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Sample records for voltage-clamp studies revealed

  1. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    Directory of Open Access Journals (Sweden)

    Palade Philip T

    2010-11-01

    Full Text Available Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR in cardiac myocytes, with voltage clamp (VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR, and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo. Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU, in which resides the mechanistic basis of CICR. The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel. It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its

  2. How the early voltage clamp studies of José del Castillo inform "modern" neuroscience.

    Science.gov (United States)

    Zottoli, Steven J

    2012-10-01

    The description of ionic currents that flow across the membrane of the squid giant axon during an action potential sparked an interest in determining whether there were similar currents in vertebrates. The preparation of choice was the node of Ranvier in single myelinated fibers in frog. José del Castillo spent 3 years on the United States mainland from 1956 to 1959. During that time, he collaborated with Jerome Y. Lettvin and John W. Moore. I discuss how these individuals met one another and some of their scientific discoveries using the voltage clamp to study squid giant axons and frog nodes. Much of this work was conducted at the Marine Biological Laboratory in Woods Hole, MA, and I attempt to convey a sense of the unique scientific "melting pot" that existed at the Marine Biological Laboratory and the broader effect that del Castillo had on "modern" neuroscience.

  3. Quadratic sinusoidal analysis of voltage clamped neurons.

    Science.gov (United States)

    Magnani, Christophe; Moore, Lee E

    2011-11-01

    Nonlinear biophysical properties of individual neurons are known to play a major role in the nervous system, especially those active at subthreshold membrane potentials that integrate synaptic inputs during action potential initiation. Previous electrophysiological studies have made use of a piecewise linear characterization of voltage clamped neurons, which consists of a sequence of linear admittances computed at different voltage levels. In this paper, a fundamentally new theory is developed in two stages. First, analytical equations are derived for a multi-sinusoidal voltage clamp of a Hodgkin-Huxley type model to reveal the quadratic response at the ionic channel level. Second, the resulting behavior is generalized to a novel Hermitian neural operator, which uses an algebraic formulation capturing the entire quadratic behavior of a voltage clamped neuron. In addition, this operator can also be used for a nonlinear identification analysis directly applicable to experimental measurements. In this case, a Hermitian matrix of interactions is built with paired frequency probing measurements performed at specific harmonic and interactive output frequencies. More importantly, eigenanalysis of the neural operator provides a concise signature of the voltage dependent conductances determined by their particular distribution on the dendritic and somatic membrane regions of neurons. Finally, the theory is concretely illustrated by an analysis of an experimentally measured vestibular neuron, providing a remarkably compact description of the quadratic responses involved in the nonlinear processing underlying the control of eye position during head rotation, namely the neural integrator.

  4. Voltage clamp methods for the study of membrane currents and SR Ca2+ release in adult skeletal muscle fibres

    Science.gov (United States)

    Hernández-Ochoa, Erick O.; Schneider, Martin F.

    2012-01-01

    Skeletal muscle excitation-contraction (E-C)1 coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)2 Ca2+ release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca2+, due to depolarization-initiated SR Ca2+ release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or ‘high resistance gap’ techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca2+ signalling properties of mouse skeletal muscle membranes are being investigated. PMID:22306655

  5. Voltage-dependent conformational changes in human Ca2+- and voltage-activated K+ channel, revealed by voltage-clamp fluorometry

    Science.gov (United States)

    Savalli, Nicoletta; Kondratiev, Andrei; Toro, Ligia; Olcese, Riccardo

    2006-01-01

    Large conductance voltage- and Ca2+-activated K+ (BKCa) channels regulate important physiological processes such as neurotransmitter release and vascular tone. BKCa channels possess a voltage sensor mainly represented by the S4 transmembrane domain. Changes in membrane potential displace the voltage sensor, producing a conformational change that leads to channel opening. By site-directed fluorescent labeling of residues in the S3–S4 region and by using voltage clamp fluorometry, we have resolved the conformational changes the channel undergoes during activation. The voltage dependence of these conformational changes (detected as changes in fluorescence emission, fluorescence vs. voltage curves) always preceded the channel activation curves, as expected for protein rearrangements associated to the movement of the voltage sensor. Extremely slow conformational changes were revealed by fluorescent labeling of position 202, elicited by a mutual interaction of the fluorophore with the adjacent tryptophan 203. PMID:16895996

  6. Voltage-dependent conformational changes in human Ca(2+)- and voltage-activated K(+) channel, revealed by voltage-clamp fluorometry.

    Science.gov (United States)

    Savalli, Nicoletta; Kondratiev, Andrei; Toro, Ligia; Olcese, Riccardo

    2006-08-15

    Large conductance voltage- and Ca(2+)-activated K(+) (BK(Ca)) channels regulate important physiological processes such as neurotransmitter release and vascular tone. BK(Ca) channels possess a voltage sensor mainly represented by the S4 transmembrane domain. Changes in membrane potential displace the voltage sensor, producing a conformational change that leads to channel opening. By site-directed fluorescent labeling of residues in the S3-S4 region and by using voltage clamp fluorometry, we have resolved the conformational changes the channel undergoes during activation. The voltage dependence of these conformational changes (detected as changes in fluorescence emission, fluorescence vs. voltage curves) always preceded the channel activation curves, as expected for protein rearrangements associated to the movement of the voltage sensor. Extremely slow conformational changes were revealed by fluorescent labeling of position 202, elicited by a mutual interaction of the fluorophore with the adjacent tryptophan 203.

  7. Effects of deuterium oxide on the rate and dissociation constants for saxitoxin and tetrodotoxin action. Voltage-clamp studies on frog myelinated nerve

    International Nuclear Information System (INIS)

    Hahin, R.; Strichartz, G.

    1981-01-01

    The actions of tetrodotoxin (TTX) and saxitoxin (STX) in normal water and in deuterium oxide (D 20 ) have been studied in frog myelinated nerve. Substitution of D 20 for H 20 in normal Ringer's solution has no effect on the potency of TTX in blocking action potentials but increases the potency of STX by approximately 50%. Under voltage clamp, the steady-state inhibition of sodium currents by 1 nM STX is doubled in D 20 as a result of a halving of the rate of dissociation of STX from the sodium channel; the rate of block by STX is not measurably changed by D 20 . Neither steady-state inhibition nor the on- or off-rate constants of TTX are changed by D 20 substitution. The isotopic effects on STX binding are observed less than 10 min after the toxin has been added to D 20 , thus eliminating the possibility that slow-exchange (t 1/2 greater than 10 h) hydrogen-binding sites on STX are involved. The results are consistent with a hypothesis that attributes receptor-toxin stabilization to isotopic changes of hydrogen bonding; this interpretation suggests that hydrogen bonds contribute more to the binding of STX than to that of TTX at the sodium channel

  8. Potassium Chloride Versus Voltage Clamp Contractures in Ventricular Muscle

    Science.gov (United States)

    Morad, M.; Reeck, S.; Rao, M.

    1981-01-01

    In frog ventricle, developed tension was markedly larger in response to depolarization caused by a voltage clamp step than to depolarization induced by high concentrations of potassium chloride. Measurement of extracellular potassium activity at the surface and at the depth of muscle during the development of contractures showed that the diffusion of potassium is much slower than the spread of depolarization through the cross section of muscle. These two observations suggest that competition between the depolarizing and the negative inotropic effects of an increase in the extracellular potassium ion concentration may determine the time course and magnitude of contractile tension in heart muscle.

  9. Application of active electrode compensation to perform continuous voltage-clamp recordings with sharp microelectrodes.

    Science.gov (United States)

    Gómez-González, J F; Destexhe, A; Bal, T

    2014-10-01

    Electrophysiological recordings of single neurons in brain tissues are very common in neuroscience. Glass microelectrodes filled with an electrolyte are used to impale the cell membrane in order to record the membrane potential or to inject current. Their high resistance induces a high voltage drop when passing current and it is essential to correct the voltage measurements. In particular, for voltage clamping, the traditional alternatives are two-electrode voltage-clamp technique or discontinuous single electrode voltage-clamp (dSEVC). Nevertheless, it is generally difficult to impale two electrodes in a same neuron and the switching frequency is limited to low frequencies in the case of dSEVC. We present a novel fully computer-implemented alternative to perform continuous voltage-clamp recordings with a single sharp-electrode. To reach such voltage-clamp recordings, we combine an active electrode compensation algorithm (AEC) with a digital controller (AECVC). We applied two types of control-systems: a linear controller (proportional plus integrative controller) and a model-based controller (optimal control). We compared the performance of the two methods to dSEVC using a dynamic model cell and experiments in brain slices. The AECVC method provides an entirely digital method to perform continuous recording and smooth switching between voltage-clamp, current clamp or dynamic-clamp configurations without introducing artifacts.

  10. Suppression of Spiral Waves by Voltage Clamp Techniques in a Conductance-Based Cardiac Tissue Model

    International Nuclear Information System (INIS)

    Lian-Chun, Yu; Guo-Yong, Zhang; Yong, Chen; Jun, Ma

    2008-01-01

    A new control method is proposed to control the spatio-temporal dynamics in excitable media, which is described by the Morris–Lecar cells model. It is confirmed that successful suppression of spiral waves can be obtained by spatially clamping the membrane voltage of the excitable cells. The low voltage clamping induces breakup of spiral waves and the fragments are soon absorbed by low voltage obstacles, whereas the high voltage clamping generates travel waves that annihilate spiral waves through collision with them. However, each method has its shortcomings. Furthermore, a two-step method that combines both low and high voltage clamp techniques is then presented as a possible way of out this predicament. (cross-disciplinary physics and related areas of science and technology)

  11. Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry.

    Science.gov (United States)

    Zhu, Wandi; Varga, Zoltan; Silva, Jonathan R

    2016-01-01

    Very recently, voltage-clamp fluorometry (VCF) protocols have been developed to observe the membrane proteins responsible for carrying the ventricular ionic currents that form the action potential (AP), including those carried by the cardiac Na(+) channel, NaV1.5, the L-type Ca(2+) channel, CaV1.2, the Na(+)/K(+) ATPase, and the rapid and slow components of the delayed rectifier, KV11.1 and KV7.1. This development is significant, because VCF enables simultaneous observation of ionic current kinetics with conformational changes occurring within specific channel domains. The ability gained from VCF, to connect nanoscale molecular movement to ion channel function has revealed how the voltage-sensing domains (VSDs) control ion flux through channel pores, mechanisms of post-translational regulation and the molecular pathology of inherited mutations. In the future, we expect that this data will be of great use for the creation of multi-scale computational AP models that explicitly represent ion channel conformations, connecting molecular, cell and tissue electrophysiology. Here, we review the VCF protocol, recent results, and discuss potential future developments, including potential use of these experimental findings to create novel computational models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Characterization of heterologously expressed transporter genes by patch- and voltage-clamp methods: Application to cyclic nucleotide-dependent responses

    KAUST Repository

    Lemtiri-Chlieh, Fouad

    2013-09-03

    The application of patch- and voltage-clamp methods to study ion transport can be limited by many hurdles: the size of the cells to be patched and/or stabbed, the subcellular localization of the molecule of interest, and its density of expression that could be too low even in their own native environment. Functional expression of genes using recombinant DNA technology not only overcomes those hurdles but also affords additional and elegant investigations such as single-point mutation studies and subunit associations/regulations. In this chapter, we give a step-by-step description of two electrophysiological methods, patch clamp and two-electrode voltage clamp (TEVC), that are routinely used in combination with heterologous gene expression to assist researchers interested in the identification and characterization of ion transporters. We describe how to (1) obtain and maintain the cells suitable for the use with each of the above-mentioned methods (i.e., HEK-293 cells and yeast spheroplasts to use with the patch-clamp methodology and Xenopus laevis oocytes with TEVC), (2) transfect/inject them with the gene of interest, and (3) record ion transport activities. © Springer Science+Business Media New York 2013.

  13. Novel Low Loss Active Voltage Clamp Circuit for Series Connection of RCGCT thyristors

    Science.gov (United States)

    Ito, Hiroshi; Suzuki, Akihiro; Iwata, Akihiko

    This paper describes novel low loss active voltage clamp circuits for the series connection of RCGCT thyristors. For high voltage converters the series connection of power semiconductor devices is an essential technique for direct switching of high voltages. Several protection circuits have been applied to the series connection of RCGCT thyristors such as CRD snubber circuits which suppress over-voltages across RCGCT thyristors, and voltage balancing resistors to equalize voltage sharing in steady states. However, significant losses in these protection circuits lower the converter’s efficiency. We propose novel low-loss protection circuits, which have active voltage clamp snubber circuits and static voltage balancing circuits. The clamp capacitor voltage of the active voltage clamp snubber circuits are designed to be higher than the equally divided DC-Link voltage. This method can reduce the loss of the clamp circuit to no more than 1/10 of that of the conventional CRD snubber. Also the static voltage balancing circuits compensate for the voltage imbalance generated by the difference in the leakage current between the series connection RCGCT thyristors.

  14. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.; Andersen, Michael A.E.

    2005-07-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify design, increase efficiency and integration level, reduce product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp are presented. (au)

  15. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify the design, increase effic...... efficiency, reduce the product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp are presented....

  16. Equivalent circuit of frog atrial tissue as determined by voltage clamp-unclamp experiments.

    Science.gov (United States)

    Tarr, M; Trank, J

    1971-11-01

    The equivalent circuit that has been used in the analysis of nerve voltage-clamp data is that of the membrane capacity in parallel with the membrane resistance. Voltage-clamp experiments on frog atrial tissue indicate that this circuit will not suffice for this cardiac tissue. The change in membrane current associated with a step change in membrane potential does not show a rapid spike of capacitive current as would be expected for the simple parallel resistance-capacitance network. Rather, there is a step change in current followed by an exponential decay in current with a time constant of about 1 msec. This relatively slow capacitive charging current suggests that there is a resistance in series with the membrane capacity. A possible equivalent circuit is that of a series resistance external to the parallel resistance-capacitance network of the cell membranes. Another possible circuit assumes that the series resistance is an integral part of the cell membrane. The data presented in this paper demonstrate that the equivalent circuit of a bundle of frog atrial muscle is that of an external resistance in series with the cell membranes.

  17. Voltage-clamp-based methods for the detection of constitutively active acetylcholine-gated I(K,ACh) channels in the diseased heart.

    Science.gov (United States)

    Voigt, Niels; Makary, Samy; Nattel, Stanley; Dobrev, Dobromir

    2010-01-01

    Vagal nerve stimulation can promote atrial fibrillation (AF) that requires activation of the acetylcholine (ACh)-gated potassium current I(K,ACh). In chronic AF (cAF), I(K,ACh) shows strong activity despite the absence of ACh or analogous pharmacological stimulation. This receptor-independent, constitutive I(K,ACh) activity is suggested to represent an atrial-selective anti-AF therapeutic target, but the underlying molecular mechanisms are unknown. This chapter provides an overview of the voltage-clamp techniques that can be used to study constitutive I(K,ACh) activity in atrial myocytes and summarizes briefly the current knowledge about the potential underlying mechanism(s) of constitutive I(K,ACh) activity in diseased heart. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Isolated PWM DC-AC SICAM with an active capacitive voltage clamp[Pulse Density Modulated; Pulse Width Modulation

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.

    2004-03-15

    In this report an isolated PWM DC-AC SICAM with an active capacitive voltage clamp is presented. AC-DC power supply is implemented in its simplest form: diode rectifier followed by a medium-size charge-storage capacitors and possibly with an EMC filter on the mains entrance. Isolation from the AC mains is achieved using a high frequency (HF) transformer, whose voltages are not audio-modulated. The latter simplifies the design and is expected to have many advantages over the approach where the transformer voltages are modulated in regards to the audio signal reference. Input stage is built as a DC-AC inverter (push-pull, half-bridge or a full-bridge) and operated with 50% duty cycle, with all the challenges to avoid transformer saturation and obtain symmetrical operation. On the secondary side the output section is implemented as rectifier+inverter AC-AC stage, i.e. a true bidirectional bridge, which operation is aimed towards amplification of the audio signal. In order to solve the problem with the commutation of the load current, a dead time between the incoming and outgoing bidirectional switch is implemented, while a capacitive voltage clamp is used to keep the induced overvoltage to reasonable levels. The energy stored in the clamping capacitor is not wasted as in the dissipative clamps, but is rather transferred back to the primary side for further processing using an auxiliary isolated single-switch converter, i.e. an active clamping technique is used. (au)

  19. Substrate and Inhibitor-Specific Conformational Changes in the Human Serotonin Transporter Revealed by Voltage-Clamp Fluorometry

    DEFF Research Database (Denmark)

    Söderhielm, Pella C; Andersen, Jacob; Munro, Lachlan

    2015-01-01

    of TM6, Ala419 in the interface between TM8 and extracellular loop (EL) 4, and Leu481 in EL5. The reporter positions were used for time-resolved measurement of conformational changes during 5-HT transport and binding of cocaine and the selective serotonin reuptake inhibitors fluoxetine and escitalopram....... At all reporter positions, fluorescence changes observed upon substrate application were distinctly different from those observed upon inhibitor application, with respect to relative amplitude or direction. Furthermore, escitalopram, fluoxetine, and cocaine induced a very similar pattern of fluorescent...

  20. Involvement of a pertussis toxin-sensitive G-protein in excitation-contraction coupling of intact and cut-end voltage-clamped skeletal muscle fibres.

    Science.gov (United States)

    Mouzou, A; Poindessault, J P; Raymond, G

    1992-08-01

    In voltage-clamped frog muscle fibres 10 ng/ml PTX induced a decrease (approximately 35%) of tension when applied externally. Internal application in cut-end fibres significantly depressed tension after 20 min. This effect increased with time to reach 65% after 60 min. PTX shifted the voltage-dependent inactivation curve of tension by 30 mV towards hyperpolarizations and this was counteracted by raising external calcium concentration. The toxin induced a parallel decrease in tension and voltage-sensitive charge movement (49 +/- 9% and 52 +/- 6% respectively; n = 6). This was not counteracted by prior impregnation with forskolin. Internally applied GTP gamma S (500 microM) induced a simultaneous increase in tension (57 +/- 5%) and charge amount displaced (40 +/- 7%). By contrast, GDP beta S decreased tension and charge movement by 35 +/- 5% and 36 +/- 6% respectively.

  1. A novel dualistic profile of an allosteric AMPA receptor modulator identified through studies on recombinant receptors, mouse hippocampal synapses and crystal structures

    DEFF Research Database (Denmark)

    Christiansen, G B; Harbak, Barbara; Hede, S E

    2015-01-01

    -mediated neurotransmission. The aim of this study was to investigate functional and structural aspects of a novel analog of the AMPA receptor PAM cyclothiazide (CTZ) on recombinant and native glutamate receptors. We expressed rat GluA4flip and flop in Xenopus oocytes and characterized NS1376 and CTZ under two......-electrode voltage-clamp. The dose-response analyses revealed dual effects of NS1376. The modulator induced 30-fold and 42-fold reductions in glutamate potency and increased the glutamate efficacy by 3.2-fold and 5.3-fold at GluA4flip and GluA4flop, respectively. Rapid application of glutamate to excised outside...

  2. New active load voltage clamp for HF-link converters

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper proposes a new active clamp for HF-link converters, which features very high efficiency by returning the clamped energy back to the primary side through a small auxiliary converter. It also increases the reliability of HF-link converters by providing an alternative load current path du...

  3. New active load voltage clamp for HF-link converters

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.; Andersen, M.A.E.

    2005-07-01

    This paper proposes a new active clamp for HF-link converters, which features very high efficiency by returning the clamped energy back to the primary side through a small auxiliary converter. It also increases the reliability of HF-link converters by providing an alternative load current path during malfunctions of the secondary bidirectional bridge. The feasibility of the approach is shown on audio power amplifier prototype. New integrated magnetics design is presented that incorporates both the main power and auxiliary transformer on the same magnetic core. (au)

  4. New active load voltage clamp for HF-link converters

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper proposes a new active clamp for HF-link converters, which features very high efficiency by returning the clamped energy back to the primary side through a small auxiliary converter. It also increases the reliability of HF-link converters by providing an alternative load current path...

  5. Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32*

    Science.gov (United States)

    Brennan, Matthew J.; Karcz, Jennifer; Vaughn, Nicholas R.; Woolwine-Cunningham, Yvonne; DePriest, Adam D.; Escalona, Yerko; Perez-Acle, Tomas; Skerrett, I. Martha

    2015-01-01

    Tryptophan was substituted for residues in all four transmembrane domains of connexin32. Function was assayed using dual cell two-electrode voltage clamp after expression in Xenopus oocytes. Tryptophan substitution was poorly tolerated in all domains, with the greatest impact in TM1 and TM4. For instance, in TM1, 15 substitutions were made, six abolished coupling and five others significantly reduced function. Only TM2 and TM3 included a distinct helical face that lacked sensitivity to tryptophan substitution. Results were visualized on a comparative model of Cx32 hemichannel. In this model, a region midway through the membrane appears highly sensitive to tryptophan substitution and includes residues Arg-32, Ile-33, Met-34, and Val-35. In the modeled channel, pore-facing regions of TM1 and TM2 were highly sensitive to tryptophan substitution, whereas the lipid-facing regions of TM3 and TM4 were variably tolerant. Residues facing a putative intracellular water pocket (the IC pocket) were also highly sensitive to tryptophan substitution. Although future studies will be required to separate trafficking-defective mutants from those that alter channel function, a subset of interactions important for voltage gating was identified. Interactions important for voltage gating occurred mainly in the mid-region of the channel and focused on TM1. To determine whether results could be extrapolated to other connexins, TM1 of Cx43 was scanned revealing similar but not identical sensitivity to TM1 of Cx32. PMID:25969535

  6. Ethiopian population dermatoglyphic study reveals linguistic stratification of diversity.

    Directory of Open Access Journals (Sweden)

    Seile Yohannes

    Full Text Available The manifestation of ethnic, blood type, & gender-wise population variations regarding Dermatoglyphic manifestations are of interest to assess intra-group diversity and differentiation. The present study reports on the analysis of qualitaive and quantitative finger Dermatoglyphic traits of 382 individuals cross-sectionally sampled from an administrative region of Ethiopia, consisting of five ethnic cohorts from the Afro-Asiatic & Nilo-Saharan affiliations. These Dermatoglyphic parameters were then applied in the assessment of diversity & differentiation, including Heterozygosity, Fixation, Panmixia, Wahlund's variance, Nei's measure of genetic diversity, and thumb & finger pattern genotypes, which were inturn used in homology inferences as summarized by a Neighbour-Joining tree constructed from Nei's standard genetic distance. Results revealed significant correlation between Dermatoglyphics & population parameters that were further found to be in concordance with the historical accounts of the ethnic groups. Such inductions as the ancient north-eastern presence and subsequent admixure events of the Oromos (PII= 15.01, the high diversity of the Amharas (H= 0.1978, F= 0.6453, and P= 0.4144, and the Nilo-Saharan origin of the Berta group (PII= 10.66 are evidences to this. The study has further tested the possibility of applying Dermatoglyphics in population genetic & anthropologic research, highlighting on the prospect of developing a method to trace back population origins & ancient movement patterns. Additionally, linguistic clustering was deemed significant for the Ethiopian population, coinciding with recent genome wide studies that have ascertained that linguistic clustering as to being more crucial than the geographical patterning in the Ethiopian context. Finally, Dermatoglyphic markers have been proven to be endowed with a strong potential as non-invasive preliminary tools applicable prior to genetic studies to analyze ethnically sub

  7. Ethiopian population dermatoglyphic study reveals linguistic stratification of diversity.

    Science.gov (United States)

    Yohannes, Seile; Bekele, Endashaw

    2015-01-01

    The manifestation of ethnic, blood type, & gender-wise population variations regarding Dermatoglyphic manifestations are of interest to assess intra-group diversity and differentiation. The present study reports on the analysis of qualitaive and quantitative finger Dermatoglyphic traits of 382 individuals cross-sectionally sampled from an administrative region of Ethiopia, consisting of five ethnic cohorts from the Afro-Asiatic & Nilo-Saharan affiliations. These Dermatoglyphic parameters were then applied in the assessment of diversity & differentiation, including Heterozygosity, Fixation, Panmixia, Wahlund's variance, Nei's measure of genetic diversity, and thumb & finger pattern genotypes, which were inturn used in homology inferences as summarized by a Neighbour-Joining tree constructed from Nei's standard genetic distance. Results revealed significant correlation between Dermatoglyphics & population parameters that were further found to be in concordance with the historical accounts of the ethnic groups. Such inductions as the ancient north-eastern presence and subsequent admixure events of the Oromos (PII= 15.01), the high diversity of the Amharas (H= 0.1978, F= 0.6453, and P= 0.4144), and the Nilo-Saharan origin of the Berta group (PII= 10.66) are evidences to this. The study has further tested the possibility of applying Dermatoglyphics in population genetic & anthropologic research, highlighting on the prospect of developing a method to trace back population origins & ancient movement patterns. Additionally, linguistic clustering was deemed significant for the Ethiopian population, coinciding with recent genome wide studies that have ascertained that linguistic clustering as to being more crucial than the geographical patterning in the Ethiopian context. Finally, Dermatoglyphic markers have been proven to be endowed with a strong potential as non-invasive preliminary tools applicable prior to genetic studies to analyze ethnically sub-divided populations and

  8. Pulse and Trapezoidal Voltage Clamp Applied To Jurkat Cells: A T- Lymphocyte Cell Line

    Science.gov (United States)

    1993-04-01

    by the wholp cell patch technique, use a protocol of volLage pulses similar to that of Hodgkin and Huxley in their famous 1952 series of papers on...with the voltage pulses that produced them. We call the above protocol the HH protocol after Hodgkin and Huxley . Upward deflection in the current...exchaust ed SECURIT* Y CLASSIFICATION OF TWIS PAGE All other edition~s are obsolete UNCLASStIF IED UNCLASS IFI ED SECURITY CLASSIFICATION Of T,1 PAGZ

  9. Active gate driver for dv/dt control and active voltage clamping in an IGBT stack

    DEFF Research Database (Denmark)

    Rasmussen, Tonny Wederberg

    2005-01-01

    For high voltages converters stacks of IGBTs can be used if the static and dynamic voltage sharing among the IGBTs can be applied. dVCE/dt should also be controlled in order not to damage insulation material. This paper describes theory and measurements of an active gate driver for stacking IGBTs....... For the measurements two series connected standard IGBTs made for hard switching applications are used. Problems are shown and proposals for improvements are given....

  10. Microscopic study reveals the singular origins of growth

    Science.gov (United States)

    Yaari, G.; Nowak, A.; Rakocy, K.; Solomon, S.

    2008-04-01

    Anderson [Science 177, 293 (1972)] proposed the concept of complexity in order to describe the emergence and growth of macroscopic collective patterns out of the simple interactions of many microscopic agents. In the physical sciences this paradigm was implemented systematically and confirmed repeatedly by successful confrontation with reality. In the social sciences however, the possibilities to stage experiments to validate it are limited. During the 90's a series of dramatic political and economic events have provided the opportunity to do so. We exploit the resulting empirical evidence to validate a simple agent based alternative to the classical logistic dynamics. The post-liberalization empirical data from Poland confirm the theoretical prediction that the dynamics is dominated by singular rare events which insure the resilience and adaptability of the system. We have shown that growth is led by few singular “growth centers" (Fig. 1), that initially developed at a tremendous rate (Fig. 3), followed by a diffusion process to the rest of the country and leading to a positive growth rate uniform across the counties. In addition to the interdisciplinary unifying potential of our generic formal approach, the present work reveals the strong causal ties between the “softer" social conditions and their “hard" economic consequences.

  11. Implementing Japanese Lesson Study in Foreign Countries: Misconceptions Revealed

    Science.gov (United States)

    Fujii, Toshiakira

    2014-01-01

    This paper is based on data gathered during visits to Uganda and Malawi, conducted by the International Math-teacher Professionalization Using Lesson Study (IMPULS) project and the Japanese International Cooperation Agency (JICA). The author's observations and experiences highlighted misconceptions about lesson study. The paper concludes that some…

  12. Study Reveals Brain Biology behind Self-Control

    Science.gov (United States)

    Sparks, Sarah D.

    2011-01-01

    A new neuroscience twist on a classic psychology study offers some clues to what makes one student able to buckle down for hours of homework before a test while his classmates party. The study published in the September 2011 edition of "Proceedings of the National Academy of Science," suggests environmental cues may "hijack" the brain's mechanisms…

  13. Inferences on radiation carcinogenesis revealed by selected studies in animals

    International Nuclear Information System (INIS)

    Bustad, L.K.; Goldman, M.; Rosenblatt, L.

    1976-01-01

    Studies of heterogeneous populations of animals with long lives and humans, exposed to various radionuclides and particularly those related to the nuclear energy fuel cycle, are instructive for deriving inferences relative to the cinogenic risk of energy-related radiation. Dose-response curves for various radionuclides [with varying half-lives, qualities of radiation (LET), and metabolic characteristics] provide similarities regardless of the species studied or the tissues at risk

  14. Developmental palaeontology of Reptilia as revealed by histological studies.

    Science.gov (United States)

    Scheyer, Torsten M; Klein, Nicole; Sander, P Martin

    2010-06-01

    Among the fossilized ontogenetic series known for tetrapods, only more basal groups like temnospondyl amphibians have been used extensively in developmental studies, whereas reptilian and synapsid data have been largely neglected so far. However, before such ontogenetic series can be subject to study, the relative age and affiliation of putative specimens within a series has to be verified. Bone histology has a long-standing tradition as being a source of palaeobiological and growth history data in fossil amniotes and indeed, the analysis of bone microstructures still remains the most important and most reliable tool for determining the absolute ontogenetic age of fossil vertebrates. It is also the only direct way to reconstruct life histories and growth strategies for extinct animals. Herein the record of bone histology among Reptilia and its application to elucidate and expand fossilized ontogenies as a source of developmental data are reviewed. (c) 2009 Elsevier Ltd. All rights reserved.

  15. Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity.

    Science.gov (United States)

    Athanasiadis, Georgios; Cheng, Jade Y; Vilhjálmsson, Bjarni J; Jørgensen, Frank G; Als, Thomas D; Le Hellard, Stephanie; Espeseth, Thomas; Sullivan, Patrick F; Hultman, Christina M; Kjærgaard, Peter C; Schierup, Mikkel H; Mailund, Thomas

    2016-10-01

    Denmark has played a substantial role in the history of Northern Europe. Through a nationwide scientific outreach initiative, we collected genetic and anthropometrical data from ∼800 high school students and used them to elucidate the genetic makeup of the Danish population, as well as to assess polygenic predictions of phenotypic traits in adolescents. We observed remarkable homogeneity across different geographic regions, although we could still detect weak signals of genetic structure reflecting the history of the country. Denmark presented genomic affinity with primarily neighboring countries with overall resemblance of decreasing weight from Britain, Sweden, Norway, Germany, and France. A Polish admixture signal was detected in Zealand and Funen, and our date estimates coincided with historical evidence of Wend settlements in the south of Denmark. We also observed considerably diverse demographic histories among Scandinavian countries, with Denmark having the smallest current effective population size compared to Norway and Sweden. Finally, we found that polygenic prediction of self-reported adolescent height in the population was remarkably accurate (R 2 = 0.639 ± 0.015). The high homogeneity of the Danish population could render population structure a lesser concern for the upcoming large-scale gene-mapping studies in the country. Copyright © 2016 by the Genetics Society of America.

  16. New study reveals twice as many asteroids as previously believed

    Science.gov (United States)

    2002-05-01

    The ISO satellite Credits: ESA ISO An artist's impression of the ISO spacecraft. The ISO Deep Asteroid Search indicates that there are between 1.1 million and 1.9 million 'space rocks' larger than 1 kilometre in diameter in the so-called 'main asteroid belt', about twice as many as previously believed. However, astronomers think it is premature to revise current assessments of the risk of the Earth being hit by an asteroid. Despite being in our own Solar System, asteroids can be more difficult to study than very distant galaxies. With sizes of up to one thousand kilometres in diameter, the brightness of these rocky objects may vary considerably in just a few minutes. They move very quickly with respect to the stars - they have been dubbed 'vermin of the sky' because they often appear as trails on long exposure images. This elusiveness explains why their actual number and size distribution remains uncertain. Most of the almost 40,000 asteroids catalogued so far (1) orbit the Sun forming the 'main asteroid belt', between Mars and Jupiter, too far to pose any threat to Earth. However, space-watchers do keep a closer eye on another category of asteroids, the 'Near Earth Asteroids' or 'NEAs', which are those whose orbits cross, or are likely to cross, that of our planet. The ISO Deep Asteroid Search (IDAS), the first systematic search for these objects performed in infrared light, focused on main belt asteroids. Because it is impossible to simply point the telescope at the whole main belt and count, astronomers choose selected regions of the belt and then use a theoretical model to extrapolate the data to the whole belt. Edward Tedesco (TerraSystems, Inc., New Hampshire, United States) and François-Xavier Desert (Observatoire de Grenoble, France) observed their main belt selected areas in 1996 and 1997 with ESA's ISO. They found that in the middle region of the belt the density of asteroids was 160 asteroids larger than 1 kilometre per square degree - an area of the

  17. Improvising in music: A learning biography study to reveal skill acquisition

    NARCIS (Netherlands)

    Wopereis, Iwan; Van Merriënboer, Jeroen; Kirschner, Paul A.

    2010-01-01

    Wopereis, I. G. J. H., Van Merriënboer, J. J. G., & Kirschner, P. A. (2010). Improvising in music: A learning biography study to reveal skill acquisition. In K. Gomez, L. Lyons, & J. Radinsky (Eds.), Proceedings of the 9th International Conference of the Learning Sciences: Vol. 2 (pp. 419-420).

  18. Monitoring studies should consider temporal variability to reveal relations between cyanobacterial abundance and environmental variables

    Directory of Open Access Journals (Sweden)

    JULIANA WOJCIECHOWSKI

    2015-09-01

    Full Text Available One of the main goals of monitoring cyanobacteria blooms in aquatic environments is to reveal the relationship between cyanobacterial abundance and environmental variables. Studies typically correlate data that were simultaneously sampled. However, samplings occur sparsely over time and may not reveal the short-term responses of cyanobacterial abundance to environmental changes. In this study, we tested the hypothesis that stronger cyanobacteria x environment relationships in monitoring are found when the temporal variability of sampling points is incorporated in the statistical analyses. To this end, we investigated relationships between cyanobacteria and seven environmental variables that were sampled twice yearly for three years across 11 reservoirs, and data from an intensive monitoring in one of these reservoirs. Poor correlations were obtained when correlating data simultaneously sampled. In fact, the 'highly recurrent' role of phosphorus in cyanobacteria blooms is not properly observed in all sampling periods. On the other hand, the strongest correlation values for the total phosphorus x cyanobacteria relationship were observed when we used the variation of sampling points. We have also shown that environment variables better explain cyanobacteria when a time lag is considered. We conclude that, in cyanobacteria monitoring, the best approach to reveal determinants of cyanobacteria blooms is to consider environmental variability.

  19. Comparative study of the human ficolins reveals unique features of Ficolin-3 (Hakata antigen)

    DEFF Research Database (Denmark)

    Hummelshoj, Tina; Fog, Lea Munthe; Madsen, Hans O

    2007-01-01

    The ficolins and mannose-binding lectin (MBL) are collagen-like defence proteins that serve as recognition molecules in lectin complement pathway. Differential features that may indicate diverse functions of these proteins are poorly understood. In this study we compared important biological...... features of the ficolins and MBL. We investigated the tissue distribution of the FCN1-3 and the MBL2 genes encoding the ficolins and MBL by quantitative PCR. Recombinant proteins were produced and structural and biological characteristics were investigated and compared. Our main findings were that FCN3 m......RNA was highly expressed in the liver and lung compared with the other genes revealing the lung as the tissue with the highest FCN3 expression pattern. Ficolin-3 revealed higher complement activating capacity compared with Ficolin-2, MBL and Ficolin-1 and was highly resistant to bacterial collagenase treatment...

  20. Insights into antiviral innate immunity revealed by studying hepatitis C virus.

    Science.gov (United States)

    Horner, Stacy M

    2015-08-01

    Experimental studies on the interactions of the positive strand RNA virus hepatitis C virus (HCV) with the host have contributed to several discoveries in the field of antiviral innate immunity. These include revealing the antiviral sensing pathways that lead to the induction of type I interferon (IFN) during HCV infection and also the importance of type III IFNs in the antiviral immune response to HCV. These studies on HCV/host interactions have contributed to our overall understanding of viral sensing and viral evasion of the antiviral intracellular innate immune response. In this review, I will highlight how these studies of HCV/host interactions have led to new insights into antiviral innate immunity. Overall, I hope to emphasize that studying antiviral immunity in the context of virus infection is necessary to fully understand antiviral immunity and how it controls the outcome of viral infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Curvature-electric effects in artificial and natural membranes studied using patch-clamp techniques.

    Science.gov (United States)

    Petrov, A G; Ramsey, R L; Usherwood, P N

    1989-01-01

    Methods for applying sound pressure to membrane patches formed at the tips of patch-clamp pipettes have been developed. Artificial membrane patches were formed from diphytanoyl phosphatidylcholine using a pipette dipping technique. Natural membrane patches were excised (inside-out mode) from collagenase-treated locust muscle membrane. Curvature-electric signals were registered under both voltage clamp and current clamp conditions. The phenomenon of flexoelectricity in membranes has previously been attributed to curvature-induced polarization originating from the liquid crystalline properties of membranes. The estimated magnitude (2 x 10(-18) C) of the flexoelectric coefficient of the artificial lipid bilayers is consistent with previous findings while that of the muscle membrane was in certain cases several times larger. The present study is the first to report on flexoelectricity in a natural membrane and raises the question of the biological significance of this phenomenon.

  2. Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.

    Science.gov (United States)

    Audemard-Verger, A; Descloux, E; Ponard, D; Deroux, A; Fantin, B; Fieschi, C; John, M; Bouldouyre, A; Karkowsi, L; Moulis, G; Auvinet, H; Valla, F; Lechiche, C; Davido, B; Martinot, M; Biron, C; Lucht, F; Asseray, N; Froissart, A; Buzelé, R; Perlat, A; Boutboul, D; Fremeaux-Bacchi, V; Isnard, S; Bienvenu, B

    2016-05-01

    Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14

  3. A novel dualistic profile of an allosteric AMPA receptor modulator identified through studies on recombinant receptors, mouse hippocampal synapses and crystal structures.

    Science.gov (United States)

    Christiansen, G B; Harbak, B; Hede, S E; Gouliaev, A H; Olsen, L; Frydenvang, K; Egebjerg, J; Kastrup, J S; Holm, M M

    2015-12-03

    Positive allosteric modulators (PAMs) of 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptors receive increasing interest as therapeutic drugs and have long served as important experimental tools in the study of the molecular mechanisms underlying glutamate-mediated neurotransmission. The aim of this study was to investigate functional and structural aspects of a novel analog of the AMPA receptor PAM cyclothiazide (CTZ) on recombinant and native glutamate receptors. We expressed rat GluA4flip and flop in Xenopus oocytes and characterized NS1376 and CTZ under two-electrode voltage-clamp. The dose-response analyses revealed dual effects of NS1376. The modulator induced 30-fold and 42-fold reductions in glutamate potency and increased the glutamate efficacy by 3.2-fold and 5.3-fold at GluA4flip and GluA4flop, respectively. Rapid application of glutamate to excised outside-out patches showed that NS1376 markedly attenuated desensitization, supporting the increased efficacy observed in the oocytes. Furthermore, when applied to acutely isolated mouse brain slices, NS1376 reduced the field excitatory postsynaptic potentials (fEPSPs) in the hippocampus to 51.6 ± 4.3% of baseline, likely as a consequence of reduced glutamate potency. However, the modulator displayed no effects on a sub-maximal long-term potentiation (LTP) protocol. We confirmed that CTZ increases presynaptic transmitter release, a property which was not shared by NS1376. Finally, we obtained detailed molecular information through X-ray structures, docking and molecular dynamics, which revealed that NS1376 interacts at the dimer interface of the ligand-binding domain in a manner overall similar to CTZ. NS1376 reveals that minor structural changes in CTZ can result in an altered modulatory profile, both enhancing agonist efficacy while markedly reducing agonist potency. These unique properties add new aspects to the complexity of allosteric modulations in neuronal systems. Copyright

  4. Metabolomics study of cereal grains reveals the discriminative metabolic markers associated with anatomical compartments

    Directory of Open Access Journals (Sweden)

    A.A. Moazzami

    2015-06-01

    Full Text Available This study used NMR-based metabolomics to compare the metabolic profile of different anatomical compartments of cereal grains i.e. bran and endosperm in order to gain further insightsinto their possible role in the beneficial health effects of whole grain products (WG. Polar watersoluble metabolites in 64 bran and endosperm, samples from rye and wheat were observed using600 MHz NMR. Bran samples had higher contents of 12 metabolites than endosperm samples. A comparative approach revealed higher contents of azelaic acid and sebacic acid in bran than in endosperm. In a pilot study, the consumption of WG rye bread (485 g caused NMR signals in 24h urine corresponding to azelaic acid. The relatively high abundance, anatomical specificity, patternof metabolism, urinary excretion in human, antibacterial, and anticancer activities suggest further studying of azelaic acid when exposure to WG or beneficial effects of WG are investigated.

  5. Comparison among different "revealers" in the study of accelerated blood clearance phenomenon.

    Science.gov (United States)

    Liang, Kaifan; Wang, Lirong; Su, Yuqing; Liu, Mengyang; Feng, Rui; Song, Yanzhi; Deng, Yihui

    2018-03-01

    The markers are the "revealers" of accelerated blood clearance (ABC) phenomenon. PEGylated nanocarriers labeled with various markers have been used to explore the mechanism of ABC. However, different markers were labeled on different nanocarriers, and the influence of different markers on ABC phenomenon is questionable. In this study, tocopheryl nicotinate (TN), N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt (NBD-DPPE), and 1,1'-dioctadecyl-3,3,3',3'-tetra-methylindotricarbocyanine iodide (DiR) were selected as markers. ABC index (0-30min) was used as an evaluation indicator to reveal ABC phenomenon after repeated injections of PEGylated emulsions (PEs) in Wistar rats. No significant difference was observed in ABC index (0-30min) of PE labeled with the three markers (P>0.05), suggesting that the results of previous studies using these markers were comparable and interchangeable. Of the three markers, TN required tedious analytical method and showed proliferative effect on liver cells, while NBD-DPPE fluorescence was easily interfered by tissues and its phospholipid composition affected ABC analysis. On the contrary, DiR was deemed superior due to its near-infrared fluorescence, high-sensitivity, and convenient analytical detection. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Talaromyces marneffei Genomic, Transcriptomic, Proteomic and Metabolomic Studies Reveal Mechanisms for Environmental Adaptations and Virulence

    Directory of Open Access Journals (Sweden)

    Susanna K. P. Lau

    2017-06-01

    Full Text Available Talaromyces marneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus. Among the 14 Mp1p homologs, only Mp1p is a virulence factor binding a variety of host proteins, fatty acids and lipids. There are 23 polyketide synthase genes, one for melanin and two for mitorubrinic acid/mitorubrinol biosynthesis, which are virulence factors. Another polyketide synthase is for biogenesis of the diffusible red pigment, which consists of amino acid conjugates of monascorubin and rubropunctatin. Novel microRNA-like RNAs (milRNAs and processing proteins are present. The dicer protein, dcl-2, is required for biogenesis of two milRNAs, PM-milR-M1 and PM-milR-M2, which are more highly expressed in hyphal cells. Comparative transcriptomics showed that tandem repeat-containing genes were overexpressed in yeast phase, generating protein polymorphism among cells, evading host’s immunity. Comparative proteomics between yeast and hyphal cells revealed that glyceraldehyde-3-phosphate dehydrogenase, up-regulated in hyphal cells, is an adhesion factor for conidial attachment.

  7. Revealed Preference Methods for Studying Bicycle Route Choice-A Systematic Review.

    Science.gov (United States)

    Pritchard, Ray

    2018-03-07

    One fundamental aspect of promoting utilitarian bicycle use involves making modifications to the built environment to improve the safety, efficiency and enjoyability of cycling. Revealed preference data on bicycle route choice can assist greatly in understanding the actual behaviour of a highly heterogeneous group of users, which in turn assists the prioritisation of infrastructure or other built environment initiatives. This systematic review seeks to compare the relative strengths and weaknesses of the empirical approaches for evaluating whole journey route choices of bicyclists. Two electronic databases were systematically searched for a selection of keywords pertaining to bicycle and route choice. In total seven families of methods are identified: GPS devices, smartphone applications, crowdsourcing, participant-recalled routes, accompanied journeys, egocentric cameras and virtual reality. The study illustrates a trade-off in the quality of data obtainable and the average number of participants. Future additional methods could include dockless bikeshare, multiple camera solutions using computer vision and immersive bicycle simulator environments.

  8. Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms

    DEFF Research Database (Denmark)

    Rasmussen, T. B.; Hansen, J.; Nissen, P. H.

    2013-01-01

    . This study aimed to investigate protein expression in myocardial and epidermal tissue of ARVC and CS patients carrying DSP mutations in order to elucidate potential molecular disease mechanisms. Genetic investigations identified three ARVC patients carrying different heterozygous DSP mutations in addition...... to a homozygous DSP mutation in a CS patient. The protein expression of DSP in mutation carriers was evaluated in biopsies from myocardial and epidermal tissue by immunohistochemistry. Keratinocyte cultures were established from skin biopsies of mutation carriers and characterized by reverse transcriptase...... polymerase chain reaction, western blotting, and protein mass spectrometry. The results showed that the mutation carriers had abnormal DSP expression in both myocardial and epidermal tissue. The investigations revealed that the disease mechanisms varied accordingly to the specific types of DSP mutation...

