic, but not postsynaptic, intracellular injection of capsazepine blocked both activity- and 2AG-induced ecLTD, suggesting that a presynaptic TRPV-like receptor in the leech mediated this form of synaptic plasticity. These findings potentially extend the role ecLTD to nociceptive synapses and suggest that invertebrate synapses, which are thought to lack CB1/CB2 receptor orthologues, utilize a TRPV-like protein as an endocannabinoid receptor.
Hearing Loss Alters Serotonergic Modulation of Intrinsic Excitability in Auditory Cortex
Authors: Rao Deepti , Basura Gregory J. , Roche Joseph , Daniels Scott , Mancilla Jaime G. , Manis Paul B.
Published: September 2010

Sensorineural hearing loss during early childhood alters auditory cortical evoked potentials in humans and profoundly changes auditory processing in hearing-impaired animals. Multiple mechanisms underlie the early postnatal establishment of cortical circuits, but one important set of developmental mechanisms relies on the neuromodulator serotonin (5-hydroxytryptamine [5-HT]). On the other hand, early sensory activity may also regulate the establishment of adultlike 5-HT receptor expression and function. We examined the role of 5-HT in auditory cortex by first investigating how 5-HT neurotransmission and 5-HT2receptors influence the intrinsic excitability of layer II/III pyramidal neurons in brain slices of primary auditory cortex (A1). A brief application of 5-HT (50 μM) transiently and reversibly decreased firing rates, input resistance, and spike rate adaptation in normal postnatal day 12 (P12) to P21 rats. Compared with sham-operated animals, cochlear ablation increased excitability at P12–P21, but all the effects of 5-HT, except for the decrease in adaptation, were eliminated in both sham-operated and cochlear-ablated rats. At P30–P35, cochlear ablation did not increase intrinsic excitability compared with shams, but it did prevent a pronounced decrease in excitability that appeared 10 min after 5-HT application. We also tested whether the effects on excitability were mediated by 5-HT2receptors. In the presence of the 5-HT2-receptor antagonist, ketanserin, 5-HT significantly decreased excitability compared with 5-HT or ketanserin alone in both sham-operated and cochlear-ablated P12–P21 rats. However, at P30–P35, ketanserin had no effect in sham-operated and only a modest effect cochlear-ablated animals. The 5-HT2-specific agonist 5-methoxy- N, N-dimethyltryptamine also had no effect at P12–P21. These results suggest that 5-HT likely regulates pyramidal cell excitability via multiple receptor subtypes with opposing effects. These data also show that early sensorineural hearing loss affects the ability of 5-HT receptor activation to modulate A1 pyramidal cell excitability.
Target of Rapamycin Signaling in Leukemia and Lymphoma
Authors: Vu Collin , Fruman David A.
Published: September 2010

Growth factors and many oncogenes activate the lipid kinase phosphoinositide 3-kinase (PI3K), initiating a signaling cascade that includes the protein kinases AKT and target of rapamycin (TOR). The PI3K/AKT/TOR signaling pathway is a significant contributor to disease in various human cancers, including hematologic malignancies. Here we discuss different strategies to inhibit TOR for the treatment of leukemia, lymphoma, and myeloma. The TOR enzyme exists in two complexes in cells, TORC1 and TORC2. The majority of preclinical and clinical efforts to target TOR have involved using rapamycin and its analogs (rapalogs), which suppress TORC1 only partially and do not acutely inhibit TORC2. A new class of small molecules targeting the ATP-binding site of the TOR kinase, termed active-site TOR inhibitors (asTORi), achieves greater inhibition of both TOR complexes, resulting in broader suppression of the PI3K/AKT/TOR signaling network. Preclinical evidence suggests that asTORi have greater efficacy than rapalogs in Philadelphia chromosome–positive acute lymphoblastic leukemia and in T-cell lymphoma. These agents also show greater tolerability in animal models relative to rapalogs or inhibitors of PI3K. These findings encourage broader evaluation of asTORi efficacy in acute myeloid leukemia, B-cell lymphoma, myeloma, and other blood cancers. Clin Cancer Res; 16(22); 5374–80. ©2010 AACR.
Preload Dependency of Left Ventricular Torsion
Authors: Weiner Rory B. , Weyman Arthur E. , Khan Abigail May , Reingold Jason S. , Chen-Tournoux Annabel A. , Scherrer-Crosbie Marielle , Picard Michael H. , Wang Thomas J. , Baggish Aaron L.
Published: September 2010

Background—

Left ventricular (LV) rotation results from contraction of obliquely oriented myocardial fibers. The net difference between systolic apical counterclockwise rotation and basal clockwise rotation is left ventricular torsion (LVT). Although LVT is altered in various cardiac diseases, determinants of LVT are incompletely understood.