  9. Revealed Preference Methods for Studying Bicycle Route Choice—A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ray Pritchard

    2018-03-01

    Full Text Available One fundamental aspect of promoting utilitarian bicycle use involves making modifications to the built environment to improve the safety, efficiency and enjoyability of cycling. Revealed preference data on bicycle route choice can assist greatly in understanding the actual behaviour of a highly heterogeneous group of users, which in turn assists the prioritisation of infrastructure or other built environment initiatives. This systematic review seeks to compare the relative strengths and weaknesses of the empirical approaches for evaluating whole journey route choices of bicyclists. Two electronic databases were systematically searched for a selection of keywords pertaining to bicycle and route choice. In total seven families of methods are identified: GPS devices, smartphone applications, crowdsourcing, participant-recalled routes, accompanied journeys, egocentric cameras and virtual reality. The study illustrates a trade-off in the quality of data obtainable and the average number of participants. Future additional methods could include dockless bikeshare, multiple camera solutions using computer vision and immersive bicycle simulator environments.

  10. A passionate way of being: A qualitative study revealing the passion spiral

    Directory of Open Access Journals (Sweden)

    Susanna M. Halonen

    2014-06-01

    Full Text Available Being engaged in an activity one is passionate about has been tied to feeling life is worth living for. Existing research in passion has explored this phenomenon purely using quantitative research methodology, and by tying an individual’s passion to a specific activity. In this study, passion was explored in semi-structured interviews with 12 participants. The qualitative grounded theory analysis revealed a passionate way of being, with passion being located in the individual rather than in a specific activity. A new phenomenon to positive psychology, a passionate way of being is about having a purpose, creating positive impact, and pursuing variety. These key elements, amongst others, created a reinforcing, self-sustaining spiral, which offered a route to hedonic and eudaimonic happiness, generally serving to enhance life (though it could also detract from life if it became overpowering.

  11. Revealed social preference for potable groundwater: An Eastern Iowa case study

    Science.gov (United States)

    Raunikar, R. P.; Bernknopf, R. L.; Forney, W.; Mishra, S.

    2011-12-01

    The spatially explicit land use and land cover information provided by Landsat moderate-resolution land imagery (MRLI) is needed to more efficiently balance the production of goods and services over landscapes. For example, economic trade-offs are needed to provide both clean groundwater resources and other non-environmental goods and services produced by activities that affect the vadose zone and thus contribute to contamination of groundwater. These trade-off choices are made by numerous economic agents and are constrained by many social institutions including governmental regulations at many levels, contractual obligations and traditions. In effect, on a social level, society acts as if it values groundwater by foregoing other goods to protect these resources. The result of the protection afforded to groundwater resources is observable by measuring contamination in well samples. This observed level of groundwater contamination risk is the revealed preference of society as a whole for clean groundwater. We observed the risk of groundwater contamination in a sampling of well data from our study area (35 counties of Eastern Iowa.) We used a proportional hazard model to quantify the nitrate contamination survival implied by the panel of 19,873 well data, where remaining below a 10 mg/ml maximum contamination level (MCL) is defined as survival. We tested the data for evidence that the levels of protection provided to these resources is correlated with aquifer and vadose zone characteristics and geographic location and whether it changed over time and with economic and other conditions. We demonstrate the use of a nitrate conditioned hazard function for projecting the survival of wells based on nitrate exposure information over the 1940 to 2010 time period. We discuss results of simulations of the survival process that demonstrate the economic significance of this approach. We find that aquifer survival has been significantly improving over time. The principle of

  12. Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

    Science.gov (United States)

    Wu, Nan; Song, Yu-Long; Wang, Bei; Zhang, Xiang-Yang; Zhang, Xu-Jie; Wang, Ya-Li; Cheng, Ying-Yin; Chen, Dan-Dan; Xia, Xiao-Qin; Lu, Yi-Shan; Zhang, Yong-An

    2016-11-01

    The gut-associated lymphoid tissue, connected with liver via bile and blood, constructs a local immune environment of both defense and tolerance. The gut-liver immunity has been well-studied in mammals, yet in fish remains largely unknown, even though enteritis as well as liver and gallbladder syndrome emerged as a limitation in aquaculture. In this study, we performed integrative bioinformatic analysis for both transcriptomic (gut and liver) and proteomic (intestinal mucus and bile) data, in both healthy and infected tilapias. We found more categories of immune transcripts in gut than liver, as well as more adaptive immune in gut meanwhile more innate in liver. Interestingly reduced differential immune transcripts between gut and liver upon inflammation were also revealed. In addition, more immune proteins in bile than intestinal mucus were identified. And bile probably providing immune effectors to intestinal mucus upon inflammation was deduced. Specifically, many key immune transcripts in gut or liver as well as key immune proteins in mucus or bile were demonstrated. Accordingly, we proposed a hypothesized profile of fish gut-liver immunity, during either homeostasis or inflammation. Current data suggested that fish gut and liver may collaborate immunologically while keep homeostasis using own strategies, including potential unique mechanisms.

  13. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content

    Directory of Open Access Journals (Sweden)

    Zachary J. Smith

    2015-12-01

    Full Text Available Current analysis of exosomes focuses primarily on bulk analysis, where exosome-to-exosome variability cannot be assessed. In this study, we used Raman spectroscopy to study the chemical composition of single exosomes. We measured spectra of individual exosomes from 8 cell lines. Cell-line-averaged spectra varied considerably, reflecting the variation in total exosomal protein, lipid, genetic, and cytosolic content. Unexpectedly, single exosomes isolated from the same cell type also exhibited high spectral variability. Subsequent spectral analysis revealed clustering of single exosomes into 4 distinct groups that were not cell-line specific. Each group contained exosomes from multiple cell lines, and most cell lines had exosomes in multiple groups. The differences between these groups are related to chemical differences primarily due to differing membrane composition. Through a principal components analysis, we identified that the major sources of spectral variation among the exosomes were in cholesterol content, relative expression of phospholipids to cholesterol, and surface protein expression. For example, exosomes derived from cancerous versus non-cancerous cell lines can be largely separated based on their relative expression of cholesterol and phospholipids. We are the first to indicate that exosome subpopulations are shared among cell types, suggesting distributed exosome functionality. The origins of these differences are likely related to the specific role of extracellular vesicle subpopulations in both normal cell function and carcinogenesis, and they may provide diagnostic potential at the single exosome level.

  14. Brain structure, function, and genetics revealed by studies of the eye and face.

    Science.gov (United States)

    Sisodiya, Sanjay

    2008-08-01

    Understanding the structure and function of the human brain is intrinsically interesting and fundamental to improved diagnosis, treatment, and prevention of human neurological diseases, which constitute an increasing global burden. The intimate connections between brain and face, and brain and eye, have been utilized to access brain structure and function. Concepts and recent progress are reviewed here. Continued work on biological links between brain and eye or face has uncovered further genetic abnormalities causing facial or eye anomalies, which in either case may clearly indicate changes in the underlying brain. Cause and effect can be difficult to disentangle, but the use of conditional animal models can help establish whether brain changes are the result of face or eye changes or the result of a parallel influence on brain and eye or face. The application of newer methods and technologies such as parameterization of facial characteristics and comparative genomic hybridization has led to new discoveries and insights. Further interdisciplinary studies into brain structure and function through the windows of the face and the eye, with the application of genome-wide studies in larger cohorts, will potentially enable more discovery and critically may reveal unsuspected therapeutic targets in human disease.

  15. Oxidation mechanism of chalcopyrite revealed by X-ray photoelectron spectroscopy and first principles studies

    Science.gov (United States)

    Xiong, Xiaolu; Hua, Xiaoming; Zheng, Yongfei; Lu, Xionggang; Li, Shenggang; Cheng, Hongwei; Xu, Qian

    2018-01-01

    X-ray photoelectron spectroscopic (XPS) studies revealed that the iron site on the chalcopyrite (CuFeS2) surface was preferably oxidized to the Cu site when exposed to an oxidizing environment. Extensive density functional theory calculations were performed to investigate the surface structure of chalcopyrite and its reaction with both molecular oxygen (O2) and water. The adsorption and dissociation of a single O2 molecule, a single H2O molecule, as well as both molecules at the Fe and Cu sites on the CuFeS2 (001) surface were studied. Consistent with our experimental observation, the Fe site was found to be preferred for the adsorption and dissociation of O2 due to its lower energy barrier and greater exothermicity. The dissociation of H2O on the CuFeS2 (001) surface by itself was found to be unfavorable both thermodynamically and kinetically. However, the surface formed upon O2 dissociation was predicted to be much more reactive with H2O, which was attributed to favorable hydrogen transfer to the O site formed upon O2 dissociation to hydrogen transfer to the S site due to the much weaker Ssbnd H bond than the Osbnd H bond.

  16. Genetic studies revealed differences between European and North American populations of Calypogeia azurea

    Directory of Open Access Journals (Sweden)

    Buczkowska Katarzyna

    2016-06-01

    Full Text Available Calypogeia azurea, a widespread, subboreal-montane liverwort species, is one of a few representatives of the Calypogeia genus that are characterized by the occurrence of blue oil bodies. The aim of the study was to investigate the genetic variation and population structure of C. azurea originating from different parts of its distribution range (Europe and North America. Plants of C. azurea were compared with C. peruviana, another Calypogeia species with blue oil bodies. In general, 339 gametophytes from 15 populations of C. azurea were examined. Total gene diversity (HT estimated on the basis of nine isozyme loci of C. azurea at the species level was 0.201. The mean Nei’s genetic distance between European populations was equal to 0.083, whereas the mean genetic distance between populations originating from Europe and North America was 0.413. The analysis of molecular variance (AMOVA showed that 69% of C. azurea genetic variation was distributed among regions (Europe and North America, 15% - among populations within regions, and 16% - within populations. Our study revealed that C. azurea showed genetic diversity within its geographic distribution. All examined samples classified as C. azurea differed in respect of isozyme patterns from C. peruviana.

  17. Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048.

    Science.gov (United States)

    Gao, Jingjing; Yao, Licheng; Xia, Tingting; Liao, Xuebin; Zhu, Deyu; Xiang, Ye

    2018-04-01

    The human kynurenine 3-monooxygenase (hKMO) is a potential therapeutic target for neurodegenerative and neurologic disorders. Inhibition of KMO by Ro 61-8048, a potent, selective, and the most widely used inhibitor of KMO, was shown effective in various models of neurodegenerative or neurologic disorders. However, the molecular basis of hKMO inhibition by Ro 61-8048 is not clearly understood. Here, we report biochemistry studies on hKMO and crystal structures of an hKMO homolog, pfKMO from Pseudomonas fluorescens, in complex with the substrate l-kynurenine and Ro 61-8048. We found that the C-terminal ∼110 aa are essential for the enzymatic activity of hKMO and the homologous C-terminal region of pfKMO folds into a distinct, all-α-helical domain, which associates with the N-terminal catalytic domain to form a unique tunnel in proximity to the substrate-binding pocket. The tunnel binds the Ro 61-8048 molecule, which fills most of the tunnel, and Ro 61-8048 is hydrogen bonded with several completely conserved residues, including an essential catalytic residue. Modification of Ro 61-8048 and biochemical studies of the modified Ro 61-8048 derivatives suggested that Ro 61-8048 inhibits the enzyme in an allosteric manner by affecting the conformation of the essential catalytic residue and by blocking entry of the substrate or product release. The unique binding sites distinguish Ro 61-8048 as a noncompetitive and highly selective inhibitor from other competitive inhibitors, which should facilitate further optimization of Ro 61-8048 and the development of new inhibitory drugs to hKMO.-Gao, J., Yao, L., Xia, T., Liao, X., Zhu, D., Xiang, Y. Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048.

  18. A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease.

    Science.gov (United States)

    Rovelet-Lecrux, Anne; Legallic, Solenn; Wallon, David; Flaman, Jean-Michel; Martinaud, Olivier; Bombois, Stéphanie; Rollin-Sillaire, Adeline; Michon, Agnès; Le Ber, Isabelle; Pariente, Jérémie; Puel, Michèle; Paquet, Claire; Croisile, Bernard; Thomas-Antérion, Catherine; Vercelletto, Martine; Lévy, Richard; Frébourg, Thierry; Hannequin, Didier; Campion, Dominique

    2012-06-01

    Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases. Using high-resolution array comparative genomic hybridisation, we assessed the presence of rare CNVs in 21 unrelated ADEOAD cases, having no alteration on known genes, and 12 sporadic AD cases, with an age of onset younger than 55 years. The analysis revealed the presence of 7 singleton CNVs (4 in ADEOAD and 3 in sporadic cases) absent in 1078 controls and 912 late-onset AD cases. Strikingly, 4 out of 7 rearrangements target genes (KLK6, SLC30A3, MEOX2, and FPR2) encoding proteins that are tightly related to amyloid-β peptide metabolism or signalling. Although these variants are individually rare and restricted to particular subgroups of patients, these findings support the causal role, in human pathology, of a set of genes coding for molecules suspected for a long time to modify Aβ metabolism or signalling, and for which animal or cellular models have already been developed.

  19. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Duan, Yunyun, E-mail: xiaoyun81.love@163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); He, Yong, E-mail: yong.h.he@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Yu, Chunshui, E-mail: csyuster@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Wang, Jun, E-mail: jun_wang@bnu.edu.cn [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Huang, Jing, E-mail: sainthj@126.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Ye, Jing, E-mail: jingye.2007@yahoo.com.cn [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Parizel, Paul M., E-mail: paul.parizel@ua.ac.be [Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, 8 Belgium (Belgium); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni, E-mail: nshu55@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China)

    2012-10-15

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.

  20. Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader

    Directory of Open Access Journals (Sweden)

    William C.H. Chao

    2015-08-01

    Full Text Available The remarkable accuracy of eukaryotic cell division is partly maintained by the cohesin complex acting as a molecular glue to prevent premature sister chromatid separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4 loader complex. Here, we report the crystal structure of Scc4 bound to the N terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped by the core of the Scc4 superhelix. Electron microscopy (EM analysis reveals that the Scc2-Scc4 loader complex comprises three domains: a head, body, and hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head domain, whereas in vitro cohesin loading assays show that the central body and the hook domains are sufficient to catalyze cohesin loading onto circular DNA, but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a chromatin adaptor.

  1. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

    International Nuclear Information System (INIS)

    Liu, Yaou; Duan, Yunyun; He, Yong; Yu, Chunshui; Wang, Jun; Huang, Jing; Ye, Jing; Parizel, Paul M.; Li, Kuncheng; Shu, Ni

    2012-01-01

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS

  2. Revealing structures in narratives: A mixed-methods approach to studying interdisciplinary handoff in critical care.

    Science.gov (United States)

    Mamykina, Lena; Jiang, Silis; Collins, Sarah A; Twohig, Bridget; Hirsh, Jamie; Hripcsak, George; Stanley Hum, R; Kaufman, David R

    2016-08-01

    To examine a novel mixed-methods approach for studying patterns of clinical communication that could inform future informatics solutions, with a specific focus on handoff within interdisciplinary teams. Researchers observed, recorded, and transcribed verbal handoff discussions of different members of critical care teams. The transcripts were coded qualitatively, and then analyzed quantitatively for emerging structural patterns using categorical cluster analysis, and for degree of shared mental models (SMM) using the modified Pyramid method. An empirical study using the proposed mixed-methods approach suggested emerging patterns of communication among clinicians. For example, the temporal focus of handoff was often determined by the role of the clinician giving the handoff; the clinical content of handoff was consistent between clinicians, but varied between patients. The SMM index ranged from 0.065 (with the maximum possible overlap score of 1) to 0.007 with a median of 0.026; the overlap was higher in statements concerned with patient presentation (23.6% of these had overlap) and referring to the past (24% overlapped). This calculated SMM index was correlated with the assessment of coherence within the participating teams by independent physicians (r=0.63, p=0.038). The proposed novel mixed-methods approach helped to reveal emerging patterns in content and structure of handoff communication and highlight differences due to the clinical context, and to the different priorities of clinicians on interdisciplinary patient care teams. The approach for calculating SMM is more ecologically sensitive as it relies on naturally occurring discourse and less intrusive than traditional ways of assessing SMM, and takes initial steps toward establishing empirical foundation for the design of electronic tools to support handoff in interdisciplinary teams. Copyright © 2016. Published by Elsevier Inc.

  3. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    Science.gov (United States)

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  4. Comparative study of human mitochondrial proteome reveals extensive protein subcellular relocalization after gene duplications

    Directory of Open Access Journals (Sweden)

    Huang Yong

    2009-11-01

    Full Text Available Abstract Background Gene and genome duplication is the principle creative force in evolution. Recently, protein subcellular relocalization, or neolocalization was proposed as one of the mechanisms responsible for the retention of duplicated genes. This hypothesis received support from the analysis of yeast genomes, but has not been tested thoroughly on animal genomes. In order to evaluate the importance of subcellular relocalizations for retention of duplicated genes in animal genomes, we systematically analyzed nuclear encoded mitochondrial proteins in the human genome by reconstructing phylogenies of mitochondrial multigene families. Results The 456 human mitochondrial proteins selected for this study were clustered into 305 gene families including 92 multigene families. Among the multigene families, 59 (64% consisted of both mitochondrial and cytosolic (non-mitochondrial proteins (mt-cy families while the remaining 33 (36% were composed of mitochondrial proteins (mt-mt families. Phylogenetic analyses of mt-cy families revealed three different scenarios of their neolocalization following gene duplication: 1 relocalization from mitochondria to cytosol, 2 from cytosol to mitochondria and 3 multiple subcellular relocalizations. The neolocalizations were most commonly enabled by the gain or loss of N-terminal mitochondrial targeting signals. The majority of detected subcellular relocalization events occurred early in animal evolution, preceding the evolution of tetrapods. Mt-mt protein families showed a somewhat different pattern, where gene duplication occurred more evenly in time. However, for both types of protein families, most duplication events appear to roughly coincide with two rounds of genome duplications early in vertebrate evolution. Finally, we evaluated the effects of inaccurate and incomplete annotation of mitochondrial proteins and found that our conclusion of the importance of subcellular relocalization after gene duplication on

  5. Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study

    Directory of Open Access Journals (Sweden)

    Talayero José MP

    2010-03-01

    Full Text Available Abstract Background Rotavirus is the leading cause of acute gastroenteritis (AGE and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE is well documented, there are few data on the impact of RVGE on the families of affected children. Methods Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL, conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. Results 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, ≥ 5 on a 10-point visual analogue scale. Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. Conclusions Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.

  6. Numerous risk factors for Helicobacter pylori antibiotic resistance revealed by extended anamnesis: a Bulgarian study.

    Science.gov (United States)

    Boyanova, Lyudmila; Ilieva, Juliana; Gergova, Galina; Davidkov, Lubomir; Spassova, Zoya; Kamburov, Victor; Katsarov, Nikolai; Mitov, Ivan

    2012-01-01

    The aim of this study was to assess risk factors for primary Helicobacter pylori antibiotic resistance by an extended anamnesis. In total, 519 H. pylori strains from untreated symptomatic adults who answered a questionnaire were evaluated. Strain susceptibility was assessed by a breakpoint susceptibility test. Primary resistance rates were 29.5 % for metronidazole, 17.9 % for clarithromycin, 7.3 % for metronidazole+clarithromycin, 4.0 % for tetracycline and 10.8 % for ciprofloxacin. On multivariate analysis, younger (≤65 years) age was an independent predictor for metronidazole resistance. To our knowledge, for the first time, being a member of the health-care profession was revealed as a risk factor for H. pylori resistance to metronidazole and both metronidazole and clarithromycin. Respiratory and urinary tract infections were independent predictors of clarithromycin and ciprofloxacin resistance, respectively. The presence of co-infections was an independent risk factor for clarithromycin, metronidazole and ciprofloxacin resistance. Surprisingly, female sex was the only predictor for tetracycline resistance. The antibiotic resistance rates were not associated with disease type, place of residence, birthplace, educational level, non-steroidal anti-inflammatory drug or proton pump inhibitor use, smoking or dietary factors, such as consumption of coffee, yogurt, green tea, raw garlic, raw onion, honey or meat. There was a trend for higher metronidazole resistance in strains from diabetic patients. In conclusion, the extended anamnesis of H. pylori-positive patients should include data on patient age, sex, whether they are in the health-care profession, co-infections and possibly diabetes to improve the choice of empiric therapy. Tailored treatment based on the extended anamnesis is suggested, and susceptibility testing of the strains is recommended for patients at risk for antibiotic resistance, especially to clarithromycin, fluoroquinolones or both metronidazole

  7. Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse.

    Science.gov (United States)

    Lewis, S L; Holl, H M; Streeter, C; Posbergh, C; Schanbacher, B J; Place, N J; Mallicote, M F; Long, M T; Brooks, S A

    2017-03-01

    Equine obesity can cause life-threatening secondary chronic conditions, similar to those in humans and other animal species. Equine metabolic syndrome (EMS), primarily characterized by hyperinsulinemia, is often present in obese horses and ponies. Due to clinical similarities to conditions such as pituitary pars intermedia dysfunction (formerly equine Cushing's disease), conclusive diagnosis of EMS often proves challenging. Aside from changes in diet and exercise, few targeted treatments are available for EMS, emphasizing the need for early identification of at-risk individuals to enable implementation of preventative measures. A genomewide association study (GWAS) using Arabian horses with a history of severe laminitis secondary to EMS revealed significant genetic markers near a single candidate gene () that may play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T > C), was correlated with elevated insulin values and increased frequency of laminitis ( = 0.0024 and = 9.663 × 10, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values ( = 0.0056) and BCS ( = 0.0063). Screening of the predicted coding regions by sequencing identified a polymorphic guanine homopolymer and 5 haplotypes in the 3' untranslated region (UTR). An 11 guanine (11-G) allele at was correlated with elevated insulin values in the GWAS population ( = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 ( = 0.0055 and = 0.0162, respectively). The BIEC2-263524-C and the 3' UTR -11(G) polymorphisms were correlated at a 98% frequency, indicating strong linkage disequilibrium across this 150-kb haplotype. Assays for these markers could diagnose horses with a genetic predisposition to develop obesity. Additionally, discovery of FAM174A function may improve our understanding of the etiology of this troubling illness in the horse and

  8. Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

    Science.gov (United States)

    Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

    2017-09-01

    The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

  9. Study of a twisted ATLAS SCT Barrel deformation as revealed by a photogrammetric survey

    CERN Document Server

    Dobson, E; Heinemann, F; Karagoz-Unel, M

    2007-01-01

    A photogrammetry survey on the SCT barrels was performed as an engineering check on the structure of the ATLAS Semiconductor Tracker (SCT) shortly after construction. Analysis of the data obtained revealed small scale elliptical deformation as well as a twist of the structure. The results of the survey are presented as well as interpolation of the measured targets to the module positions and a comparison with track based alignment measurements.

  10. How Do Multiple-Star Systems Form? VLA Study Reveals "Smoking Gun"

    Science.gov (United States)

    2006-12-01

    system, all the antennas could provide data for us. In addition, we improved the level of detail by using the Pie Town, NM, antenna of the Very Long Baseline Array, as part of an expanded system," Lim said. The implementation and improvement of the 43 GHz receiving system was a collaborative program among the German Max Planck Institute, the Mexican National Autonomous University, and the U.S. National Radio Astronomy Observatory. Two popular theoretical models for the formation of multiple-star systems are, first, that the two protostars and their surrounding dusty disks fragment from a larger parent disk, and, second, that the protostars form independently and then one captures the other into a mutual orbit. "Our new study shows that the disks of the two main protostars are aligned with each other, and also are aligned with the larger, surrounding disk. In addition, their orbital motion resembles the rotation of the larger disk. This is a 'smoking gun' supporting the fragmentation model," Lim said. However, the new study also revealed a third young star with a dust disk. "The disk of this one is misaligned with those of the other two, so it may be the result of either fragmentation or capture," Takakuwa said. The misalignment of the third disk could have come through gravitational interactions with the other two, larger, protostars, the scientists said. They plan further observations to try to resolve the question. "We have a very firm indication that two of these protostars and their dust disks formed from the same, larger disk-like cloud, then broke out from it in a fragmentation process. That strongly supports one theoretical model for how multiple-star systems are formed. The misalignment of the third protostar and its disk leaves open the possibility that it could have formed elsewhere and been captured, and we'll continue to work on reconstructing the history of this fascinating system," Lim summarized. The National Radio Astronomy Observatory is a facility of

  11. Revealing a room temperature ferromagnetism in cadmium oxide nanoparticles: An experimental and first-principles study

    KAUST Repository

    Bououdina, Mohamed

    2015-03-26

    We obtain a single cadmium oxide phase from powder synthesized by a thermal decomposition method of cadmium acetate dehydrate. The yielded powder is annealed in air, vacuum, and H2 gas in order to create point defects. Magnetization-field curves reveal the appearance of diamagnetic behavior with a ferromagnetic component for all the powders. Powder annealing under vacuum and H2 atmosphere leads to a saturation magnetization 1.15 memu g-1 and 1.2 memu g-1 respectively with an increase by 45% and 16% compared to the one annealed in air. We show that annealing in vacuum produces mainly oxygen vacancies while annealing in H2 gas creates mainly Cd vacancy leading to room temperature ferromagnetic (RTFM) component together with known diamagnetic properties. Ab initio calculations performed on the CdO nanoparticles show that the magnetism is governed by polarized hybrid states of the Cd d and O p orbitals together with the vacancy. © The Royal Society of Chemistry 2015.

  12. Simultaneous imaging and functional studies reveal a tight correlation between calcium and actin networks.

    Science.gov (United States)

    Bascom, Carlisle S; Winship, Lawrence J; Bezanilla, Magdalena

    2018-03-20

    Tip-growing cells elongate in a highly polarized manner via focused secretion of flexible cell-wall material. Calcium has been implicated as a vital factor in regulating the deposition of cell-wall material. However, deciphering the molecular and mechanistic calcium targets in vivo has remained challenging. Here, we investigated intracellular calcium dynamics in the moss Physcomitrella patens , which provides a system with an abundant source of genetically identical tip-growing cells, excellent cytology, and a large molecular genetic tool kit. To visualize calcium we used a genetically encoded cytosolic FRET probe, revealing a fluctuating tipward gradient with a complex oscillatory profile. Wavelet analysis coupled with a signal-sifting algorithm enabled the quantitative comparison of the calcium behavior in cells where growth was inhibited mechanically, pharmacologically, or genetically. We found that cells with suppressed growth have calcium oscillatory profiles with longer frequencies, suggesting that there is a feedback between the calcium gradient and growth. To investigate the mechanistic basis for this feedback we simultaneously imaged cytosolic calcium and actin, which has been shown to be essential for tip growth. We found that high cytosolic calcium promotes disassembly of a tip-focused actin spot, while low calcium promotes assembly. In support of this, abolishing the calcium gradient resulted in dramatic actin accumulation at the tip. Together these data demonstrate that tipward calcium is quantitatively linked to actin accumulation in vivo and that the moss P. patens provides a powerful system to uncover mechanistic links between calcium, actin, and growth.

  13. Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

    Science.gov (United States)

    Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

    2017-07-01

    The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

  14. Experiments Are Revealing a Foundation Species: A Case Study of Eastern Hemlock (Tsuga canadensis

    Directory of Open Access Journals (Sweden)

    Aaron M. Ellison

    2014-01-01

    Full Text Available Foundation species are species that create and define particular ecosystems; control in large measure the distribution and abundance of associated flora and fauna; and modulate core ecosystem processes, such as energy flux and biogeochemical cycles. However, whether a particular species plays a foundational role in a system is not simply asserted. Rather, it is a hypothesis to be tested, and such tests are best done with large-scale, long-term manipulative experiments. The utility of such experiments is illustrated through a review of the Harvard Forest Hemlock Removal Experiment (HF-HeRE, a multidecadal, multihectare experiment designed to test the foundational role of eastern hemlock, Tsuga canadensis, in eastern North American forests. Experimental removal of T. canadensis has revealed that after 10 years, this species has pronounced, long-term effects on associated flora and fauna, but shorter-term effects on energy flux and nutrient cycles. We hypothesize that on century-long scales, slower changes in soil microbial associates will further alter ecosystem processes in T. canadensis stands. HF-HeRE may indeed continue for >100 years, but at such time scales, episodic disturbances and changes in regional climate and land cover can be expected to interact in novel ways with these forests and their foundation species.

  15. Vesicle Encapsulation Studies Reveal that Single Molecule Ribozyme Heterogeneities Are Intrinsic

    Science.gov (United States)

    Okumus, Burak; Wilson, Timothy J.; Lilley, David M. J.; Ha, Taekjip

    2004-01-01

    Single-molecule measurements have revealed that what were assumed to be identical molecules can differ significantly in their static and dynamic properties. One of the most striking examples is the hairpin ribozyme, which was shown to exhibit two to three orders of magnitude variation in folding kinetics between molecules. Although averaged behavior of single molecules matched the bulk solution data, it was not possible to exclude rigorously the possibility that the variations around the mean values arose from different ways of interacting with the surface environment. To test this, we minimized the molecules' interaction with the surface by encapsulating DNA or RNA molecules inside 100- to 200-nm diameter unilamellar vesicles, following the procedures described by Haran and coworkers. Vesicles were immobilized on a supported lipid bilayer via biotin-streptavidin linkages. We observed no direct binding of DNA or RNA on the supported bilayer even at concentrations exceeding 100 nM, indicating that these molecules do not bind stably on the membrane. Since the vesicle diameter is smaller than the resolution of optical microscopy, the lateral mobility of the molecules is severely constrained, allowing long observation periods. We used fluorescence correlation spectroscopy, nuclease digestion, and external buffer exchange to show that the molecules were indeed encapsulated within the vesicles. When contained within vesicles, the natural form of the hairpin ribozyme exhibited 50-fold variation in both folding and unfolding rates in 0.5 mM Mg2+, which is identical to what was observed from the molecules tethered directly on the surface. This strongly indicates that the observed heterogeneity in dynamic properties does not arise as an artifact of surface attachment, but is intrinsic to the nature of the molecules. PMID:15454471

  16. Molecular recognition of the neurotransmitter acetylcholine by an acetylcholine binding protein reveals determinants of binding to nicotinic acetylcholine receptors.

    Science.gov (United States)

    Olsen, Jeppe A; Balle, Thomas; Gajhede, Michael; Ahring, Philip K; Kastrup, Jette S

    2014-01-01

    Despite extensive studies on nicotinic acetylcholine receptors (nAChRs) and homologues, details of acetylcholine binding are not completely resolved. Here, we report the crystal structure of acetylcholine bound to the receptor homologue acetylcholine binding protein from Lymnaea stagnalis. This is the first structure of acetylcholine in a binding pocket containing all five aromatic residues conserved in all mammalian nAChRs. The ligand-protein interactions are characterized by contacts to the aromatic box formed primarily by residues on the principal side of the intersubunit binding interface (residues Tyr89, Trp143 and Tyr185). Besides these interactions on the principal side, we observe a cation-π interaction between acetylcholine and Trp53 on the complementary side and a water-mediated hydrogen bond from acetylcholine to backbone atoms of Leu102 and Met114, both of importance for anchoring acetylcholine to the complementary side. To further study the role of Trp53, we mutated the corresponding tryptophan in the two different acetylcholine-binding interfaces of the widespread α4β2 nAChR, i.e. the interfaces α4(+)β2(-) and α4(+)α4(-). Mutation to alanine (W82A on the β2 subunit or W88A on the α4 subunit) significantly altered the response to acetylcholine measured by oocyte voltage-clamp electrophysiology in both interfaces. This shows that the conserved tryptophan residue is important for the effects of ACh at α4β2 nAChRs, as also indicated by the crystal structure. The results add important details to the understanding of how this neurotransmitter exerts its action and improves the foundation for rational drug design targeting these receptors.

  17. The shady past of female boxers – what case studies in the USA reveal

    DEFF Research Database (Denmark)

    Pfister, Gertrud Ursula; Gems, Gerald

    2017-01-01

    This study attempts to rectify the invisibility of female boxers and to narrow a research gap by examining the careers of four prominent female champions who managed to excel in the sport despite the social, psychological and physical restrictions imposed by the gender order of American society...... in the nineteenth century. The little studied roles of female boxers present some historiographical issues detailed in the study, which examines and analyses the social construction of gender, and the rejection of prescribed roles by the female boxers, who used the vaudeville and theatrical stages to negotiate...

  18. Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy

    OpenAIRE

    Pillas, Demetris; Hoggart, Clive J.; Evans, David M.; O'Reilly, Paul F.; Sipil?, Kirsi; L?hdesm?ki, Raija; Millwood, Iona Y.; Kaakinen, Marika; Netuveli, Gopalakrishnan; Blane, David; Charoen, Pimphen; Sovio, Ulla; Pouta, Anneli; Freimer, Nelson; Hartikainen, Anna-Liisa

    2010-01-01

    Author Summary Genome-wide association studies have been used to identify genetic variants conferring susceptibility to diseases, intermediate phenotypes, and physiological traits such as height, hair color, and age at menarche. Here we analyze the NFBC1966 and ALSPAC birth cohorts to investigate the genetic determinants of a key developmental process: primary tooth development. The prospective nature of our studies allows us to exploit accurate measurements of age at first tooth eruption and...

  19. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

    Directory of Open Access Journals (Sweden)

    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  20. Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Xuelin Zhang

    2016-10-01

    Full Text Available Abstract Non-alcoholic fatty liver disease (NAFLD is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD, the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS, genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13 may promote the development of NAFLD.

  1. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels

    NARCIS (Netherlands)

    J.B. Richards (Brent); D. Waterworth (Dawn); S. O'Rahilly (Stephen); M.-F. Hivert (Marie-France); R.J.F. Loos (Ruth); J.R.B. Perry (John); T. Tanaka (Toshiko); N.J. Timpson (Nicholas); R.K. Semple (Robert); N. Soranzo (Nicole); K. Song (Kijoung); N. Rocha (Nuno); E. Grundberg (Elin); J. Dupuis (Josée); J.C. Florez (Jose); C. Langenberg (Claudia); I. Prokopenko (Inga); R. Saxena (Richa); R. Sladek (Rob); Y.S. Aulchenko (Yurii); D.M. Evans (David); G. Waeber (Gérard); M.S. Burnett; N. Sattar (Naveed); J. Devaney (Joseph); C. Willenborg (Christina); A. Hingorani (Aroon); J.C.M. Witteman (Jacqueline); P. Vollenweider (Peter); B. Glaser (Beate); C. Hengstenberg (Christian); L. Ferrucci (Luigi); D. Melzer (David); K. Stark (Klaus); J. Deanfield (John); J. Winogradow (Janina); M. Grassl (Martina); A.S. Hall (Alistair); J.M. Egan (Josephine); J.R. Thompson (John); S.L. Ricketts (Sally); I.R. König (Inke); W. Reinhard (Wibke); S.M. Grundy (Scott); H.E. Wichmann (Heinz Erich); P. Barter (Phil); R. Mahley (Robert); Y.A. Kesaniemi (Antero); D.J. Rader (Daniel); M.P. Reilly (Muredach); S.E. Epstein (Stephen); A.F.R. Stewart (Alexandre); P. Tikka-Kleemola (Päivi); H. Schunkert (Heribert); K.A. Burling (Keith); J. Erdmann (Jeanette); P. Deloukas (Panagiotis); T. Pastinen (Tomi); N.J. Samani (Nilesh); R. McPherson (Ruth); G.D. Smith; T.M. Frayling (Timothy); N.J. Wareham (Nick); J.B. Meigs (James); V. Mooser (Vincent); T.D. Spector (Tim)

    2009-01-01

    textabstractThe adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of

  2. How Can We Explain Poverty? Case Study of Dee Reveals the Complexities

    Science.gov (United States)

    Seccombe, Karen

    2011-01-01

    Many theories have been offered to explain why people are impoverished. This article by Karen Seccombe uses the case study of "Dee," a newly single mother, to explore four of the most common: individualism, social structuralism, the culture of poverty, and fatalism. She concludes that poverty is a highly complex phenomenon, and it is likely that…

  3. Cerebrovascular accident and abnormal focus of hyperactivity revealed by dynamic study in scintiangioencephalography

    International Nuclear Information System (INIS)

    Planchon, C.A.; Perez, R.; Lebourges, J.

    1980-01-01

    A 75-year-old female was admitted to the hospital for suspicion of a cerebrovascular accident. An important focus of hyperactivity was noted during a dynamic study by scintiangioencephalography, consistent with a highly vascular tumor, but corresponding in fact to a focal transitory hyperfusion with accompanying intense neuronal activity. (orig.)

  4. Four studies of economic behavior : integrating revealed and stated preferences data

    NARCIS (Netherlands)

    de Ree, J.J.

    2010-01-01

    This thesis estimates equivalence scales for Indonesia, proposes a new type of test of the life-cycle model, shows how important economic and demographic characteristics of Dutch households evolve over age, cohorts and time, and studies the decision problem to when and how much to work, save and

  5. The neural substrates of script knowledge deficits as revealed by a PET study in Huntington's disease

    NARCIS (Netherlands)

    Allain, P.; Gaura, V.; Fasotti, L.; Chauvire, V.; Prundean, A.; Sherer-Gagou, C.; Bonneau, D.; Bachoud-Levi, A.C.; Dubas, F.; Remy, P.; Verny, C.

    2011-01-01

    Introduction Previous neuropsychological investigations have suggested that both the prefrontal cortex and the basal ganglia are involved in the management of script event knowledge required in planning behavior. Methods This study was designated to map, the correlations between resting-state brain

  6. The study of fkbp and ubiquitin reveals interesting aspects of Artemia stress history.

    Science.gov (United States)

    Maniatsi, Stefania; Farmaki, Theodora; Abatzopoulos, Theodore J

    2015-08-01

    Research on stress responses in animals has increased greatly during the last decades. Though most studies focus on the cellular and molecular bases of the stress response mechanisms, the ecological and evolutionary aspects of stress responses gain more and more interest. Here, we use species and parthenogenetic strains of the genus Artemia, an extremophile model organism, to study, for the first time, a protein well known for its chaperone activity and its involvement in stress responses. More specifically, transcription and protein accumulation of an FK506-Binding Protein (FKBP) homologue were investigated under heat and salt stresses. Additionally, the mRNA levels of ubiquitin, a heat-inducible protein related to the proteasomal pathway, were quantitated under these conditions. Biochemical and phylogenetic analyses showed that the studied FKBP orthologue is a typical representative of the family that clusters with other crustacean sequences. The expression was increased in both fkbp and ubiquitin genes after salt and heat stresses. However, our results in combination with the fact that Artemia species and parthenogenetic strains, selected for this study, exhibit different heat or salt tolerance provide useful hints about the evolutionary significance of FKBP and ubiquitin. Regarding FKBP, mRNA expression and protein accumulation seem to depend on the environmental conditions and the evolutionary history of each Artemia population while ubiquitin has a clear and more conserved role under heat shock. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. A Qualitative Study Revealing the Relationship Between Cultural Indicators and Attitudes Toward the Ads

    Directory of Open Access Journals (Sweden)

    Emine Sahin

    2014-12-01

    Full Text Available The companies, in International markets, are required to examine the attitudes and the behaviours to recognize the consumer to be able to make their products preferable under constantly growing competitive conditions. Therefore, it is of great importance to know cultural values of the customers in the country's where global brands compete and to shape ads which is one of the marketing communication tools in this direction. In this respect, knowing the cultural similarities or differences of the countries where the ads are used (such as that country's religion, language, norms and cultural values gains importance. The consumer attitudes towards the ads change in accordance with their cultural similarities or dissimilarities and this attitude change determines the tendency of shopping. According to Geert Hofstede, social anthropologist who analyzes the cultural levels and the relationships among them the basic elements of the culture consists of symbols, heroes, rituals and values underlying them. Thorough symbols, a number of cultural values are conveyed to ads. The problem of this study which was carried out in order to determine attitude change towards the ads including cultural differences is “Is there a difference in the attitudes towards the ads including different cultural symbols? How it is distributed according to gender differences?" In this study, a qualitative research method was applied and interviewed with 20 test subject. 20 students studying in one of the universities in Turkey were selected with formal sampling, they were asked questions, and it was tried to determine the difference between the ad of Doğuş Çay-a tea brand which uses the symbols and local accent of Black sea region in Turkey in its ads- and the ad of Lipton which is an international British tea brand. At the end of the study, it was found out that sample’s the attitude was positive towards ad of Doğuş Çay, not Lipton.

  8. Continuous acoustic studies of overwintering sprat Sprattus sprattus reveal flexible behavior

    KAUST Repository

    Solberg, I

    2012-09-19

    The clupeid fish Sprattus sprattus was studied in a 150 m deep Norwegian fjord throughout an entire overwintering period during which the fjord froze over and a major water renewal occurred. A bottom-mounted (upward-facing) echosounder provided continuous high-resolution data and enabled studies of swimming speed and behavior of individual sprat in addition to population behavior. The continuous acoustic studies were supplemented with intermittent field campaigns. The sprat displayed different behavioral modes with changing environmental conditions. During the first part of the winter, the majority of the population occurred in deep waters during both day and night, yet exhibited a shallower night-time distribution. Individual sprat swam alternately up and down, a ‘rise and sink’ behavior likely a compensation for negative buoyancy because of swim bladder compression. Because feeding was negligible in deep waters, the swimming pattern was not inferred as prey search behavior. Another part of the population schooled at shallower depths during the day and carried out vertical migration to upper waters at night. However, individuals were observed as they switched between these behavioral groups. A sudden change in both swimming behavior and vertical distribution occurred as the fjord became ice covered. Near-bottom ‘rise and sink’ swimming was replaced by schooling in mid-water during the day, and the sprat aggregated in dense layers near the surface at night. We suggest that the ice made the sprat shift their antipredator strategy from hiding at depth to hiding in schools in the darker waters below the ice. This long-term acoustic study has shown that sprat have a flexible behavioral repertoire, displaying different overwintering strategies within a population, depending on environmental conditions.

  9. Attitude towards computer-based learning: determinants as revealed by a controlled interventional study.

    Science.gov (United States)

    Hahne, Amina Katharina; Benndorf, Ralf; Frey, Peter; Herzig, Stefan

    2005-09-01

    Curriculum-wide implementation of computer-based learning (CBL) in undergraduate medical education remains elusive. Unlike many pilot tests of singular learning programmes, dropout rates are high and acceptance seems low in the long run. We studied the effect of a new CBL programme, suitable for curriculum-wide implementation, on Year 3 medical students' attitudes towards CBL. Students from 2 universities participating in a mandatory pharmacology course were given access to a CBL programme covering cardiovascular drug therapy in a controlled randomised study (n = 167). Learner properties and attitude towards CBL were measured using psychometric scales, and knowledge by multiple-choice questions (pre- and post-test). Attitude towards CBL worsened in the CBL group (n = 70). Individual learners' properties did not explain this effect. The perceived programme quality was rated only 'average', which may contribute to the lower post-test values of attitude towards CBL. Learning outcomes were similar between the control group (n = 97) and students using CBL (n = 44). Learning efforts were shifted from self-study towards CBL. The initial enthusiasm of students was not maintained when using a programme designed to complement or even replace traditional teaching. Curriculum-wide implementation of CBL might be hampered by the discouragement of users.

  10. Effective binding of perhalogenated closo-borates to serum albumins revealed by spectroscopic and ITC studies

    Science.gov (United States)

    Kuperman, Marina V.; Losytskyy, Mykhaylo Yu.; Bykov, Alexander Yu.; Yarmoluk, Sergiy M.; Zhizhin, Konstantin Yu.; Kuznetsov, Nikolay T.; Varzatskii, Oleg A.; Gumienna-Kontecka, Elzbieta; Kovalska, Vladyslava B.

    2017-08-01

    The interactions of boron cluster compounds closo-borates with biomolecules are widely studied due to their efficiency as agents for boron neutron capture therapy of cancer. In present work the binding abilities of anionic halogen closo-borates [B10Hal10]2- (Hal = Cl, Br, I) and [B12Hal12]2- (Hal = Cl, I) towards bovine and human serum albumins were investigated by spectroscopic and isothermal titration calorimetry (ITC) methods. The protein fluorescence quenching method and ITC studies confirmed the complex formation. The degree of protein fluorescence quenching increased from chlorine to iodine boron derivatives that is attributed to external heavy atom effect. The ITC data point on the existence in the protein structure of two types of binding sites: with higher and lower affinity to closo-borates. Albumin-closo-borate complex binding ratio, n (4-5 anions per protein molecule) is higher than for the parent hydrogen closo-borates (2 anions per protein molecule). Binding constants estimated by fluorescent and ITC methods indicate higher affinity of halogen closo-borates to albumins (K in the range of 104-106 M-1) comparing to that of the hydrogen closo-borate (K about 103 M-1). Due to their high affinity and high binding ratio to albumins halogen closo-borates are proposed for further studies as agents for boron neutron capture therapy.

  11. Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

    Science.gov (United States)

    Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M

    2017-09-01

    The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h 2 SNP ]), partitioned heritability, and genetic correlations (r g ) between anorexia nervosa and 159 other phenotypes. Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h 2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

  12. Comparative structural and enzymatic studies on Salmonella typhimurium diaminopropionate ammonia lyase reveal its unique features.