Methods and Results—

LV end-diastolic volume, LV apical and basal rotation, peak systolic LVT, and peak early diastolic untwisting rate were measured by speckle-tracking echocardiography in healthy subjects (n=8) before and after infusion of a weight-based normal saline bolus (2.1±0.3 L). Saline infusion led to a significant increase in end-diastolic LV internal diameter (45.9±3.7 versus 47.6±4.2 mm;
P
=0.002) and LV end-diastolic volume (90.0±21.6 versus 98.3±19.6 mL;
P
=0.01). Stroke volume (51.3±10.9 versus 63.0±15.5 mL;
P
=0.003) and cardiac output (3.4±0.8 versus 4.4±1.5 L/min;
P
=0.007) increased, whereas there was no change in heart rate and blood pressure. There was a significant increase in the magnitude of peak systolic apical rotation (7.5±2.4° versus 10.5±2.8°;
P
<0.001) but no change in basal rotation (−4.1±2.3° versus −4.8±3.1°;
P
=0.44). Accordingly, peak systolic LVT increased by 33% after saline infusion (11.2±1.3° versus 14.9±1.7°;
P
<0.001). This saline-induced increase in LVT was associated with a marked increase in peak early diastolic untwisting rate (72.3±21.4 versus 136.8±30.0 degrees/s;
P
<0.001).

Conclusions—

Peak systolic LVT and peak early diastolic untwisting rate are preload-dependent. Changes in LV preload should be considered when interpreting results of future LVT studies.
Load Modulation of BOLD Response and Connectivity Predicts Working Memory Performance in Younger and Older Adults
Authors: Nagel Irene E. , Preuschhof Claudia , Li Shu-Chen , Nyberg Lars , Bäckman Lars , Lindenberger Ulman , Heekeren Hauke R.
Published: September 2010

Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity with age trends in WM performance. Using functional magnetic resonance imaging, we investigated the relations among WM performance, neural activity in the WM network, and adult age using a parametric letter n-back task in 30 younger adults (21–31 years) and 30 older adults (60–71 years). Individual differences in the WM network's responsivity to increasing task difficulty were related to WM performance, with a more responsive BOLD signal predicting greater WM proficiency. Furthermore, individuals with higher WM performance showed greater change in connectivity between left dorsolateral prefrontal cortex and left premotor cortex across load. We conclude that a more responsive WM network contributes to higher WM performance, regardless of adult age. Our results support the notion that individual differences in WM performance are important to consider when studying the WM network, particularly in age-comparative studies.
Erroneous Model Field Representations in Multiple Pseudoproxy Studies: Corrections and Implications*
Authors: Smerdon Jason E. , Kaplan Alexey , Amrhein Daniel E.
Published: September 2010

Pseudoproxy experiments evaluate statistical methods used to reconstruct climate fields from paleoclimatic proxies during the Common Era. These experiments typically employ output from millennial simulations by general circulation models (GCMs). It is demonstrated that multiple published pseudoproxy studies have used erroneously processed GCM surface temperature fields: the NCAR Community Climate System Model (CCSM), version 1.4, field was incorrectly oriented geographically and the GKSS ECHO-g FOR1 field was corrupted by a hemispheric-scale smoothing in the Western Hemisphere. These problems are not associated with the original model simulations; they instead arose because of incorrect processing of the model data for the pseudoproxy experiments. The consequences of these problems are evaluated for the studies in which the incorrect fields were used. Some quantitative results are invalidated by the findings: these include all experiments that used the corrupted ECHO-g field and those aspects of previous CCSM experiments that focused on Niño-3 reconstructions. Other results derived from the CCSM field can be reinterpreted based on the information provided herein and their qualitative characteristics remain similar.