    Science.gov (United States)

    Deka, G; Bisht, S; Savithri, H S; Murthy, M R N

    2018-05-01

    Cellular metabolism of amino acids is controlled by a large number of pyridoxal 5'-phosphate (PLP) dependent enzymes. Diaminopropionate ammonia lyase (DAPAL), a fold type II PLP-dependent enzyme, degrades both the D and L forms of diaminopropionic acid (DAP) to pyruvate and ammonia. Earlier studies on the Escherichia coli DAPAL (EcDAPAL) had suggested that a disulfide bond located close to the active site may be crucial for maintaining the geometry of the substrate entry channel and the active site. In order to obtain further insights into the catalytic properties of DAPAL, structural and functional studies on Salmonella typhimurium DAPAL (StDAPAL) were initiated. The three-dimensional X-ray crystal structure of StDAPAL was determined at 2.5 Å resolution. As expected, the polypeptide fold and dimeric organization of StDAPAL is similar to those of EcDAPAL. A phosphate group was located in the active site of StDAPAL and expulsion of this phosphate is probably essential to bring Asp125 to a conformation suitable for proton abstraction from the substrate (D-DAP). The unique disulfide bond of EcDAPAL was absent in StDAPAL, although the enzyme displayed comparable catalytic activity. Site directed mutagenesis of the cysteine residues involved in disulfide bond formation in EcDAPAL followed by functional and biophysical studies further confirmed that the disulfide bond is not necessary either for substrate binding or for catalysis. The activity of StDAPAL but not EcDAPAL was enhanced by monovalent cations suggesting subtle differences in the active site geometries of these two closely related enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

    Science.gov (United States)

    Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

    2014-01-01

    Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

  14. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

    Directory of Open Access Journals (Sweden)

    Rico Rueedi

    2014-02-01

    Full Text Available Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8 and independent associations between single nucleotide polymorphisms (SNP and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44 and lysine (rs8101881, P = 1.2×10(-33, respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

  15. In vitro studies reveal antiurolithic effect of Terminalia arjuna using quantitative morphological information from computerized microscopy

    Directory of Open Access Journals (Sweden)

    A. Mittal

    2015-10-01

    Full Text Available ABSTRACT Purpose: For most cases, urolithiasis is a condition where excessive oxalate is present in the urine. Many reports have documented free radical generation followed by hyperoxaluria as a consequence of which calcium oxalate (CaOx deposition occurs in the kidney tissue. The present study is aimed to exam the antilithiatic potency of the aqueous extract (AE of Terminalia arjuna (T. arjuna. Materials and Methods: The antilithiatic activity of Terminalia arjuna was investigated in vitro nucleation, aggregation and growth of the CaOx crystals as well as the morphology of CaOx crystals using the inbuilt software ‘Image-Pro Plus 7.0’ of Olympus upright microscope (BX53. Antioxidant activity of AE of Terminalia arjuna bark was also determined in vitro. Results: Terminalia arjuna extract exhibited a concentration dependent inhibition of nucleation and aggregation of CaOx crystals. The AE of Terminalia arjuna bark also inhibited the growth of CaOx crystals. At the same time, the AE also modified the morphology of CaOx crystals from hexagonal to spherical shape with increasing concentrations of AE and reduced the dimensions such as area, perimeter, length and width of CaOx crystals in a dose dependent manner. Also, the Terminalia arjuna AE scavenged the DPPH (2, 2-diphenyl-1-picrylhydrazyl radicals with an IC50 at 13.1µg/mL. Conclusions: The study suggests that Terminalia arjuna bark has the potential to scavenge DPPH radicals and inhibit CaOx crystallization in vitro. In the light of these studies, Terminalia arjuna can be regarded as a promising candidate from natural plant sources of antilithiatic and antioxidant activity with high value.

  16. Earthquake studies reveal the magmatic plumbing system of the Katmai volcanoes

    Science.gov (United States)

    Thurber, Clifford; Murphy, Rachel; Prejean, Stephanie G.; Haney, Matthew M.; Bennington, Ninfa; Powell, Lee; Paskievitch, John F.

    2012-01-01

    The 1912 eruption of Novarupta was the largest of the 1900s (Fierstein and Hildreth 2001, Hildreth et al. 2003). A century later, fundamental questions remain regarding the source of the magma for that eruption. A previous seismic study of the Katmai area (Jolly et al. 2007) identified a single large area of anomalous structure in the subsurface centered beneath Katmai Pass (Figure 2), but the magma source for the 1912 eruption is thought to have been beneath Mt. Katmai (Hildreth et al. 2003). This mystery was a prime motivation for the research project described here.

  17. RNA-Seq study reveals genetic responses of diverse wild soybean accessions to increased ozone levels.

    Science.gov (United States)

    Waldeck, Nathan; Burkey, Kent; Carter, Thomas; Dickey, David; Song, Qijian; Taliercio, Earl

    2017-06-29

    Ozone is an air pollutant widely known to cause a decrease in productivity in many plant species, including soybean (Glycine max (L.) Merr). While the response of cultivated soybean to ozone has been studied, very little information is available regarding the ozone response of its wild relatives. Ozone-resistant wild soybean accessions were identified by measuring the response of a genetically diverse group of 66 wild soybean (Glycine soja Zucc. and Sieb.) accessions to elevated ozone levels. RNA-Seq analyses were performed on leaves of different ages from selected ozone-sensitive and ozone-resistant accessions that were subjected to treatment with an environmentally relevant level of ozone. Many more genes responded to elevated ozone in the two ozone-sensitive accessions than in the ozone-resistant accessions. Analyses of the ozone response genes indicated that leaves of different ages responded differently to ozone. Older leaves displayed a consistent reduction in expression of genes involved in photosynthesis in response to ozone, while changes in expression of defense genes dominated younger leaf tissue in response to ozone. As expected, there is a substantial difference between the response of ozone-sensitive and ozone-resistant accessions. Genes associated with photosystem 2 were substantially reduced in expression in response to ozone in the ozone-resistant accessions. A decrease in peptidase inhibitors was one of several responses specific to one of the ozone resistant accessions. The decrease in expression in genes associated with photosynthesis confirms that the photosynthetic apparatus may be an early casualty in response to moderate levels of ozone. A compromise of photosynthesis would substantially impact plant growth and seed production. However, the resistant accessions may preserve their photosynthetic apparatus in response to the ozone levels used in this study. Older leaf tissue of the ozone-resistant accessions showed a unique down-regulation of

  18. Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy

    Science.gov (United States)

    Sipilä, Kirsi; Lähdesmäki, Raija; Millwood, Iona Y.; Kaakinen, Marika; Netuveli, Gopalakrishnan; Blane, David; Charoen, Pimphen; Sovio, Ulla; Pouta, Anneli; Freimer, Nelson; Hartikainen, Anna-Liisa; Laitinen, Jaana; Vaara, Sarianna; Glaser, Beate; Crawford, Peter; Timpson, Nicholas J.; Ring, Susan M.; Deng, Guohong; Zhang, Weihua; McCarthy, Mark I.; Deloukas, Panos; Peltonen, Leena

    2010-01-01

    Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5×10−8, and 5 with suggestive association (P<5×10−6). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years. PMID:20195514

  19. A large study reveals no Association between APOE and Parkinson’s disease

    Science.gov (United States)

    Federoff, Monica; Jimenez-Rolando, Belen; Nalls, Michael A; Singleton, Andrew B

    2012-01-01

    Background Research focusing on the role of APOE in Parkinson’s disease (PD) has been largely inconclusive, creating a broad discrepancy in association studies. Objective To elucidate the role of APOE alleles in PD risk by studying a large sample size and controlling for population substructure. Patients and Methods In total, 3465 case and control samples were genotyped, obtained from the NINDS Neurogenetics repository. Results No significant differences in ε4 dosages exist between PD cases and controls. The frequency of ε4 carriers differed slightly between cases and controls at 24% (580/2412) and 26% (270/1053), respectively. Likewise, mean dosages of APOE ε2 were not significantly different between cases and controls. APOE ε2 carriers were observed at a frequency of 13.6% (329/2412) among cases and 15% (158/1053) among controls. Logistic regression models evaluating PD as possibly associated with ε4 or ε2 carrier status and allele dosages yielded no significant results. The mean MMSE score among all PD cases was 28.35 (SD = 2.58) and memory loss was reported in only 11.9% (105/879) of cases. Linear regression models comparing MMSE scores as predicted by ε4 or ε2 carrier status and allele dosages were not significant. Conclusions There is no association between APOE epsilon alleles and Parkinson’s disease. PMID:22349451

  20. A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration.

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    Benjamin J Winter

    Full Text Available To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis.A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus specific, real-time PCR.Case patients were reflective of interstitial cystitis epidemiology with age range from 26-88 years (median 58 and female predominance (41/50 F. There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02. Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89-24.4. There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17-17.4.The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation.

  1. A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration.

    Science.gov (United States)

    Winter, Benjamin J; O'Connell, Helen E; Bowden, Scott; Carey, Marcus; Eisen, Damon P

    2015-01-01

    To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Case patients were reflective of interstitial cystitis epidemiology with age range from 26-88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (pinterstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89-24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17-17.4). The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation.

  2. Time-resolved toxicity study reveals the dynamic interactions between uncoated silver nanoparticles and bacteria.

    Science.gov (United States)

    Dong, Feng; Mohd Zaidi, Nurul Fitriah; Valsami-Jones, Eugenia; Kreft, Jan-Ulrich

    2017-06-01

    It is still unclear whether the toxicity of silver nanoparticles (AgNPs) can be attributed solely to the release of Ag + or whether dissolved and nanoparticulate Ag act in parallel; this is due to the difficulty in distinguishing Ag + - from AgNP-effects. Also, AgNPs undergo changes during toxicity tests. This is the first study to investigate the influence of AgNP dissolution over time on viable counts at high time resolution and low cell density, avoiding the apparently reduced toxicity at higher cell densities identified in our study. Uncapped AgNPs were synthesized to avoid any interference from surface coatings. The transformations of AgNPs during storage were reduced. Lowering the concentration of AgNPs reduced their aggregation in Davis minimal medium (DMM). Also, AgNPs dissolved more slowly in DMM than in water. The minimum inhibitory concentrations (MICs) of Ag + and AgNPs increased with cell density according to a power law, suggesting that binding to cells decreased effective concentrations. However, AgNPs acted as a reservoir of Ag, releasing new Ag + to maintain the Ag stress. The toxicity of AgNPs was dominated by dissolved Ag. Combining controlled conditions, high time-resolution and low cell density, we could demonstrate different roles of ionic and nano Ag in bacterial death caused by AgNPs.

  3. Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

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    P Roberto Bakker

    Full Text Available OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

  4. Transcriptome and Proteome Studies Reveal Candidate Attachment Genes during the Development of the Barnacle Amphibalanus Amphitrite

    KAUST Repository

    Al-Aqeel, Sarah

    2016-09-21

    The acorn barnacle, Balanus amphitrite, is the main biofouling organism in marine environments. In the present study we profiled the transcriptome and proteome of B. amphitrite at different life stages (nauplius II, nauplius VI, and cyprid) from the Red Sea, where the average water surface temperature is 34°C and the salinity reaches 41%. We identified 65,784 expressed contigs, and a total of 1387 expressed proteins measured by quantitative proteomics. We found that osmotic stress, salt stress, hyperosmotic response and the Wnt signaling pathway were strongly up-regulated during the planktonic stage, while the MAPK pathway, lipid metabolism, and cuticle development genes were down-regulated. In the transition stage between the nauplius VI and the cyprid, genes that are involved in blood coagulation, cuticle development and eggshell formation were highly up-regulated, while the nitric oxide pathway, which stimulates the swimming and feeding response in marine invertebrates, was down-regulated. We are able to report for the first time that sound sensory system proteins are highly abundant in the nauplius VI stage, implying that these proteins are good targets for the development of new antifouling compounds. The results presented here together with the new genome-wide datasets for a non-model specie represent an important resource for the study of biofouling and development. Proteomics data are available via ProteomeXchange with identifier PXD004679.

  5. Transcriptome and proteome studies reveal candidate attachment genes during the development of the barnacle Amphibalanus Amphitrite

    Directory of Open Access Journals (Sweden)

    Sarah Al-Aqeel

    2016-09-01

    Full Text Available The acorn barnacle, Balanus amphitrite, is the main biofouling organism in marine environments. In the present study we profiled the transcriptome and proteome of B. amphitrite at different life stages (nauplius II, nauplius VI and cyprid from the Red Sea, where the average water surface temperature is 34°C and the salinity reaches 41‰. We identified 65,784 expressed contigs, and a total of 1,387 expressed proteins measured by quantitative proteomics. We found that osmotic stress, salt stress, hyperosmotic response and the Wnt signaling pathway were strongly up-regulated during the planktonic stage, while the MAPK pathway, lipid metabolism, and cuticle development genes were down-regulated. In the transition stage between the nauplius VI and the cyprid, genes that are involved in blood coagulation, cuticle development and eggshell formation were highly up-regulated, while the nitric oxide pathway, which stimulates the swimming and feeding response in marine invertebrates, was down-regulated. We are able to report for the first time that sound sensory system proteins are highly abundant in the nauplius VI stage, implying that these proteins are good targets for the development of new antifouling compounds. The results presented here together with the new genome-wide datasets for a non-model specie represent an important resource for the study of biofouling and development.

  6. [Changing to a career in general practice - a qualitative study reveals motives of specialists].

    Science.gov (United States)

    Schwill, Simon; Magez, Julia; Jäger, Cornelia; von Meißner, Wolfgang Cg; Szecsenyi, Joachim; Flum, Elisabeth

    2016-12-01

    In 2011, the national German Medical Association (Bundesärztekammer) published guidelines for a slim-lined training program in general practice (Quereinstieg) for qualified medical specialists in other fields (e. g., surgeons, internists or anesthesiologists). This step is part of a strategy to prevent further shortages of general practitioners in Germany. In the state of Baden-Wuerttemberg, qualified medical specialists are allowed to complete their general practice training in approximately two years instead of five. The aim of this study was to understand the reasons of specialists for changing to a career in general practice. The postgraduate training program Verbundweiterbildung plus Baden-Württemberg had 597 trainees at the time of the study in December 2015. Previously qualified specialists in another medical discipline were identified and invited to participate in this study. Qualitative data was gathered using semi-structured interviews with content analysis of the interviews performed by three independent members of the research team. In total, 36 out of 597 trainees were identified as previously qualified specialists in another medical discipline. All 36 were invited to take part and 15 agreed to participate in this study. Overall, 15 interviews were performed, with a mean time of 24.19minutes. Participants with a median age of 40 years (33-59 years) - mainly anesthesiologists (n=7), surgeons (n=3) and internists (n=3) - presented with an average of 6.5 years of professional experience in their specialty. First, the participants' motivation to switch career arose from the wish to intensify the quality of patient contacts with a holistic approach including family and social background and from the infinite variety of general practice. Another reason given for a career change was self-employment opportunities. Finally, feelings of frustration over poor working conditions in hospitals resulted in a job search elsewhere in medicine, taking account of

  7. Smartphones reveal angler behavior: A case study of a popular mobile fishing application in Alberta, Canada

    Science.gov (United States)

    Papenfuss, Jason T.; Phelps, Nicholas; Fulton, David C.; Venturelli, Paul A.

    2015-01-01

    Successfully managing fisheries and controlling the spread of invasive species depends on the ability to describe and predict angler behavior. However, finite resources restrict conventional survey approaches and tend to produce retrospective data that are limited in time or space and rely on intentions or attitudes rather than actual behavior. In this study, we used three years of angler data from a popular mobile fishing application in Alberta, Canada, to determine province-wide, seasonal patterns of (1) lake popularity that were consistent with conventional data and (2) anthropogenic lake connectivity that has not been widely described in North America. Our proof-of-concept analyses showed that mobile apps can be an inexpensive source of high-resolution, real-time data for managing fisheries and invasive species. We also identified key challenges that underscore the need for further research and development in this new frontier that combines big data with increased stakeholder interaction and cooperation.

  8. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.

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    J Brent Richards

    2009-12-01

    Full Text Available The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D and coronary heart disease (CHD. We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531 and sought validation of the lead single nucleotide polymorphisms (SNPs in 5 additional cohorts (n = 6,202. Five SNPs were genome-wide significant in their relationship with adiponectin (P< or =5x10(-8. We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19 for lead SNP, rs266717, n = 14,733. A novel variant in the ARL15 (ADP-ribosylation factor-like 15 gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8, n = 14,733. This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6, n = 22,421 more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3, n = 10,128, and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.

  9. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

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    Jingwei Yuan

    Full Text Available Egg number (EN, egg laying rate (LR and age at first egg (AFE are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens.

  10. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8

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    Sehgal SA

    2016-05-01

    Full Text Available Sheikh Arslan Sehgal,1–4 Shazia Mannan,1 Sannia Ali1 1Department of Bioscience, COMSATS Institute of Information Technology, Sahiwal, Pakistan; 2State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan Abstract: Charcot–Marie–Tooth (CMT disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand–receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT. Keywords: bioinformatics, computer

  11. Identification of Pleiotropic Cancer Susceptibility Variants from Genome-Wide Association Studies Reveals Functional Characteristics.

    Science.gov (United States)

    Wu, Yi-Hsuan; Graff, Rebecca E; Passarelli, Michael N; Hoffman, Joshua D; Ziv, Elad; Hoffmann, Thomas J; Witte, John S

    2018-01-01

    Background: There exists compelling evidence that some genetic variants are associated with the risk of multiple cancer sites (i.e., pleiotropy). However, the biological mechanisms through which the pleiotropic variants operate are unclear. Methods: We obtained all cancer risk associations from the National Human Genome Research Institute-European Bioinformatics Institute GWAS Catalog, and correlated cancer risk variants were clustered into groups. Pleiotropic variant groups and genes were functionally annotated. Associations of pleiotropic cancer risk variants with noncancer traits were also obtained. Results: We identified 1,431 associations between variants and cancer risk, comprised of 989 unique variants associated with 27 unique cancer sites. We found 20 pleiotropic variant groups (2.1%) composed of 33 variants (3.3%), including novel pleiotropic variants rs3777204 and rs56219066 located in the ELL2 gene. Relative to single-cancer risk variants, pleiotropic variants were more likely to be in genes (89.0% vs. 65.3%, P = 2.2 × 10 -16 ), and to have somewhat larger risk allele frequencies (median RAF = 0.49 versus 0.39, P = 0.046). The 27 genes to which the pleiotropic variants mapped were suggestive for enrichment in response to radiation and hypoxia, alpha-linolenic acid metabolism, cell cycle, and extension of telomeres. In addition, we observed that 8 of 33 pleiotropic cancer risk variants were associated with 16 traits other than cancer. Conclusions: This study identified and functionally characterized genetic variants showing pleiotropy for cancer risk. Impact: Our findings suggest biological pathways common to different cancers and other diseases, and provide a basis for the study of genetic testing for multiple cancers and repurposing cancer treatments. Cancer Epidemiol Biomarkers Prev; 27(1); 75-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. An Epidemiological Study of Population Health Reveals Social Smoking as a Major Cardiovascular Risk Factor.

    Science.gov (United States)

    Gawlik, Kate Sustersic; Melnyk, Bernadette Mazurek; Tan, Alai

    2017-01-01

    To present nationally representative data on the prevalence of "social" smoking and its relationship to cardiovascular health. A population-based, cross-sectional survey on cardiovascular health and its risk factors across the United States. Million Hearts ® cardiovascular screenings that took place in community settings. De-identified data were collected on a convenient sample of 39, 555 participants. Reported smoking status, blood pressure, and total cholesterol. The prevalence of current smoking, social smoking, and non-smoking were cross-tabulated and stratified by sample characteristics. The adjusted estimates were derived from multiple logistic regression models, adjusting for demographics and other biometric measures. Ten percent identified as social smokers. Social smokers were more likely to be aged between 21 and 40, male, and Hispanic. Social smokers had significantly higher risks of having hypertension (odds ratio [OR]: 2.08, 95% confidence interval [CI]: 1.80-2.41) and elevated cholesterol (OR: 1.53, 95% CI: 1.33-1.75) than non-smokers. There was no significant difference between social smokers and current smokers (OR = 0.94, 95% CI = 0.80-1.14 for hypertension and OR = 0.95, 95% CI = 0.81-1.11 for elevated cholesterol). This is the first population health study to compare the blood pressure and cholesterol levels of people who self-identify as current verses social smokers. Although previous smoking behavior was not controlled for in the analysis, this study demonstrates there is no significant difference in the prevalence of elevated blood pressure or cholesterol among the 2 smoking groups.

  13. Estrogenic activity of commercial milk as revealed in immature hamster uterotrophic assay – pilot study

    Science.gov (United States)

    Radko, Lidia; Minta, Maria; Stypuła-Trębas, Sylwia

    The risk for public health posed by endocrine disruptors present in food is relatively new issue. Our current understanding of human exposure is mainly based on the residue analysis of selected compounds. With such approach potential, effects of mixtures, including so-far unidentified compounds are not taken into consideration. Therefore, the knowledge of overall hormonal activity in food samples is of big importance. Milk and dairy products are a rich source of estrogens but very rarely undergo testing for estrogenic activity. For this reason the rodent uterotrophic bioassay is one of the most useful tool. This preliminary study was conducted in immature hamsters to assess commercially available milk. The endpoint measured was uterine weight increase. Fifteen-day old females received ad libitum throughout 7 days commercially available milk i.e. raw goat’s, raw cow’s, processed 3.2% UHT, and for comparison soy milk. The animals of negative control group received water but positive control group got 17β - estradiol (E2) at the concentration of 100 ng/ml. All samples of milk showed estrogenic activity as follow: goat’s >cow’s >soy >processed milk. Significant increase of uteri weights were recorded in goat’s (pmilk (pmilk experimental groups ranged from 0.112% to 0.153% and in positive control this value was 0.493%. The results suggest that commercially available milk has a weak uterotrophic activity. Further in vivo and in vitro studies are warranted to gain more insight into the estrogenic risk from milk and other dairy products.

  14. The Study of Iodine Status among Schoolchildren from Kyiv and Ways to Correct the Revealed Violations

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    O.A. Stroi

    2016-08-01

    Full Text Available Relevance. Lack of iodine in the environment is one of the topical medico-social problems in many countries of the world. Iodine deficiency is an important risk factor for the developmental delay, memory loss, or the ability for analysis and abstract thinking. Traditionally in Ukraine the problem of iodine deficiency was relevant in Western regions, but recent studies indicate the existence of moderate iodine deficiency in all areas. The aim of our study was to assess the iodine status of primary schoolchildren from Kyiv. Materials and methods. The examination of 52 children aged 6–12 years was performed, which involved a survey of families on awareness of the consequences of iodine deficiency and frequency of consumption of foods containing iodine, objective and ultrasound thyroid investigation, determination of urine iodine content in single portions of urine. Results. Iodine deficiency was detected in 87 % of pupils, mostly mild. Diffuse goiter grade 1 was diagnosed in 23 % of patients. To correct iodine deficiency, we have used new generation product — jodis-concentrate as an aqueous solution. Conclusions. Research of iodine status in schoolchildren aged 6–12 years in Kyiv showed the presence of mild iodine deficiency in 87 % of them (in 68 and 19 %, respectively. In 12 (23 % children, we have diagnosed thyroid volume increase under normal echogenicity and homogeneous echostructure. Lack of iodine nutrition is caused by poor nutrition, lack of mass, group and individual iodine prophylaxis, low sanitary hygienic culture of the population. Pupils with iodine deficiency were administered an individual subsidy of iodine in the form of an aqueous solution of jodis-concentrate for 12 months, which has significantly improved the iodine status of children, normalized the level of urine iodine content. Early detection of iodine deficiency and its correction are the promising directions of modern pediatrics in terms of the prevention of thyroid

  15. Morphological Study of the Encystment and Excystment of Vermamoeba vermiformis Revealed Original Traits.

    Science.gov (United States)

    Fouque, Emilie; Yefimova, Marina; Trouilhé, Marie-Cécile; Quellard, Nathalie; Fernandez, Béatrice; Rodier, Marie-Hélène; Thomas, Vincent; Humeau, Philippe; Héchard, Yann

    2015-01-01

    Free-living amoebae are ubiquitous protozoa commonly found in water. Among them, Acanthamoeba and Vermamoeba (formerly Hartmannella) are the most represented genera. In case of stress, such as nutrient deprivation or osmotic stress, these amoebae initiate a differentiation process, named encystment. It leads to the cyst form, which is a resistant form enabling amoebae to survive in harsh conditions and resist disinfection treatments. Encystment has been thoroughly described in Acanthamoeba but poorly in Vermamoeba. Our study was aimed to follow the encystment/excystment processes by microscopic observations. We show that encystment is quite rapid, as mature cysts were obtained in 9 h, and that cyst wall is composed of two layers. A video shows that a locomotive form is likely involved in clustering cysts together during encystment. As for Acanthamoeba, autophagy is likely active during this process. Specific vesicles, possibly involved in ribophagy, were observed within the cytoplasm. Remarkably, mitochondria rearranged around the nucleus within the cyst, suggesting high needs in energy. Unlike Acanthamoeba and Naegleria, no ostioles were observed in the cyst wall suggesting that excystment is original. During excystment, large vesicles, likely filled with hydrolases, were found in close proximity to cyst wall and digest it. Trophozoite moves inside its cyst wall before exiting during excystment. In conclusion, Vermamoeba encystment/excystment displays original trends as compare to Acanthamoeba. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

  16. Revealing transboundary and local air pollutant sources affecting Metro Manila through receptor modeling studies

    International Nuclear Information System (INIS)

    Pabroa, Preciosa Corazon B.; Bautista VII, Angel T.; Santos, Flora L.; Racho, Joseph Michael D.

    2011-01-01

    Ambient fine particulate matter (PM 2 .5) levels at the Metro Manila air sampling stations of the Philippine Nuclear Research Research Institute were found to be above the WHO guideline value of 10 μg m 3 indicating, in general, very poor air quality in the area. The elemental components of the fine particulate matter were obtained using the energy-dispersive x-ray fluorescence spectrometry. Positive matrix factorization, a receptor modelling tool, was used to identify and apportion air pollution sources. Location of probable transboundary air pollutants were evaluated using HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory Model) while location of probable local air pollutant sources were determined using the conditional probability function (CPF). Air pollutant sources can either be natural or anthropogenic. This study has shown natural air pollutant sources such as volcanic eruptions from Bulusan volcano in 2006 and from Anatahan volcano in 2005 to have impacted on the region. Fine soils was shown to have originated from China's Mu US Desert some time in 2004. Smoke in the fine fraction in 2006 show indications of coming from forest fires in Sumatra and Borneo. Fine particulate Pb in Valenzuela was shown to be coming from the surrounding area. Many more significant air pollution impacts can be evaluated with the identification of probable air pollutant sources with the use of elemental fingerprints and locating these sources with the use of HYSPLIT and CPF. (author)

  17. Phylogenetic and molecular epidemiological studies reveal evidence of multiple past recombination events between infectious laryngotracheitis viruses.

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    Sang-Won Lee

    Full Text Available In contrast to the RNA viruses, the genome of large DNA viruses such as herpesviruses have been considered to be relatively stable. Intra-specific recombination has been proposed as an important, but underestimated, driving force in herpesvirus evolution. Recently, two distinct field strains of infectious laryngotracheitis virus (ILTV have been shown to have arisen from independent recombination events between different commercial ILTV vaccines. In this study we sequenced the genomes of additional ILTV strains and also utilized other recently updated complete genome sequences of ILTV to confirm the existence of a number of ILTV recombinants in nature. Multiple recombination events were detected in the unique long and repeat regions of the genome, but not in the unique short region. Most recombinants contained a pair of crossover points between two distinct lineages of ILTV, corresponding to the European origin and the Australian origin vaccine strains of ILTV. These results suggest that there are two distinct genotypic lineages of ILTV and that these commonly recombine in the field.

  18. Epizoanthus spp. associations revealed using DNA markers: a case study from Kochi, Japan.

    Science.gov (United States)

    Reimer, James Davis; Hirose, Mamiko; Nishisaka, Taiki; Sinniger, Frederic; Itani, Gyo

    2010-09-01

    Zoanthids (Cnidaria, Hexacorallia) of the genus Epizoanthus are often found in association with other marine invertebrates, including gastropods and hermit crabs. However, little information exists on the specificity and nature of these associations due to a lack of investigation into Epizoanthus species diversity, and the taxonomy of Epizoanthus is therefore confused. In this study, analyses of morphological data (tentacle number, polyp size, etc) and molecular data (mitochondrial cytochrome oxidase subunit 1 = COI, 16S ribosomal DNA = 16S rDNA) were used to examine Epizoanthus specimens from Tosa Bay, Kochi, Japan. The Epizoanthus specimens were found on both live gastropods (Gemmula unedo) and hermit crabs (Paguristes palythophilus) inhabiting G. unedo and G. cosmoi shells. While morphological analyses did not show clear differences between examined specimens, both COI and mt 16S rDNA clearly divided the specimens into two groups, one associated only with hermit crabs (= Epizoanthus sp. C), and another associated only with living gastropods (= Epizoanthus sp. S). Unexpectedly, DNA sequences from both groups did not match with two previously reported Epizoanthus species from Japan (E. indicus, E. ramosus), indicating they both may be undescribed species. These results highlight the utility of DNA "barcoding" of unknown zoanthids, and will provide a foundation for re-examinations of Epizoanthus species diversity and specificity, which will be critical in understanding the evolution of these unique marine invertebrates.

  19. [Salmonella typhi vaccination response study reveals defective antibody production selective IgA deficiency patient].

    Science.gov (United States)

    Pleguezuelo, Daniel E; Gianelli, Carla

    2015-01-01

    Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre-vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production.

  20. Drawings of Blood Cells Reveal People's Perception of Their Blood Disorder: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Steven Ramondt

    Full Text Available Sickle cell disease (SCD and thalassemia are rare but chronic blood disorders. Recent literature showed impaired quality of life (QOL in people with these blood disorders. Assessing one of the determinants of QOL (i.e. illness perceptions therefore, is an important next research area.We aimed to explore illness perceptions of people with a blood disorder with drawings in addition to the Brief Illness Perception Questionnaire (Brief IPQ. Drawings are a novel method to assess illness perceptions and the free-range answers drawings offer can add additional insight into how people perceive their illness.We conducted a cross-sectional study including 17 participants with a blood disorder. Participants' illness perceptions were assessed by the Brief IPQ and drawings. Brief IPQ scores were compared with reference groups from the literature (i.e. people with asthma or lupus erythematosus.Participants with SCD or thalassemia perceived their blood disorder as being more chronic and reported more severe symptoms than people with either asthma or lupus erythematosus. In the drawings of these participants with a blood disorder, a greater number of blood cells drawn was negatively correlated with perceived personal control (P<0.05, indicating that a greater quantity in the drawing is associated with more negative or distressing beliefs.Participants with a blood disorder perceive their disease as fairly threatening compared with people with other chronic illnesses. Drawings can add additional insight into how people perceive their illness by offering free-range answers.

  1. Genome-wide Association Study of Dermatomyositis Reveals Genetic Overlap with other Autoimmune Disorders

    Science.gov (United States)

    Miller, Frederick W.; Cooper, Robert G.; Vencovsky, Jiri; Rider, Lisa G.; Danko, Katalin; Wedderburn, Lucy R.; Lundberg, Ingrid E.; Pachman, Lauren M.; Reed, Ann M.; Ytterberg, Steven R.; Padyukov, Leonid; Selva-O’Callaghan, Albert; Radstake, Timothy; Isenberg, David A.; Chinoy, Hector; Ollier, William E. R.; O’Hanlon, Terrance P.; Peng, Bo; Lee, Annette; Lamb, Janine A.; Chen, Wei; Amos, Christopher I.; Gregersen, Peter K.

    2014-01-01

    Objective To identify new genetic associations with juvenile and adult dermatomyositis (DM). Methods We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1178) and controls (n = 4724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Results Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5x10−8) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that three SNPs linked with three genes were associated with DM, with a false discovery rate (FDR) < 0.05. These genes were phospholipase C like 1 (PLCL1, rs6738825, FDR=0.00089), B lymphoid tyrosine kinase (BLK, rs2736340, FDR=0.00031), and chemokine (C-C motif) ligand 21 (CCL21, rs951005, FDR=0.0076). None of these genes was previously reported to be associated with DM. Conclusion Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches. PMID:23983088

  2. Mutational studies of the Aux/IAA proteins in Physcomitrella reveal novel insights into their function.

    Science.gov (United States)

    Tao, Sibo; Estelle, Mark

    2018-02-20

    The plant hormone auxin regulates many aspects of plant growth and development. Auxin signaling involves hormone perception by the TRANSPORT INHIBITOR RESPONSE/AUXIN F-BOX (TIR1/AFB)-Aux/IAA co-receptor system, and the subsequent degradation of the Aux/IAA transcriptional repressors by the ubiquitin proteasome pathway. This leads to the activation of downstream gene expression and diverse physiological responses. Here, we investigate how the structural elements in the Aux/IAAs determine their function in Auxin perception and transcriptional repression. We took advantage of the facile genetics of the moss Physcomitrella patens to determine the activity of wild-type and mutant PpIAA1a proteins in a Δaux/iaa null background. In this way, Aux/IAA function was characterized at the molecular and physiological levels without the interference of genetic redundancy. We identified and characterized degron variants in Aux/IAAs that affect their stability and Auxin response. We also demonstrated that neither the Aux/IAA EAR motif nor Aux/IAA oligomerization is essential for the repressive function of Aux/IAA. Our study demonstrates how key elements within the Aux/IAA proteins fine tune stability and repressor activity, as well as the long-term developmental outcome. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  3. Large cross-sectional study of presbycusis reveals rapid progressive decline in auditory temporal acuity.

    Science.gov (United States)

    Ozmeral, Erol J; Eddins, Ann C; Frisina, D Robert; Eddins, David A

    2016-07-01

    The auditory system relies on extraordinarily precise timing cues for the accurate perception of speech, music, and object identification. Epidemiological research has documented the age-related progressive decline in hearing sensitivity that is known to be a major health concern for the elderly. Although smaller investigations indicate that auditory temporal processing also declines with age, such measures have not been included in larger studies. Temporal gap detection thresholds (TGDTs; an index of auditory temporal resolution) measured in 1071 listeners (aged 18-98 years) were shown to decline at a minimum rate of 1.05 ms (15%) per decade. Age was a significant predictor of TGDT when controlling for audibility (partial correlation) and when restricting analyses to persons with normal-hearing sensitivity (n = 434). The TGDTs were significantly better for males (3.5 ms; 51%) than females when averaged across the life span. These results highlight the need for indices of temporal processing in diagnostics, as treatment targets, and as factors in models of aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Genome association study through nonlinear mixed models revealed new candidate genes for pig growth curves

    Directory of Open Access Journals (Sweden)

    Fabyano Fonseca e Silva

    Full Text Available ABSTRACT: Genome association analyses have been successful in identifying quantitative trait loci (QTLs for pig body weights measured at a single age. However, when considering the whole weight trajectories over time in the context of genome association analyses, it is important to look at the markers that affect growth curve parameters. The easiest way to consider them is via the two-step method, in which the growth curve parameters and marker effects are estimated separately, thereby resulting in a reduction of the statistical power and the precision of estimates. One efficient solution is to adopt nonlinear mixed models (NMM, which enables a joint modeling of the individual growth curves and marker effects. Our aim was to propose a genome association analysis for growth curves in pigs based on NMM as well as to compare it with the traditional two-step method. In addition, we also aimed to identify the nearest candidate genes related to significant SNP (single nucleotide polymorphism markers. The NMM presented a higher number of significant SNPs for adult weight (A and maturity rate (K, and provided a direct way to test SNP significance simultaneously for both the A and K parameters. Furthermore, all significant SNPs from the two-step method were also reported in the NMM analysis. The ontology of the three candidate genes (SH3BGRL2, MAPK14, and MYL9 derived from significant SNPs (simultaneously affecting A and K allows us to make inferences with regards to their contribution to the pig growth process in the population studied.

  5. Association studies and legume synteny reveal haplotypes determining seed size in Vigna unguiculata

    Directory of Open Access Journals (Sweden)

    Mitchell R Lucas

    2013-04-01

    Full Text Available Highly specific seed market classes for cowpea and other grain legumes exists because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large-seeded lines. In this work we applied SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker based selection approaches to increase the frequency of progeny with large seed. For ~800 samples derived from eight bi-parental populations, QTL analysis was used to identify markers linked to ten trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total ten QTL were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

  6. Association Studies and Legume Synteny Reveal Haplotypes Determining Seed Size in Vigna unguiculata.

    Science.gov (United States)

    Lucas, Mitchell R; Huynh, Bao-Lam; da Silva Vinholes, Patricia; Cisse, Ndiaga; Drabo, Issa; Ehlers, Jeffrey D; Roberts, Philip A; Close, Timothy J

    2013-01-01

    Highly specific seed market classes for cowpea and other grain legumes exist because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large seeded lines. In this work we applied 1,536-plex SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker-based selection approaches to increase the frequency of progeny with large seed. For 804 individuals derived from eight bi-parental populations, QTL analysis was used to identify markers linked to 10 trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total 10 QTLs were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

  7. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Ulrike Esslinger

    Full Text Available Dilated cardiomyopathy (DCM is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS to assess the contribution of missense variants to sporadic DCM.116,855 single nucleotide variants (SNVs were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value<0.01. The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3. In silico fine mapping identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF<0.01 demonstrated significant association for TTN variants only (P = 0.0085. All candidate genes but one (SLC39A8 exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. We also investigated a panel of 48 known cardiomyopathy genes. Collectively, rare (n = 228, P = 0.0033 or common (n = 36, P = 0.019 variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here.We identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology.

  8. Microarray studies on lager brewer's yeasts reveal cell status in the process of autolysis.

    Science.gov (United States)

    Xu, Weina; Wang, Jinjing; Li, Qi

    2014-08-01

    In this work, we performed DNA microarray studies on lager brewer's yeast Saccharomyces pastorianus to investigate changes in gene expression in the process of autolysis. The two strains we used were Qing2 and 5-2. Strain 5-2 is a mutant of Qing2 and autolyzes much more slowly than its parent strain. Four samples of these two strains during different autolysis stages (0% and 15%) were tested using DNA microarray containing > 10,000 yeast's genes. Analysis of genes with the same transcription pattern (up- or down-regulated in both strains) showed that the same 99 genes were up-regulated (transcription levels were increased), and the same 97 genes were down-regulated (transcription levels were decreased) by fivefold or more during autolysis. Genes involved in energy production/utilization, protein anabolism, and stress response were down-regulated. Genes related to cell wall organization and biogenesis, starvation response and DNA damage response were up-regulated. Analysis of genes with opposite transcription patterns (up-regulated in one strain and down-regulated in the other one) showed that 246 genes were up-regulated in 5-2 (autolyzes slowly) and down-regulated in Qing2 (autolyzes rapidly). Another 18 genes had opposite transcription levels, indicating that the strain which autolyzes slowly had better cell vitality despite the same autolysis stage. These findings might further promote the global understanding of autolysis in yeast. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  9. Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

    Directory of Open Access Journals (Sweden)

    John R Shaffer

    2016-08-01

    Full Text Available Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array imputed to the 1000 Genomes reference panel (Phase 3. We observed genome-wide significant associations (p < 5 x 10-8 for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

  10. A comparative phylogeographic study reveals discordant evolutionary histories of alpine ground beetles (Coleoptera, Carabidae).

    Science.gov (United States)

    Weng, Yi-Ming; Yang, Man-Miao; Yeh, Wen-Bin

    2016-04-01

    Taiwan, an island with three major mountain ranges, provides an ideal topography to study mountain-island effect on organisms that would be diversified in the isolation areas. Glaciations, however, might drive these organisms to lower elevations, causing gene flow among previously isolated populations. Two hypotheses have been proposed to depict the possible refugia for alpine organisms during glaciations. Nunatak hypothesis suggests that alpine species might have stayed in situ in high mountain areas during glaciations. Massif de refuge, on the other hand, proposes that alpine species might have migrated to lower ice-free areas. By sampling five sympatric carabid species of Nebria and Leistus, and using two mitochondrial genes and two nuclear genes, we evaluated the mountain-island effect on alpine carabids and tested the two proposed hypotheses with comparative phylogeographic method. Results from the phylogenetic relationships, network analysis, lineage calibration, and genetic structure indicate that the deep divergence among populations in all L. smetanai, N. formosana, and N. niitakana was subjected to long-term isolation, a phenomenon in agreement with the nunatak hypothesis. However, genetic admixture among populations of N. uenoiana and some populations of L. nokoensis complex suggests that gene flow occurred during glaciations, as a massif de refuge depicts. The speciation event in N. niitakana is estimated to have occurred before 1.89 million years ago (Mya), while differentiation among isolated populations in N. niitakana, N. formosana, L. smetanai, and L. nokoensis complex might have taken place during 0.65-1.65 Mya. While each of the alpine carabids arriving in Taiwan during different glaciation events acquired its evolutionary history, all of them had confronted the existing mountain ranges.

  11. Genomic markers reveal introgressive hybridization in the Indo-West Pacific mangroves: a case study.

    Directory of Open Access Journals (Sweden)

    Mei Sun

    2011-05-01

    Full Text Available Biodiversity of mangrove ecosystems is difficult to assess, at least partly due to lack of genetic verification of morphology-based documentation of species. Natural hybridization, on the one hand, plays an important role in evolution as a source of novel gene combinations and a mechanism of speciation. However, on the other hand, recurrent introgression allows gene flow between species and could reverse the process of genetic differentiation among populations required for speciation. To understand the dynamic evolutionary consequences of hybridization, this study examines genomic structure of hybrids and parental species at the population level. In the Indo-West Pacific, Bruguiera is one of the dominant mangrove genera and species ranges overlap extensively with one another. Morphological intermediates between sympatric Bruguiera gymnorrhiza and Bruguiera sexangula have been reported as a variety of B. sexangula or a new hybrid species, B. × rhynchopetala. However, the direction of hybridization and extent of introgression are unclear. A large number of species-specific inter-simple sequence repeat (ISSR markers were found in B. gymnorrhiza and B. sexangula, and the additive ISSR profiling of B. × rhynchopetala ascertained its hybrid status and identified its parental origin. The varying degree of scatterness among hybrid individuals in Principal Coordinate Analysis and results from NewHybrids analysis indicate that B. × rhynchopetala comprises different generations of introgressants in addition to F(1s. High genetic relatedness between B. × rhynchopetala and B. gymnorrhiza based on nuclear and chloroplast sequences suggests preferential hybrid backcrosses to B. gymnorrhiza. We conclude that B. × rhynchopetala has not evolved into an incipient hybrid species, and its persistence can be explained by recurrent hybridization and introgression. Genomic data provide insights into the hybridization dynamics of mangrove plants. Such information

  12. Neospora caninum tachyzoite immunome study reveals differences among three biologically different isolates.

    Science.gov (United States)

    Regidor-Cerrillo, Javier; García-Lunar, Paula; Pastor-Fernández, Iván; Álvarez-García, Gema; Collantes-Fernández, Esther; Gómez-Bautista, Mercedes; Ortega-Mora, Luis M

    2015-09-15

    Pathogenesis of bovine neosporosis is determined by different host- and parasite-dependent factors, including isolate virulence. A previous study identified that several Neospora caninum tachyzoite proteins were more abundant in virulent isolates, Nc-Liv and Nc-Spain7, compared with the low-virulent isolate Nc-Spain1H. Herein, we explored differences in the immunomes of these three isolates. Protein extracts from the Nc-Liv, Nc-Spain1H and Nc-Spain7 isolates were analysed in a 3×3 design by 2-DE immunoblot using sera from experimentally infected mice with these same three isolates. All isolates displayed a highly similar antigenic pattern when they were assessed using the same serum. Most of the reactive spots were located in the acidic region (pH 3-7) and grouped in 3 antigenic areas (250-70, 45-37 and 35-15 KDa). Differences found in the immunome depended on the sera used, regardless of the extract employed. In this sense, sera from Nc-Liv and Nc-Spain7 infected mice recognized the highest number of antigens, followed by Nc-Spain1H infected mice sera. In fact, 4 proteins identified by MS were not consistently detected in each isolate extract by sera from low-virulent Nc-Spain1H-infected mice: serine-threonine phosphatase 2C and superoxide dismutase (related to metabolism), gliding associated protein GAP45 (related to tachyzoites invasion), and NcGRA1 (located on dense granules). Similarly, 4 non-identified spots and another 2 spots chains located in 45-37 kDa area were not detected by this pooled sera. Variations between virulent Nc-Spain7 and Nc-Liv were limited to the absence of recognition by sera from Nc-Spain7-infected mice of GAP45 and the spot chains located in the 45-37 kDa area. These results suggest that variations in the immunome profiles rely on the immune response induced by each isolate and that these differentially recognized antigens could be investigated as putative virulence markers of neosporosis. Copyright © 2015 Elsevier B.V. All rights

  13. Effects of conformational peptide probe DP4 on bidirectional signaling between DHPR and RyR1 calcium channels in voltage-clamped skeletal muscle fibers.

    Science.gov (United States)

    Olojo, Rotimi O; Hernández-Ochoa, Erick O; Ikemoto, Noriaki; Schneider, Martin F

    2011-05-18

    In skeletal muscle, excitation-contraction coupling involves the activation of dihydropyridine receptors (DHPR) and type-1 ryanodine receptors (RyR1) to produce depolarization-dependent sarcoplasmic reticulum Ca²⁺ release via orthograde signaling. Another form of DHPR-RyR1 communication is retrograde signaling, in which RyRs modulate the gating of DHPR. DP4 (domain peptide 4), is a peptide corresponding to residues Leu²⁴⁴²-Pro²⁴⁷⁷ of the central domain of the RyR1 that produces RyR1 channel destabilization. Here we explore the effects of DP4 on orthograde excitation-contraction coupling and retrograde RyR1-DHPR signaling in isolated murine muscle fibers. Intracellular dialysis of DP4 increased the peak amplitude of Ca²⁺ release during step depolarizations by 64% without affecting its voltage-dependence or kinetics, and also caused a similar increase in Ca²⁺ release during an action potential waveform. DP4 did not modify either the amplitude or the voltage-dependence of the intramembrane charge movement. However, DP4 augmented DHPR Ca²⁺ current density without affecting its voltage-dependence. Our results demonstrate that the conformational changes induced by DP4 regulate both orthograde E-C coupling and retrograde RyR1-DHPR signaling. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Effects of Conformational Peptide Probe DP4 on Bidirectional Signaling between DHPR and RyR1 Calcium Channels in Voltage-Clamped Skeletal Muscle Fibers

    OpenAIRE

    Olojo, Rotimi O.; Hernández-Ochoa, Erick O.; Ikemoto, Noriaki; Schneider, Martin F.

    2011-01-01

    In skeletal muscle, excitation-contraction coupling involves the activation of dihydropyridine receptors (DHPR) and type-1 ryanodine receptors (RyR1) to produce depolarization-dependent sarcoplasmic reticulum Ca2+ release via orthograde signaling. Another form of DHPR-RyR1 communication is retrograde signaling, in which RyRs modulate the gating of DHPR. DP4 (domain peptide 4), is a peptide corresponding to residues Leu2442-Pro2477 of the central domain of the RyR1 that produces RyR1 channel d...

  15. Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

    Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...... of depression or for monitoring treatment response....

  16. Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study

    International Nuclear Information System (INIS)

    Lesoil, Charles; Nonaka, Takahiro; Sekiguchi, Hiroshi; Osada, Toshiya; Miyata, Makoto; Afrin, Rehana; Ikai, Atsushi

    2010-01-01

    Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349 kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the 'leg' of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70 pN. These findings strongly support the idea that Gli349 is the 'leg' protein of M. mobile, responsible for binding and also most probably force generation during gliding motility.

  17. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  18. Diffuse CO2 degassing studies to reveal hidden geothermal resources in oceanic volcanic islands: The Canarian archipelago case study

    Science.gov (United States)

    Rodríguez, F.; Perez, N. M.; García-Merino, M.; Padron, E.; Melián, G.; Asensio-Ramos, M.; Hernandez Perez, P. A.; Padilla, G.; Barrancos, J.; Cótchico, M. A.

    2016-12-01

    The Canary Islands, owing to their recent volcanism, are the only Spanish territory with potential high enthalpy geothermal resources. The final goal of geothermal exploration in a specific area is to locate and define the size, shape, structure of hidden geothermal resources, and determine their characteristics (fluid type, temperature, chemical composition an ability to produce energy). At those areas where there is not any evidence of endogenous fluids manifestations at surface, that traditionally evidence the presence of an active geothermal system) the geochemical methods for geothermal exploration must include soil gas surveys. This is the case of five mining licenses for geothermal exploration in the Canay Islands, four in Tenerife and one in Gran Canaria Island. We report herein the results of diffuse CO2 emission studies in the five mining licenses during 2011-2014. The primary objective of the study was to sort the possible geothermal potential of these five mining licenses, thus reducing the uncertainty inherent to the selection of the areas with highest geothermal potential for future exploration works. The criterion used to sort the different areas was the contribution of volcano-hydrothermal CO2 in the degassing at each study area. Several hundreds of measurements of diffuse CO2 emission, soil CO2 concentration and isotopic composition were performed at each study area. Based in three different endmembers (biogenic, atmospheric and deep-seated CO2) with different CO2 concentrations (100, 0.04 and 100% respectively) and isotopic compositions (-20, -8 and -3 per mil vs. VPDB respectively) a mass balance to distinguish the different contribution of each endmember in the soil CO2 at each sampling site was made. The percentage of the volcano-hydrothermal contribution in the current diffuse CO2 degassing was in the range 2-19%.The Abeque mining license, that comprises part of the north-west volcanic rift of Tenerife, seemed to show the highest geothermal

  19. Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

    Science.gov (United States)

    Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

    2016-10-07

    Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

  20. Fungal diversity of "Tomme d'Orchies" cheese during the ripening process as revealed by a metagenomic study.

    Science.gov (United States)

    Ceugniez, Alexandre; Taminiau, Bernard; Coucheney, Françoise; Jacques, Philippe; Delcenserie, Véronique; Daube, Georges; Drider, Djamel

    2017-10-03

    Tomme d'Orchies is an artisanal pressed and uncooked cheese produced and marketed in the north of France. This study aimed at showing the fungal microbiota evolution of this cheese using a metagenetic based Illumina technology targeting the ITS2 domain of 5.8S fungal rDNAs. To this end, samples were taken from the rind and the core of different cheeses, after 0, 1, 3, 7, 14 and 21days of ripening. The data underpinned the prevalence of Yarrowia lipolytica and Galactomyces geotrichum for both microbiotas. Unusual species including Clavispora lusitaniae, Kazachstania unispora and Cladosporium cladosporioides were also detected, but their origins remain to be ascertained. The metagenomic revealed also the presence of Kluyveromyces and Debaryomyces species. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Altered Na+ transport after an intracellular alpha-subunit deletion reveals strict external sequential release of Na+ from the Na/K pump.

    Science.gov (United States)

    Yaragatupalli, Siddhartha; Olivera, J Fernando; Gatto, Craig; Artigas, Pablo

    2009-09-08

    The Na/K pump actively exports 3 Na(+) in exchange for 2 K(+) across the plasmalemma of animal cells. As in other P-type ATPases, pump function is more effective when the relative affinity for transported ions is altered as the ion binding sites alternate between opposite sides of the membrane. Deletion of the five C-terminal residues from the alpha-subunit diminishes internal Na(+) (Na(i)(+)) affinity approximately 25-fold [Morth et al. (2007) Nature 450:1043-1049]. Because external Na(+) (Na(o)(+)) binding is voltage-dependent, we studied the reactions involving this process by using two-electrode and inside-out patch voltage clamp in normal and truncated (DeltaKESYY) Xenopus-alpha1 pumps expressed in oocytes. We observed that DeltaKESYY (i) decreased both Na(o)(+) and Na(i)(+) apparent affinities in the absence of K(o)(+), and (ii) did not affect apparent Na(o)(+) affinity at high K(o)(+). These results support a model of strict sequential external release of Na(+) ions, where the Na(+)-exclusive site releases Na(+) before the sites shared with K(+) and the DeltaKESYY deletion only reduces Na(o)(+) affinity at the shared sites. Moreover, at nonsaturating K(o)(+), DeltaKESYY induced an inward flow of Na(+) through Na/K pumps at negative potentials. Guanidinium(+) can also permeate truncated pumps, whereas N-methyl-D-glucamine cannot. Because guanidinium(o)(+) can also traverse normal Na/K pumps in the absence of both Na(o)(+) and K(o)(+) and can also inhibit Na/K pump currents in a Na(+)-like voltage-dependent manner, we conclude that the normal pathway transited by the first externally released Na(+) is large enough to accommodate guanidinium(+).

  2. An integrated study reveals diverse methanogens, Thaumarchaeota, and yet-uncultivated archaeal lineages in Armenian hot springs.

    Science.gov (United States)

    Hedlund, Brian P; Dodsworth, Jeremy A; Cole, Jessica K; Panosyan, Hovik H

    2013-07-01

    Culture-independent and enrichment techniques, with an emphasis on members of the Archaea, were used to determine the composition and structure of microbial communities inhabiting microbial mats in the source pools of two geothermal springs near the towns of Arzakan and Jermuk in Armenia. Amplification of small-subunit rRNA genes using "universal" primers followed by pyrosequencing (pyrotags) revealed highly diverse microbial communities in both springs, with >99 % of pyrosequences corresponding to members of the domain Bacteria. The spring in Arzakan was colonized by a photosynthetic mat dominated by Cyanobacteria, in addition to Proteobacteria, Bacteroidetes, Chloroflexi, Spirochaeta and a diversity of other Bacteria. The spring in Jermuk was colonized by phylotypes related to sulfur, iron, and hydrogen chemolithotrophs in the Betaproteobacteria and Epsilonproteobacteria, along with a diversity of other Bacteria. Analysis of near full-length small subunit rRNA genes amplified using Archaea-specific primers showed that both springs are inhabited by a diversity of methanogens, including Methanomicrobiales and Methanosarcinales and relatives of Methanomassiliicoccus luminyensis, close relatives of the ammonia-oxidizing archaeon (AOA) "Candidatus Nitrososphaera gargensis", and the yet-uncultivated Miscellaneous Crenarchaeotal Group and Deep Hydrothermal Vent Crenarchaeota group 1. Methanogenic enrichments confirmed the predicted physiological diversity, revealing methylotrophic, acetoclastic, and hydrogenotrophic methanogenesis at 45 and 55 °C, but not 65 °C. This is one of only a few studies combining cultivation-independent and -dependent approaches to study archaea in moderate-temperature (37-73 °C) terrestrial geothermal environments and suggests important roles for methanogenic archaea and AOA in the carbon and nitrogen biogeochemical cycles in these environments.

  3. A transcriptomic study reveals differentially expressed genes and pathways respond to simulated acid rain in Arabidopsis thaliana.

    Science.gov (United States)

    Liu, Ting-Wu; Niu, Li; Fu, Bin; Chen, Juan; Wu, Fei-Hua; Chen, Juan; Wang, Wen-Hua; Hu, Wen-Jun; He, Jun-Xian; Zheng, Hai-Lei

    2013-01-01

    Acid rain, as a worldwide environmental issue, can cause serious damage to plants. In this study, we provided the first case study on the systematic responses of arabidopsis (Arabidopsis thaliana (L.) Heynh.) to simulated acid rain (SiAR) by transcriptome approach. Transcriptomic analysis revealed that the expression of a set of genes related to primary metabolisms, including nitrogen, sulfur, amino acid, photosynthesis, and reactive oxygen species metabolism, were altered under SiAR. In addition, transport and signal transduction related pathways, especially calcium-related signaling pathways, were found to play important roles in the response of arabidopsis to SiAR stress. Further, we compared our data set with previously published data sets on arabidopsis transcriptome subjected to various stresses, including wound, salt, light, heavy metal, karrikin, temperature, osmosis, etc. The results showed that many genes were overlapped in several stresses, suggesting that plant response to SiAR is a complex process, which may require the participation of multiple defense-signaling pathways. The results of this study will help us gain further insights into the response mechanisms of plants to acid rain stress.

  4. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    International Nuclear Information System (INIS)

    Matheis, Katja A.; Com, Emmanuelle; Gautier, Jean-Charles; Guerreiro, Nelson; Brandenburg, Arnd; Gmuender, Hans; Sposny, Alexandra; Hewitt, Philip; Amberg, Alexander; Boernsen, Olaf; Riefke, Bjoern; Hoffmann, Dana; Mally, Angela; Kalkuhl, Arno; Suter, Laura; Dieterle, Frank; Staedtler, Frank

    2011-01-01

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  5. Revealing the control of migratory fueling: An integrated approach combining laboratory and field studies in northern wheatears Oenanthe oenanthe

    Directory of Open Access Journals (Sweden)

    Franz BAIRLEIN,Volker DIERSCHKE, Julia DELINGAT, Cas EIKENAAR, Ivan MAGGINI, Marc BULTE, Heiko SCHMALJOHANN

    2013-06-01

    Full Text Available Migratory birds rely on fueling prior to migratory flights. Fueling in migrants is controlled by intrinsic as well as extrinsic factors. From captive studies we have started understanding the internal mechanisms controlling bird migration. Field studies have demonstrated the effects of external factors, such as food availability, weather, competitors, parasites or diseases, on the stopover behavior of migrants. However, an integrated approach is still missing to study coherently how the innate migration program interacts with the varying environmental cues and to estimate the contribution of the innate migration program and the environment to realized migration. The northern wheatear Oenanthe oenanthe offers a unique opportunity for integrated studies. It breeds across almost the whole Holarctic with just a “gap” between eastern Canada and Alaska. All breeding populations overwinter in sub-Saharan Africa which makes the northern wheatear one of the most long-distant migratory songbirds with extraordinary long non-stop flights across oceans. It is a nocturnal migrant which travels without parental or social aid/guidance. Thus, young birds rely entirely on endogenous mechanisms of timing, route selection and fueling on their first outbound migration. By establishing indoor housing under controlled conditions the endogenous control mechanisms of northern wheatear migration could be revealed. At the same time, environmental factors controlling fueling could be investigated in the field. On migration wheatears occur in a variety of habitats with sparse vegetation where their stopover behavior could be quantitatively studied in the light of “optimal migration” theory by the use of remote balances, radio-tagging and even experimentally manipulated food availability. The present paper summarizes our approach to understand the control of migration in northern wheatears by combining field and laboratory studies at various spatial and temporal

  6. Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Ravn, Lasse Steen; Schmitt, Nicole

    2007-01-01

    and two-electrode voltage-clamp revealed that Kir3.4-G247R basal current was reduced compared to wild-type Kir3.4 and co-expression with the muscarinic acetylcholine receptor type 2 showed that also the acetylcholine induced current was severely reduced in Kir3.4-G247R, indicating that the mutation...... the lack of clear clinical manifestations and further studies are necessary to elucidate if mutations in Kir3.4 are predisposing AF. Udgivelsesdato: 2007-Dec-28...

  7. Systematic Synthesis and Binding Study of HIV V3 Glycopeptides Reveal the Fine Epitopes of Several Broadly Neutralizing Antibodies.

    Science.gov (United States)

    Orwenyo, Jared; Cai, Hui; Giddens, John; Amin, Mohammed N; Toonstra, Christian; Wang, Lai-Xi

    2017-06-16

    A class of new glycan-reactive broadly neutralizing antibodies represented by PGT121, 10-1074, and PGT128 has recently been discovered that targets specific N-glycans and the peptide region around the V3 domain. However, the glycan specificity and fine epitopes of these bNAbs remain to be further defined. We report here a systematic chemoenzymatic synthesis of homogeneous V3 glycopeptides derived from the HIV-1 JR-FL strain carrying defined N-glycans at N332, N301, and N295 sites. Antibody binding studies revealed that both the nature and site of glycosylation in the context of the V3 domain were critical for high-affinity binding. It was found that antibody PGT128 exhibited specificity for high-mannose N-glycan with glycosylation site promiscuity, PGT121 showed binding specificity for glycopeptide carrying a sialylated N-glycan at N301 site, and 10-1074 was specific for glycopeptide carrying a high-mannose N-glycan at N332 site. The synthesis and binding studies permit a detailed assessment of the glycan specificity and the requirement of peptide in the context of antibody-antigen recognition. The identified glycopeptides can be used as potential templates for HIV vaccine design.

  8. A genome-wide association study on androstenone levels in pigs reveals a cluster of candidate genes on chromosome 6

    Directory of Open Access Journals (Sweden)

    Groenen Martien AM

    2010-05-01

    Full Text Available Abstract Background In many countries, male piglets are castrated shortly after birth because a proportion of un-castrated male pigs produce meat with an unpleasant flavour and odour. Main compounds of boar taint are androstenone and skatole. The aim of this high-density genome-wide association study was to identify single nucleotide polymorphisms (SNPs associated with androstenone levels in a commercial sire line of pigs. The identification of major genetic effects causing boar taint would accelerate the reduction of boar taint through breeding to finally eliminate the need for castration. Results The Illumina Porcine 60K+SNP Beadchip was genotyped on 987 pigs divergent for androstenone concentration from a commercial Duroc-based sire line. The association analysis with 47,897 SNPs revealed that androstenone levels in fat tissue were significantly affected by 37 SNPs on pig chromosomes SSC1 and SSC6. Among them, the 5 most significant SNPs explained together 13.7% of the genetic variance in androstenone. On SSC6, a larger region of 10 Mb was shown to be associated with androstenone covering several candidate genes potentially involved in the synthesis and metabolism of androgens. Besides known candidate genes, such as cytochrome P450 A19 (CYP2A19, sulfotransferases SULT2A1, and SULT2B1, also new members of the cytochrome P450 CYP2 gene subfamilies and of the hydroxysteroid-dehydrogenases (HSD17B14 were found. In addition, the gene encoding the ß-chain of the luteinizing hormone (LHB which induces steroid synthesis in the Leydig cells of the testis at onset of puberty maps to this area on SSC6. Interestingly, the gene encoding the α-chain of LH is also located in one of the highly significant areas on SSC1. Conclusions This study reveals several areas of the genome at high resolution responsible for variation of androstenone levels in intact boars. Major genetic factors on SSC1 and SSC6 showing moderate to large effects on androstenone

  9. New analysis of a rat feeding study with a genetically modified maize reveals signs of hepatorenal toxicity.

    Science.gov (United States)

    Séralini, Gilles-Eric; Cellier, Dominique; de Vendomois, Joël Spiroux

    2007-05-01

    Health risk assessment of genetically modified organisms (GMOs) cultivated for food or feed is under debate throughout the world, and very little data have been published on mid- or long-term toxicological studies with mammals. One of these studies performed under the responsibility of Monsanto Company with a transgenic corn MON863 has been subjected to questions from regulatory reviewers in Europe, where it was finally approved in 2005. This necessitated a new assessment of kidney pathological findings, and the results remained controversial. An Appeal Court action in Germany (Münster) allowed public access in June 2005 to all the crude data from this 90-day rat-feeding study. We independently re-analyzed these data. Appropriate statistics were added, such as a multivariate analysis of the growth curves, and for biochemical parameters comparisons between GMO-treated rats and the controls fed with an equivalent normal diet, and separately with six reference diets with different compositions. We observed that after the consumption of MON863, rats showed slight but dose-related significant variations in growth for both sexes, resulting in 3.3% decrease in weight for males and 3.7% increase for females. Chemistry measurements reveal signs of hepatorenal toxicity, marked also by differential sensitivities in males and females. Triglycerides increased by 24-40% in females (either at week 14, dose 11% or at week 5, dose 33%, respectively); urine phosphorus and sodium excretions diminished in males by 31-35% (week 14, dose 33%) for the most important results significantly linked to the treatment in comparison to seven diets tested. Longer experiments are essential in order to indicate the real nature and extent of the possible pathology; with the present data it cannot be concluded that GM corn MON863 is a safe product.

  10. Genetic analysis of Apuleia leiocarpa as revealed by random amplified polymorphic DNA markers: prospects for population genetic studies.

    Science.gov (United States)

    Lencina, K H; Konzen, E R; Tsai, S M; Bisognin, D A

    2016-12-19

    Apuleia leiocarpa (Vogel) J.F. MacBride is a hardwood species native to South America, which is at serious risk of extinction. Therefore, it is of prime importance to examine the genetic diversity of this species, information required for developing conservation, sustainable management, and breeding strategies. Although scarcely used in recent years, random amplified polymorphic DNA markers are useful resources for the analysis of genetic diversity and structure of tree species. This study represents the first genetic analysis based on DNA markers in A. leiocarpa that aimed to investigate the levels of polymorphism and to select markers for the precise characterization of its genetic structure. We adapted the original DNA extraction protocol based on cetyltrimethyl ammonium bromide, and describe a simple procedure that can be used to obtain high-quality samples from leaf tissues of this tree. Eighteen primers were selected, revealing 92 bands, from which 75 were polymorphic and 61 were sufficient to represent the overall genetic structure of the population without compromising the precision of the analysis. Some fragments were conserved among individuals, which can be sequenced and used to analyze nucleotide diversity parameters through a wider set of A. leiocarpa individuals and populations. The individuals were separated into 11 distinct groups with variable levels of genetic diversity, which is important for selecting desirable genotypes and for the development of a conservation and sustainable management program. Our results are of prime importance for further investigations concerning the genetic characterization of this important, but vulnerable species.

  11. Barcoding Turkish Culex mosquitoes to facilitate arbovirus vector incrimination studies reveals hidden diversity and new potential vectors.

    Science.gov (United States)

    Gunay, Filiz; Alten, Bulent; Simsek, Fatih; Aldemir, Adnan; Linton, Yvonne-Marie

    2015-03-01

    As a precursor to planned arboviral vector incrimination studies, an integrated systematics approach was adopted using morphology and DNA barcoding to examine the Culex fauna present in Turkey. The mitochondrial COI gene (658bp) were sequenced from 185 specimens collected across 11 Turkish provinces, as well as from colony material. Although by morphology only 9 species were recognised, DNA barcoding recovered 13 distinct species including: Cx. (Barraudius) modestus, Cx. (Culex) laticinctus, Cx. (Cux.) mimeticus, Cx. (Cux.) perexiguus, Cx. (Cux.) pipiens, Cx. (Cux.) pipiens form molestus, Cx. (Cux.) quinquefasciatus, Cx. (Cux.) theileri, Cx. (Cux.) torrentium, Cx. (Cux.) tritaeniorhynchus and Cx. (Maillotia) hortensis. The taxon formerly identified as Cx. (Neoculex) territans was shown to comprise two distinct species, neither of which correspond to Cx. territans s.s. These include Cx. (Neo.) impudicus and another uncertain species, which may be Cx. (Neo.) europaeus or Cx. (Neo.) martinii (herein=Cx. (Neo.) sp. 1). Detailed examination of the Pipiens Group revealed Cx. pipiens, Cx. pipiens f. molestus and the widespread presence of the highly efficient West Nile virus vector Cx. quinquefasciatus for the first time. Four new country records are reported, increasing the Culex of Turkey to 15 recognised species and Cx. pipiens f. molestus. A new taxonomic checklist is provided, annotated with respective vector competencies for transmission of arboviruses. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Genetic and genomic diversity studies of Acacia symbionts in Senegal reveal new species of Mesorhizobium with a putative geographical pattern.

    Directory of Open Access Journals (Sweden)

    Fatou Diouf

    Full Text Available Acacia senegal (L Willd. and Acacia seyal Del. are highly nitrogen-fixing and moderately salt tolerant species. In this study we focused on the genetic and genomic diversity of Acacia mesorhizobia symbionts from diverse origins in Senegal and investigated possible correlations between the genetic diversity of the strains, their soil of origin, and their tolerance to salinity. We first performed a multi-locus sequence analysis on five markers gene fragments on a collection of 47 mesorhizobia strains of A. senegal and A. seyal from 8 localities. Most of the strains (60% clustered with the M. plurifarium type strain ORS 1032T, while the others form four new clades (MSP1 to MSP4. We sequenced and assembled seven draft genomes: four in the M. plurifarium clade (ORS3356, ORS3365, STM8773 and ORS1032T, one in MSP1 (STM8789, MSP2 (ORS3359 and MSP3 (ORS3324. The average nucleotide identities between these genomes together with the MLSA analysis reveal three new species of Mesorhizobium. A great variability of salt tolerance was found among the strains with a lack of correlation between the genetic diversity of mesorhizobia, their salt tolerance and the soils samples characteristics. A putative geographical pattern of A. senegal symbionts between the dryland north part and the center of Senegal was found, reflecting adaptations to specific local conditions such as the water regime. However, the presence of salt does not seem to be an important structuring factor of Mesorhizobium species.

  13. Genetic and genomic diversity studies of Acacia symbionts in Senegal reveal new species of Mesorhizobium with a putative geographical pattern.

    Science.gov (United States)

    Diouf, Fatou; Diouf, Diegane; Klonowska, Agnieszka; Le Queré, Antoine; Bakhoum, Niokhor; Fall, Dioumacor; Neyra, Marc; Parrinello, Hugues; Diouf, Mayecor; Ndoye, Ibrahima; Moulin, Lionel

    2015-01-01

    Acacia senegal (L) Willd. and Acacia seyal Del. are highly nitrogen-fixing and moderately salt tolerant species. In this study we focused on the genetic and genomic diversity of Acacia mesorhizobia symbionts from diverse origins in Senegal and investigated possible correlations between the genetic diversity of the strains, their soil of origin, and their tolerance to salinity. We first performed a multi-locus sequence analysis on five markers gene fragments on a collection of 47 mesorhizobia strains of A. senegal and A. seyal from 8 localities. Most of the strains (60%) clustered with the M. plurifarium type strain ORS 1032T, while the others form four new clades (MSP1 to MSP4). We sequenced and assembled seven draft genomes: four in the M. plurifarium clade (ORS3356, ORS3365, STM8773 and ORS1032T), one in MSP1 (STM8789), MSP2 (ORS3359) and MSP3 (ORS3324). The average nucleotide identities between these genomes together with the MLSA analysis reveal three new species of Mesorhizobium. A great variability of salt tolerance was found among the strains with a lack of correlation between the genetic diversity of mesorhizobia, their salt tolerance and the soils samples characteristics. A putative geographical pattern of A. senegal symbionts between the dryland north part and the center of Senegal was found, reflecting adaptations to specific local conditions such as the water regime. However, the presence of salt does not seem to be an important structuring factor of Mesorhizobium species.

  14. Study of fluid dynamics reveals direct communications between lymphatic vessels and venous blood vessels at lymph nodes of mice.

    Science.gov (United States)

    Takeda, Kazu; Mori, Shiro; Kodama, Tetsuya

    2017-06-01

    Cancer cells metastasize to lymph nodes, with distant metastasis resulting in poor prognosis. The role of lymph node metastasis (LNM) in the spread of cancer to distant organs remain incompletely characterized. The visualization of flow dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 10mm in diameter, has revealed that lymph nodes have the potential to be a direct source of systemic metastasis. However, it is not known whether these fluid dynamics characteristics are universal phenomena present in other strains of laboratory mice. Here we show that the fluid dynamics observed in MXH10/Mo-lpr/lpr mice are the same as those observed in C57BL/6J, BALB/cAJcl and NOD/ShiJic-scidJcl mice. Furthermore, when fluorescent solution was injected into a tumor-bearing lymph node, the flow dynamics observed in the efferent lymphatic vessels and thoracoepigastric vein depended on the type of tumor cell. Our results indicate that fluid dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice are generalized phenomena seen in conventional laboratory mice. We anticipate our results can facilitate studies of the progression of lymphatic metastasis to hematogenous metastasis via lymph nodes and the early diagnosis and treatment of LNM. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Association Study Reveals Novel Genes Related to Yield and Quality of Fruit in Cape Gooseberry (Physalis peruviana L.

    Directory of Open Access Journals (Sweden)

    Francy L. García-Arias

    2018-03-01

    Full Text Available Association mapping has been proposed as an efficient approach to assist plant breeding programs to investigate the genetic basis of agronomic traits. In this study, we evaluated 18 traits related to yield, (FWP, NF, FWI, and FWII, fruit size-shape (FP, FA, MW, WMH, MH, HMW, DI, FSI, FSII, OVO, OBO, and fruit quality (FIR, CF, and SST, in a diverse collection of 100 accessions of Physalis peruviana including wild, landraces, and anther culture derived lines. We identified seven accessions with suitable traits: fruit weight per plant (FWP > 7,000 g/plant and cracked fruits (CF < 4%, to be used as parents in cape gooseberry breeding program. In addition, the accessions were also characterized using Genotyping By Sequencing (GBS. We discovered 27,982 and 36,142 informative SNP markers based on the alignment against the two cape gooseberry references transcriptomes. Besides, 30,344 SNPs were identified based on alignment to the tomato reference genome. Genetic structure analysis showed that the population could be divided into two or three sub-groups, corresponding to landraces-anther culture and wild accessions for K = 2 and wild, landraces, and anther culture plants for K = 3. Association analysis was carried out using a Mixed Linear Model (MLM and 34 SNP markers were significantly associated. These results reveal the basis of the genetic control of important agronomic traits and may facilitate marker-based breeding in P. peruviana.

  16. Association Study Reveals Novel Genes Related to Yield and Quality of Fruit in Cape Gooseberry (Physalis peruviana L.).

    Science.gov (United States)

    García-Arias, Francy L; Osorio-Guarín, Jaime A; Núñez Zarantes, Victor M

    2018-01-01

    Association mapping has been proposed as an efficient approach to assist plant breeding programs to investigate the genetic basis of agronomic traits. In this study, we evaluated 18 traits related to yield, (FWP, NF, FWI, and FWII), fruit size-shape (FP, FA, MW, WMH, MH, HMW, DI, FSI, FSII, OVO, OBO), and fruit quality (FIR, CF, and SST), in a diverse collection of 100 accessions of Physalis peruviana including wild, landraces, and anther culture derived lines. We identified seven accessions with suitable traits: fruit weight per plant (FWP) > 7,000 g/plant and cracked fruits (CF) cape gooseberry breeding program. In addition, the accessions were also characterized using Genotyping By Sequencing (GBS). We discovered 27,982 and 36,142 informative SNP markers based on the alignment against the two cape gooseberry references transcriptomes. Besides, 30,344 SNPs were identified based on alignment to the tomato reference genome. Genetic structure analysis showed that the population could be divided into two or three sub-groups, corresponding to landraces-anther culture and wild accessions for K = 2 and wild, landraces, and anther culture plants for K = 3. Association analysis was carried out using a Mixed Linear Model (MLM) and 34 SNP markers were significantly associated. These results reveal the basis of the genetic control of important agronomic traits and may facilitate marker-based breeding in P. peruviana .

  17. The geography of demography: long-term demographic studies and species distribution models reveal a species border limited by adaptation.

    Science.gov (United States)

    Eckhart, V M; Geber, M A; Morris, W F; Fabio, E S; Tiffin, P; Moeller, D A

    2011-10-01

    Potential causes of species' geographic distribution limits fall into two broad classes: (1) limited adaptation across spatially variable environments and (2) limited opportunities to colonize unoccupied areas. Combining demographic studies, analyses of demographic responses to environmental variation, and species distribution models, we investigated the causes of range limits in a model system, the eastern border of the California annual plant Clarkia xantiana ssp. xantiana. Vital rates of 20 populations varied with growing season temperature and precipitation: fruit number and overwinter survival of 1-year-old seeds declined steeply, while current-year seed germination increased modestly along west-to-east gradients in decreasing temperature, decreasing mean precipitation, and increasing variation in precipitation. Long-term stochastic finite rate of increase, λ(s), exhibited a fourfold range and varied among geologic surface materials as well as with temperature and precipitation. Growth rate declined significantly toward the eastern border, falling below 1 in three of the five easternmost populations. Distribution models employing demographically important environmental variables predicted low habitat favorability beyond the eastern border. Models that filtered or weighted population presences by λ(s) predicted steeper eastward declines in favorability and assigned greater roles in setting the distribution to among-year variation in precipitation and to geologic surface material. These analyses reveal a species border likely set by limited adaptation to declining environmental quality.

  18. Pharmacological studies of charge movement in frog skeletal muscle.

    Science.gov (United States)

    Hui, C S

    1983-04-01

    Charge movements in frog twitch fibres were studied using the three-microelectrode voltage-clamp technique. In a solution made moderately hypertonic with 350 mM-sucrose, fibre contraction was effectively blocked and a secondary hump appeared in the decay phase of the 'on' part of charge movement. At small depolarizations, the hump (Q gamma) is small and slow. As depolarization is increased, Q gamma becomes larger in magnitude and faster in kinetics until it merges with the main part of charge movement (Q beta). As the fibre is perfused extracellularly with a test solution saturated with dantrolene sodium, Q gamma disappears in about 30 min whereas the kinetics of Q beta are slowed down. After equilibration in the dantrolene sodium solution, the total moveable charge is reduced by about 20%, which could very well be the charge carried by Q gamma. Tetracaine also suppresses Q gamma but does not seem to have any effect on the kinetics of Q beta. The suppression of Q gamma appears to be dose-dependent, with complete abolition occurring at about 4 mM-tetracaine. Dissection of charge movement with tetracaine indicates that Q gamma might be bell-shaped and capacitive in nature. Q beta and Q gamma might be two distinct species of charge and Q gamma would probably be more closely associated with calcium release from the sarcoplasmic reticulum.

  19. Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs.

    Directory of Open Access Journals (Sweden)

    Markus Drag

    Full Text Available Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed to identify expression quantitative trait loci (eQTLs with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS were slaughtered at ~100 kg. Gene expression profiles were obtained by RNA-Seq, and genotype data were obtained by an Illumina 60K Porcine SNP chip. Following quality control and filtering, 10,545 and 12,731 genes from liver and testis were included in the eQTL analysis, together with 20,827 SNP variants. A total of 205 and 109 single-tissue eQTLs associated with 102 and 58 unique genes were identified in liver and testis, respectively. By employing a multivariate Bayesian hierarchical model, 26 eQTLs were identified as significant multi-tissue eQTLs. The highest densities of eQTLs were found on pig chromosomes SSC12, SSC1, SSC13, SSC9 and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits curated by the Animal Genome PigQTL database to be significantly overlapped by the genomic coordinates of cis-acting eQTLs. Finally, a subset of 35 cis-acting eQTLs overlapped with known boar taint QTL traits. These eQTLs could be useful in the development of a DNA test for boar taint but careful monitoring of other overlapping QTL traits should be performed to avoid any negative consequences of selection.

  20. Observable phenomena that reveal medical students' clinical reasoning ability during expert assessment of their history taking: a qualitative study

    NARCIS (Netherlands)

    Haring, C.M.; Cools, B.M.; Gurp, P.J.M. van; Meer, J.W.M. van der; Postma, C.T.

    2017-01-01

    BACKGROUND: During their clerkships, medical students are meant to expand their clinical reasoning skills during their patient encounters. Observation of these encounters could reveal important information on the students' clinical reasoning abilities, especially during history taking. METHODS: A

  1. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

    Science.gov (United States)

    Widdows, Kate L.; Panitchob, Nuttanont; Crocker, Ian P.; Please, Colin P.; Hanson, Mark A.; Sibley, Colin P.; Johnstone, Edward D.; Sengers, Bram G.; Lewis, Rohan M.; Glazier, Jocelyn D.

    2015-01-01

    Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [14C]l-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]l-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with l-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms. PMID:25761365

  2. Shifts in river-floodplain relationship reveal the impacts of river regulation: A case study of Dongting Lake in China

    Science.gov (United States)

    Lu, Cai; Jia, Yifei; Jing, Lei; Zeng, Qing; Lei, Jialin; Zhang, Shuanghu; Lei, Guangchun; Wen, Li

    2018-04-01

    Better understanding of the dynamics of hydrological connectivity between river and floodplain is essential for the ecological integrity of river systems. In this study, we proposed a regime-switch modelling (RSM) framework, which integrates change point analysis with dynamic linear regression, to detect and date change points in linear regression, and to quantify the relative importance of natural variations and anthropogenic disturbances. The approach was applied to the long-term hydrological time series to investigate the evolution of river-floodplain relation in Dongting Lake in the last five decades, during which the Yangtze River system experienced unprecedented anthropogenic manipulations. Our results suggested that 1) there were five distinct regimes during which the influence of inflows and local climate on lake water level changed significantly. The detected change points were well corresponding to the major events occurred upon the Yangtze; 2) although the importance of inflows from the Yangtze was greater than that of the tributaries flows over the five regimes, the relative contribution gradually decreased from regime 1 to regime 5. The weakening of hydrological forcing from the Yangtze was mainly attributed to the reduction in channel capacity resulting from sedimentation in the outfalls and water level dropping caused by river bed scour in the mainstream; 3) the effects of local climate was much smaller than these of inflows; and 4) since the operation of The Three Gorges Dam in 2006, the river-floodplain relationship entered a new equilibrium in that all investigated variables changed synchronously in terms of direction and magnitude. The results from this study reveal the mechanisms underlying the alternated inundation regime in Dongting Lake. The identified change points, some of which have not been previously reported, will allow a reappraisal of the current dam and reservoir operation strategies not only for flood/drought risk management but

  3. Transcriptome Profiling and Genetic Study Reveal Amplified Carboxylesterase Genes Implicated in Temephos Resistance, in the Asian Tiger Mosquito Aedes albopictus.

    Directory of Open Access Journals (Sweden)

    Linda Grigoraki

    2015-05-01

    Full Text Available The control of Aedes albopictus, a major vector for viral diseases, such as dengue fever and chikungunya, has been largely reliant on the use of the larvicide temephos for many decades. This insecticide remains a primary control tool for several countries and it is a potential reliable reserve, for emergency epidemics or new invasion cases, in regions such as Europe which have banned its use. Resistance to temephos has been detected in some regions, but the mechanism responsible for the trait has not been investigated.Temephos resistance was identified in an Aedes albopictus population isolated from Greece, and subsequently selected in the laboratory for a few generations. Biochemical assays suggested the association of elevated carboxylesterases (CCE, but not target site resistance (altered AChE, with this phenotype. Illumina transcriptomic analysis revealed the up-regulation of three transcripts encoding CCE genes in the temephos resistant strain. CCEae3a and CCEae6a showed the most striking up-regulation (27- and 12-folds respectively, compared to the reference susceptible strain; these genes have been previously shown to be involved in temephos resistance also in Ae. aegypti. Gene amplification was associated with elevated transcription levels of both CCEae6a and CCEae3a genes. Genetic crosses confirmed the genetic link between CCEae6a and CCEae3a amplification and temephos resistance, by demonstrating a strong association between survival to temephos exposure and gene copy numbers in the F2 generation. Other transcripts, encoding cytochrome P450s, UDP-glycosyltransferases (UGTs, cuticle and lipid biosynthesis proteins, were upregulated in resistant mosquitoes, indicating that the co-evolution of multiple mechanisms might contribute to resistance.The identification of specific genes associated with insecticide resistance in Ae. albopictus for the first time is an important pre-requirement for insecticide resistance management. The genomic

  4. Long-Term Field Study Reveals Subtle Effects of the Invasive Alga Sargassum muticum upon the Epibiota of Zostera marina.

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    Stacey DeAmicis

    Full Text Available Invasive species can alter coastal ecosystems both directly, e.g. through competition for substratum and nutrients, and indirectly. Indirect effects may be mediated by creation of dissimilar or inimical habitats, changes in predator and/or prey assemblages, alterations in associated biota, and perturbations of water movement and thermal regimes. Previous studies have shown that invasive algae can modify native habitat architecture, disrupt intricately linked food webs and alter epibiotic assemblages. In the UK, the seagrass Zostera marina supports a diverse epibiotic assemblage, influencing key factors such as sediment dynamics, depositional regime and trophic linkages. Increasing encroachment of the invasive alga Sargassum muticum into seagrass meadows changes the physical and chemical characteristics of the local environment and creates the potential for changes in the epibionts associated with the seagrass blades, threatening the integrity of the seagrass ecosystem. We investigated the effects of S. muticum invasion upon the epibiota of Z. marina in a drowned river valley in SW England seasonally from spring to autumn over four years in an in-situ manipulative experiment, comparing permanent quadrats with and without artificially introduced S. muticum. Epibiota were weighed, identified to the most detailed operational taxonomic unit (OTU possible, and unitary organisms were enumerated. Multivariate PERMANOVA+ analysis revealed significant differences in epibiont assemblages between Sargassum treatments. Linear mixed effects models indicated that differences in epibiota assemblage composition were not reflected as significant differences in mean biomass per sample, or number of epibiont OTUs per sample. We conclude that S. muticum invasion into Z. marina meadows may significantly alter the species composition and abundance distribution of epibiotic assemblages found on the blades of the seagrass. Thus S. muticum invasion could have more wide

  5. Genome-Wide Association Study Reveals Four Loci for Lipid Ratios in the Korean Population and the Constitutional Subgroup.

    Directory of Open Access Journals (Sweden)

    Taehyeung Kim

    Full Text Available Circulating lipid ratios are considered predictors of cardiovascular risks and metabolic syndrome, which cause coronary heart diseases. One constitutional type of Korean medicine prone to weight accumulation, the Tae-Eum type, predisposes the consumers to metabolic syndrome, hypertension, diabetes mellitus, etc. Here, we aimed to identify genetic variants for lipid ratios using a genome-wide association study (GWAS and followed replication analysis in Koreans and constitutional subgroups. GWASs in 5,292 individuals of the Korean Genome and Epidemiology Study and replication analyses in 2,567 subjects of the Korea medicine Data Center were performed to identify genetic variants associated with triglyceride (TG to HDL cholesterol (HDLC, LDL cholesterol (LDLC to HDLC, and non-HDLC to HDLC ratios. For subgroup analysis, a computer-based constitution analysis tool was used to categorize the constitutional types of the subjects. In the discovery stage, seven variants in four loci, three variants in three loci, and two variants in one locus were associated with the ratios of log-transformed TG:HDLC (log[TG]:HDLC, LDLC:HDLC, and non-HDLC:HDLC, respectively. The associations of the GWAS variants with lipid ratios were replicated in the validation stage: for the log[TG]:HDLC ratio, rs6589566 near APOA5 and rs4244457 and rs6586891 near LPL; for the LDLC:HDLC ratio, rs4420638 near APOC1 and rs17445774 near C2orf47; and for the non-HDLC:HDLC ratio, rs6589566 near APOA5. Five of these six variants are known to be associated with TG, LDLC, and/or HDLC, but rs17445774 was newly identified to be involved in lipid level changes in this study. Constitutional subgroup analysis revealed effects of variants associated with log[TG]:HDLC and non-HDLC:HDLC ratios in both the Tae-Eum and non-Tae-Eum types, whereas the effect of the LDLC:HDLC ratio-associated variants remained only in the Tae-Eum type. In conclusion, we identified three log[TG]:HDLC ratio

  6. Genome-Wide Association Study Reveals Four Loci for Lipid Ratios in the Korean Population and the Constitutional Subgroup.

    Science.gov (United States)

    Kim, Taehyeung; Park, Ah Yeon; Baek, Younghwa; Cha, Seongwon

    2017-01-01

    Circulating lipid ratios are considered predictors of cardiovascular risks and metabolic syndrome, which cause coronary heart diseases. One constitutional type of Korean medicine prone to weight accumulation, the Tae-Eum type, predisposes the consumers to metabolic syndrome, hypertension, diabetes mellitus, etc. Here, we aimed to identify genetic variants for lipid ratios using a genome-wide association study (GWAS) and followed replication analysis in Koreans and constitutional subgroups. GWASs in 5,292 individuals of the Korean Genome and Epidemiology Study and replication analyses in 2,567 subjects of the Korea medicine Data Center were performed to identify genetic variants associated with triglyceride (TG) to HDL cholesterol (HDLC), LDL cholesterol (LDLC) to HDLC, and non-HDLC to HDLC ratios. For subgroup analysis, a computer-based constitution analysis tool was used to categorize the constitutional types of the subjects. In the discovery stage, seven variants in four loci, three variants in three loci, and two variants in one locus were associated with the ratios of log-transformed TG:HDLC (log[TG]:HDLC), LDLC:HDLC, and non-HDLC:HDLC, respectively. The associations of the GWAS variants with lipid ratios were replicated in the validation stage: for the log[TG]:HDLC ratio, rs6589566 near APOA5 and rs4244457 and rs6586891 near LPL; for the LDLC:HDLC ratio, rs4420638 near APOC1 and rs17445774 near C2orf47; and for the non-HDLC:HDLC ratio, rs6589566 near APOA5. Five of these six variants are known to be associated with TG, LDLC, and/or HDLC, but rs17445774 was newly identified to be involved in lipid level changes in this study. Constitutional subgroup analysis revealed effects of variants associated with log[TG]:HDLC and non-HDLC:HDLC ratios in both the Tae-Eum and non-Tae-Eum types, whereas the effect of the LDLC:HDLC ratio-associated variants remained only in the Tae-Eum type. In conclusion, we identified three log[TG]:HDLC ratio-associated variants, two LDLC

  7. Insights for Planetarium and Museum Educators Revealed by the iSTAR international Study of Astronomical Reasoning Database

    Science.gov (United States)

    Slater, T. F.; Tatge, C. B.; Ratcliff, M.; Slater, S. J.

    2016-12-01

    Dedicated sky watchers through the centuries have long sought to find the best teaching methods to efficiently and effectively transfer vast amounts of accumulated star knowledge to the next generation of sky watchers. Although detailed maps specifying the names and locations of stars have been carefully displayed on spherical globes for thousands of years, it is the 1923 installation of a Zeiss-made, large, mechanical star projector in Munich that is often cited as the first modern projection planetarium for teaching astronomy. In the 1930's, impressive planetariums were installed Chicago, Los Angeles and New York, which then in turn served as a catalyst for additional planetarium construction. Planetarium construction increased rapidly in the United States due to federal funding to schools and museums through the 1958 US National Defense Education Act and the US went from one planetarium in 1930, to six in 1940, to about 100 in 1960, increasing to 200 in 1963, 450 by 1967—even before humans had landed on the Moon—and more than 1,000 by 1975. Today, nearly 3,000 permanent planetarium facilities are available to show the stars and heavenly motions to children and adults alike across the world, with perhaps another thousand portable planetariums adding to the available teaching venues. Simultaneous with their construction, discipline-based astronomy education have been trying to better understand, and ultimately improve, how people learn astronomy in the planetarium. A systematic analysis of planetarium education research articles, dissertations, and theses found in the recently constructed, community-wide, international Study of Astronomical Reasoning iSTAR database at istardatabase.org reveal that many of the systematic studies conducted in the 1960s and 1970s using domes served by servo-mechanical star projects have been reproduced again in recent decades in theaters using digital video projection showing nearly the same results: student-passive, information

  8. Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.

    Science.gov (United States)

    Reyes-Reyes, E Merit; Šalipur, Francesca R; Shams, Mitra; Forsthoefel, Matthew K; Bates, Paula J

    2015-08-01

    AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. In the current study, we have investigated the significance and molecular mechanisms of AS1411-induced macropinocytosis. Our results indicate that the antiproliferative activity of AS1411 in various cell lines correlated with its capacity to stimulate macropinocytosis. In DU145 prostate cancer cells, AS1411 induced activation of EGFR, Akt, p38, and Rac1. Activation of Akt and p38 were not critical for AS1411 activity because Akt activation was not observed in all AS1411-responsive cell lines and knockdown of p38 had no effect on AS1411's ability to inhibit proliferation. On the other hand, activation of EGFR and Rac1 appeared to play a role in AS1411 activity in all cancer cell lines examined (DU145, MDA-MB-468, A549, LNCaP) and their inhibition significantly reduced AS1411-mediated macropinocytosis and AS1411 antiproliferative activity. Interestingly, downregulation of nucleolin expression by siRNA also produced a substantial increase in activated Rac1, revealing a previously unknown role for nucleolin as a negative regulator of Rac1 activation. Our results are consistent with a model whereby AS1411 binding to nucleolin leads to sustained activation of Rac1 and causes methuosis, a novel type of nonapoptotic cell death characterized by hyperstimulation of macropinocytosis. We speculate that methuosis is a tumor/metastasis suppressor mechanism that opposes the malignant functions of Rac1 and that

  9. Mutagenesis and computational docking studies support the existence of a histamine binding site at the extracellular β3+β3- interface of homooligomeric β3 GABAA receptors.

    Science.gov (United States)

    Hoerbelt, Paul; Ramerstorfer, Joachim; Ernst, Margot; Sieghart, Werner; Thomson, Jeffrey L; Hough, Lindsay B; Fleck, Mark W

    2016-09-01

    Histamine is an important neurotransmitter that exerts its physiological actions through H1-4 metabotropic receptors in mammals. It also directly activates ionotropic GABAA receptor (GABAAR) β3 homooligomers and potentiates GABA responses in αβ heterooligomers in vitro, but the respective histamine binding sites in GABAARs are unknown. We hypothesized that histamine binds at the extracellular β+β- interface at a position homologous to the GABA binding site of heterooligomeric GABAARs. To test this, we individually mutated several residues at the putative ligand binding minus side of a rat GABAAR β3 wild type subunit and of a β3 subunit that was made insensitive to trace Zn(2+) inhibition [β3(H267A); called (Z)β3]. (Z)β3, (Z)β3(Y62L), (Z)β3(Q64A), (Z)β3(Q64E), α1(Z)β3, or α1(Z)β3(Y62L) receptors were studied in HEK293T cells using whole cell voltage clamp recording. β3, β3(Y62C), β3(Q64C), β3(N41C), β3(D43C), β3(A45C) or β3(M115C) receptors were examined in Xenopus oocytes using two-electrode voltage clamp. Histamine directly activated (Z)β3 and β3 homooligomers and potentiated GABA actions in α1(Z)β3 heterooligomers. Receptors containing (Z)β3(Y62L), β3(Y62C) and β3(D43C) showed markedly reduced histamine potency, but homo- and heterooligomers with (Z)β3(Q64E) exhibited increased potency. The GABAAR αβ(γ) competitive antagonist bicuculline elicited sub-maximal agonist currents through (Z)β3 homooligomers, the potency of which was strongly decreased by (Z)β3(Y62L). Mutations β3(N41C), β3(A45C) and β3(M115C) disturbed receptor expression or assembly. Computational docking into the crystal structure of homooligomeric β3 receptors resulted in a histamine pose highly consistent with the experimental findings, suggesting that histamine activates β3 receptors via a site homologous to the GABA site in αβγ receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Eastern Ionian Sea paleoceanographic conditions during the Plio - Pleistocene as revealed through the study of fish otoliths

    Science.gov (United States)

    Agiadi, K.; Triantaphyllou, M. V.; Girone, A.; Karakitsios, V.; Dermitzakis, M. D.

    2009-04-01

    water column. This increase in the tropical group of surface and intermediate waters, along with a decrease accordingly of both subtropical and temperate taxa, can be attributed to a climatic optimum at this time. However notable is the strong presence also of cold species Nansenia groenlandica and Benthosema glaciale in deeper water layers (mostly below 500 meters). Considering this event, it seems that warmer Atlantic water inflow in the Mediterranean, as a result of higher mean temperatures at this time, could be responsible for the upper part of the water column temperature increase. In addition, the formation of deeper water with lower temperatures than before could be attributed to increased river run off in the Adriatic Sea, which then inflows to the study areas. The paleoceanographic conditions appear generally stable until the uppermost part of the Pliocene, with colder temperatures prevailing gradually with an increase in relative abundance of Maurolicus muelleri combined with a decrease of Electrona risso. In the uppermost Pliocene and lowermost Pleistocene (around 1.73 Ma) the relative abundance of Electrona risso increases again in both study areas. Finally, the conditions in the upper part of the stratigraphic sequences return to temperate, with notable the presence of Myctophum punctatum, typically associated with upwelling conditions (Whitehead et al., 1984). Fish otoliths, as indicators of the paleoceanographic conditions throughout the water column, play a most significant role in the reconstruction of the deep - sea conditions. The presented palaeoecologic analysis of the Teleost fauna reveals distinct phases in the evolution of climate and oceanography during the Late Pliocene - Early Pleistocene interval. Notwithstanding the general deterioration of climate progressing into the Pleistocene era, it appears that the Mediterranean paleocirculation in conjunction with regional topography were modulated by the constantly changing global climatic

  11. Studies on the Virome of the Entomopathogenic Fungus Beauveria bassiana Reveal Novel dsRNA Elements and Mild Hypervirulence.

    Directory of Open Access Journals (Sweden)

    Ioly Kotta-Loizou

    2017-01-01

    Full Text Available The entomopathogenic fungus Beauveria bassiana has a wide host range and is used as a biocontrol agent against arthropod pests. Mycoviruses have been described in phytopathogenic fungi while in entomopathogenic fungi their presence has been reported only rarely. Here we show that 21.3% of a collection of B. bassiana isolates sourced from worldwide locations, harbor dsRNA elements. Molecular characterization of these elements revealed the prevalence of mycoviruses belonging to the Partitiviridae and Totiviridae families, the smallest reported virus to date, belonging to the family Narnaviridae, and viruses unassigned to a family or genus. Of particular importance is the discovery of members of a newly proposed family Polymycoviridae in B. bassiana. Polymycoviruses, previously designated as tetramycoviruses, consist of four non-conventionally encapsidated capped dsRNAs. The presence of additional non-homologous genomic segments in B. bassiana polymycoviruses and other fungi illustrates the unprecedented dynamic nature of the viral genome. Finally, a comparison of virus-free and virus-infected isogenic lines derived from an exemplar B. bassiana isolate revealed a mild hypervirulent effect of mycoviruses on the growth of their host isolate and on its pathogenicity against the greater wax moth Galleria mellonella, highlighting for the first time the potential of mycoviruses as enhancers of biocontrol agents.

  12. Culture-based study of endophytes associated with rubber trees in Peru reveals a new class of Pezizomycotina: Xylonomycetes.

    Science.gov (United States)

    Gazis, R; Miadlikowska, J; Lutzoni, F; Arnold, A E; Chaverri, P

    2012-10-01

    Through a culture-based survey of living sapwood and leaves of rubber trees (Hevea spp.) in remote forests of Peru, we discovered a new major lineage of Ascomycota, equivalent to a class rank. Multilocus phylogenetic analyses reveal that this new lineage originated during the radiation of the 'Leotiomyceta', which resulted not only in the evolution of the Arthoniomycetes, Dothideomycetes, Eurotiomycetes, Geoglossomycetes, Lecanoromycetes, Leotiomycetes, Lichinomycetes, and Sordariomycetes, but also of the majority of hyperdiverse foliar endophytes. Because its origin is nested within this major burst of fungal diversification, we could not recover strong support for its phylogenetic relationship within the 'Leotiomyceta'. Congruent with their long phylogenetic history and distinctive preference for growing in sapwood, this new lineage displays unique morphological, physiological, and ecological traits relative to known endophytes and currently described members of the 'Leotiomyceta'. In marked contrast to many foliar endophytes, the strains we isolated fail to degrade cellulose and lignin in vitro. Discovery of the new class, herein named Xylonomycetes and originally mis-identified by ITSrDNA sequencing alone, highlights the importance of inventorying tropical endophytes from unexplored regions, using multilocus data sets to infer the phylogenetic placement of unknown strains, and the need to sample diverse plant tissues using traditional methods to enhance efforts to discover the evolutionary, taxonomic, and functional diversity of symbiotrophic fungi. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control.

    Science.gov (United States)

    Jacques, Antoine; Laurent, Marion; Ribière-Chabert, Magali; Saussac, Mathilde; Bougeard, Stéphanie; Budge, Giles E; Hendrikx, Pascal; Chauzat, Marie-Pierre

    2017-01-01

    Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed.

  14. A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control.

    Directory of Open Access Journals (Sweden)

    Antoine Jacques

    Full Text Available Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed.

  15. Study results of picking high amplitude reflectors in turbidite channel to reveal detail of methane hydrate concentrated zone

    Energy Technology Data Exchange (ETDEWEB)

    Shimoda, N.; Saeki, T.; Inamori, T.; Kobayashi, T.; Fujii, T. [Japan Oil, Gas and Metals National Corp., Mihama-ku, Chiba (Japan). Technology Research Center

    2008-07-01

    Bottom simulating reflectors are found extensively in the eastern Nankai Trough. BSR is considered as a bottom of methane hydrate bearing sediments. High resolution three-dimensional seismic surveys were conducted in 2002 and a multi-well drilling campaign was executed in 2004. This paper discussed the resource potential of methane hydrate in this area. The paper discussed an evaluation of more than 10 methane hydrate concentrated zones in the Nankai Trough. Methane hydrated concentrated zones in this area are roughly classified into 2 types of turbidite sedimentary facies from the seismic geomorphological point of view known as lobe and channel. This paper attempted to interpret a detailed structure of a channel type methane hydrate concentrated zone. High amplitude reflector patches may indicate sand dominated bodies with high methane hydrate concentration. It was concluded that picked reflector patches demonstrated that the methane hydrate concentrated zone was biforked at a lower current area. Detailed observations also revealed that the methane hydrate concentrated zone was developed in a channel complex of which fluid migration was slowly shifted.

  16. Genome-wide study of an elite rice pedigree reveals a complex history of genetic architecture for breeding improvement.

    Science.gov (United States)

    Chen, Shaoxia; Lin, Zechuan; Zhou, Degui; Wang, Chongrong; Li, Hong; Yu, Renbo; Deng, Hanchao; Tang, Xiaoyan; Zhou, Shaochuan; Wang Deng, Xing; He, Hang

    2017-04-04

    Improving breeding has been widely utilized in crop breeding and contributed to yield and quality improvement, yet few researches have been done to analyze genetic architecture underlying breeding improvement comprehensively. Here, we collected genotype and phenotype data of 99 cultivars from the complete pedigree including Huanghuazhan, an elite, high-quality, conventional indica rice that has been grown over 4.5 million hectares in southern China and from which more than 20 excellent cultivars have been derived. We identified 1,313 selective sweeps (SSWs) revealing four stage-specific selection patterns corresponding to improvement preference during 65 years, and 1113 conserved Huanghuazhan traceable blocks (cHTBs) introduced from different donors and conserved in >3 breeding generations were the core genomic regions for superior performance of Huanghuazhan. Based on 151 quantitative trait loci (QTLs) identified for 13 improved traits in the pedigree, we reproduced their improvement process in silico, highlighting improving breeding works well for traits controlled by major/major + minor effect QTLs, but was inefficient for traits controlled by QTLs with complex interactions or explaining low levels of phenotypic variation. These results indicate long-term breeding improvement is efficient to construct superior genetic architecture for elite performance, yet molecular breeding with designed genotype of QTLs can facilitate complex traits improvement.

  17. Prevalence and molecular epidemiology of Staphylococcus aureus in Swedish nursing homes - as revealed in the SHADES study.

    Science.gov (United States)

    Stark, L; Olofsson, M; Löfgren, S; Mölstad, S; Lindgren, P-E; Matussek, A

    2014-06-01

    Knowledge of carriage and population dynamics of Staphylococcus aureus is crucial for infection risk assessment and to reveal transmission patterns of strains. We report the prevalence and molecular epidemiology of S. aureus in elderly people (n = 290) living in nursing homes in three cities in the south of Sweden. The overall carriage prevalence rate was 48% when results from nares (31%) and throat (34%) samples were combined. Common spa types were equally distributed but a frequent type, t160, was found only in one of the regions. Carriage of different spa types was detected in 23% of individuals and antimicrobial resistance rates were higher in S. aureus isolates from those carrying more than one spa type. Five of the 21 individuals who carried different spa types were colonized simultaneously with resistant and non-resistant strains. Seventeen per cent of the individuals carried S. aureus of the same spa type on all occasions. Methicillin resistance was not detected. In conclusion we found a high prevalence of S. aureus in this elderly population with a high rate of dual colonization with different spa types. We also found signs of institutional spread of one strain.

  18. Dynamic clamp as a tool to study the functional effects of individual membrane currents

    NARCIS (Netherlands)

    Berecki, Géza; Verkerk, Arie O.; van Ginneken, Antoni C. G.; Wilders, Ronald

    2014-01-01

    Today, the patch-clamp technique is the main technique in electrophysiology to record action potentials or membrane current from isolated cells, using a patch pipette to gain electrical access to the cell. The common recording modes of the patch-clamp technique are current clamp and voltage clamp.

  19. Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies

    International Nuclear Information System (INIS)

    Dusinska, Maria; Staruchova, Marta; Horska, Alexandra; Smolkova, Bozena; Collins, Andrew; Bonassi, Stefano; Volkovova, Katarina

    2012-01-01

    Glutathione S-transferases (GSTs) are members of a multigene family of isoenzymes that are important in the control of oxidative stress and in phase II metabolism. Acting non-enzymically, GSTs can modulate signalling pathways of cell proliferation, cell differentiation and apoptosis. Using a molecular epidemiology approach, we have investigated a potential involvement of GSTs in DNA damage processing, specifically the modulation of DNA repair in a group of 388 healthy adult volunteers; 239 with at least 5 years of occupational exposure to asbestos, stone wool or glass fibre, and 149 reference subjects. We measured DNA damage in lymphocytes using the comet assay (alkaline single cell gel electrophoresis): strand breaks (SBs) and alkali-labile sites, oxidised pyrimidines with endonuclease III, and oxidised purines with formamidopyrimidine DNA glycosylase. We also measured GST activity in erythrocytes, and the capacity for base excision repair (BER) in a lymphocyte extract. Polymorphisms in genes encoding three GST isoenzymes were determined, namely deletion of GSTM1 and GSTT1 and single nucleotide polymorphism Ile105Val in GSTP1. Consumption of vegetables and wine correlated negatively with DNA damage and modulated BER. GST activity correlated with oxidised bases and with BER capacity, and differed depending on polymorphisms in GSTP1, GSTT1 and GSTM1. A significantly lower BER rate was associated with the homozygous GSTT1 deletion in all asbestos site subjects and in the corresponding reference group. Multifactorial analysis revealed effects of sex and exposure in GSTP1 Ile/Val heterozygotes but not in Ile/Ile homozygotes. These variants affected also SBs levels, mainly by interactions of GSTP1 genotype with exposure, with sex, and with smoking habit; and by an interaction between sex and smoking. Our results show that GST polymorphisms and GST activity can apparently influence DNA stability and repair of oxidised bases, suggesting a potential new role for these

  20. Observational study on the fine structure and dynamics of a solar jet. II. Energy release process revealed by spectral analysis

    Science.gov (United States)

    Sakaue, Takahito; Tei, Akiko; Asai, Ayumi; Ueno, Satoru; Ichimoto, Kiyoshi; Shibata, Kazunari

    2018-01-01

    We report on a solar jet phenomenon associated with the C5.4 class flare on 2014 November 11. The data of the jet was provided by the Solar Dynamics Observatory, the X-Ray Telescope (XRT) aboard Hinode, and the Interface Region Imaging Spectrograph and Domeless Solar Telescope (DST) at Hida Observatory, Kyoto University. These plentiful data enabled us to present this series of papers to discuss all the processes of the observed phenomena, including energy storage, event trigger, and energy release. In this paper, we focus on the energy release process of the observed jet, and mainly describe our spectral analysis on the Hα data of DST to investigate the internal structure of the Hα jet and its temporal evolution. This analysis reveals that in the physical quantity distributions of the Hα jet, such as line-of-sight velocity and optical thickness, there is a significant gradient in the direction crossing the jet. We interpret this internal structure as the consequence of the migration of the energy release site, based on the idea of ubiquitous reconnection. Moreover, by measuring the horizontal flow of the fine structures in the jet, we succeeded in deriving the three-dimensional velocity field and the line-of-sight acceleration field of the Hα jet. The analysis result indicates that part of the ejecta in the Hα jet experienced additional acceleration after it had been ejected from the lower atmosphere. This secondary acceleration was found to occur in the vicinity of the intersection between the trajectories of the Hα jet and the X-ray jet observed by Hinode/XRT. We propose that a fundamental cause of this phenomenon is magnetic reconnection involving the plasmoid in the observed jet.

  1. Extensive genomic plasticity in Pseudomonas aeruginosa revealed by identification and distribution studies of novel genes among clinical isolates.

    Science.gov (United States)

    Shen, Kai; Sayeed, Sameera; Antalis, Patricia; Gladitz, John; Ahmed, Azad; Dice, Bethany; Janto, Benjamin; Dopico, Richard; Keefe, Randy; Hayes, Jay; Johnson, Sandra; Yu, Sujun; Ehrlich, Nathan; Jocz, Jennifer; Kropp, Laura; Wong, Ray; Wadowsky, Robert M; Slifkin, Malcolm; Preston, Robert A; Erdos, Geza; Post, J Christopher; Ehrlich, Garth D; Hu, Fen Z

    2006-09-01

    The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.

  2. Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies

    Energy Technology Data Exchange (ETDEWEB)

    Dusinska, Maria, E-mail: Maria.DUSINSKA@nilu.no [CEE-Health Effects Group, NILU - Norwegian Institute for Air Research, Kjeller (Norway); Staruchova, Marta; Horska, Alexandra [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia); Smolkova, Bozena [Laboratory of Cancer Genetics, Cancer Research Institute of the Slovak Academy of Sciences, Bratislava (Slovakia); Collins, Andrew [Department of Nutrition, Faculty of Medicine, University of Oslo (Norway); Bonassi, Stefano [Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome (Italy); Volkovova, Katarina [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia)

    2012-08-01

    Glutathione S-transferases (GSTs) are members of a multigene family of isoenzymes that are important in the control of oxidative stress and in phase II metabolism. Acting non-enzymically, GSTs can modulate signalling pathways of cell proliferation, cell differentiation and apoptosis. Using a molecular epidemiology approach, we have investigated a potential involvement of GSTs in DNA damage processing, specifically the modulation of DNA repair in a group of 388 healthy adult volunteers; 239 with at least 5 years of occupational exposure to asbestos, stone wool or glass fibre, and 149 reference subjects. We measured DNA damage in lymphocytes using the comet assay (alkaline single cell gel electrophoresis): strand breaks (SBs) and alkali-labile sites, oxidised pyrimidines with endonuclease III, and oxidised purines with formamidopyrimidine DNA glycosylase. We also measured GST activity in erythrocytes, and the capacity for base excision repair (BER) in a lymphocyte extract. Polymorphisms in genes encoding three GST isoenzymes were determined, namely deletion of GSTM1 and GSTT1 and single nucleotide polymorphism Ile105Val in GSTP1. Consumption of vegetables and wine correlated negatively with DNA damage and modulated BER. GST activity correlated with oxidised bases and with BER capacity, and differed depending on polymorphisms in GSTP1, GSTT1 and GSTM1. A significantly lower BER rate was associated with the homozygous GSTT1 deletion in all asbestos site subjects and in the corresponding reference group. Multifactorial analysis revealed effects of sex and exposure in GSTP1 Ile/Val heterozygotes but not in Ile/Ile homozygotes. These variants affected also SBs levels, mainly by interactions of GSTP1 genotype with exposure, with sex, and with smoking habit; and by an interaction between sex and smoking. Our results show that GST polymorphisms and GST activity can apparently influence DNA stability and repair of oxidised bases, suggesting a potential new role for these

  3. Proteomics reveals changes in hepatic proteins during chicken embryonic development: an alternative model to study human obesity

    OpenAIRE

    Peng, Mengling; Li, Shengnan; He, Qianian; Zhao, Jinlong; Li, Longlong; Ma, Haitian

    2018-01-01

    Background Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development. Results In this study, the abundances of 293 hepatic proteins...

  4. Priming can affect naming colours using the study-test procedure. Revealing the role of task conflict.

    Science.gov (United States)

    Sharma, Dinkar

    2016-11-14

    The Stroop paradigm has been widely used to study attention whilst its use to explore implicit memory have been mixed. Using the non-colour word Stroop task we tested contrasting predictions from the proactive-control/task-conflict model (Kalanthroff, Avnit, Henik, Davelaar & Usher, 2015) that implicate response conflict and task conflict for the priming effects. Using the study-test procedure 60 native English speakers were tested to determine whether priming effects from words that had previously been studied would cause interference when presented in a colour naming task. The results replicate a finding by MacLeod (1996) who showed no differences between the response latencies to studied and unstudied words. However, this pattern was predominately in the first half of the study where it was also found that both studied and unstudied words in a mixed block were slower to respond to than a block of pure unstudied words. The second half of the study showed stronger priming interference effects as well as a sequential modulation effect in which studied words slowed down the responses of studied words on the next trial. We discuss the role of proactive and reactive control processes and conclude that task conflict best explains the pattern of priming effects reported. Copyright © 2016. Published by Elsevier B.V.

  5. Epidemiological study of paediatric germ cell tumours revealed the incidence and distribution that was expected, but a low mortality rate

    DEFF Research Database (Denmark)

    Evers, Madeline; Rechnitzer, Catherine; Graem, Niels

    2017-01-01

    Aim: Germ cell tumours (GCTs) are a rare heterogeneous tumour group derived from primordial germ cells, which can be benign or malignant and occur in the gonads or extragonadally. This study mapped the paediatric GCTs in Denmark from 1984 to 2013 to study the incidence and outcome. Methods: We id...

  6. An integrative genetic study of rice metabolism, growth and stochastic variation reveals potential C/N partitioning loci

    DEFF Research Database (Denmark)

    Li, Baohua; Zhang, Yuanyuan; Mohammadi, Seyed Abolghasem

    2016-01-01

    metabolites suggesting that they may influence carbon and nitrogen partitioning, with one locus co-localizing with SUSIBA2 (WRKY78). Comparing QTLs for metabolomic and a variety of growth related traits identified few overlaps. Interestingly, the rice population displayed fewer loci controlling stochastic...... on identifying genes controlling major effect loci. To complement these studies, we conducted a replicated metabolomics analysis on a japonica (Lemont) by indica (Teqing) rice recombinant inbred line population and focused on the genetic variation for primary metabolism. Using independent replicated studies, we......Studying the genetic basis of variation in plant metabolism has been greatly facilitated by genomic and metabolic profiling advances. In this study, we use metabolomics and growth measurements to map QTL in rice, a major staple crop. Previous rice metabolism studies have largely focused...

  7. Main and epistatic loci studies in soybean for Sclerotinia sclerotiorum resistance reveal multiple modes of resistance in multi-environments

    OpenAIRE

    Moellers, Tara C.; Singh, Arti; Zhang, Jiaoping; Brungardt, Jae; Kabbage, Mehdi; Mueller, Daren S.; Grau, Craig R.; Ranjan, Ashish; Smith, Damon L.; Chowda-Reddy, R. V.; Singh, Asheesh K.

    2017-01-01

    Genome-wide association (GWAS) and epistatic (GWES) studies along with expression studies in soybean [Glycine max (L.) Merr.] were leveraged to dissect the genetics of Sclerotinia stem rot (SSR) [caused by Sclerotinia sclerotiorum (Lib.) de Bary], a significant fungal disease causing yield and quality losses. A large association panel of 466 diverse plant introduction accessions were phenotyped in multiple field and controlled environments to: (1) discover sources of resistance, (2) identify ...

  8. An Integrative Genetic Study of Rice Metabolism, Growth and Stochastic Variation Reveals Potential C/N Partitioning Loci

    Science.gov (United States)

    Li, Baohua; Zhang, Yuanyuan; Mohammadi, Seyed Abolghasem; Huai, Dongxin; Zhou, Yongming; Kliebenstein, Daniel J.

    2016-07-01

    Studying the genetic basis of variation in plant metabolism has been greatly facilitated by genomic and metabolic profiling advances. In this study, we use metabolomics and growth measurements to map QTL in rice, a major staple crop. Previous rice metabolism studies have largely focused on identifying genes controlling major effect loci. To complement these studies, we conducted a replicated metabolomics analysis on a japonica (Lemont) by indica (Teqing) rice recombinant inbred line population and focused on the genetic variation for primary metabolism. Using independent replicated studies, we show that in contrast to other rice studies, the heritability of primary metabolism is similar to Arabidopsis. The vast majority of metabolic QTLs had small to moderate effects with significant polygenic epistasis. Two metabolomics QTL hotspots had opposing effects on carbon and nitrogen rich metabolites suggesting that they may influence carbon and nitrogen partitioning, with one locus co-localizing with SUSIBA2 (WRKY78). Comparing QTLs for metabolomic and a variety of growth related traits identified few overlaps. Interestingly, the rice population displayed fewer loci controlling stochastic variation for metabolism than was found in Arabidopsis. Thus, it is possible that domestication has differentially impacted stochastic metabolite variation more than average metabolite variation.

  9. Extensive Field Survey, Laboratory and Greenhouse Studies Reveal Complex Nature of Pseudomonas syringae-Associated Hazelnut Decline in Central Italy.

    Science.gov (United States)

    Lamichhane, Jay Ram; Bartoli, Claudia; Varvaro, Leonardo

    2016-01-01

    Pseudomonas avellanae (Pav) has been reported as the causal agent of bacterial decline and bacterial canker of hazelnut in Italy and Greece, respectively. Both hazelnut diseases were reported to be similar in terms of symptoms, severity and persistence. In this study, we found that both symptomatic and asymptomatic trees in the field were colonized by Pav. Multilocus Sequence Typing (MLST) analysis showed that Pav strains isolated during this study in Italy belong to the P. syringae phylogroup 1 and they are closely related to Pav strains previously isolated in Greece from hazelnut bacterial canker. On the other hand, strains isolated in earlier studies from hazelnut decline in Italy belong to both phylogroup 1 and 2 of P. syringae. Both phylogroup 1 strains of P. syringae from Greece and Italy are different than strains isolated in this study in terms of their capacity to excrete fluorescent pigments on different media. Despite the same plant genotype and cropping practices adopted, the incidence of hazelnut decline ranged from nearly 0 to 91% across our study sites. No disease developed on plants inoculated with Pav through wounding while leaf scar inoculations produced only mild disease symptoms. Based on our results and the previously reported correlation between pedo-climatic conditions and hazelnut decline, we conclude that hazelnut decline in central Italy could be incited by a combination of predisposing (adverse pedo-climatic conditions) and contributing factors (Pav). Because this is a true decline different from "bacterial canker" described in Greece, we refer to it as hazelnut decline (HD).

  10. High Resolution MRI Reveals Detailed Layer Structures in Early Human Fetal Stages: In Vitro Study with Histologic Correlation.

    Science.gov (United States)

    Wang, Rongpin; Dai, Guangping; Takahashi, Emi

    2015-01-01

    An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly-changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI) studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW), which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. T2-weighted imaging was performed on fetal brain specimens ranging from 10 GW to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW). Early second trimester (15-18 GW) was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high-resolution structural imaging and color-coding processing with histological analysis may be a potential tool for

  11. High resolution MRI reveals detailed layer structures in early human fetal stages: In vitro study with histologic correlation

    Directory of Open Access Journals (Sweden)

    Rongpin eWang

    2015-11-01

    Full Text Available An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly-changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW, which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. T2-weighted imaging was performed on fetal brain specimens ranging from 10 GW to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW. Early second trimester (15-18 GW was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high-resolution structural imaging and color-coding processing with histological analysis may be a potential

  12. Introgression study reveals two quantitative trait loci involved in interspecific variation in memory retention among Nasonia wasp species

    NARCIS (Netherlands)

    Hoedjes, K.M.; Smid, H.M.; Vet, L.E.M.; Werren, J.H.

    2014-01-01

    Genes involved in the process of memory formation have been studied intensively in model organisms; however, little is known about the mechanisms that are responsible for natural variation in memory dynamics. There is substantial variation in memory retention among closely related species in the

  13. Toxicity of ozone and nitrogen dioxide to alveolar macrophages: comparative study revealing differences in their mechanism of toxic action

    NARCIS (Netherlands)

    Rietjens, I. M.; Poelen, M. C.; Hempenius, R. A.; Gijbels, M. J.; Alink, G. M.

    1986-01-01

    The toxicity of ozone and nitrogen dioxide is generally ascribed to their oxidative potential. In this study their toxic mechanism of action was compared using an intact cell model. Rat alveolar macrophages were exposed by means of gas diffusion through a Teflon film. In this in vitro system, ozone

  14. Telling Themselves Who They Are: What One Out-of-School Time Study Revealed about Underachieving Readers

    Science.gov (United States)

    Alvermann, Donna E.; Hagood, Margaret C.; Heron-Hruby, Alison; Hughes, Preston; Williams, Kevin B.; Yoon, Jun-Chae

    2007-01-01

    The purpose of this study was to explore whether or not adolescents who are deemed underachievers and who struggle to read school-assigned textbooks will engage with popular culture texts of their own choosing (e.g., magazines, comics, TV, video games, music CDs, graffiti, e-mail, and other Internet-mediated texts). The 60 student participants,…

  15. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

    NARCIS (Netherlands)

    Bigdeli, Tim B.; Ripke, Stephan; Bacanu, Silviu-Alin; Lee, Sang Hong; Wray, Naomi R.; Gejman, Pablo V.; Rietschel, Marcella; Cichon, Sven; St Clair, David; Corvin, Aiden; Kirov, George; McQuillin, Andrew; Gurling, Hugh; Rujescu, Dan; Andreassen, Ole A.; Werge, Thomas; Blackwood, Douglas H. R.; Pato, Carlos N.; Pato, Michele T.; Malhotra, Anil K.; O'Donovan, Michael C.; Kendler, Kenneth S.; Fanous, Ayman H.; Neale, Benjamin M.; Walters, James T. R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberley D.; Chan, Raymond C. K.; Chan, Ronald Y. L.; Chen, Eric Y. H.; Cheng, Wei; Cheung, Eric F. C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kahn, René S.; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Lee, Jimmy; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik K. E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O'Callaghan, Eadbhard; O'Dushlaine, Colm; O'Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; van, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Posthuma, Danielle; Powell, John; Price, Alkes; Pulver, Ann E.; Purcell, Shaun; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; Spencer, Chris C. A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Visscher, Peter M.; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T.; Weiser, Mark; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wong, Emily H. M.; Wormley, Brandon K.; Simon, Hualin; Zai, Clement C.; Zheng, Xuebin; Zimprich, Fritz; Stefansson, Kari; Adolfsson, Rolf; Bramon, Elvira; Buxbaum, Joseph D.; Børglum, Anders D.; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Gill, Michael; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jönsson, Erik G.; Knight, Jo; Lencz, Todd; Levinson, Douglas F.; Li, Qingqin S.; Liu, Jianjun; McCarroll, Steven A.; Moran, Jennifer L.; Mortensen, Preben B.; Mowry, Bryan J.; Nöthen, Markus M.; Ophoff, Roel A.; Owen, Michael J.; Petryshen, Tracey L.; Riley, Brien P.; Sham, Pak C.; Sklar, Pamela; Clair, David St; Weinberger, Daniel R.; Wendland, Jens R.; Daly, Mark J.; Sullivan, Patrick F.

    2016-01-01

    Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of

  16. Incipient speciation revealed in Anastrepha fraterculus (Diptera; Tephritidae) by studies on mating compatibility, sex pheromones, hybridisation and cytology

    Science.gov (United States)

    It is suggested that the nominal species Anastrepha fraterculus is a species complex and previous studies showed high levels of pre-zygotic isolation between two laboratory strains from Argentina and Peru. To further analyze this observation, experiments were carried out on the same populations and...

  17. A Seasonal Study Reveals the Occurrence of Exotic Rotifers, the River Antigua, Veracruz, Close to the Gulf of Mexico

    NARCIS (Netherlands)

    Nandini, S.; Sarma, S. S. S.; Gulati, R. D.

    Zooplankton studies in Mexican rivers are few despite the fact that Mexico has >200 rivers. We present data on the seasonal diversity of rotifers during 2013–2014 from the river La Antigua, near Veracruz. We collected samples from 15 stations along a horizontal gradient of ~5 km, from the upper

  18. Concerns and Expectations of Students Participating in Study Abroad Programmes: Blogging to Reveal the Dynamic Student Voice

    Science.gov (United States)

    Bell, Robin

    2016-01-01

    Study abroad programmes have become increasingly popular with university students and within academia. They are often seen as an experiential opportunity to expand student learning and development, including increases in global, international and intercultural competences. However, despite the increasing popularity of and participation in study…

  19. Extensive Field Survey, Laboratory and Greenhouse Studies Reveal Complex Nature of Pseudomonas syringae-Associated Hazelnut Decline in Central Italy.

    Directory of Open Access Journals (Sweden)

    Jay Ram Lamichhane

    Full Text Available Pseudomonas avellanae (Pav has been reported as the causal agent of bacterial decline and bacterial canker of hazelnut in Italy and Greece, respectively. Both hazelnut diseases were reported to be similar in terms of symptoms, severity and persistence. In this study, we found that both symptomatic and asymptomatic trees in the field were colonized by Pav. Multilocus Sequence Typing (MLST analysis showed that Pav strains isolated during this study in Italy belong to the P. syringae phylogroup 1 and they are closely related to Pav strains previously isolated in Greece from hazelnut bacterial canker. On the other hand, strains isolated in earlier studies from hazelnut decline in Italy belong to both phylogroup 1 and 2 of P. syringae. Both phylogroup 1 strains of P. syringae from Greece and Italy are different than strains isolated in this study in terms of their capacity to excrete fluorescent pigments on different media. Despite the same plant genotype and cropping practices adopted, the incidence of hazelnut decline ranged from nearly 0 to 91% across our study sites. No disease developed on plants inoculated with Pav through wounding while leaf scar inoculations produced only mild disease symptoms. Based on our results and the previously reported correlation between pedo-climatic conditions and hazelnut decline, we conclude that hazelnut decline in central Italy could be incited by a combination of predisposing (adverse pedo-climatic conditions and contributing factors (Pav. Because this is a true decline different from "bacterial canker" described in Greece, we refer to it as hazelnut decline (HD.

  20. Extensive Field Survey, Laboratory and Greenhouse Studies Reveal Complex Nature of Pseudomonas syringae-Associated Hazelnut Decline in Central Italy

    Science.gov (United States)

    Lamichhane, Jay Ram; Bartoli, Claudia; Varvaro, Leonardo

    2016-01-01

    Pseudomonas avellanae (Pav) has been reported as the causal agent of bacterial decline and bacterial canker of hazelnut in Italy and Greece, respectively. Both hazelnut diseases were reported to be similar in terms of symptoms, severity and persistence. In this study, we found that both symptomatic and asymptomatic trees in the field were colonized by Pav. Multilocus Sequence Typing (MLST) analysis showed that Pav strains isolated during this study in Italy belong to the P. syringae phylogroup 1 and they are closely related to Pav strains previously isolated in Greece from hazelnut bacterial canker. On the other hand, strains isolated in earlier studies from hazelnut decline in Italy belong to both phylogroup 1 and 2 of P. syringae. Both phylogroup 1 strains of P. syringae from Greece and Italy are different than strains isolated in this study in terms of their capacity to excrete fluorescent pigments on different media. Despite the same plant genotype and cropping practices adopted, the incidence of hazelnut decline ranged from nearly 0 to 91% across our study sites. No disease developed on plants inoculated with Pav through wounding while leaf scar inoculations produced only mild disease symptoms. Based on our results and the previously reported correlation between pedo-climatic conditions and hazelnut decline, we conclude that hazelnut decline in central Italy could be incited by a combination of predisposing (adverse pedo-climatic conditions) and contributing factors (Pav). Because this is a true decline different from “bacterial canker” described in Greece, we refer to it as hazelnut decline (HD). PMID:26840951

  1. Empirical study of travel mode forecasting improvement for the combined revealed preference/stated preference data–based discrete choice model

    Directory of Open Access Journals (Sweden)

    Yanfu Qiao

    2016-01-01

    Full Text Available The combined revealed preference/stated preference data–based discrete choice model has provided the actual choice-making restraints as well as reduced the prediction errors. But the random error variance of alternatives belonging to different data would impact its universality. In this article, we studied the traffic corridor between Chengdu and Longquan with the revealed preference/stated preference joint model, and the single stated preference data model separately predicted the choice probability of each mode. We found the revealed preference/stated preference joint model is universal only when there is a significant difference between the random error terms in different data. The single stated preference data would amplify the travelers’ preference and cause prediction error. We proposed a universal way that uses revealed preference data to modify the single stated preference data parameter estimation results to achieve the composite utility and reduce the prediction error. And the result suggests that prediction results are more reasonable based on the composite utility than the results based on the single stated preference data, especially forecasting the mode share of bus. The future metro line will be the main travel mode in this corridor, and 45% of passenger flow will transfer to the metro.

  2. Personality traits related to juvenile myoclonic epilepsy: MRI reveals prefrontal abnormalities through a voxel-based morphometry study.

    Science.gov (United States)

    de Araújo Filho, Gerardo Maria; Jackowski, Andrea Parolin; Lin, Katia; Guaranha, Mirian S B; Guilhoto, Laura M F F; da Silva, Henrique Hattori; Caboclo, Luís Otávio Sales Ferreira; Júnior, Henrique Carrete; Bressan, Rodrigo Affonseca; Yacubian, Elza Márcia T

    2009-06-01

    Studies involving juvenile myoclonic epilepsy (JME) patients have demonstrated an elevated prevalence of cluster B personality disorders (PD) characterized as emotional instability, immaturity, unsteadiness, lack of discipline, and rapid mood changes. We aimed to verify a possible correlation between structural brain abnormalities in magnetic resonance image (MRI) and the PD in JME using voxel-based morphometry (VBM). Sixteen JME patients with cluster B PD, 38 JME patients without psychiatric disorders, and 30 healthy controls were submitted to a psychiatric evaluation through SCID I and II and to a MRI scan. Significant reduction in thalami and increase in mesiofrontal and frontobasal regions' volumes were observed mainly in JME patients with PD. Structural alterations of the orbitofrontal cortex (OFC), involved in regulation of mood reactivity, impulsivity, and social behavior, were also observed. This study supports the hypothesis of frontobasal involvement in the pathophysiology of cluster B PD related to JME.

  3. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

    DEFF Research Database (Denmark)

    Bigdeli, Tim B.; Ripke, Stephan; Bacanu, Silviu-Alin

    2016-01-01

    of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N......Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence......=978), cases reporting no such family history (N=4,503), and unscreened controls (N=8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup...

  4. Genome-Wide Association Study Reveals Four Loci for Lipid Ratios in the Korean Population and the Constitutional Subgroup

    OpenAIRE

    Kim, Taehyeung; Park, Ah Yeon; Baek, Younghwa; Cha, Seongwon

    2017-01-01

    Circulating lipid ratios are considered predictors of cardiovascular risks and metabolic syndrome, which cause coronary heart diseases. One constitutional type of Korean medicine prone to weight accumulation, the Tae-Eum type, predisposes the consumers to metabolic syndrome, hypertension, diabetes mellitus, etc. Here, we aimed to identify genetic variants for lipid ratios using a genome-wide association study (GWAS) and followed replication analysis in Koreans and constitutional subgroups. GW...

  5. Genome-Wide Association Study Reveals Novel Loci for SC7 Resistance in a Soybean Mutant Panel

    OpenAIRE

    Che, Zhijun; Liu, Hailun; Yi, Fanglei; Cheng, Hao; Yang, Yuming; Wang, Li; Du, Jingyi; Zhang, Peipei; Wang, Jiao; Yu, Deyue

    2017-01-01

    Soybean mosaic virus (SMV) is a member of Potyvirus genus that causes severe yield loss and destroys seed quality in soybean [Glycine max (L.) Merr.]. It is important to explore new resistance sources and discover new resistance loci to SMV, which will provide insights to improve breeding strategies for SMV resistance. Here, a genome-wide association study was conducted to accelerate molecular breeding for the improvement of resistance to SMV in soybean. A population of 165 soybean mutants de...

  6. Genome-Wide Association Study Reveals Novel Genes Associated with Culm Cellulose Content in Bread Wheat (Triticum aestivum, L.

    Directory of Open Access Journals (Sweden)

    Simerjeet Kaur

    2017-11-01

    Full Text Available Plant cell wall formation is a complex, coordinated and developmentally regulated process. Cellulose is the most dominant constituent of plant cell walls. Because of its paracrystalline structure, cellulose is the main determinant of mechanical strength of plant tissues. As the most abundant polysaccharide on earth, it is also the focus of cellulosic biofuel industry. To reduce culm lodging in wheat and for improved ethanol production, delineation of the variation for stem cellulose content could prove useful. We present results on the analysis of the stem cellulose content of 288 diverse wheat accessions and its genome-wide association study (GWAS. Cellulose concentration ranged from 35 to 52% (w/w. Cellulose content was normally distributed in the accessions around a mean and median of 45% (w/w. Genome-wide marker-trait association study using 21,073 SNPs helped identify nine SNPs that were associated (p < 1E-05 with cellulose content. Four strongly associated (p < 8.17E-05 SNP markers were linked to wheat unigenes, which included β-tubulin, Auxin-induced protein 5NG4, and a putative transmembrane protein of unknown function. These genes may be directly or indirectly involved in the formation of cellulose in wheat culms. GWAS results from this study have the potential for genetic manipulation of cellulose content in bread wheat and other small grain cereals to enhance culm strength and improve biofuel production.

  7. A comprehensive study of oculocutaneous albinism type 1 reveals three previously unidentified alleles on the TYR gene.

    Science.gov (United States)

    Lin, Yu-Ying; Wei, Ai-Hua; He, Xin; Zhou, Zhi-Yong; Lian, Shi; Zhu, Wei

    2014-01-01

    Oculocutaneous albinism (OCA) is a congenital genetic disorder characterized by defects in melanin production. OCA type 1 (OCA1) is the most serious and common type of OCA. This study characterized mutations associated with OCA1 in a series of Chinese patients. We recruited 41 unrelated patients with OCA and 100 healthy subjects from the Chinese Han population. Genomic DNA was extracted from their blood samples. Mutational analysis of tyrosinase (TYR) genes was conducted using polymerase chain reaction (PCR) and direct sequencing, specifically to test the 100 control subjects and exclude the possibility of polymorphism. Mutational analysis and bioinformatics study were performed in TYR mutations. Among the 24 (58.5%) patients with OCA1, 21 different TYR mutations were identified, including three previously unidentified alleles (PUAs): one frameshift mutation (c.216delA) and two missense mutations (A241T and N364K). The proband mutation A241T carries three possible mutations in complex OCA. The findings of this study expand current knowledge and data of mutations associated with OCA1 in China and allow us to estimate or explore the mutation spectrum and relative frequencies of the TYR gene in the Chinese population.

  8. Genome-Wide Association Study Reveals Novel Loci for SC7 Resistance in a Soybean Mutant Panel

    Directory of Open Access Journals (Sweden)

    Zhijun Che

    2017-10-01

    Full Text Available Soybean mosaic virus (SMV is a member of Potyvirus genus that causes severe yield loss and destroys seed quality in soybean [Glycine max (L. Merr.]. It is important to explore new resistance sources and discover new resistance loci to SMV, which will provide insights to improve breeding strategies for SMV resistance. Here, a genome-wide association study was conducted to accelerate molecular breeding for the improvement of resistance to SMV in soybean. A population of 165 soybean mutants derived from two soybean parents was used in this study. There were 104 SNPs identified significantly associated with resistance to SC7, some of which were located within previous reported quantitative trait loci. Three putative genes on chromosome 1, 9, and 12 were homologous to WRKY72, eEF1Bβ, and RLP9, which were involved in defense response to insect and disease in Arabidopsis. Moreover, the expression levels of these three genes changed in resistance and susceptible soybean accessions after SMV infection. These three putative genes may involve in the resistance to SC7 and be worthy to further research. Collectively, markers significantly associated with resistance to SC7 will be helpful in molecular marker-assisted selection for breeding resistant soybean accessions to SMV, and the candidate genes identified would advance the functional study of resistance to SMV in soybean.

  9. Genome-Wide Association Study Reveals Novel Loci for SC7 Resistance in a Soybean Mutant Panel

    Science.gov (United States)

    Che, Zhijun; Liu, Hailun; Yi, Fanglei; Cheng, Hao; Yang, Yuming; Wang, Li; Du, Jingyi; Zhang, Peipei; Wang, Jiao; Yu, Deyue

    2017-01-01

    Soybean mosaic virus (SMV) is a member of Potyvirus genus that causes severe yield loss and destroys seed quality in soybean [Glycine max (L.) Merr.]. It is important to explore new resistance sources and discover new resistance loci to SMV, which will provide insights to improve breeding strategies for SMV resistance. Here, a genome-wide association study was conducted to accelerate molecular breeding for the improvement of resistance to SMV in soybean. A population of 165 soybean mutants derived from two soybean parents was used in this study. There were 104 SNPs identified significantly associated with resistance to SC7, some of which were located within previous reported quantitative trait loci. Three putative genes on chromosome 1, 9, and 12 were homologous to WRKY72, eEF1Bβ, and RLP9, which were involved in defense response to insect and disease in Arabidopsis. Moreover, the expression levels of these three genes changed in resistance and susceptible soybean accessions after SMV infection. These three putative genes may involve in the resistance to SC7 and be worthy to further research. Collectively, markers significantly associated with resistance to SC7 will be helpful in molecular marker-assisted selection for breeding resistant soybean accessions to SMV, and the candidate genes identified would advance the functional study of resistance to SMV in soybean. PMID:29075282

  10. Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility

    Directory of Open Access Journals (Sweden)

    Ashok Agarwal

    2016-01-01

    Full Text Available To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2 involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker "fingerprint" to assess sperm quality on the basis of molecular parameters.

  11. Ultra-long–term human salt balance studies reveal interrelations between sodium, potassium, and chloride intake and excretion12

    Science.gov (United States)

    Birukov, Anna; Rakova, Natalia; Lerchl, Kathrin; Engberink, Rik HG Olde; Johannes, Bernd; Wabel, Peter; Moissl, Ulrich; Rauh, Manfred; Luft, Friedrich C; Titze, Jens

    2016-01-01

    Background: The intake of sodium, chloride, and potassium is considered important to healthy nutrition and cardiovascular disease risk. Estimating the intake of these electrolytes is difficult and usually predicated on urine collections, commonly for 24 h, which are considered the gold standard. We reported on data earlier for sodium but not for potassium or chloride. Objective: We were able to test the value of 24-h urine collections in a unique, ultra-long–term balance study conducted during a simulated trip to Mars. Design: Four healthy men were observed while ingesting 12 g salt/d, 9 g salt/d, and 6 g salt/d, while their potassium intake was maintained at 4 g/d for 105 d. Six healthy men were studied while ingesting 12 g salt/d, 9 g salt/d, and 6 g salt/d, with a re-exposure of 12 g/d, while their potassium intake was maintained at 4 g/d for 205 d. Food intake and other constituents were recorded every day for each subject. All urine output was collected daily. Results: Long-term urine recovery rates for all 3 electrolytes were very high. Rather than the expected constant daily excretion related to daily intake, we observed remarkable daily variation in excretion, with a 7-d infradian rhythm at a relatively constant intake. We monitored 24-h aldosterone excretion in these studies and found that aldosterone appeared to be the regulator for all 3 electrolytes. We report Bland–Altman analyses on the value of urine collections to estimate intake. Conclusions: A single 24-h urine collection cannot predict sodium, potassium, or chloride intake; thus, multiple collections are necessary. This information is important when assessing electrolyte intake in individuals. PMID:27225435

  12. Ultra-long-term human salt balance studies reveal interrelations between sodium, potassium, and chloride intake and excretion.

    Science.gov (United States)

    Birukov, Anna; Rakova, Natalia; Lerchl, Kathrin; Engberink, Rik Hg Olde; Johannes, Bernd; Wabel, Peter; Moissl, Ulrich; Rauh, Manfred; Luft, Friedrich C; Titze, Jens

    2016-07-01

    The intake of sodium, chloride, and potassium is considered important to healthy nutrition and cardiovascular disease risk. Estimating the intake of these electrolytes is difficult and usually predicated on urine collections, commonly for 24 h, which are considered the gold standard. We reported on data earlier for sodium but not for potassium or chloride. We were able to test the value of 24-h urine collections in a unique, ultra-long-term balance study conducted during a simulated trip to Mars. Four healthy men were observed while ingesting 12 g salt/d, 9 g salt/d, and 6 g salt/d, while their potassium intake was maintained at 4 g/d for 105 d. Six healthy men were studied while ingesting 12 g salt/d, 9 g salt/d, and 6 g salt/d, with a re-exposure of 12 g/d, while their potassium intake was maintained at 4 g/d for 205 d. Food intake and other constituents were recorded every day for each subject. All urine output was collected daily. Long-term urine recovery rates for all 3 electrolytes were very high. Rather than the expected constant daily excretion related to daily intake, we observed remarkable daily variation in excretion, with a 7-d infradian rhythm at a relatively constant intake. We monitored 24-h aldosterone excretion in these studies and found that aldosterone appeared to be the regulator for all 3 electrolytes. We report Bland-Altman analyses on the value of urine collections to estimate intake. A single 24-h urine collection cannot predict sodium, potassium, or chloride intake; thus, multiple collections are necessary. This information is important when assessing electrolyte intake in individuals. © 2016 American Society for Nutrition.

  13. Carbohydrate catabolic flexibility in the mammalian intestinal commensal Lactobacillus ruminis revealed by fermentation studies aligned to genome annotations

    LENUS (Irish Health Repository)

    2011-08-30

    Abstract Background Lactobacillus ruminis is a poorly characterized member of the Lactobacillus salivarius clade that is part of the intestinal microbiota of pigs, humans and other mammals. Its variable abundance in human and animals may be linked to historical changes over time and geographical differences in dietary intake of complex carbohydrates. Results In this study, we investigated the ability of nine L. ruminis strains of human and bovine origin to utilize fifty carbohydrates including simple sugars, oligosaccharides, and prebiotic polysaccharides. The growth patterns were compared with metabolic pathways predicted by annotation of a high quality draft genome sequence of ATCC 25644 (human isolate) and the complete genome of ATCC 27782 (bovine isolate). All of the strains tested utilized prebiotics including fructooligosaccharides (FOS), soybean-oligosaccharides (SOS) and 1,3:1,4-β-D-gluco-oligosaccharides to varying degrees. Six strains isolated from humans utilized FOS-enriched inulin, as well as FOS. In contrast, three strains isolated from cows grew poorly in FOS-supplemented medium. In general, carbohydrate utilisation patterns were strain-dependent and also varied depending on the degree of polymerisation or complexity of structure. Six putative operons were identified in the genome of the human isolate ATCC 25644 for the transport and utilisation of the prebiotics FOS, galacto-oligosaccharides (GOS), SOS, and 1,3:1,4-β-D-Gluco-oligosaccharides. One of these comprised a novel FOS utilisation operon with predicted capacity to degrade chicory-derived FOS. However, only three of these operons were identified in the ATCC 27782 genome that might account for the utilisation of only SOS and 1,3:1,4-β-D-Gluco-oligosaccharides. Conclusions This study has provided definitive genome-based evidence to support the fermentation patterns of nine strains of Lactobacillus ruminis, and has linked it to gene distribution patterns in strains from different sources

  14. Proteomics reveals changes in hepatic proteins during chicken embryonic development: an alternative model to study human obesity.

    Science.gov (United States)

    Peng, Mengling; Li, Shengnan; He, Qianian; Zhao, Jinlong; Li, Longlong; Ma, Haitian

    2018-01-08

    Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development. In this study, the abundances of 293 hepatic proteins in 19-day old of chicken embryos compared with 14-day old and 160 hepatic proteins at hatching compared with 19-day old embryos were significantly changed. Pathway analysis showed that fatty acid degradation (upregulated ACAA2, CPT1A, and ACOX1), protein folding (upregulated PDIs, CALR3, LMAN1, and UBQLN1) and gluconeogenesis (upregulated ACSS1, AKR1A1, ALDH3A2, ALDH7A1, and FBP2) were enhanced from embryonic day 14 (E14) to E19 of chicken embryo development. Analysis of the differentially abundant proteins indicated that glycolysis was not the main way to produce energy from E19 to hatching day during chicken embryo development. In addition, purine metabolism was enhanced, as deduced from increased IMPDH2, NT5C, PGM2, and XDH abundances, and the decrease of growth rate could be overcome by increasing the abundance of ribosomal proteins from E19 to the hatching day. The levels of certain proteins were coordinated with each other to regulate the changes in metabolic pathways to satisfy the requirement for growth and development at different stages of chicken embryo development. Importantly, ACAA2, CPT1A, and ACOX1 might be key factors to control fat deposition during chicken embryonic development. These results provided information showing that chicken is a useful model to further investigate the mechanism of obesity and insulin resistance in humans.

  15. Proteomic analysis of grape berry cell cultures reveals that developmentally regulated ripening related processes can be studied using cultured cells.

    Directory of Open Access Journals (Sweden)

    Ramaschandra G Sharathchandra

    Full Text Available BACKGROUND: This work describes a proteomics profiling method, optimized and applied to berry cell suspensions to evaluate organ-specific cultures as a platform to study grape berry ripening. Variations in berry ripening within a cluster(s on a vine and in a vineyard are a major impediment towards complete understanding of the functional processes that control ripening, specifically when a characterized and homogenous sample is required. Berry cell suspensions could overcome some of these problems, but their suitability as a model system for berry development and ripening needs to be established first. METHODOLOGY/PRINCIPAL FINDINGS: In this study we report on the proteomic evaluation of the cytosolic proteins obtained from synchronized cell suspension cultures that were established from callus lines originating from green, véraison and ripe Vitis vinifera berry explants. The proteins were separated using liquid phase IEF in a Microrotofor cell and SDS PAGE. This method proved superior to gel-based 2DE. Principal component analysis confirmed that biological and technical repeats grouped tightly and importantly, showed that the proteomes of berry cultures originating from the different growth/ripening stages were distinct. A total of twenty six common bands were selected after band matching between different growth stages and twenty two of these bands were positively identified. Thirty two % of the identified proteins are currently annotated as hypothetical. The differential expression profile of the identified proteins, when compared with published literature on grape berry ripening, suggested common trends in terms of relative abundance in the different developmental stages between real berries and cell suspensions. CONCLUSIONS: The advantages of having suspension cultures that accurately mimic specific developmental stages are profound and could significantly contribute to the study of the intricate regulatory and signaling networks

  16. Morphological studies of the pineal gland in the common gull (Larus canus) reveal uncommon features of pinealocytes.

    Science.gov (United States)

    Przybylska-Gornowicz, Barbara; Lewçzuk, Bogdan; Prusik, Magdalena; Kalicki, Miroslaw; Ziółkowska, Natalia

    2012-04-01

    The avian pineal is a directly photosensory organ taking part in the organization of the circadian and seasonal rhythms. It plays an important role in regulation of many behavior and physiological phenomena including migration. The aim of the study was to investigate morphology of the pineal organ in the common gull (Larus canus). The light and electron microscopic studies were performed on the pineals of juvenile birds living in natural conditions of the Baltic Sea coast, which have been untreatably injured during strong storms in autumn and qualified for euthanasia. The investigated pineals consisted of a wide, triangular, superficially localized distal part and a narrow, elongated proximal part, attached via the choroid plexus to the intercommissural region of the diencephalon. The accessory pineal tissue was localized caudally to the choroid plexus. Based on the histological criteria, the organ was classified as the solid-follicular type. Two types of cells of fotoreceptory line were distinguished: rudimentary-receptor pinealocytes and secretory pinealocytes. Both types of cells were characterized by unusual features, which have been not previously described in avian pinealocytes: the presence of paracrystalline structures in the basal processes and their endings, the storage of glycogen in the form of large accumulations and the arrangement of mitochondria in clusters. Further studies on other species of wild water birds dwelling in condition of cold seas are necessary to explain if the described features of pinealocytes are specific for genus Larus, family Laridae or a larger group of water birds living in similar environmental conditions. Copyright © 2012 Wiley Periodicals, Inc.

  17. Framing effects reveal discrete lexical-semantic and sublexical procedures in reading: an fMRI study.

    Science.gov (United States)

    Danelli, Laura; Marelli, Marco; Berlingeri, Manuela; Tettamanti, Marco; Sberna, Maurizio; Paulesu, Eraldo; Luzzatti, Claudio

    2015-01-01

    According to the dual-route model, a printed string of letters can be processed by either a grapheme-to-phoneme conversion (GPC) route or a lexical-semantic route. Although meta-analyses of the imaging literature support the existence of distinct but interacting reading procedures, individual neuroimaging studies that explored neural correlates of reading yielded inconclusive results. We used a list-manipulation paradigm to provide a fresh empirical look at this issue and to isolate specific areas that underlie the two reading procedures. In a lexical condition, we embedded disyllabic Italian words (target stimuli) in lists of either loanwords or trisyllabic Italian words with unpredictable stress position. In a GPC condition, similar target stimuli were included within lists of pseudowords. The procedure was designed to induce participants to emphasize either the lexical-semantic or the GPC reading procedure, while controlling for possible linguistic confounds and keeping the reading task requirements stable across the two conditions. Thirty-three adults participated in the behavioral study, and 20 further adult participants were included in the fMRI study. At the behavioral level, we found sizeable effects of the framing manipulations that included slower voice onset times for stimuli in the pseudoword frames. At the functional anatomical level, the occipital and temporal regions, and the intraparietal sulcus were specifically activated when subjects were reading target words in a lexical frame. The inferior parietal and anterior fusiform cortex were specifically activated in the GPC condition. These patterns of activation represented a valid classifying model of fMRI images associated with target reading in both frames in the multi-voxel pattern analyses. Further activations were shared by the two procedures in the occipital and inferior parietal areas, in the premotor cortex, in the frontal regions and the left supplementary motor area. These regions are most

  18. A systematic review of the literature reveals trends and gaps in integrated pest management studies conducted in the United States.

    Science.gov (United States)

    Young, Stephen L

    2017-08-01

    Integrated pest management (IPM) is a broad-based approach for addressing pests that negatively affect human and environmental health and economic profitability. Weeds, insects and disease-causing pathogens (diseases) are the pests most often associated with IPM. A systematic review, widely used in other scientific disciplines, was employed to determine the most commonly studied IPM topics and summarize the reasons for these trends and the gaps. In a field synopsis of the literature, 1679 relevant published papers were identified and categorized into one of the following five broad areas: IPM and organic (organic), climate change and pests (climate), rural and urban IPM (rural and urban), next-generation education (education) and advanced production systems (technology). Papers were examined in greater detail for at least one of the three main pests in a systematic review. A majority (85%) of IPM papers have been in the area of rural and urban IPM, primarily addressing agriculture (78%). Professionals, landowners and the general public were the focus of a majority (95%) of IPM papers on education. Technology is an increasing area of focus in the literature. Over the past 40 years, IPM papers have primarily (75%) addressed insects and been limited mostly to rural and urban settings. Climate change, technology and education specific to pest management studies are increasingly being published and will help broaden the focus that could result in increased adoption and development of IPM. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  19. Structural, mutational and biophysical studies reveal a canonical mode of molecular recognition between immune receptor TIGIT and nectin-2

    Energy Technology Data Exchange (ETDEWEB)

    Samanta, Dibyendu; Guo, Haisu; Rubinstein, Rotem; Ramagopal, Udupi A.; Almo, Steven C.

    2017-01-01

    In addition to antigen-specific stimulation of T cell receptor (TCR) by a peptide-MHC complex, the functional outcome of TCR engagement is regulated by antigen-independent costimulatory signals. Costimulatory signals are provided by an array of interactions involving activating and inhibitory receptors expressed on T cells and their cognate ligands on antigen presenting cells. T cell immunoglobulin and ITIM domain (TIGIT), a recently identified immune receptor expressed on T and NK cells, upon interaction with either of its two ligands, nectin-2 or poliovirus receptor (PVR), inhibits activation of T and NK cells. Here we report the crystal structure of the human TIGIT ectodomain, which exhibits the classic two-layer β-sandwich topology observed in other immunoglobulin super family (IgSF) members. Biophysical studies indicate that TIGIT is monomeric in solution but can form a dimer at high concentrations, consistent with the observation of a canonical immunoglobulin-like dimer interface in the crystalline state. Based on existing structural data, we present a model of the TIGIT:nectin-2 complex and utilized complementary biochemical studies to map the nectin-binding interface on TIGIT. Our data provide important structural and biochemical determinants responsible for the recognition of nectin-2 by TIGIT. Defining the TIGIT:nectin-2 binding interface provides the basis for rational manipulation of this molecular interaction for the development of immunotherapeutic reagents in autoimmunity and cancer.

  20. Study of the magnetization behavior of ferromagnetic nanowire array: Existence of growth defects revealed by micromagnetic simulations

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen Vien, G., E-mail: gilles.nguyen@univ-brest.fr [Laboratoire de Magnétisme de Bretagne, EA 4522, Université de Bretagne Occidentale, CS 93837, 29238 Brest-Cedex 3 (France); Rioual, S. [Laboratoire de Magnétisme de Bretagne, EA 4522, Université de Bretagne Occidentale, CS 93837, 29238 Brest-Cedex 3 (France); Gloaguen, F. [Chimie, Electrochimie Moléculaires et Chimie Analytique, UMR CNRS 6521, Université de Bretagne Occidentale, CS 93837, 29238 Brest-Cedex 3 (France); Rouvellou, B.; Lescop, B. [Laboratoire de Magnétisme de Bretagne, EA 4522, Université de Bretagne Occidentale, CS 93837, 29238 Brest-Cedex 3 (France)

    2016-03-01

    High aspect ratio nanowires were electrodeposited in nanoporous anodic alumina template by a potentiostatic method. The angular dependence of the coercive field and remanence magnetization extracted from magnetometry measurements are compared with micromagnetic simulations. Inclusion of magnetostatic interactions between Ni nanowires in simulations is required to explain some of the properties of the magnetization reversal. However, it is not sufficient to reproduce fully the angular dependence of the coercive field. Due to the polycrystalline nature of nanowires and thus to the presence of grain boundaries, defects are included in simulations. A good agreement between theory and experiment is then clearly highlighted, in particular in the nanowire easy axis direction. The achieved results allow a description of several experimental data published in the literature and consequently to get a better understanding of reversal mechanisms that operate in such nanowire arrays. A complementary study of composite nanowire array is successfully performed to prove the adequacy of the simulations method to describe the magnetic properties of nanowire array. - Highlights: • High axial squareness nanowire array are synthetized by a potentiostatic method. • Nanowires are modeled as non-ideal magnetic particles. • Segmentation of nanowire is required to describe the angular dependence of coercivity. • Respective role of magnetostatic coupling and nanowire segmentation in nanowire array are studied. • Micromagnetic simulations lead to quantitative agreement for well-defined composite nanowire array.

  1. Population and pedigree studies reveal a lack of association between the dopamine D sub 2 receptor gene and alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Bolos, A.M.; Goldman, D.; Brown, G.L. (National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (USA)); Lucas-Derse, S.; Ramsburg, M. (Program Resources Inc., Frederick, MD (USA))

    1990-12-26

    Using the dopamine D{sub 2} receptor clone {lambda}hD2G1, Blum et al recently found that the D{sub 2}/Taq 1 allele (A1) was present in 69{percent} of 35 deceased alcoholics but in only 20{percent} of an equal number of controls. To assess this association further, the authors evaluated the D{sub 2}/Taq 1 polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3{prime} noncoding region of the D{sub 2} receptor gene. They studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D{sub 2}/Taq 1 or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP polymorphism provided independent information against linkage at the D{sub 2} receptor locus. This study does not support a widespread or consistent association between the D{sub 2} receptor gene and alcoholism.

  2. A comprehensive study design reveals treatment- and transcript abundance–dependent concordance between RNA-seq and microarray data

    Science.gov (United States)

    Wang, Charles; Gong, Binsheng; Bushel, Pierre R.; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Xu, Joshua; Fang, Hong; Hong, Huixiao; Shen, Jie; Su, Zhenqiang; Meehan, Joe; Li, Xiaojin; Yang, Lu; Li, Haiqing; Łabaj, Paweł P.; Kreil, David P.; Megherbi, Dalila; Florian, Caiment; Gaj, Stan; van Delft, Joost; Kleinjans, Jos; Scherer, Andreas; Viswanath, Devanarayan; Wang, Jian; Yang, Yong; Qian, Hui-Rong; Lancashire, Lee J.; Bessarabova, Marina; Nikolsky, Yuri; Furlanello, Cesare; Chierici, Marco; Albanese, Davide; Jurman, Giuseppe; Riccadonna, Samantha; Filosi, Michele; Visintainer, Roberto; Zhang, Ke K.; Li, Jianying; Hsieh, Jui-Hua; Svoboda, Daniel L.; Fuscoe, James C.; Deng, Youping; Shi, Leming; Paules, Richard S.; Auerbach, Scott S.; Tong, Weida

    2014-01-01

    RNA-seq facilitates unbiased genome-wide gene-expression profiling. However, its concordance with the well-established microarray platform must be rigorously assessed for confident uses in clinical and regulatory application. Here we use a comprehensive study design to generate Illumina RNA-seq and Affymetrix microarray data from the same set of liver samples of rats under varying degrees of perturbation by 27 chemicals representing multiple modes of action (MOA). The cross-platform concordance in terms of differentially expressed genes (DEGs) or enriched pathways is highly correlated with treatment effect size, gene-expression abundance and the biological complexity of the MOA. RNA-seq outperforms microarray (90% versus 76%) in DEG verification by quantitative PCR and the main gain is its improved accuracy for low expressed genes. Nonetheless, predictive classifiers derived from both platforms performed similarly. Therefore, the endpoint studied and its biological complexity, transcript abundance, and intended application are important factors in transcriptomic research and for decision-making. PMID:25150839

  3. Age Effects in L2 Grammar Processing as Revealed by ERPs and How (Not) to Study Them.

    Science.gov (United States)

    Meulman, Nienke; Wieling, Martijn; Sprenger, Simone A; Stowe, Laurie A; Schmid, Monika S

    2015-01-01

    In this study we investigate the effect of age of acquisition (AoA) on grammatical processing in second language learners as measured by event-related brain potentials (ERPs). We compare a traditional analysis involving the calculation of averages across a certain time window of the ERP waveform, analyzed with categorical groups (early vs. late), with a generalized additive modeling analysis, which allows us to take into account the full range of variability in both AoA and time. Sixty-six Slavic advanced learners of German listened to German sentences with correct and incorrect use of non-finite verbs and grammatical gender agreement. We show that the ERP signal depends on the AoA of the learner, as well as on the regularity of the structure under investigation. For gender agreement, a gradual change in processing strategies can be shown that varies by AoA, with younger learners showing a P600 and older learners showing a posterior negativity. For verb agreement, all learners show a P600 effect, irrespective of AoA. Based on their behavioral responses in an offline grammaticality judgment task, we argue that the late learners resort to computationally less efficient processing strategies when confronted with (lexically determined) syntactic constructions different from the L1. In addition, this study highlights the insights the explicit focus on the time course of the ERP signal in our analysis framework can offer compared to the traditional analysis.

  4. The Epidemiological Study of Coxsackievirus A6 revealing Hand, Foot and Mouth Disease Epidemic patterns in Guangdong, China.

    Science.gov (United States)

    Zeng, Hanri; Lu, Jing; Zheng, Huanying; Yi, Lina; Guo, Xue; Liu, Leng; Rutherford, Shannon; Sun, Limei; Tan, Xiaohua; Li, Hui; Ke, Changwen; Lin, Jinyan

    2015-05-21

    Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two major causative pathogens in hand, foot and mouth disease (HFMD) epidemics. However, CVA6, previously largely ignored, became the predominant pathogen in China in 2013. In this study, we describe the epidemiological trends of CVA6 during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study results show that CVA6 has been one of three major causative agents of HFMD epidemics since 2009. The periodic rotation and dominance of the three pathogens, EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major circulating CVA6 strains collected from 2009 to 2013 are distinct from the earlier strains collected before 2009. In conclusion, the discovery from this research investigating epidemiological trends of CVA6 from 2008 to 2013 explains the possible pattern of the continuous HFMD epidemic in China. The etiological change pattern also highlights the need for improvement for pathogen surveillance and vaccine strategies for HFMD control in China.

  5. Transcriptomics and proteomic studies reveal acaricidal mechanism of octadecanoic acid-3, 4 - tetrahydrofuran diester against Sarcoptes scabiei var. cuniculi.

    Science.gov (United States)

    Song, Xu; Chen, Zhenzhen; Jia, Renyong; Cao, Mei; Zou, Yuanfeng; Li, Lixia; Liang, Xiaoxia; Yin, Lizi; He, Changliang; Yue, Guizhou; Yin, Zhongqiong

    2017-03-31

    In our previous study, a new compound, octadecanoic acid-3, 4-tetrahydrofuran diester, possessing potent acaricidal activity was obtained from neem oil. This study performed RNA-seq transcriptomics and iTRAQ proteomics to uncover the acaricidal mechanism of the compound against Sarcoptes scabiei var. cuniculi. The results of transcriptomics indicated that after treatment with octadecanoic acid-3, 4-tetrahydrofuran diester, genes related to "Energy metabolism" were significantly up-/down-regulated, including citrate cycle, oxidative phosphorylation pathway and fatty acid metabolism. Proteomics analysis showed accordant changes of proteins related to oxidative phosphorylation pathway. The target proteins of the compound were NADH dehydrogenase, Ubiquinol-cytochrome c reductase, Cytochrome c oxidase, ATP synthase, enolase and superoxide dismutase. In transcriptomics-proteomics correlation analysis, the concordance rate between protein abundances and their corresponding mRNAs was 57%, while others (43%) were discordant changes, suggesting divergent regulating effects of octadecanoic acid-3, 4-tetrahydrofuran diester. These results suggested that the acaricidal mechanism of octadecanoic acid-3, 4-tetrahydrofuran diester attributed to interference with energy metabolism, especially oxidative phosphorylation pathway.

  6. pARIS-htt: an optimised expression platform to study huntingtin reveals functional domains required for vesicular trafficking.

    Science.gov (United States)

    Pardo, Raúl; Molina-Calavita, Maria; Poizat, Ghislaine; Keryer, Guy; Humbert, Sandrine; Saudou, Frédéric

    2010-06-01

    Huntingtin (htt) is a multi-domain protein of 350 kDa that is mutated in Huntington's disease (HD) but whose function is yet to be fully understood. This absence of information is due in part to the difficulty of manipulating large DNA fragments by using conventional molecular cloning techniques. Consequently, few studies have addressed the cellular function(s) of full-length htt and its dysfunction(s) associated with the disease. We describe a flexible synthetic vector encoding full-length htt called pARIS-htt (Adaptable, RNAi Insensitive &Synthetic). It includes synthetic cDNA coding for full-length human htt modified so that: 1) it is improved for codon usage, 2) it is insensitive to four different siRNAs allowing gene replacement studies, 3) it contains unique restriction sites (URSs) dispersed throughout the entire sequence without modifying the translated amino acid sequence, 4) it contains multiple cloning sites at the N and C-ter ends and 5) it is Gateway compatible. These modifications facilitate mutagenesis, tagging and cloning into diverse expression plasmids. Htt regulates dynein/dynactin-dependent trafficking of vesicles, such as brain-derived neurotrophic factor (BDNF)-containing vesicles, and of organelles, including reforming and maintenance of the Golgi near the cell centre. We used tests of these trafficking functions to validate various pARIS-htt constructs. We demonstrated, after silencing of endogenous htt, that full-length htt expressed from pARIS-htt rescues Golgi apparatus reformation following reversible microtubule disruption. A mutant form of htt that contains a 100Q expansion and a htt form devoid of either HAP1 or dynein interaction domains are both unable to rescue loss of endogenous htt. These mutants have also an impaired capacity to promote BDNF vesicular trafficking in neuronal cells. We report the validation of a synthetic gene encoding full-length htt protein that will facilitate analyses of its structure/function. This may help

  7. RNA-seq reveals more consistent reference genes for gene expression studies in human non-melanoma skin cancers

    Directory of Open Access Journals (Sweden)

    Van L.T. Hoang

    2017-08-01

    Full Text Available Identification of appropriate reference genes (RGs is critical to accurate data interpretation in quantitative real-time PCR (qPCR experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes that are consistently expressed across all samples. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as qPCR RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.

  8. Revealing the potency of Annona muricata leaves extract as FOXO1 inhibitor for diabetes mellitus treatment through computational study.

    Science.gov (United States)

    Damayanti, Dini Sri; Utomo, Didik Huswo; Kusuma, Chandra

    2016-12-01

    FOXO1 protein inactivation in the nucleus is one of targets for the treatment of diabetes mellitus. Annona muricata leaves contain flavonoid and phenolic compound alkaloids that were known to be able to increase pancreatic β cell proliferation in animal experiment. This research aimed to predict the active compound ability of the Annona muricata leaves to bind and inhibit FOXO1 protein through in silico study. Analysis of molecular docking was performed by using Autodock Vina PyRx. this research proved that anonaine, rutin, muricatocin a, isolaureline, xylopine, and kaempferol 3-O-rutinoside had an equal or smaller free binding energy compared to the control compound. Rutin and Muricatocin A had the same binding ability toward 66% amino acid residues, compared to control compound with hydrogen bond type, while xylopine, anonaine, isolaureline, kaempferol 3-O-rutinoside had a similar binding ability towards 33% amino acid residues compared to control compound with hydrogen bond type.

  9. Analysis of Latino populations from GALA and MEC studies reveals genomic loci with biased local ancestry estimation

    Science.gov (United States)

    Pasaniuc, Bogdan; Sankararaman, Sriram; Torgerson, Dara G.; Gignoux, Christopher; Zaitlen, Noah; Eng, Celeste; Rodriguez-Cintron, William; Chapela, Rocio; Ford, Jean G.; Avila, Pedro C.; Rodriguez-Santana, Jose; Chen, Gary K.; Le Marchand, Loic; Henderson, Brian; Reich, David; Haiman, Christopher A.; Gonzàlez Burchard, Esteban; Halperin, Eran

    2013-01-01

    Motivation: Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging. Results: Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels. Availability and implementation: We provide the reconstructed reference panels together with the maps of MILANC rates as a public resource for researchers analyzing local ancestry in Latinos at http://bogdanlab.pathology.ucla.edu. Contact: bpasaniuc@mednet.ucla.edu Supplementary information: Supplementary data are

  10. A microdiversity study of anammox bacteria reveals a novel Candidatus Scalindua phylotype in marine oxygen minimum zones.

    Science.gov (United States)

    Woebken, Dagmar; Lam, Phyllis; Kuypers, Marcel M M; Naqvi, S Wajih A; Kartal, Boran; Strous, Marc; Jetten, Mike S M; Fuchs, Bernhard M; Amann, Rudolf

    2008-11-01

    The anaerobic oxidation of ammonium (anammox) contributes significantly to the global loss of fixed nitrogen and is carried out by a deep branching monophyletic group of bacteria within the phylum Planctomycetes. Various studies have implicated anammox to be the most important process responsible for the nitrogen loss in the marine oxygen minimum zones (OMZs) with a low diversity of marine anammox bacteria. This comprehensive study investigated the anammox bacteria in the suboxic zone of the Black Sea and in three major OMZs (off Namibia, Peru and in the Arabian Sea). The diversity and population composition of anammox bacteria were investigated by both, the 16S rRNA gene sequences and the 16S-23S rRNA internal transcribed spacer (ITS). Our results showed that the anammox bacterial sequences of the investigated samples were all closely related to the Candidatus Scalindua genus. However, a greater microdiversity of marine anammox bacteria than previously assumed was observed. Both phylogenetic markers supported the classification of all sequences in two distinct anammox bacterial phylotypes: Candidatus Scalindua clades 1 and 2. Scalindua 1 could be further divided into four distinct clusters, all comprised of sequences from either the Namibian or the Peruvian OMZ. Scalindua 2 consisted of sequences from the Arabian Sea and the Peruvian OMZ and included one previously published 16S rRNA gene sequence from Lake Tanganyika and one from South China Sea sediment (97.9-99.4% sequence identity). This cluster showed only anammox bacteria of Scalindua clade 2 represent a novel anammox bacterial species, for which the name Candidatus Scalindua arabica is proposed. As sequences of this new cluster were found in the Arabian Sea, the Peruvian OMZ, in Lake Tanganyika and in South China sediment, we assume a global distribution of Candidatus Scalindua arabica as it is observed for Candidatus Scalindua sorokinii/brodae (or Scalindua clade 1).

  11. First plastid phylogenomic study reveals potential cyto-nuclear discordance in the evolutionary history of Ficus L. (Moraceae).

    Science.gov (United States)

    Bruun-Lund, Sam; Clement, Wendy L; Kjellberg, Finn; Rønsted, Nina

    2017-04-01

    Standard Sanger chloroplast markers provide limited information to resolve species level relationships within plants, in particular within large genera. Figs (Ficus L., Moraceae) compose one of the 50 largest genera of angiosperms with ∼750 species occurring in the tropics and subtropics worldwide. Figs, in addition to being a keystone food resource in rainforests, are well-known for the mutualistic interactions with their pollinating wasps. It is regarded as a model system for understanding co-evolution dating back more than 75million years. However, despite significant taxon sampling, combinations of low copy nuclear, nuclear ribosomal and chloroplast regions have not been able to confidently resolve relationships among major groups of figs. Using a high throughput sequencing approach we attempted to resolve the major lineages of Ficus based on plastome data. In this study, we show that the use of a de novo assembled plastome from within the genus provides less ambiguity and higher coverage across the 59 Ficus and 6 outgroup plastome assemblies compared to using the nearest available reference plastome outside the genus resulting in improved resolution and higher support of the phylogenetic relationships within Ficus inferred from plastome data. Chloroplast genome data confidently resolved relationships among major groups of figs and largely support current understanding based on nuclear sequence data including passively pollinated Neotropical section Pharmacosycea as sister lineage to all other Ficus. However, conflicts between the new plastome topology and previous nuclear studies are observed for both individual species as well as relationships among some sections at deeper levels. Conflicts could be caused by lack of resolution in the nuclear data or may indicate potential cyto-nuclear discordance as previously observed in an African lineage of Ficus. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Observational cross-sectional study revealing less aggressive treatment in Japanese elderly than nonelderly patients with rheumatoid arthritis.

    Science.gov (United States)

    Ogasawara, Michihiro; Tamura, Naoto; Onuma, Shin; Kusaoi, Makio; Sekiya, Fumio; Matsudaira, Ran; Kempe, Kazuo; Yamaji, Ken; Takasaki, Yoshinari

    2010-12-01

    Elderly patients with rheumatoid arthritis (RA) have more aging-related complications than nonelderly patients with RA. The objective of the study was to investigate the treatment status of elderly patients with RA. Between January and March 2008, 969 patients with RA were enrolled in this observational cross-sectional study. Prescription of disease-modifying antirheumatic drugs (DMARDs) and corticosteroids and laboratory data related to RA, including matrix metalloproteinase 3, rheumatoid factor, and anti-cyclic citrullinated peptide antibody levels, were compared between the elderly and the nonelderly patients. Fewer DMARDs were prescribed to the elderly patients (1.40 [SD, 0.57] vs. 1.51 [SD, 0.61]; P = 0.029). Furthermore, a lower percentage of patients received methotrexate (MTX) (47.2% vs. 56.9%; P = 0.0001), a lower average dosage of MTX was administered (5.46 [SD, 1.66] mg/wk vs. 5.96 [SD, 1.77] mg/wk; P = 0.0001), and fewer biologic DMARDs were used (1.46% vs. 5.59% for infliximab, P = 0.0008; 0.58% vs. 3.19% for etanercept, P = 0.0038) in the elderly group. The laboratory data suggested that the disease status was uncontrolled to a greater extent, and complications were more common in the elderly group. Elderly patients with RA receive less aggressive treatment than nonelderly patients with RA, despite laboratory evidence for poorly controlled disease status among the elderly. The use of a less aggressive regimen could be attributed to the higher prevalence of complications and problems. Therefore, the elderly with RA should be considered a different patient population from the viewpoint of treatment and be administered specialized medical care.

  13. A Voxel-Based Morphometry Study Reveals Local Brain Structural Alterations associated With Ambient Fine Particles in older women

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    Ramon Casanova

    2016-10-01

    Full Text Available Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters <2.5µm has been linked with cognitive deficits in older adults. Using fine-grained voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure.Methods: Brain MRI data were obtained from 1,365 women (aged 71-89 in the Women’s Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space. Based on geocoded residential locations and air monitoring data from the U.S. Environmental Protection Agency, we employed a spatiotemporal model to estimate long-term (3-year average exposure to ambient PM2.5 preceding MRI scans. Voxel-wise linear regression models were fit separately to gray matter (GM and white matter (WM maps to analyze associations between brain structure and PM2.5 exposure, with adjustment for potential confounders. Results: Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. No statistically significant associations were observed between PM2.5 exposure and hippocampal volumes. Conclusions: Long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. While our previous work linked WM decreased volumes to PM2.5 air pollution, this is the first neuroimaging study reporting associations between air pollution exposure and smaller volumes of cortical GM. Our data support the hypothesized synaptic neurotoxicity of airborne particles.

  14. Ultrasonic P- and S-Wave Attenuation and Petrophysical Properties of Deccan Flood Basalts, India, as Revealed by Borehole Studies

    Science.gov (United States)

    Vedanti, Nimisha; Malkoti, Ajay; Pandey, O. P.; Shrivastava, J. P.

    2018-03-01

    Petrophysical properties and ultrasonic P- and S-wave attenuation measurements on 35 Deccan basalt core specimens, recovered from Killari borehole site in western India, provide unique reference data-sets for a lesser studied Deccan Volcanic Province. These samples represent 338-m-thick basaltic column, consisting four lava flows each of Ambenali and Poladpur Formations, belonging to Wai Subgroup of the Deccan volcanic sequence. These basalt samples are found to be iron-rich (average FeOT: 13.4 wt%), but relatively poor in silica content (average SiO2: 47.8 wt%). The saturated massive basalt cores are characterized by a mean density of 2.91 g/cm3 (range 2.80-3.01 g/cm3) and mean P- and S-wave velocities of 5.89 km/s (range 5.01-6.50 km/s) and 3.43 km/s (range 2.84-3.69 km/s), respectively. In comparison, saturated vesicular basalt cores show a wide range in density (2.40-2.79 g/cm3) as well as P-wave (3.28-4.78 km/s) and S-wave (1.70-2.95 km/s) velocities. Based on the present study, the Deccan volcanic sequence can be assigned a weighted mean density of 2.74 g/cm3 and a low V p and V s of 5.00 and 3.00 km/s, respectively. Such low velocities in Deccan basalts can be attributed mainly to the presence of fine-grained glassy material, high iron contents, and hydrothermally altered secondary mineral products, besides higher porosity in vesicular samples. The measured Q values in saturated massive basalt cores vary enormously (Q p: 33-1960 and Q s: 35-506), while saturated vesicular basalt samples exhibit somewhat lesser variation in Q p (6-46) as well as Q s (5-49). In general, high-porosity rocks exhibit high attenuation, but we observed the high value of attenuation in some of the massive basalt core samples also. In such cases, energy loss is mainly due to the presence of fine-grained glassy material as well as secondary alteration products like chlorophaeite, that could contribute to intrinsic attenuation. Dominance of weekly bound secondary minerals might also be

  15. Detailed seamount-scale studies of ferromanganese crusts reveal new insights into their formation and resource assessment.

    Science.gov (United States)

    Murton, B. J.; Lusty, P.; Yeo, I. A.; Howarth, S.

    2017-12-01

    The seafloor hosts abundant mineral deposits critical for low-carbon economies and emerging technologies. These include ferromanganese crusts (FeMnC) that grow on seamounts. While the broad distribution of FeMnC is known, local controls on growth, composition and formation are not. Here, we describe a detailed study of a gyot in the NE Atlantic (Tropic Seamount) that explores the controls, from the surface to the seafloor, exerted on FeMnC growth from current energy, surface productivity, sediment distribution, seafloor morphology, substrate lithology, sediments mobility and thickness, and seamount subsidence. During cruise JC142 (2016), we mapped the seamount with EM120 multibeam, mapped the 400km2 summit with AUV multibeam, sidescan sonar, sub-bottom profiler and 361,644 photographs. During 28 ROV dives we drilled 58 core and collected 344 individual rock samples. We found FeMnC at all depths, with the thickest (<20cm) located at the greatest depths (3000-4000m). The thinnest are on the summit plateau, with the centre and southern edge having the thickest sediment. FeMnC pavements form many different terraces on the summit. Frequent undercuts expose a calcareous substrate. Elsewhere, cobbles and pebbles form the nucleolus for crusts up to 10cm thick, with growth into the sediment. Many substrates are found to comprise semi-consolidated sediment. The presence of thick crusts at the base of the seamount contradicts accepted understanding of FeMnC deposition just below the oxygen minimum zone (OMZ). In areas on the eastern and western spurs, between 2500m and 1000m, where current energy is greatest, sessile fauna are most abundant. Dense coral debris at these locations appears to inhibit crust formation and coral and sponge `gardens' are frequent on near vertical cliffs. The observation that crusts have grown downwards into and over soft sediment is enigmatic since present understanding requires hard substrates to be exposed to seawater for crusts to grow, and any

  16. Classification and regression tree and spatial analyses reveal geographic heterogeneity in genome wide linkage study of Indian visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Michaela Fakiola

    2010-12-01

    Full Text Available Genome wide linkage studies (GWLS have provided evidence for loci controlling visceral leishmaniasis on Chromosomes 1p22, 6q27, 22q12 in Sudan and 6q27, 9p21, 17q11-q21 in Brazil. Genome wide studies from the major focus of disease in India have not previously been reported.We undertook a GWLS in India in which a primary ∼10 cM (515 microsatellites scan was carried out in 58 multicase pedigrees (74 nuclear families; 176 affected, 353 total individuals and replication sought in 79 pedigrees (102 nuclear families; 218 affected, 473 total individuals. The primary scan provided evidence (≥2 adjacent markers allele-sharing LOD≥0.59; nominal P≤0.05 for linkage on Chromosomes 2, 5, 6, 7, 8, 10, 11, 20 and X, with peaks at 6p25.3-p24.3 and 8p23.1-p21.3 contributed to largely by 31 Hindu families and at Xq21.1-q26.1 by 27 Muslim families. Refined mapping confirmed linkage across all primary scan families at 2q12.2-q14.1 and 11q13.2-q23.3, but only 11q13.2-q23.3 replicated (combined LOD = 1.59; P = 0.0034. Linkage at 6p25.3-p24.3 and 8p23.1-p21.3, and at Xq21.1-q26.1, was confirmed by refined mapping for primary Hindu and Muslim families, respectively, but only Xq21.1-q26.1 replicated across all Muslim families (combined LOD 1.49; P = 0.0045. STRUCTURE and SMARTPCA did not identify population genetic substructure related to religious group. Classification and regression tree, and spatial interpolation, analyses confirm geographical heterogeneity for linkages at 6p25.3-p24.3, 8p23.1-p21.3 and Xq21.1-q26.1, with specific clusters of families contributing LOD scores of 2.13 (P = 0.0009, 1.75 (P = 0.002 and 1.84 (P = 0.001, respectively.GWLS has identified novel loci that show geographical heterogeneity in their influence on susceptibility to VL in India.

  17. Influences of climate change on California and Nevada regions revealed by a high-resolution dynamical downscaling study

    Science.gov (United States)

    Pan, Lin-Lin; Chen, Shu-Hua; Cayan, Dan; Lin, Mei-Ying; Hart, Quinn; Zhang, Ming-Hua; Liu, Yubao; Wang, Jianzhong

    2011-11-01

    In this study, the influence of climate change to California and Nevada regions was investigated through high-resolution (4-km grid spacing) dynamical downscaling using the WRF (Weather Research & Forecasting) model. The dynamical downscaling was performed to both the GFS (Global forecast model) reanalysis (called GFS-WRF runs) from 2000-2006 and PCM (Parallel Climate Model) simulations (called PCM-WRF runs) from 1997-2006 and 2047-2056. The downscaling results were first validated by comparing current model outputs with the observational analysis PRISM (Parameter-elevation Regressions on Independent Slopes Model) dataset. In general, the dominant features from GFS-WRF runs and PCM-WRF runs were consistent with each other, as well as with PRISM results. The influences of climate change on the California and Nevada regions can be inferred from the model future runs. The averaged temperature showed a positive trend in the future, as in other studies. The temperature increases by around 1-2°C under the assumption of business as usual over 50 years. This leads to an upward shifting of the freezing level (the contour line of 0°C temperature) and more rain instead of snow in winter (December, January, and February). More hot days (>32.2°C or 90°F) and extreme hot days (>37.8°C or 100°F) are predicted in the Sacramento Valley and the southern parts of California and Nevada during summer (June, July, and August). More precipitation is predicted in northern California but not in southern California. Rainfall frequency slightly increases in the coast regions, but not in the inland area. No obvious trend of the surface wind was indicated. The probability distribution functions (PDF) of daily temperature, wind and precipitation for California and Nevada showed no significant change in shape in either winter or summer. The spatial distributions of precipitation frequency from GFS-WRF and PCM-WRF were highly correlated (r = 0.83). However, overall positive shifts were seen

  18. In vivo magnetic resonance studies reveal neuroanatomical and neurochemical abnormalities in the serine racemase knockout mouse model of schizophrenia.

    Science.gov (United States)

    Puhl, Matthew D; Mintzopoulos, Dionyssios; Jensen, J Eric; Gillis, Timothy E; Konopaske, Glenn T; Kaufman, Marc J; Coyle, Joseph T

    2015-01-01

    Decreased availability of the N-methyl-D-aspartate receptor (NMDAR) co-agonist D-serine is thought to promote NMDAR hypofunction and contribute to the pathophysiology of schizophrenia, including neuroanatomical abnormalities, such as cortical atrophy and ventricular enlargement, and neurochemical abnormalities, such as aberrant glutamate and γ-aminobutyric acid (GABA) signaling. It is thought that these abnormalities directly relate to the negative symptoms and cognitive impairments that are hallmarks of the disorder. Because of the genetic complexity of schizophrenia, animal models of the disorder are extremely valuable for the study of genetically predisposing factors. Our laboratory developed a transgenic mouse model lacking serine racemase (SR), the synthetic enzyme of d-serine, polymorphisms of which are associated with schizophrenia. Null mutants (SR-/-) exhibit NMDAR hypofunction and cognitive impairments. We used 9.4 T magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to compare in vivo brain structure and neurochemistry in wildtype (WT) and SR-/- mice. Mice were anesthetized with isoflurane for MRI and MRS scans. Compared to WT controls, SR-/- mice exhibited 23% larger ventricular volumes (pcomparable to those previously reported in humans with schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Extracts of North Sea macroalgae reveal specific activity patterns against attachment and proliferation of benthic diatoms: a laboratory study.

    Science.gov (United States)

    Lam, C; Grage, A; Schulz, D; Schulte, A; Harder, T

    2008-01-01

    A variety of macroalgae (Ceramium rubrum, Corallina officinalis, Palmaria palmata, Mastocarpus stellatus, Fucus vesiculosus, Cladophora rupestris, Ulva sp.) were investigated by scanning electron microscopy to visualize epiphytic colonizers. The macroalgae differed in terms of their epiphytic coverage of bacteria, fungi and diatoms. Macroalgae, largely devoid of epiphytic diatoms, were hypothesized to employ effective antifouling means to reduce epiphytic coverage, whilst heavily fouled macroalgae were proposed to lack antifouling strategies. To test these hypotheses from an allelochemical perspective with regard to fouling diatoms, dichloromethane-methanol (1:1) crude extracts of macroalgae were concentrated in dimethylsulfoxide and investigated in diatom attachment and proliferation assays using four benthic diatoms (Nitzschia sp., Navicula phyllepta, Navicula arenaria and Amphora sp.). Algal extracts exhibited a distinct pattern of activity against the test diatoms, suggesting a targeted and selective effect of macroalgal metabolites on individual fouling diatoms. The main outcome of this study was that visual inspection and quantitative categorization of epiphytic colonizers on macroalgal thalli could not be used to predict reliably whether macroalgae employed a chemical defense mechanism.

  20. Different speciation for bromine in brown and red algae, revealed by in vivo X-ray absorption spectroscopic studies.

    Science.gov (United States)

    Küpper, Frithjof C; Leblanc, Catherine; Meyer-Klaucke, Wolfram; Potin, Philippe; Feiters, Martin C

    2014-08-01

    Members of various algal lineages are known to be strong producers of atmospherically relevant halogen emissions, that is a consequence of their capability to store and metabolize halogens. This study uses a noninvasive, synchrotron-based technique, X-ray absorption spectroscopy, for addressing in vivo bromine speciation in the brown algae Ectocarpus siliculosus, Ascophyllum nodosum, and Fucus serratus, the red algae Gracilaria dura, G. gracilis, Chondrus crispus, Osmundea pinnatifida, Asparagopsis armata, Polysiphonia elongata, and Corallina officinalis, the diatom Thalassiosira rotula, the dinoflagellate Lingulodinium polyedrum and a natural phytoplankton sample. The results highlight a diversity of fundamentally different bromine storage modes: while most of the stramenopile representatives and the dinoflagellate store mostly bromide, there is evidence for Br incorporated in nonaromatic hydrocarbons in Thalassiosira. Red algae operate various organic bromine stores - including a possible precursor (by the haloform reaction) for bromoform in Asparagopsis and aromatically bound Br in Polysiphonia and Corallina. Large fractions of the bromine in the red algae G. dura and C. crispus and the brown alga F. serratus are present as Br(-) defects in solid KCl, similar to what was reported earlier for Laminaria parts. These results are discussed according to different defensive strategies that are used within algal taxa to cope with biotic or abiotic stresses. © 2014 Phycological Society of America.

  1. Comparative studies of mitochondrial proteomics reveal an intimate protein network of male sterility in wheat (Triticum aestivum L.)

    Science.gov (United States)

    Wang, Shuping; Zhang, Gaisheng; Zhang, Yingxin; Song, Qilu; Chen, Zheng; Wang, Junsheng; Guo, Jialin; Niu, Na; Wang, Junwei; Ma, Shoucai

    2015-01-01

    Plant male sterility has often been associated with mitochondrial dysfunction; however, the mechanism in wheat (Triticum aestivum L.) has not been elucidated. This study set out to probe the mechanism of physiological male sterility (PHYMS) induced by the chemical hybridizing agent (CHA)-SQ-1, and cytoplasmic male sterility (CMS) of wheat at the proteomic level. A total of 71 differentially expressed mitochondrial proteins were found to be involved in pollen abortion and further identified by MALDI-TOF/TOF MS (matrix-assisted laser desorption/ionization-time of fight/time of flight mass spectrometry). These proteins were implicated in different cellular responses and metabolic processes, with obvious functional tendencies toward the tricarboxylic acid cycle, the mitochondrial electron transport chain, protein synthesis and degradation, oxidation stress, the cell division cycle, and epigenetics. Interactions between identified proteins were demonstrated by bioinformatics analysis, enabling a more complete insight into biological pathways involved in anther abortion and pollen defects. Accordingly, a mitochondria-mediated male sterility protein network in wheat is proposed; this network was further confirmed by physiological data, RT-PCR (real-time PCR), and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) assay. The results provide intriguing insights into the metabolic pathway of anther abortion induced by CHA-SQ-1 and also give useful clues to identify the crucial proteins of PHYMS and CMS in wheat. PMID:26136264

  2. A longitudinal study of Caenorhabditis elegans larvae reveals a novel locomotion switch, regulated by Gαs signaling

    Science.gov (United States)

    Nagy, Stanislav; Wright, Charles; Tramm, Nora; Labello, Nicholas; Burov, Stanislav; Biron, David

    2013-01-01

    Despite their simplicity, longitudinal studies of invertebrate models are rare. We thus sought to characterize behavioral trends of Caenorhabditis elegans, from the mid fourth larval stage through the mid young adult stage. We found that, outside of lethargus, animals exhibited abrupt switching between two distinct behavioral states: active wakefulness and quiet wakefulness. The durations of epochs of active wakefulness exhibited non-Poisson statistics. Increased Gαs signaling stabilized the active wakefulness state before, during and after lethargus. In contrast, decreased Gαs signaling, decreased neuropeptide release, or decreased CREB activity destabilized active wakefulness outside of, but not during, lethargus. Taken together, our findings support a model in which protein kinase A (PKA) stabilizes active wakefulness, at least in part through two of its downstream targets: neuropeptide release and CREB. However, during lethargus, when active wakefulness is strongly suppressed, the native role of PKA signaling in modulating locomotion and quiescence may be minor. DOI: http://dx.doi.org/10.7554/eLife.00782.001 PMID:23840929

  3. A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

    LENUS (Irish Health Repository)

    Whelan, R

    2012-02-01

    OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

  4. Deformation mechanisms in a precipitation-strengthened ferritic superalloy revealed by in situ neutron diffraction studies at elevated temperatures

    International Nuclear Information System (INIS)

    Huang, Shenyan; Gao, Yanfei; An, Ke; Zheng, Lili; Wu, Wei; Teng, Zhenke; Liaw, Peter K.

    2015-01-01

    The ferritic superalloy Fe–10Ni–6.5Al–10Cr–3.4Mo strengthened by ordered (Ni,Fe)Al B2-type precipitates is a candidate material for ultra-supercritical steam turbine applications above 923 K. Despite earlier success in improving its room-temperature ductility, the creep resistance of this material at high temperatures needs to be further improved, which requires a fundamental understanding of the high-temperature deformation mechanisms at the scales of individual phases and grains. In situ neutron diffraction has been utilized to investigate the lattice strain evolution and the microscopic load-sharing mechanisms during tensile deformation of this ferritic superalloy at elevated temperatures. Finite-element simulations based on the crystal plasticity theory are employed and compared with the experimental results, both qualitatively and quantitatively. Based on these interphase and intergranular load-partitioning studies, it is found that the deformation mechanisms change from dislocation slip to those related to dislocation climb, diffusional flow and possibly grain boundary sliding, below and above 873 K, respectively. Insights into microstructural design for enhancing creep resistance are also discussed

  5. Structure Function Studies of Vaccinia Virus Host Range Protein K1 Reveal a Novel Functional Surface for Ankyrin Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yongchao; Meng, Xiangzhi; Xiang, Yan; Deng, Junpeng (Texas-HSC); (OKLU)

    2010-06-15

    Poxvirus host tropism at the cellular level is regulated by virus-encoded host range proteins acting downstream of virus entry. The functioning mechanisms of most host range proteins are unclear, but many contain multiple ankyrin (ANK) repeats, a motif that is known for ligand interaction through a concave surface. We report here the crystal structure of one of the ANK repeat-containing host range proteins, the vaccinia virus K1 protein. The structure, at a resolution of 2.3 {angstrom}, showed that K1 consists entirely of ANK repeats, including seven complete ones and two incomplete ones, one each at the N and C terminus. Interestingly, Phe82 and Ser83, which were previously shown to be critical for K1's function, are solvent exposed and located on a convex surface, opposite the consensus ANK interaction surface. The importance of this convex surface was further supported by our additional mutagenesis studies. We found that K1's host range function was negatively affected by substitution of either Asn51 or Cys47 and completely abolished by substitution of both residues. Cys47 and Asn51 are also exposed on the convex surface, spatially adjacent to Phe82 and Ser83. Altogether, our data showed that K1 residues on a continuous convex ANK repeat surface are critical for the host range function, suggesting that K1 functions through ligand interaction and does so with a novel ANK interaction surface.

  6. What Images Reveal: a Comparative Study of Science Images between Australian and Taiwanese Junior High School Textbooks

    Science.gov (United States)

    Ge, Yun-Ping; Unsworth, Len; Wang, Kuo-Hua; Chang, Huey-Por

    2017-07-01

    From a social semiotic perspective, image designs in science textbooks are inevitably influenced by the sociocultural context in which the books are produced. The learning environments of Australia and Taiwan vary greatly. Drawing on social semiotics and cognitive science, this study compares classificational images in Australian and Taiwanese junior high school science textbooks. Classificational images are important kinds of images, which can represent taxonomic relations among objects as reported by Kress and van Leeuwen (Reading images: the grammar of visual design, 2006). An analysis of the images from sample chapters in Australian and Taiwanese high school science textbooks showed that the majority of the Taiwanese images are covert taxonomies, which represent hierarchical relations implicitly. In contrast, Australian classificational images included diversified designs, but particularly types with a tree structure which depicted overt taxonomies, explicitly representing hierarchical super-ordinate and subordinate relations. Many of the Taiwanese images are reminiscent of the specimen images in eighteenth century science texts representing "what truly is", while more Australian images emphasize structural objectivity. Moreover, Australian images support cognitive functions which facilitate reading comprehension. The relationships between image designs and learning environments are discussed and implications for textbook research and design are addressed.

  7. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  8. Life-table studies revealed significant effects of deforestation on the development and survivorship of Anopheles minimus larvae.

    Science.gov (United States)

    Wang, Xiaoming; Zhou, Guofa; Zhong, Daibin; Wang, Xiaoling; Wang, Ying; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

    2016-06-06

    Many developing countries are experiencing rapid ecological changes such as deforestation and shifting agricultural practices. These environmental changes may have an important consequence on malaria due to their impact on vector survival and reproduction. Despite intensive deforestation and malaria transmission in the China-Myanmar border area, the impact of deforestation on malaria vectors in the border area is unknown. We conducted life table studies on Anopheles minimus larvae to determine the pupation rate and development time in microcosms under deforested, banana plantation, and forested environments. The pupation rate of An. minimus was 3.8 % in the forested environment. It was significantly increased to 12.5 % in banana plantations and to 52.5 % in the deforested area. Deforestation reduced larval-to-pupal development time by 1.9-3.3 days. Food supplementation to aquatic habitats in forested environments and banana plantations significantly increased larval survival rate to a similar level as in the deforested environment. Deforestation enhanced the survival and development of An. minimus larvae, a major malaria vector in the China-Myanmar border area. Experimental determination of the life table parameters on mosquito larvae under a variety of environmental conditions is valuable to model malaria transmission dynamics and impact by climate and environmental changes.

  9. Single ferromagnetic fluctuations in UCoGe revealed by 73Ge- and 59Co-NMR studies

    Science.gov (United States)

    Manago, Masahiro; Ishida, Kenji; Aoki, Dai

    2018-02-01

    73Ge and 59Co nuclear magnetic resonance (NMR) and nuclear quadrupole resonance (NQR) measurements have been performed on a 73Ge-enriched single-crystalline sample of the ferromagnetic superconductor UCoGe in the paramagnetic state. The 73Ge NQR parameters deduced from NQR and NMR are close to those of another isostructural ferromagnetic superconductor URhGe. The Knight shifts of the Ge and Co sites are well scaled to each other when the magnetic field is parallel to the b or c axis. The hyperfine coupling constants of Ge are estimated to be close to those of Co. The large difference of spin susceptibilities between the a and b axes could lead to the different response of the superconductivity and ferromagnetism with the field parallel to these directions. The temperature dependence of the nuclear spin-lattice relaxation rates 1 /T1 at the two sites is similar to each other above 5 K. These results indicate that the itinerant U-5 f electrons are responsible for the ferromagnetism in this compound, consistent with previous studies. The similarities and differences in the three ferromagnetic superconductors are discussed.

  10. Lateral facial profile may reveal the risk for sleep disordered breathing in children--the PANIC-study.

    Science.gov (United States)

    Ikävalko, Tiina; Närhi, Matti; Lakka, Timo; Myllykangas, Riitta; Tuomilehto, Henri; Vierola, Anu; Pahkala, Riitta

    2015-01-01

    To evaluate the lateral view photography of the face as a tool for assessing morphological properties (i.e. facial convexity) as a risk factor for sleep disordered breathing (SDB) in children and to test how reliably oral health and non-oral healthcare professionals can visually discern the lateral profile of the face from the photographs. The present study sample consisted of 382 children 6-8 years of age who were participants in the Physical Activity and Nutrition in Children (PANIC) Study. Sleep was assessed by a sleep questionnaire administered by the parents. SDB was defined as apnoeas, frequent or loud snoring or nocturnal mouth breathing observed by the parents. The facial convexity was assessed with three different methods. First, it was clinically evaluated by the reference orthodontist (T.I.). Second, lateral view photographs were taken to visually sub-divide the facial profile into convex, normal or concave. The photos were examined by a reference orthodontist and seven different healthcare professionals who work with children and also by a dental student. The inter- and intra-examiner consistencies were calculated by Kappa statistics. Three soft tissue landmarks of the facial profile, soft tissue Glabella (G`), Subnasale (Sn) and soft tissue Pogonion (Pg`) were digitally identified to analyze convexity of the face and the intra-examiner reproducibility of the reference orthodontist was determined by calculating intra-class correlation coefficients (ICCs). The third way to express the convexity of the face was to calculate the angle of facial convexity (G`-Sn-Pg`) and to group it into quintiles. For analysis the lowest quintile (≤164.2°) was set to represent the most convex facial profile. The prevalence of the SDB in children with the most convex profiles expressed with the lowest quintile of the angle G`-Sn-Pg` (≤164.2°) was almost 2-fold (14.5%) compared to those with normal profile (8.1%) (p = 0.084). The inter-examiner Kappa values between the

  11. Serum BAFF in Indian patients with IIM: a retrospective study reveals novel clinico-phenotypic associations in children and adults.

    Science.gov (United States)

    Gupta, Latika; Chaurasia, Smriti; Srivastava, Puja; Dwivedi, Sanjay; Lawrence, Able; Misra, Ramnath

    2018-03-07

    We studied the serum levels of B cell survival factors BAFF and APRIL in patients with idiopathic inflammatory myositis (IIM) and their relation with clinical and autoantibodies. Seventy-five patients (51 females and 24 males) with IIM (Bohan and Peter's criteria 1975) and 25 healthy adults were analyzed for BAFF, APRIL and IL-17 by ELISA, and myositis-specific and associated antibodies (MSA and MAA) using line immunoblot assay. Of the 75 patients, 59 were adults, 42 had Dermatomyositis (DM), and 17 had Polymyositis. Median disease duration was 5 (3-12) months. BAFF levels were higher in IIM than healthy controls [p = 0.001], and in children with jDM than adults [p = 0.026]. BAFF levels were higher in adults with arthritis [p = 0.018], weight loss [p = 0.007], and PAH [p = 0.004]. Among the various MSAs, lowest levels were seen in those with anti-SRP [p = 0.043]. Median follow-up duration was 145 patient years. Twelve patients relapsed, while nine were in drug-free remission. BAFF were similar between these groups. Serum APRIL levels were elevated in limited number of patients with myositis, and the levels did not differ amongst the clinico-serologic phenotypes. IL-17 levels were higher in individuals positive for anti-SRP [p = 0.028]. Serum BAFF levels are elevated in IIM, more so in children. BAFF levels may be useful as biomarker for PAH and arthritis. Anti-SRP positivity is associated with elevated IL-17 levels suggesting role in pathogenesis.

  12. A study of lactose metabolism in Lactococcus garvieae reveals a genetic marker for distinguishing between dairy and fish biotypes.

    Science.gov (United States)

    Fortina, Maria Grazia; Ricci, Giovanni; Borgo, Francesca

    2009-06-01

    Dairy and fish isolates of Lactococcus garvieae were tested for their ability to utilize lactose and to grow in milk. Fish isolates were unable to assimilate lactose, but unexpectedly, they possessed the ability to grow in milk. Genetic studies, carried out constructing different vectorette libraries, provided evidence that in fish isolates, no genes involved in lactose utilization were present. For L. garvieae dairy isolates, a single system for the catabolism of lactose was found. It consists of a lactose transport and hydrolysis depending on a phosphoenolpyruvate-dependent phosphotransferase system combined with a phospho-beta-galactosidase. The genes involved were highly similar at the nucleotide sequence level to their counterparts in Lactococcus lactis; however, while in many L. lactis strains these genes are plasmid encoded, in L. garvieae they are chromosomally located. Thus, in the species L. garvieae, the phospho-beta-galactosidase gene, detectable in all strains of dairy origin but lacking in fish isolates, can be considered a reliable genetic marker for distinguishing biotypes in the two diverse ecological niches. Moreover, we obtained information regarding the complete nucleotide sequence of the gal operon in L. garvieae, consisting of a galactose permease and the Leloir pathway enzymes. This is one of the first reports concerning the determination of the nucleotide sequences of genes (other than the 16S rDNA gene) in L. garvieae and should be considered a step in a continuous effort to explore the genome of this species, with the aim of determining the real relationship between the presence of L. garvieae in dairy products and food safety.

  13. Functional Complementation Studies Reveal Different Interaction Partners of Escherichia coli IscS and Human NFS1.

    Science.gov (United States)

    Bühning, Martin; Friemel, Martin; Leimkühler, Silke

    2017-08-29

    The trafficking and delivery of sulfur to cofactors and nucleosides is a highly regulated and conserved process among all organisms. All sulfur transfer pathways generally have an l-cysteine desulfurase as an initial sulfur-mobilizing enzyme in common, which serves as a sulfur donor for the biosynthesis of sulfur-containing biomolecules like iron-sulfur (Fe-S) clusters, thiamine, biotin, lipoic acid, the molybdenum cofactor (Moco), and thiolated nucleosides in tRNA. The human l-cysteine desulfurase NFS1 and the Escherichia coli homologue IscS share a level of amino acid sequence identity of ∼60%. While E. coli IscS has a versatile role in the cell and was shown to have numerous interaction partners, NFS1 is mainly localized in mitochondria with a crucial role in the biosynthesis of Fe-S clusters. Additionally, NFS1 is also located in smaller amounts in the cytosol with a role in Moco biosynthesis and mcm 5 s 2 U34 thio modifications of nucleosides in tRNA. NFS1 and IscS were conclusively shown to have different interaction partners in their respective organisms. Here, we used functional complementation studies of an E. coli iscS deletion strain with human NFS1 to dissect their conserved roles in the transfer of sulfur to a specific target protein. Our results show that human NFS1 and E. coli IscS share conserved binding sites for proteins involved in Fe-S cluster assembly like IscU, but not with proteins for tRNA thio modifications or Moco biosynthesis. In addition, we show that human NFS1 was almost fully able to complement the role of IscS in Moco biosynthesis when its specific interaction partner protein MOCS3 from humans was also present.

  14. A Holistic Landscape Description Reveals That Landscape Configuration Changes More over Time than Composition: Implications for Landscape Ecology Studies.

    Directory of Open Access Journals (Sweden)

    Anne Mimet

    Full Text Available Space-for-time substitution-that is, the assumption that spatial variations of a system can explain and predict the effect of temporal variations-is widely used in ecology. However, it is questionable whether it can validly be used to explain changes in biodiversity over time in response to land-cover changes.Here, we hypothesize that different temporal vs spatial trajectories of landscape composition and configuration may limit space-for-time substitution in landscape ecology. Land-cover conversion changes not just the surface areas given over to particular types of land cover, but also affects isolation, patch size and heterogeneity. This means that a small change in land cover over time may have only minor repercussions on landscape composition but potentially major consequences for landscape configuration.Using land-cover maps of the Paris region for 1982 and 2003, we made a holistic description of the landscape disentangling landscape composition from configuration. After controlling for spatial variations, we analyzed and compared the amplitudes of changes in landscape composition and configuration over time.For comparable spatial variations, landscape configuration varied more than twice as much as composition over time. Temporal changes in composition and configuration were not always spatially matched.The fact that landscape composition and configuration do not vary equally in space and time calls into question the use of space-for-time substitution in landscape ecology studies. The instability of landscapes over time appears to be attributable to configurational changes in the main. This may go some way to explaining why the landscape variables that account for changes over time in biodiversity are not the same ones that account for the spatial distribution of biodiversity.

  15. Hair analysis reveals subtle HPA axis suppression associated with use of local corticosteroids: The Lifelines cohort study.

    Science.gov (United States)

    Wester, Vincent L; Noppe, Gerard; Savas, Mesut; van den Akker, Erica L T; de Rijke, Yolanda B; van Rossum, Elisabeth F C

    2017-06-01

    Scalp hair is increasingly used to measure the long-term exposure to endogenous glucocorticoids hormones. Long-term cortisone (HairE) and cortisol (HairF) have been associated with obesity, metabolic syndrome, cardiovascular disease and psychopathology. However, little is known about the influence of the use of local corticosteroids and major stressful life events on hair glucocorticoids. We determined HairE and HairF using liquid chromatography - tandem mass spectrometry in 295 adult participants of the population-based Lifelines cohort study (75% females, median age 42). We collected anthropometry and fasting metabolic laboratory values, questionnaires on hair characteristics, recent use of corticosteroids, and recent major stressful life events. After adjustment for covariates, hair glucocorticoids increased with age, male sex, black or brown hair color, and frequency of sweating on the scalp, and decreased with higher hair washing frequency (PHairE was decreased in participants who used systemic corticosteroids (5.4 vs. 8.5pg/mg hair, P=0.041), and in participants who only used local agents such as inhaled, topical and nasal corticosteroids (6.8 vs. 8.5pg/mg, P=0.005). Recent life events were positively associated with HairF after adjustment for age and sex (P=0.026), but this association lost significance after adjustment for hair related characteristics (P>0.05). HairE can be a useful marker to detect mild adrenal suppression due to corticosteroid use in the general population, even when only inhaled, nasal or topical corticosteroids are used, which suggests that these commonly used agents induce systemic effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Structure-kinetic relationship studies of cannabinoid CB2receptor agonists reveal substituent-specific lipophilic effects on residence time.

    Science.gov (United States)

    Soethoudt, Marjolein; Hoorens, Mark W H; Doelman, Ward; Martella, Andrea; van der Stelt, Mario; Heitman, Laura H

    2018-03-21

    A decade ago, the drug-target residence time model has been (re-)introduced, which describes the importance of binding kinetics of ligands on their protein targets. Since then, it has been applied successfully for multiple protein targets, including GPCRs, for the development of lead compounds with slow dissociation kinetics (i.e. long target residence time) to increase in vivo efficacy or with short residence time to prevent on-target associated side effects. To date, this model has not been applied in the design and pharmacological evaluation of novel selective ligands for the cannabinoid CB 2 receptor (CB 2 R), a GPCR with therapeutic potential in the treatment of tissue injury and inflammatory diseases. Here, we have investigated the relationships between physicochemical properties, binding kinetics and functional activity in two different signal transduction pathways, G protein activation and β-arrestin recruitment. We synthesized 24 analogues of 3-cyclopropyl-1-(4-(6-((1,1-dioxidothiomorpholino)methyl)-5-fluoropyridin-2-yl)benzyl)imidazoleidine-2,4-dione (LEI101), our previously reported in vivo active and CB 2 R-selective agonist, with varying basicity and lipophilicity. We identified a positive correlation between target residence time and functional potency due to an increase in lipophilicity on the alkyl substituents, which was not the case for the amine substituents. Basicity of the agonists did not show a relationship with affinity, residence time or functional activity. Our findings provide important insights about the effects of physicochemical properties of the specific substituents of this scaffold on the binding kinetics of agonists and their CB 2 R pharmacology. This work therefore shows how CB 2 R agonists can be designed to have optimal kinetic profiles, which could aid the lead optimization process in drug discovery for the study or treatment of inflammatory diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights

  17. Dynamics of metal-humate complexation equilibria as revealed by isotope exchange studies - a matter of concentration and time

    Science.gov (United States)

    Lippold, Holger; Eidner, Sascha; Kumke, Michael U.; Lippmann-Pipke, Johanna

    2017-01-01

    Complexation with dissolved humic matter can be crucial in controlling the mobility of toxic or radioactive contaminant metals. For speciation and transport modelling, a dynamic equilibrium process is commonly assumed, where association and dissociation run permanently. This is, however, questionable in view of reported observations of a growing resistance to dissociation over time. In this study, the isotope exchange principle was employed to gain direct insight into the dynamics of the complexation equilibrium, including kinetic inertisation phenomena. Terbium(III), an analogue of trivalent actinides, was used as a representative of higher-valent metals. Isotherms of binding to (flocculated) humic acid, determined by means of 160Tb as a radiotracer, were found to be identical regardless of whether the radioisotope was introduced together with the bulk of stable 159Tb or subsequently after pre-equilibration for up to 3 months. Consequently, there is a permanent exchange of free and humic-bound Tb since all available binding sites are occupied in the plateau region of the isotherm. The existence of a dynamic equilibrium was thus evidenced. There was no indication of an inertisation under these experimental conditions. If the small amount of 160Tb was introduced prior to saturation with 159Tb, the expected partial desorption of 160Tb occurred at much lower rates than observed for the equilibration process in the reverse procedure. In addition, the rates decreased with time of pre-equilibration. Inertisation phenomena are thus confined to the stronger sites of humic molecules (occupied at low metal concentrations). Analysing the time-dependent course of isotope exchange according to first-order kinetics indicated that up to 3 years are needed to attain equilibrium. Since, however, metal-humic interaction remains reversible, exchange of metals between humic carriers and mineral surfaces cannot be neglected on the long time scale to be considered in predictive

  18. A Holistic Landscape Description Reveals That Landscape Configuration Changes More over Time than Composition: Implications for Landscape Ecology Studies.

    Science.gov (United States)

    Mimet, Anne; Pellissier, Vincent; Houet, Thomas; Julliard, Romain; Simon, Laurent

    2016-01-01

    Space-for-time substitution-that is, the assumption that spatial variations of a system can explain and predict the effect of temporal variations-is widely used in ecology. However, it is questionable whether it can validly be used to explain changes in biodiversity over time in response to land-cover changes. Here, we hypothesize that different temporal vs spatial trajectories of landscape composition and configuration may limit space-for-time substitution in landscape ecology. Land-cover conversion changes not just the surface areas given over to particular types of land cover, but also affects isolation, patch size and heterogeneity. This means that a small change in land cover over time may have only minor repercussions on landscape composition but potentially major consequences for landscape configuration. Using land-cover maps of the Paris region for 1982 and 2003, we made a holistic description of the landscape disentangling landscape composition from configuration. After controlling for spatial variations, we analyzed and compared the amplitudes of changes in landscape composition and configuration over time. For comparable spatial variations, landscape configuration varied more than twice as much as composition over time. Temporal changes in composition and configuration were not always spatially matched. The fact that landscape composition and configuration do not vary equally in space and time calls into question the use of space-for-time substitution in landscape ecology studies. The instability of landscapes over time appears to be attributable to configurational changes in the main. This may go some way to explaining why the landscape variables that account for changes over time in biodiversity are not the same ones that account for the spatial distribution of biodiversity.

  19. Structural determinants of species-selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies.

    Science.gov (United States)

    Kaufmann, Kristian W; Dawson, Eric S; Henry, L Keith; Field, Julie R; Blakely, Randy D; Meiler, Jens

    2009-02-15

    To identify potential determinants of substrate selectivity in serotonin (5-HT) transporters (SERT), models of human and Drosophila serotonin transporters (hSERT, dSERT) were built based on the leucine transporter (LeuT(Aa)) structure reported by Yamashita et al. (Nature 2005;437:215-223), PBDID 2A65. Although the overall amino acid identity between SERTs and the LeuT(Aa) is only 17%, it increases to above 50% in the first shell of the putative 5-HT binding site, allowing de novo computational docking of tryptamine derivatives in atomic detail. Comparison of hSERT and dSERT complexed with substrates pinpoints likely structural determinants for substrate binding. Forgoing the use of experimental transport and binding data of tryptamine derivatives for construction of these models enables us to critically assess and validate their predictive power: A single 5-HT binding mode was identified that retains the amine placement observed in the LeuT(Aa) structure, matches site-directed mutagenesis and substituted cysteine accessibility method (SCAM) data, complies with support vector machine derived relations activity relations, and predicts computational binding energies for 5-HT analogs with a significant correlation coefficient (R = 0.72). This binding mode places 5-HT deep in the binding pocket of the SERT with the 5-position near residue hSERT A169/dSERT D164 in transmembrane helix 3, the indole nitrogen next to residue Y176/Y171, and the ethylamine tail under residues F335/F327 and S336/S328 within 4 A of residue D98. Our studies identify a number of potential contacts whose contribution to substrate binding and transport was previously unsuspected. (c) 2008 Wiley-Liss, Inc.

  20. Budget of shallow magma plumbing system at Asama Volcano, Japan, revealed by ground deformation and volcanic gas studies

    Science.gov (United States)

    Kazahaya, Ryunosuke; Aoki, Yosuke; Shinohara, Hiroshi

    2015-05-01

    Multiple cycles of the intensive volcanic gas discharge and ground deformation (inflation and deflation) were observed at Asama Volcano, Japan, from 2000 to 2011. Magma budget of the shallow magma plumbing system was estimated on the basis of the volcanic gas emission rates and ground deformation data. Recent inflations observed in 2004 and 2008 were modeled as a dike intrusion to 2-3 km west of Asama Volcano. Previous studies proposed that magma ascends from a midcrustal magma reservoir to the dike and reaches the surface via a sinuous conduit which connects the dike to the summit. The intensive volcanic sulfur dioxide discharge of up to 4600 t/d at the volcano was modeled by magma convective degassing through this magma pathway. The volcano deflates as shrinkage of the magma in a reservoir by volcanic gas discharge. We estimated the volume change of the dike modeled based on the GPS observations, the volume decrease of the magma by the volcanic gas discharge, and the amount of degassed magma produced to calculate the magma budget. The results show that the volume decrease of the magma by the volcanic gas discharge was larger than the volume change of the dike during the inflation periods. This indicates that a significant volume of magma at least more than 2 times larger than the volume change of the dike was supplied from the midcrustal magma reservoir to the dike. The volume decrease of the dike was comparable with the volume decrease of the magma by the volcanic gas discharge during the deflation periods. The long-term deflation trend of the dike and the volume of degassed magma (108-9 m3) suggest that the degassed magma produced is not stored in the dike and the magma is mainly supplied from the midcrustal magma reservoir. In both periods, the volume of degassed magma produced was 1 order of magnitude larger than the volume change of the dike. This indicates that the actual volume of the magma supplied from the midcrustal magma reservoir is up to 1 order of

  1. Accuracy of claims-based algorithms for epilepsy research: Revealing the unseen performance of claims-based studies.

    Science.gov (United States)

    Moura, Lidia M V R; Price, Maggie; Cole, Andrew J; Hoch, Daniel B; Hsu, John

    2017-04-01

    To evaluate published algorithms for the identification of epilepsy cases in medical claims data using a unique linked dataset with both clinical and claims data. Using data from a large, regional health delivery system, we identified all patients contributing biologic samples to the health system's Biobank (n = 36K). We identified all subjects with at least one diagnosis potentially consistent with epilepsy, for example, epilepsy, convulsions, syncope, or collapse, between 2014 and 2015, or who were seen at the epilepsy clinic (n = 1,217), plus a random sample of subjects with neither claims nor clinic visits (n = 435); we then performed a medical chart review in a random subsample of 1,377 to assess the epilepsy diagnosis status. Using the chart review as the reference standard, we evaluated the test characteristics of six published algorithms. The best-performing algorithm used diagnostic and prescription drug data (sensitivity = 70%, 95% confidence interval [CI] 66-73%; specificity = 77%, 95% CI 73-81%; and area under the curve [AUC] = 0.73, 95%CI 0.71-0.76) when applied to patients age 18 years or older. Restricting the sample to adults aged 18-64 years resulted in a mild improvement in accuracy (AUC = 0.75,95%CI 0.73-0.78). Adding information about current antiepileptic drug use to the algorithm increased test performance (AUC = 0.78, 95%CI 0.76-0.80). Other algorithms varied in their included data types and performed worse. Current approaches for identifying patients with epilepsy in insurance claims have important limitations when applied to the general population. Approaches incorporating a range of information, for example, diagnoses, treatments, and site of care/specialty of physician, improve the performance of identification and could be useful in epilepsy studies using large datasets. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  2. Mechanistic Studies and Modeling Reveal the Origin of Differential Inhibition of Gag Polymorphic Viruses by HIV-1 Maturation Inhibitors.

    Science.gov (United States)

    Lin, Zeyu; Cantone, Joseph; Lu, Hao; Nowicka-Sans, Beata; Protack, Tricia; Yuan, Tian; Yang, Hong; Liu, Zheng; Drexler, Dieter; Regueiro-Ren, Alicia; Meanwell, Nicholas A; Cockett, Mark; Krystal, Mark; Lataillade, Max; Dicker, Ira B

    2016-11-01

    HIV-1 maturation inhibitors (MIs) disrupt the final step in the HIV-1 protease-mediated cleavage of the Gag polyprotein between capsid p24 capsid (CA) and spacer peptide 1 (SP1), leading to the production of infectious virus. BMS-955176 is a second generation MI with improved antiviral activity toward polymorphic Gag variants compared to a first generation MI bevirimat (BVM). The underlying mechanistic reasons for the differences in polymorphic coverage were studied using antiviral assays, an LC/MS assay that quantitatively characterizes CA/SP1 cleavage kinetics of virus like particles (VLPs) and a radiolabel binding assay to determine VLP/MI affinities and dissociation kinetics. Antiviral assay data indicates that BVM does not achieve 100% inhibition of certain polymorphs, even at saturating concentrations. This results in the breakthrough of infectious virus (partial antagonism) regardless of BVM concentration. Reduced maximal percent inhibition (MPI) values for BVM correlated with elevated EC50 values, while rates of HIV-1 protease cleavage at CA/SP1 correlated inversely with the ability of BVM to inhibit HIV-1 Gag polymorphic viruses: genotypes with more rapid CA/SP1 cleavage kinetics were less sensitive to BVM. In vitro inhibition of wild type VLP CA/SP1 cleavage by BVM was not maintained at longer cleavage times. BMS-955176 exhibited greatly improved MPI against polymorphic Gag viruses, binds to Gag polymorphs with higher affinity/longer dissociation half-lives and exhibits greater time-independent inhibition of CA/SP1 cleavage compared to BVM. Virological (MPI) and biochemical (CA/SP1 cleavage rates, MI-specific Gag affinities) data were used to create an integrated semi-quantitative model that quantifies CA/SP1 cleavage rates as a function of both MI and Gag polymorph. The model outputs are in accord with in vitro antiviral observations and correlate with observed in vivo MI efficacies. Overall, these findings may be useful to further understand antiviral

  3. Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study.

    Science.gov (United States)

    Lerman, Joseph B; Joshi, Aditya A; Chaturvedi, Abhishek; Aberra, Tsion M; Dey, Amit K; Rodante, Justin A; Salahuddin, Taufiq; Chung, Jonathan H; Rana, Anshuma; Teague, Heather L; Wu, Jashin J; Playford, Martin P; Lockshin, Benjamin A; Chen, Marcus Y; Sandfort, Veit; Bluemke, David A; Mehta, Nehal N

    2017-07-18

    Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25). Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy. Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32, P =0.02) and similar HRP prevalence ( P =0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22, P =0.001), NCB (1.18±0.33 versus 1.03±0.21, P =0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1-31.7; P =0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (β=0.45, 0.23-0.67; P psoriasis had greater NCB and increased HRP prevalence than

  4. Genome-Wide Association Study Reveals Genetic Architecture of Eating Behaviors in Pigs and its Implications for Humans Obesity by Comparative Genome Mapping

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behaviors inDanish Duroc boars and its potential implications for eating behaviors in humans.Individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of dailyvisits to feeder (NVD), time spent to eat...... for geneticimprovement of pig feed efficiency. The results of pig-human comparative genemapping revealed some important genomic regions and/or genes on the humangenome that may influence eating behavior in human and consequently affect thedevelopment of obesity and metabolic syndromes. This is the first...... such translationalgenomics study to report potential candidate genes for eating behavior in humans...

  5. A genome-wide association study of a global rice panel reveals resistance in Oryza sativa to root-knot nematodes

    Science.gov (United States)

    Dimkpa, Stanley O. N.; Lahari, Zobaida; Shrestha, Roshi; Douglas, Alex; Gheysen, Godelieve; Price, Adam H.

    2016-01-01

    The root-knot nematode Meloidogyne graminicola is one of the most serious nematode pests worldwide and represents a major constraint on rice production. While variation in the susceptibility of Asian rice (Oryza sativa) exists, so far no strong and reliable resistance has been reported. Quantitative trait loci for partial resistance have been reported but no underlying genes have been tagged or cloned. Here, 332 accessions of the Rice Diversity Panel 1 were assessed for gall formation, revealing large variation across all subpopulations of rice and higher susceptibility in temperate japonica accessions. Accessions Khao Pahk Maw and LD 24 appeared to be resistant, which was confirmed in large pot experiments where no galls were observed. Detailed observations on these two accessions revealed no nematodes inside the roots 2 days after inoculation and very few females after 17 days (5 in Khao Pahk Maw and 100 in the susceptible controls). These two cultivars appear ideal donors for breeding root-knot nematode resistance. A genome-wide association study revealed 11 quantitative trait loci, two of which are close to epistatic loci detected in the Bala x Azucena population. The discussion highlights a small number of candidate genes worth exploring further, in particular many genes with lectin domains and genes on chromosome 11 with homology to the Hordeum Mla locus. PMID:26552884

  6. The importance of catchment vegetation for alkalinity, phosphorus burial and macrophytes as revealed by a recent paleolimnological study in a soft water lake

    DEFF Research Database (Denmark)

    Klamt, Anna-Marie; Jensen, Henning S.; Mortensen, Morten Fischer

    2017-01-01

    sediment cores. This novel combination of proxies revealed that 1) the reduction of deciduous trees in the watershed seemingly reduced the calcium (Ca) supply to the lake and thereby its buffering capacity. This development was accompanied by decreased abundances of Ca-dependent species and subsequent...... the amounts of macrofossils of isoetid species and characeans, indicating a reduction in their maximum distribution depth because of lower water transparency. Overall, the results of our paleolimnological study are of importance within lake management by convincingly showing how land use changes may...

  7. Genome-wide association studies with proteomics data reveal genes important for synthesis, transport and packaging of globulins in legume seeds.

    Science.gov (United States)

    Le Signor, Christine; Aimé, Delphine; Bordat, Amandine; Belghazi, Maya; Labas, Valérie; Gouzy, Jérôme; Young, Nevin D; Prosperi, Jean-Marie; Leprince, Olivier; Thompson, Richard D; Buitink, Julia; Burstin, Judith; Gallardo, Karine

    2017-06-01

    Improving nutritional seed quality is an important challenge in grain legume breeding. However, the genes controlling the differential accumulation of globulins, which are major contributors to seed nutritional value in legumes, remain largely unknown. We combined a search for protein quantity loci with genome-wide association studies on the abundance of 7S and 11S globulins in seeds of the model legume species Medicago truncatula. Identified genomic regions and genes carrying polymorphisms linked to globulin variations were then cross-compared with pea (Pisum sativum), leading to the identification of candidate genes for the regulation of globulin abundance in this crop. Key candidates identified include genes involved in transcription, chromatin remodeling, post-translational modifications, transport and targeting of proteins to storage vacuoles. Inference of a gene coexpression network of 12 candidate transcription factors and globulin genes revealed the transcription factor ABA-insensitive 5 (ABI5) as a highly connected hub. Characterization of loss-of-function abi5 mutants in pea uncovered a role for ABI5 in controlling the relative abundance of vicilin, a sulfur-poor 7S globulin, in pea seeds. This demonstrates the feasibility of using genome-wide association studies in M. truncatula to reveal genes that can be modulated to improve seed nutritional value. © 2017 INRA. New Phytologist © 2017 New Phytologist Trust.

  8. Identity of major sulfur-cycle prokaryotes in freshwater lake ecosystems revealed by a comprehensive phylogenetic study of the dissimilatory adenylylsulfate reductase.

    Science.gov (United States)

    Watanabe, Tomohiro; Kojima, Hisaya; Fukui, Manabu

    2016-11-08

    Adenylylsulfate reductase is a heterodimeric complex of two subunits, AprB and AprA, and is a key enzyme in dissimilatory sulfate reduction and sulfur oxidation. Common use of aprA as a functional marker gene has revealed the diversity of sulfur-cycle prokaryotes in diverse environments. In this study, we established a comprehensive sequence set of apr genes and employed it to reanalyze apr phylogeny, evaluate the coverage of a widely used primer set (AprA-1-FW/AprA-5-RV), and categorize environmental aprA sequences. Phylogenetic tree construction revealed new members of Apr lineage II and several previously unrecognized lateral gene transfer events. Using the established phylogenetic tree, we classified all previously reported aprA sequences amplified from freshwater lakes with the primer pair AprA-1-FW/AprA-5-RV in addition to the aprA sequences newly retrieved from freshwater lakes; the obtained results were complemented by 16S rRNA clone library analysis. Apr-based classifications of some of operational taxonomic units were supported by 16S rRNA-based analysis. This study updates our knowledge on the phylogeny of aprBA and shows the identities of several sulfur-cycle bacteria, which could not be classified to a known taxa until now. The established apr sequence set is publicly available and can be applied to assign environmental sequences to known lineages.

  9. Detailed polymorphism study on cytomegalovirus DNA polymerase gene to reveal the most suitable genomic targets for quantitative Real-time PCR

    Science.gov (United States)

    Bilenoğlu, Onur; Altındiş, Mustafa; Öz, Ersoy; Yücel-Öz, Yeliz; İrigül-Sönmez, Öykü; Ünal, Can Bora

    2015-01-01

    The human cytomegalovirus (HCMV) is an important human pathogen primarily affecting immunocompromised patients, like transplant recipients or HIV-infected individuals. Early diagnosis of cytomegalovirus (CMV) infection in high-risk patients is essential in order to start preemptive treatments. pol (UL54) gene encoding for HCMV viral DNA polymerase is a well-defined target for HCMV detection in clinical samples and identifying most highly conserved regions for primer design remains crucial. Though real-time polymerase chain reaction (qPCR) is a rapid and sensitive method for HCMV detection, failure to detect some HCMV strains due to primer and target mismatches have led the researchers to explore more sensitive and reliable methods. Hence, to understand the broader diversity of the pol mutations in HCMV and to specify the most suitable region for primer-probe design to be used in qPCR assay, we studied both nucleotide and amino acid heterogeneities in 60 HCMV positive samples that were collected to represent national mutational prevalence of pol gene of HCMV in Turkey. The test was designed with a new set of primers-probe for HCMV detection and quantification based on the sequencing data which revealed the most conserved region on the pol gene. Statistical probit analysis was applied on qPCR studies which revealed a 95% detection limit of 100 copies/mL. In addition, linearity, reproducibility, and precision of the new test were assessed for diagnostic purposes. PMID:26295291

  10. Detailed polymorphism study on cytomegalovirus DNA polymerase gene to reveal the most suitable genomic targets for quantitative Real-time PCR

    Directory of Open Access Journals (Sweden)

    Onur Bilenoğlu

    2015-06-01

    Full Text Available The human cytomegalovirus (HCMV is an important human pathogen primarily affecting immunocompromised patients, like transplant recipients or HIV- infected individuals. Early diagnosis of cytomegalovirus (CMV infection in high-risk patients is essential in order to start preemptive treatments. pol (UL54 gene encoding for HCMV viral DNA polymerase is a well-defined target for HCMV detection in clinical samples and identifying most highly conserved regions for primer design remains crucial. Though real-time polymerase chain reaction (qPCR is a rapid and sensitive method for HCMV detection, failure to detect some HCMV strains due to primer and target mismatches have led the researchers to explore more sensitive and reliable methods. Hence, to understand the broader diversity of the pol mutations in HCMV and to specify the most suitable region for primer-probe design to be used in qPCR assay, we studied both nucleotide and amino acid heterogeneities in 60 HCMV positive samples that were collected to represent national mutational prevalence of pol gene of HCMV in Turkey. The test was designed with a new set of primers- probe for HCMV detection and quantification based on the sequencing data which revealed the most conserved region on the pol gene. Statistical probit analysis was applied on qPCR studies which revealed a 95% detection limit of 100 copies/mL. In addition, linearity, reproducibility, and precision of the new test were assessed for diagnostic purposes.

  11. Detailed polymorphism study on cytomegalovirus DNA polymerase gene to reveal the most suitable genomic targets for quantitative Real-time PCR.

    Science.gov (United States)

    Bilenoğlu, Onur; Altındiş, Mustafa; Öz, Ersoy; Yücel-Öz, Yeliz; İrigül-Sönmez, Öykü; Ünal, Can Bora

    2015-06-23

    The human cytomegalovirus (HCMV) is an important human pathogen primarily affecting immunocompromised patients, like transplant recipients or HIV- infected individuals. Early diagnosis of cytomegalovirus (CMV) infection in high-risk patients is essential in order to start preemptive treatments. pol (UL54) gene encoding for HCMV viral DNA polymerase is a well-defined target for HCMV detection in clinical samples and identifying most highly conserved regions for primer design remains crucial. Though real-time polymerase chain reaction (qPCR) is a rapid and sensitive method for HCMV detection, failure to detect some HCMV strains due to primer and target mismatches have led the researchers to explore more sensitive and reliable methods. Hence, to understand the broader diversity of the pol mutations in HCMV and to specify the most suitable region for primer-probe design to be used in qPCR assay, we studied both nucleotide and amino acid heterogeneities in 60 HCMV positive samples that were collected to represent national mutational prevalence of pol gene of HCMV in Turkey. The test was designed with a new set of primers- probe for HCMV detection and quantification based on the sequencing data which revealed the most conserved region on the pol gene. Statistical probit analysis was applied on qPCR studies which revealed a 95% detection limit of 100 copies/mL. In addition, linearity, reproducibility, and precision of the new test were assessed for diagnostic purposes.

  12. Patterns of traffic polycyclic aromatic hydrocarbon pollution in mountain areas can be revealed by lichen biomonitoring: a case study in the Dolomites (Eastern Italian Alps).

    Science.gov (United States)

    Nascimbene, Juri; Tretiach, Mauro; Corana, Federica; Lo Schiavo, Fiorella; Kodnik, Danijela; Dainese, Matteo; Mannucci, Barbara

    2014-03-15

    In mountain areas of touristic interest the evaluation of the impact of human activities is crucial for ensuring long-term conservation of ecosystem biodiversity, functions and services. This study aimed at verifying the biological impact of polycyclic aromatic hydrocarbon (PAH) emissions due to traffic along the roads leading to seven passes of the Dolomites (SE Alps), which were recently declared a UNESCO World Heritage Site. Thalli of the epiphytic lichen Pseudevernia furfuracea, collected at increasing distances from the roads, were used as biomonitors. Our study revealed a gradient of decreasing PAH pollution within 300 m from the roads. Differences among passes were evident mainly for samples collected nearest to the roads, but PAH concentrations at 300 m were almost always higher than those of undisturbed reference sites, indicating that traffic PAH pollution may impact natural ecosystems and lichen diversity at relatively long distances from the emission source. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Trophic calculations reveal the mechanism of population-level variation in mercury concentrations between marine ecosystems: Case studies of two polar seabirds

    International Nuclear Information System (INIS)

    Brasso, Rebecka L.; Polito, Michael J.

    2013-01-01

    Highlights: • Ecosystem-specific baseline and consumer δ 15 N paired for population-specific trophic level. • Source of population-level variation in mercury exposure identified in two seabirds. • High mercury and trophic position suggests trophic driver of population-level variation. • Trophic similarities, differing mercury reveals geographic differences in bioavailability. -- Abstract: The incorporation of quantitative trophic level analysis in ecotoxicological studies provides explanatory power to identify the factors, trophic or environmental, driving population-level variation in mercury exposure at large geographic scales. In the Antarctic marine ecosystem, mercury concentrations and stable isotope values in Adélie penguins (Pygoscelis adeliae) were compared between the Antarctic Peninsula and the Ross Sea. Correcting tissue δ 15 N values for baseline δ 15 N values revealed population-level differences in trophic position which contributes to differences in mercury. Data from Thick-billed murres (Uria lomvia) were synthesized from published values from Baffin Bay and Svalbard to demonstrate the utility of baseline δ 15 N values in identifying differences in environmental mercury exposure independent of diet. Here, we demonstrate the importance of calculating population-specific trophic level data to uncover the source of variation in mercury concentrations between geographically distinct populations of marine predators

  14. Impact of the hydropower installations on the environment as revealed in the environmental impact studies of the Institute of Hydroelectric Studies and Design

    International Nuclear Information System (INIS)

    Teodorescu, Dan

    1996-01-01

    The results of the studies of hydropower installation impact on the environment carried out by ISPH are presented. These studies are based on the recommendations of the UN Program for the Environment, as well as those of the European Community. In the period 1993-1995 more than 15 impact studies have been carried out taking into account aspects related to geology, geomorphology, seismology, hydrology, cultural-historical patrimony archaeology, tourism and aesthetics. Both high water fall and low water fall installations located at different altitudes have been analysed. Consequently, the construction of the dams were different. From the studies, three categories of problems can be reported: 1. specific problems of a certain hydropower installation; 2. specific problems of a certain type of hydropower installation; 3. general problems regardless of the power installation type. (author)

  15. A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD

    Directory of Open Access Journals (Sweden)

    Dagmar Bruenig

    2016-01-01

    Full Text Available Posttraumatic stress disorder (PTSD is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met, has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n=257 screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n=3625. A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future.

  16. Studying the MicroRNA role as a survival predictor and revealing its part in malignancy level determination in patients with supratentorial gliomas of brain

    Science.gov (United States)

    Stupak, E. V.; Veryaskina, Yu. A.; Titov, S. E.; Achmerova, L. G.; Stupak, V. V.; Dolzhenko, D. A.; Rabinovich, S. S.; Narodov, A. A.; Ivanov, M. K.; Zhimulev, I. F.; Kolesnikov, N. N.

    2017-09-01

    The numerous data show, that microRNA (miRNA) are direct participants of carcinogenesis. Also miRNA plays the role of a diagnostic and prognostic marker for different types of cancer, including gliomas. The aim of this research is to make the comparative analysis of 10 micro RNA (miR-124, -125b, -16, -181b, -191, -21, -221, -223, -31 and -451) expression profiles. The analysis was made for gliomas with different malignancy degree, then compared with the samples of the adjacent not changed tissues (n = 90). During the study the specific profiles of miRNA expression for various histotypes of tumors were revealed. It was determined, that miRNA acts as a predictor of patient survival in the cases with malignant supratentorial brain tumors. The diagnostic approaches based on miRNA expression profile were designed. It will help to determine the malignancy level and to predict the course of the disease.

  17. Genome-wide association study reveals genetic architecture of eating behavior in pigs and its implications for humans obesity by comparative mapping

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behavior in Danish Duroc boars and its potential implications for eating behavior in humans. Data regarding individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of daily visits to feeder (NVD......1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results...... are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome...

  18. What does patient feedback reveal about the NHS? A mixed methods study of comments posted to the NHS Choices online service

    Science.gov (United States)

    Brookes, Gavin; Baker, Paul

    2017-01-01

    Objective To examine the key themes of positive and negative feedback in patients’ online feedback on NHS (National Health Service) services in England and to understand the specific issues within these themes and how they drive positive and negative evaluation. Design Computer-assisted quantitative and qualitative studies of 228 113 comments (28 971 142 words) of online feedback posted to the NHS Choices website. Comments containing the most frequent positive and negative evaluative words are qualitatively examined to determine the key drivers of positive and negative feedback. Participants Contributors posting comments about the NHS between March 2013 and September 2015. Results Overall, NHS services were evaluated positively approximately three times more often than negatively. The four key areas of focus were: treatment, communication, interpersonal skills and system/organisation. Treatment exhibited the highest proportion of positive evaluative comments (87%), followed by communication (77%), interpersonal skills (44%) and, finally, system/organisation (41%). Qualitative analysis revealed that reference to staff interpersonal skills featured prominently, even in comments relating to treatment and system/organisational issues. Positive feedback was elicited in cases of staff being caring, compassionate and knowing patients’’ names, while rudeness, apathy and not listening were frequent drivers of negative feedback. Conclusions Although technical competence constitutes an undoubtedly fundamental aspect of healthcare provision, staff members were much more likely to be evaluated both positively and negatively according to their interpersonal skills. Therefore, the findings reported in this study highlight the salience of such ‘soft’ skills to patients and emphasise the need for these to be focused upon and developed in staff training programmes, as well as ensuring that decisions around NHS funding do not result in demotivated and rushed staff. The

  19. What does patient feedback reveal about the NHS? A mixed methods study of comments posted to the NHS Choices online service.

    Science.gov (United States)

    Brookes, Gavin; Baker, Paul

    2017-04-27

    To examine the key themes of positive and negative feedback in patients' online feedback on NHS (National Health Service) services in England and to understand the specific issues within these themes and how they drive positive and negative evaluation. Computer-assisted quantitative and qualitative studies of 228 113 comments (28 971 142 words) of online feedback posted to the NHS Choices website. Comments containing the most frequent positive and negative evaluative words are qualitatively examined to determine the key drivers of positive and negative feedback. Contributors posting comments about the NHS between March 2013 and September 2015. Overall, NHS services were evaluated positively approximately three times more often than negatively. The four key areas of focus were: treatment, communication, interpersonal skills and system/organisation. Treatment exhibited the highest proportion of positive evaluative comments (87%), followed by communication (77%), interpersonal skills (44%) and, finally, system/organisation (41%). Qualitative analysis revealed that reference to staff interpersonal skills featured prominently, even in comments relating to treatment and system/organisational issues. Positive feedback was elicited in cases of staff being caring, compassionate and knowing patients'' names, while rudeness, apathy and not listening were frequent drivers of negative feedback. Although technical competence constitutes an undoubtedly fundamental aspect of healthcare provision, staff members were much more likely to be evaluated both positively and negatively according to their interpersonal skills. Therefore, the findings reported in this study highlight the salience of such 'soft' skills to patients and emphasise the need for these to be focused upon and developed in staff training programmes, as well as ensuring that decisions around NHS funding do not result in demotivated and rushed staff. The findings also reveal a significant overlap between the four key

  20. Urbanization impact on sulfur content of groundwater revealed by the study of urban speleothem-like deposits: Case study in Paris, France.

    Science.gov (United States)

    Pons-Branchu, E; Roy-Barman, M; Jean-Soro, L; Guillerme, A; Branchu, P; Fernandez, M; Dumont, E; Douville, E; Michelot, J L; Phillips, A M

    2017-02-01

    Speleothem-like deposits that develop underground in urban areas are an archive of the environmental impact of anthropic activities that has been little studied so far. In this paper, the sulfate content in shallow groundwater from northern Paris (France) is compared with the sulfur content in two 300-year-old urban carbonate deposits that grew in a historical underground aqueduct. The present-day waters of the aqueduct have very high sulfur and calcium contents, suggesting pollution from gypsum dissolution. However, geological gypsum levels are located below the water table. Sulfur content was measured by micro-X-ray fluorescence in these very S-rich carbonate deposits (0.5 to 1% of S). A twofold S increase during the second half of the 1800s was found in both samples. These dates correspond to two major periods of urbanization above the site. We discus three possible S sources: anthropic sources (industries, fertilizers…), volcanic eruptions and input within the water through gypsum brought for urbanization above the studied site (backfill with quarry waste) since the middle of the 19th century. For the younger second half of the studied section, S input from gypsum brought during urbanization was confirmed by the study of isotopic sulfur composition (δ 34 S=+15.2‰ at the top). For the oldest part, several sulfur peaks could be related to early industrial activity in Paris, that caused high local air pollution, as reported in historical archives but also to historical gypsum extraction. This study provides information on the origin and timing of the very high SO 4 2- levels measured nowadays within the shallow groundwater, thus demonstrating the interest in using carbonate deposits in urban areas as a proxy for the history of urbanization or human activities and their impact on water bodies. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.

    Science.gov (United States)

    Baron-Cohen, Simon; Murphy, Laura; Chakrabarti, Bhismadev; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Warrier, Varun

    2014-01-01

    Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of pmathematical ability, and it highlights a number of interesting markers for future study.

  2. An expressive bodily movement repertoire for marimba performance, revealed through observers’ Laban effort-shape analyses, and allied musical features: two case studies

    Directory of Open Access Journals (Sweden)

    Mary C Broughton

    2016-08-01

    Full Text Available Musicians’ expressive bodily movements can influence observers’ perception of performance. Furthermore, individual differences in observers’ music and motor expertise can shape how they perceive and respond to music performance. However, few studies have investigated the bodily movements that different observers of music performance perceive as expressive, in order to understand how they might relate to the music being produced, and the particular instrument type. In this paper, we focus on marimba performance through two case studies – one solo and one collaborative context. This study aims to investigate the existence of a core repertoire of marimba performance expressive bodily movements, identify key music-related features associated with the core repertoire, and explore how observers’ perception of expressive bodily movements might vary according to individual differences in their music and motor expertise. Of the six professional musicians who observed and analyzed the marimba performances, three were percussionists and experienced marimba players. Following training, observers implemented the Laban effort-shape movement analysis system to analyze marimba players’ bodily movements that they perceived as expressive in audio-visual recordings of performance. Observations that were agreed by all participants as being the same type of action at the same location in the performance recording were examined in each case study, then across the two studies. A small repertoire of bodily movements emerged that the observers perceived as being expressive. Movements were primarily allied to elements of the music structure, technique, and expressive interpretation, however, these elements appeared to be interactive. A type of body sway movement and more localized sound generating actions were perceived as expressive. These movements co-occurred and also appeared separately. Individual participant data revealed slightly more variety in the

  3. An Expressive Bodily Movement Repertoire for Marimba Performance, Revealed through Observers' Laban Effort-Shape Analyses, and Allied Musical Features: Two Case Studies.

    Science.gov (United States)

    Broughton, Mary C; Davidson, Jane W

    2016-01-01

    Musicians' expressive bodily movements can influence observers' perception of performance. Furthermore, individual differences in observers' music and motor expertise can shape how they perceive and respond to music performance. However, few studies have investigated the bodily movements that different observers of music performance perceive as expressive, in order to understand how they might relate to the music being produced, and the particular instrument type. In this paper, we focus on marimba performance through two case studies-one solo and one collaborative context. This study aims to investigate the existence of a core repertoire of marimba performance expressive bodily movements, identify key music-related features associated with the core repertoire, and explore how observers' perception of expressive bodily movements might vary according to individual differences in their music and motor expertise. Of the six professional musicians who observed and analyzed the marimba performances, three were percussionists and experienced marimba players. Following training, observers implemented the Laban effort-shape movement analysis system to analyze marimba players' bodily movements that they perceived as expressive in audio-visual recordings of performance. Observations that were agreed by all participants as being the same type of action at the same location in the performance recording were examined in each case study, then across the two studies. A small repertoire of bodily movements emerged that the observers perceived as being expressive. Movements were primarily allied to elements of the music structure, technique, and expressive interpretation, however, these elements appeared to be interactive. A type of body sway movement and more localized sound generating actions were perceived as expressive. These movements co-occurred and also appeared separately. Individual participant data revealed slightly more variety in the types and locations of actions

  4. Chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1992-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. In this paper the work carried out at Berkeley from the spring of 1942 to the summer of 1945 is described briefly. The aqueous chemistry of plutonium is quite remarkable. Important insights were obtained from tracer experiments, but the full complexity was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were based on aqueous solutions, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, an equilibrium was rapidly established among the four aqueous oxidation states, while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element are reported

  5. A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Simon Baron-Cohen

    Full Text Available Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419 versus low (n = 183 mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10(-5, 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10(-6. In this analysis, one of the SNPs (rs789859 showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115 were nominally significant (lowest p-value 3.278 × 10(-4. Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64. The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study.

  6. Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits.

    Directory of Open Access Journals (Sweden)

    Tamar Sofer

    Full Text Available Admixture mapping can be used to detect genetic association regions in admixed populations, such as Hispanics/Latinos, by estimating associations between local ancestry allele counts and the trait of interest. We performed admixture mapping of the blood pressure traits systolic and diastolic blood pressure (SBP, DBP, mean arterial pressure (MAP, and pulse pressure (PP, in a dataset of 12,116 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL. Hispanics/Latinos have three predominant ancestral populations (European, African, and Amerindian, for each of which we separately tested local ancestry intervals across the genome. We identified four regions that were significantly associated with a blood pressure trait at the genome-wide admixture mapping level. A 6p21.31 Amerindian ancestry association region has multiple known associations, but none explained the admixture mapping signal. We identified variants that completely explained this signal. One of these variants had p-values of 0.02 (MAP and 0.04 (SBP in replication testing in Pima Indians. A 11q13.4 Amerindian ancestry association region spans a variant that was previously reported (p-value = 0.001 in a targeted association study of Blood Pressure (BP traits and variants in the vitamin D pathway. There was no replication evidence supporting an association in the identified 17q25.3 Amerindian ancestry association region. For a region on 6p12.3, associated with African ancestry, we did not identify any candidate variants driving the association. It may be driven by rare variants. Whole genome sequence data may be necessary to fine map these association signals, which may contribute to disparities in BP traits between diverse populations.

  7. Longitudinal Study of Hepatitis A Infection by Saliva Sampling: The Kinetics of HAV Markers in Saliva Revealed the Application of Saliva Tests for Hepatitis A Study

    Science.gov (United States)

    Amado Leon, Luciane Almeida; de Almeida, Adilson José; de Paula, Vanessa Salete; Tourinho, Renata Santos; Villela, Daniel Antunes Maciel; Gaspar, Ana Maria Coimbra; Lewis-Ximenez, Lia Laura; Pinto, Marcelo Alves

    2015-01-01

    Despite the increasing numbers of studies investigating hepatitis A diagnostic through saliva, the frequency and the pattern of hepatitis A virus (HAV) markers in this fluid still remains unknown. To address this issue, we carried on a longitudinal study to examine the kinetics of HAV markers in saliva, in comparison with serum samples. The present study followed-up ten patients with acute hepatitis A infection during 180 days post diagnosis (dpd). Total anti-HAV was detected in paired serum and saliva samples until the end of the follow-up, showing a peak titer at 90th. However, total anti-HAV level was higher in serum than in saliva samples. This HAV marker showed a probability of 100% to be detected in both serum and saliva during 180 dpd. The IgM anti-HAV could be detected in saliva up to 150 dpd, showing the highest frequency at 30th, when it was detected in all individuals. During the first month of HAV infection, this acute HAV marker showed a detection probability of 100% in paired samples. The detection of IgM anti-HAV in saliva was not dependent on its level in serum, HAV-RNA detection and/or viral load, since no association was found between IgM anti-HAV positivity in saliva and any of these parameter (p>0.05). Most of the patients (80%) were found to contain HAV-RNA in saliva, mainly at early acute phase (30th day). However, it was possible to demonstrate the HAV RNA presence in paired samples for more than 90 days, even after seroconversion. No significant relationship was observed between salivary HAV-RNA positivity and serum viral load, demonstrating that serum viral load is not predictive of HAV-RNA detection in saliva. Similar viral load was seen in paired samples (on average 104 copies/mL). These data demonstrate that the best diagnostic coverage can be achieved by salivary anti-HAV antibodies and HAV-RNA tests during 30–90 dpd. The long detection and high probability of specific-HAV antibodies positivity in saliva samples make the assessment of

  8. Longitudinal Study of Hepatitis A Infection by Saliva Sampling: The Kinetics of HAV Markers in Saliva Revealed the Application of Saliva Tests for Hepatitis A Study.

    Directory of Open Access Journals (Sweden)

    Luciane Almeida Amado Leon

    Full Text Available Despite the increasing numbers of studies investigating hepatitis A diagnostic through saliva, the frequency and the pattern of hepatitis A virus (HAV markers in this fluid still remains unknown. To address this issue, we carried on a longitudinal study to examine the kinetics of HAV markers in saliva, in comparison with serum samples. The present study followed-up ten patients with acute hepatitis A infection during 180 days post diagnosis (dpd. Total anti-HAV was detected in paired serum and saliva samples until the end of the follow-up, showing a peak titer at 90th. However, total anti-HAV level was higher in serum than in saliva samples. This HAV marker showed a probability of 100% to be detected in both serum and saliva during 180 dpd. The IgM anti-HAV could be detected in saliva up to 150 dpd, showing the highest frequency at 30th, when it was detected in all individuals. During the first month of HAV infection, this acute HAV marker showed a detection probability of 100% in paired samples. The detection of IgM anti-HAV in saliva was not dependent on its level in serum, HAV-RNA detection and/or viral load, since no association was found between IgM anti-HAV positivity in saliva and any of these parameter (p>0.05. Most of the patients (80% were found to contain HAV-RNA in saliva, mainly at early acute phase (30th day. However, it was possible to demonstrate the HAV RNA presence in paired samples for more than 90 days, even after seroconversion. No significant relationship was observed between salivary HAV-RNA positivity and serum viral load, demonstrating that serum viral load is not predictive of HAV-RNA detection in saliva. Similar viral load was seen in paired samples (on average 104 copies/mL. These data demonstrate that the best diagnostic coverage can be achieved by salivary anti-HAV antibodies and HAV-RNA tests during 30-90 dpd. The long detection and high probability of specific-HAV antibodies positivity in saliva samples make the

  9. Genome-wide association study reveals novel variants for growth and egg traits in Dongxiang blue-shelled and White Leghorn chickens.

    Science.gov (United States)

    Liao, R; Zhang, X; Chen, Q; Wang, Z; Wang, Q; Yang, C; Pan, Y

    2016-10-01

    This study was designed to investigate the genetic basis of growth and egg traits in Dongxiang blue-shelled chickens and White Leghorn chickens. In this study, we employed a reduced representation sequencing approach called genotyping by genome reducing and sequencing to detect genome-wide SNPs in 252 Dongxiang blue-shelled chickens and 252 White Leghorn chickens. The Dongxiang blue-shelled chicken breed has many specific traits and is characterized by blue-shelled eggs, black plumage, black skin, black bone and black organs. The White Leghorn chicken is an egg-type breed with high productivity. As multibreed genome-wide association studies (GWASs) can improve precision due to less linkage disequilibrium across breeds, a multibreed GWAS was performed with 156 575 SNPs to identify the associated variants underlying growth and egg traits within the two chicken breeds. The analysis revealed 32 SNPs exhibiting a significant genome-wide association with growth and egg traits. Some of the significant SNPs are located in genes that are known to impact growth and egg traits, but nearly half of the significant SNPs are located in genes with unclear functions in chickens. To our knowledge, this is the first multibreed genome-wide report for the genetics of growth and egg traits in the Dongxiang blue-shelled and White Leghorn chickens. © 2016 Stichting International Foundation for Animal Genetics.

  10. Use DNA to learn from the past: how modern and ancient DNA studies may help reveal the past and predict the future distribution of species

    Science.gov (United States)

    Edwards, M. E.; Alsos, I. G.; Sjögren, P.; Coissac, E.; Gielly, L.; Yoccoz, N.; Føreid, M. K.; Taberlet, P.

    2015-12-01

    Knowledge of how climate change affected species distribution in the past may help us predict the effect of ongoing environmental changes. We explore how the use of modern (AFLP fingerprinting techniques) and ancient DNA (metabarcoding P6 loop of chloroplast DNA) help to reveal past distribution of vascular plant species, dispersal processes, and effect of species traits. Based on studies of modern DNA combined with species distribution models, we show the dispersal routes and barriers to dispersal throughout the circumarctic/circumboreal region, likely dispersal vectors, the cost of dispersal in term of loss of genetic diversity, and how these relates to species traits, dispersal distance, and size of colonized region. We also estimate the expected future distribution and loss of genetic diversity and show how this relates to life form and adaptations to dispersal. To gain more knowledge on time lags in past range change events, we rely on palaeorecords. Current data on past distribution are limited by the taxonomic and time resolution of macrofossil and pollen records. We show how this may be improved by studying ancient DNA of lake sediments. DNA of lake sediments recorded about half of the flora surrounding the lake. Compared to macrofossil, the taxonomic resolution is similar but the detection rate is considerable improved. By taking into account main determinants of founder effect, dispersal vectors, and dispersal lags, we may improve our ability to forecast effects of climate change, whereas more studies on ancient DNA may provide us with knowledge on distribution time lags.

  11. A genome-wide association study for equine recurrent airway obstruction in European Warmblood horses reveals a suggestive new quantitative trait locus on chromosome 13.

    Science.gov (United States)

    Schnider, D; Rieder, S; Leeb, T; Gerber, V; Neuditschko, M

    2017-12-01

    Recurrent airway obstruction (RAO), also known as heaves, is an asthma-like respiratory disease. Its development is strongly influenced by environmental risk factors such as sensitization and exposure to moldy hay, straw bedding and stabling indoors. A hereditary component has been documented in previous studies; however, so far no causative genetic variant that influences the risk of developing RAO has been identified. In this study, we revised an existing dataset and selected 384 horses for genotyping on the Affymetrix high-density equine SNP array. We performed an allelic case-control genome-wide association study, which revealed a suggestively significant association on equine chromosome 13 at 32 843 309 bp. This SNP is located in the protein-coding gene TXNDC11, which is possibly involved in the folding process of the multiprotein complexes DUOX1 and DUOX2. In humans, these proteins are known to take part in regulating the production of H 2 O 2 in the respiratory tract epithelium as well as in MUC5AC mucin expression. Therefore, TXNDC11 may be considered a functional candidate gene, and further research is needed to explore its potential role in RAO-affected horses. © 2017 Stichting International Foundation for Animal Genetics.

  12. Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD.

    Science.gov (United States)

    Okizuka, Yo; Takeshima, Yasuhiro; Itoh, Kyoko; Zhang, Zhujun; Awano, Hiroyuki; Maruyama, Koichi; Kumagai, Toshiyuki; Yagi, Mariko; Matsuo, Masafumi

    2010-03-30

    Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD. We enrolled 324 patients referred to the Kobe University Hospital with suspected DMD. Mutations in the dystrophin or the SGCG genes were analyzed using not only genomic DNA but also cDNA. In 322 of the 324 patients, responsible mutations in the dystrophin were successfully revealed, confirming DMD diagnosis. The remaining two patients had normal dystrophin expression but absence of gamma-sarcoglycan in skeletal muscle. Mutation analysis of the SGCG gene revealed homozygous deletion of exon 6 in one patient, while the other had a novel single nucleotide insertion in exon 7 in one allele and deletion of exon 6 in the other allele. These mutations created a stop codon that led to a gamma-sarcoglycan deficiency, and we therefore diagnosed these two patients as having LGMD2C. Thus, the relative incidence of LGMD2C among Japanese DMD-like patients can be calculated as 1 in 161 patients suspected to have DMD (2 of 324 patients = 0.6%). Taking into consideration the DMD incidence for the overall population (1/3,500 males), the incidence of LGMD2C can be estimated as 1 per 560,000 or 1.8 per million. To the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population.

  13. Structural and functional studies of the biotin protein ligase from Aquifex aeolicus reveal a critical role for a conserved residue in target specificity.

    Science.gov (United States)

    Tron, Cecile M; McNae, Iain W; Nutley, Margaret; Clarke, David J; Cooper, Alan; Walkinshaw, Malcolm D; Baxter, Robert L; Campopiano, Dominic J

    2009-03-20

    Biotin protein ligase (BPL; EC 6.3.4.15) catalyses the formation of biotinyl-5'-AMP from biotin and ATP, and the succeeding biotinylation of the biotin carboxyl carrier protein. We describe the crystal structures, at 2.4 A resolution, of the class I BPL from the hyperthermophilic bacteria Aquifex aeolicus (AaBPL) in its ligand-free form and in complex with biotin and ATP. The solvent-exposed beta- and gamma-phosphates of ATP are located in the inter-subunit cavity formed by the N- and C-terminal domains. The Arg40 residue from the conserved GXGRXG motif is shown to interact with the carboxyl group of biotin and to stabilise the alpha- and beta-phosphates of the nucleotide. The structure of the mutant AaBPL R40G in both the ligand-free and biotin-bound forms reveals that the mutated loop has collapsed, thus hindering ATP binding. Isothermal titration calorimetry indicated that the presence of biotin is not required for ATP binding to wild-type AaBPL in the absence of Mg(2+), and the binding of biotin and ATP has been determined to occur via a random but cooperative process. The affinity for biotin is relatively unaffected by the R40G mutation. In contrast, the thermodynamic data indicate that binding of ATP to AaBPL R40G is very weak in the absence or in the presence of biotin. The AaBPL R40G mutant remains catalytically active but shows poor substrate specificity; mass spectrometry and Western blot studies revealed that the mutant biotinylates both the target A. aeolicus BCCPDelta67 fragment and BSA, and is subject to self-biotinylation.

  14. Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD

    Directory of Open Access Journals (Sweden)

    Maruyama Koichi

    2010-03-01

    Full Text Available Abstract Background Limb-girdle muscular dystrophy type 2C (LGMD2C is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD. Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD. Methods We enrolled 324 patients referred to the Kobe University Hospital with suspected DMD. Mutations in the dystrophin or the SGCG genes were analyzed using not only genomic DNA but also cDNA. Results In 322 of the 324 patients, responsible mutations in the dystrophin were successfully revealed, confirming DMD diagnosis. The remaining two patients had normal dystrophin expression but absence of γ-sarcoglycan in skeletal muscle. Mutation analysis of the SGCG gene revealed homozygous deletion of exon 6 in one patient, while the other had a novel single nucleotide insertion in exon 7 in one allele and deletion of exon 6 in the other allele. These mutations created a stop codon that led to a γ-sarcoglycan deficiency, and we therefore diagnosed these two patients as having LGMD2C. Thus, the relative incidence of LGMD2C among Japanese DMD-like patients can be calculated as 1 in 161 patients suspected to have DMD (2 of 324 patients = 0.6%. Taking into consideration the DMD incidence for the overall population (1/3,500 males, the incidence of LGMD2C can be estimated as 1 per 560,000 or 1.8 per million. Conclusions To the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population.

  15. An Expressive Bodily Movement Repertoire for Marimba Performance, Revealed through Observers' Laban Effort-Shape Analyses, and Allied Musical Features: Two Case Studies

    Science.gov (United States)

    Broughton, Mary C.; Davidson, Jane W.

    2016-01-01

    Musicians' expressive bodily movements can influence observers' perception of performance. Furthermore, individual differences in observers' music and motor expertise can shape how they perceive and respond to music performance. However, few studies have investigated the bodily movements that different observers of music performance perceive as expressive, in order to understand how they might relate to the music being produced, and the particular instrument type. In this paper, we focus on marimba performance through two case studies—one solo and one collaborative context. This study aims to investigate the existence of a core repertoire of marimba performance expressive bodily movements, identify key music-related features associated with the core repertoire, and explore how observers' perception of expressive bodily movements might vary according to individual differences in their music and motor expertise. Of the six professional musicians who observed and analyzed the marimba performances, three were percussionists and experienced marimba players. Following training, observers implemented the Laban effort-shape movement analysis system to analyze marimba players' bodily movements that they perceived as expressive in audio-visual recordings of performance. Observations that were agreed by all participants as being the same type of action at the same location in the performance recording were examined in each case study, then across the two studies. A small repertoire of bodily movements emerged that the observers perceived as being expressive. Movements were primarily allied to elements of the music structure, technique, and expressive interpretation, however, these elements appeared to be interactive. A type of body sway movement and more localized sound generating actions were perceived as expressive. These movements co-occurred and also appeared separately. Individual participant data revealed slightly more variety in the types and locations of actions

  16. Quantitative meta-analysis of fMRI and PET studies reveals consistent activation in fronto-striatal-parietal regions and cerebellum during antisaccades and prosaccades

    Directory of Open Access Journals (Sweden)

    Sharna eJamadar

    2013-10-01

    Full Text Available The antisaccade task is a classic task of oculomotor control that requires participants to inhibit a saccade to a target and instead make a voluntary saccade to the mirror opposite location. By comparison, the prosaccade task requires participants to make a visually-guided saccade to the target. These tasks have been studied extensively using behavioural oculomotor, electrophysiological and neuroimaging in both non-human primates and humans. In humans, the antisaccade task is under active investigation as a potential endophenotype or biomarker for multiple psychiatric and neurological disorders. A large and growing body of literature has used functional magnetic resonance imaging (fMRI and positron emission tomography (PET to study the neural correlates of the antisaccade and prosaccade tasks. We present a quantitative meta-analysis of all published voxel-wise fMRI and PET studies (18 of the antisaccade task and show that consistent activation for antisaccades and prosaccades is obtained in a fronto-subcortical-parietal network encompassing frontal and supplementary eye fields, thalamus, striatum and intraparietal cortex. This network is strongly linked to oculomotor control and was activated to a greater extent for antisaccade than prosaccade trials. Antisaccade but not prosaccade trials additionally activated dorsolateral and ventrolateral prefrontal cortices. We also found that a number of additional regions not classically linked to oculomotor control were activated to a greater extent for antisaccade versus prosaccade trials; these regions are often reported in antisaccade studies but rarely commented upon. While the number of studies eligible to be included in this meta-analysis was small, the results of this systematic review reveal that antisaccade and prosaccade trials consistently activate a distributed network of regions both within and outside the classic definition of the oculomotor network.

  17. Gene targeting study reveals unexpected expression of brain-expressed X-linked 2 in endocrine and tissue stem/progenitor cells in mice.

    Science.gov (United States)

    Ito, Keiichi; Yamazaki, Satoshi; Yamamoto, Ryo; Tajima, Yoko; Yanagida, Ayaka; Kobayashi, Toshihiro; Kato-Itoh, Megumi; Kakuta, Shigeru; Iwakura, Yoichiro; Nakauchi, Hiromitsu; Kamiya, Akihide

    2014-10-24

    Identification of genes specifically expressed in stem/progenitor cells is an important issue in developmental and stem cell biology. Genome-wide gene expression analyses in liver cells performed in this study have revealed a strong expression of X-linked genes that include members of the brain-expressed X-linked (Bex) gene family in stem/progenitor cells. Bex family genes are expressed abundantly in the neural cells and have been suggested to play important roles in the development of nervous tissues. However, the physiological role of its individual members and the precise expression pattern outside the nervous system remain largely unknown. Here, we focused on Bex2 and examined its role and expression pattern by generating knock-in mice; the enhanced green fluorescence protein (EGFP) was inserted into the Bex2 locus. Bex2-deficient mice were viable and fertile under laboratory growth conditions showing no obvious phenotypic abnormalities. Through an immunohistochemical analysis and flow cytometry-based approach, we observed unique EGFP reporter expression patterns in endocrine and stem/progenitor cells of the liver, pyloric stomach, and hematopoietic system. Although Bex2 seems to play redundant roles in vivo, these results suggest the significance and potential applications of Bex2 in studies of endocrine and stem/progenitor cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. A Novel QTL for Powdery Mildew Resistance in Nordic Spring Barley (Hordeum vulgare L. ssp. vulgare Revealed by Genome-Wide Association Study

    Directory of Open Access Journals (Sweden)

    Therése Bengtsson

    2017-11-01

    Full Text Available The powdery mildew fungus, Blumeria graminis f. sp. hordei is a worldwide threat to barley (Hordeum vulgare L. ssp. vulgare production. One way to control the disease is by the development and deployment of resistant cultivars. A genome-wide association study was performed in a Nordic spring barley panel consisting of 169 genotypes, to identify marker-trait associations significant for powdery mildew. Powdery mildew was scored during three years (2012–2014 in four different locations within the Nordic region. There were strong correlations between data from all locations and years. In total four QTLs were identified, one located on chromosome 4H in the same region as the previously identified mlo locus and three on chromosome 6H. Out of these three QTLs identified on chromosome 6H, two are in the same region as previously reported QTLs for powdery mildew resistance, whereas one QTL appears to be novel. The top NCBI BLASTn hit of the SNP markers within the novel QTL predicted the responsible gene to be the 26S proteasome regulatory subunit, RPN1, which is required for innate immunity and powdery mildew-induced cell death in Arabidopsis. The results from this study have revealed SNP marker candidates that can be exploited for use in marker-assisted selection and stacking of genes for powdery mildew resistance in barley.

  19. Evolution of Hox-like genes in Cnidaria: Study of Hydra Hox repertoire reveals tailor-made Hox-code for Cnidarians.

    Science.gov (United States)

    Reddy, Puli Chandramouli; Unni, Manu K; Gungi, Akhila; Agarwal, Pallavi; Galande, Sanjeev

    2015-11-01

    Hox and ParaHox genes play decisive roles in patterning the anterior-posterior body axis in Bilateria. Evolutionary origin of Hox genes and primary body axis predate the divergence of Bilateria and Cnidaria. However, function of Cnidarian Hox-like genes and their regulation in axis determination is obscure due to studies limited to a few representative model systems. Present investigation is conducted using Hydra, a Hydrozoan member of phylum Cnidaria, to gain insights into the roles of Cnidarian Hox-like genes in primary axis formation. Here, we report identification of six Hox-like genes from our in-house transcriptome data. Phylogenetic analysis of these genes shows bilaterian counterparts of Hox1, Gsx and Mox. Additionally, we report CnoxB_HVUL, CnoxC2_HVUL and CnoxC3_HVUL belonging to two Cnidarian specific groups. In situ hybridization analysis of Hydra homologues provided important clues about their possible roles in pattern formation of polyps and bud development. Specifically, Hox1_HVUL is regulated by Wnt signaling and plays critical role in head formation. Collating information about expression patterns of different Hox-like genes from previous reports and this study reveals no conformity within Cnidaria. Indicating that unlike in Bilateria, there is no consolidated Hox-code determining primary body axis in Cnidaria. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Community barcoding reveals little effect of ocean acidification on the composition of coastal plankton communities: Evidence from a long-term mesocosm study in the Gullmar Fjord, Skagerrak.

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    Julia A F Langer

    Full Text Available The acidification of the oceans could potentially alter marine plankton communities with consequences for ecosystem functioning. While several studies have investigated effects of ocean acidification on communities using traditional methods, few have used genetic analyses. Here, we use community barcoding to assess the impact of ocean acidification on the composition of a coastal plankton community in a large scale, in situ, long-term mesocosm experiment. High-throughput sequencing resulted in the identification of a wide range of planktonic taxa (Alveolata, Cryptophyta, Haptophyceae, Fungi, Metazoa, Hydrozoa, Rhizaria, Straminipila, Chlorophyta. Analyses based on predicted operational taxonomical units as well as taxonomical compositions revealed no differences between communities in high CO2 mesocosms (~ 760 μatm and those exposed to present-day CO2 conditions. Observed shifts in the planktonic community composition were mainly related to seasonal changes in temperature and nutrients. Furthermore, based on our investigations, the elevated CO2 did not affect the intraspecific diversity of the most common mesozooplankter, the calanoid copepod Pseudocalanus acuspes. Nevertheless, accompanying studies found temporary effects attributed to a raise in CO2. Differences in taxa composition between the CO2 treatments could, however, only be observed in a specific period of the experiment. Based on our genetic investigations, no compositional long-term shifts of the plankton communities exposed to elevated CO2 conditions were observed. Thus, we conclude that the compositions of planktonic communities, especially those in coastal areas, remain rather unaffected by increased CO2.

  1. Distinct solubility and cytotoxicity regimes of paclitaxel-loaded cationic liposomes at low and high drug content revealed by kinetic phase behavior and cancer cell viability studies.

    Science.gov (United States)

    Steffes, Victoria M; Murali, Meena M; Park, Yoonsang; Fletcher, Bretton J; Ewert, Kai K; Safinya, Cyrus R

    2017-11-01

    Lipid-based particles are used worldwide in clinical trials as carriers of hydrophobic paclitaxel (PTXL) for cancer chemotherapy, albeit with little improvement over the standard-of-care. Improving efficacy requires an understanding of intramembrane interactions between PTXL and lipids to enhance PTXL solubilization and suppress PTXL phase separation into crystals. We studied the solubility of PTXL in cationic liposomes (CLs) composed of positively charged 2,3-dioleyloxypropyltrimethylammonium chloride (DOTAP) and neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) as a function of PTXL membrane content and its relation to efficacy. Time-dependent kinetic phase diagrams were generated from observations of PTXL crystal formation by differential-interference-contrast microscopy. Furthermore, a new synchrotron small-angle x-ray scattering in situ methodology applied to DOTAP/DOPC/PTXL membranes condensed with DNA enabled us to detect the incorporation and time-dependent depletion of PTXL from membranes by measurements of variations in the membrane interlayer and DNA interaxial spacings. Our results revealed three regimes with distinct time scales for PTXL membrane solubility: hours for >3 mol% PTXL (low), days for ≈ 3 mol% PTXL (moderate), and ≥20 days for Cell viability experiments on human cancer cell lines using CL PTXL nanoparticles (NPs) in the distinct CL PTXL solubility regimes reveal an unexpected dependence of efficacy on PTXL content in NPs. Remarkably, formulations with lower PTXL content and thus higher stability show higher efficacy than those formulated at the membrane solubility limit of ≈3 mol% PTXL (which has been the focus of most previous physicochemical studies and clinical trials of PTXL-loaded CLs). Furthermore, an additional high-efficacy regime is seen on occasion for liposome compositions with PTXL ≥9 mol% applied to cells at short time scales (hours) after formation. At longer time scales (days), CL PTXL NPs with ≥3

  2. Phylogenetic studies reveal existence of multiple lineages of a single genotype of DENV-1 (genotype III in India during 1956–2007

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    Bhattacharya D

    2009-01-01

    Full Text Available Abstract Background Dengue virus type 1 (DENV-1 have been mostly circulating silently with dominant serotypes DENV-2 and DENV-3 in India. However recent times have marked an increase in DENV-1 circulation in yearly outbreaks. Many studies have not been carried out on this virus type, leaving a lacunae pertaining to the circulating genotypes, since its earliest report in India. In the present study, we sequenced CprM gene junction of 13 DENV-1 isolated from Delhi and Gwalior (North India between 2001–2007 and one 1956 Vellore isolate as reference. For comparison, we retrieved 11 other Indian and 70 global reference sequences from NCBI database, making sure that Indian and global isolates from all decades are available for comparative analysis. Results The region was found to be AT rich with no insertion or deletion. Majority of the nucleotide substitutions were silent, except 3 non-conservative amino acid changes (I → T, A → T and L → S at amino acid positions 59,114 and 155 respectively in the Indian DENV-1 sequences, sequenced in this study. Except two 1997–98 Delhi isolates, which group in genotype I; all other Indian isolates group in genotype III. All Indian genotype III DENV-1 exhibited diversity among them, giving rise to at least 4 distinct lineages (India 1–4 showing proximity to isolates from diverse geographic locations. Conclusion The extensive phylogenetic analysis revealed consistent existence of multiple lineages of DENV-1 genotype III during the last 5 decades in India.

  3. Electronic structure of the oxygen evolving complex in photosystem II, as revealed by 55Mn Davies ENDOR studies at 2.5 K.

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    Jin, Lu; Smith, Paul; Noble, Christopher J; Stranger, Rob; Hanson, Graeme R; Pace, Ron J

    2014-05-07

    We report the first (55)Mn pulsed ENDOR studies on the S2 state multiline spin ½ centre of the oxygen evolving complex (OEC) in Photosystem II (PS II), at temperatures below 4.2 K. These were performed on highly active samples of spinach PS II core complexes, developed previously in our laboratories for photosystem spectroscopic use, at temperatures down to 2.5 K. Under these conditions, relaxation effects which have previously hindered observation of most of the manganese ENDOR resonances from the OEC coupled Mn cluster are suppressed. (55)Mn ENDOR hyperfine couplings ranging from ∼50 to ∼680 MHz are now seen on the S2 state multiline EPR signal. These, together with complementary high resolution X-band CW EPR measurements and detailed simulations, reveal that at least two and probably three Mn hyperfine couplings with large anisotropy are seen, indicating that three Mn(III) ions are likely present in the functional S2 state of the enzyme. This suggests a low oxidation state paradigm for the OEC (mean Mn oxidation level 3.0 in the S1 state) and unexpected Mn exchange coupling in the S2 state, with two Mn ions nearly magnetically silent. Our results rationalize a number of previous ligand ESEEM/ENDOR studies and labelled water exchange experiments on the S2 state of the photosystem, in a common picture which is closely consistent with recent photo-assembly (Kolling et al., Biophys. J. 2012, 103, 313-322) and large scale computational studies on the OEC (Gatt et al., Angew. Chem., Int. Ed. 2012, 51, 12025-12028, Kurashige et al. Nat. Chem. 2013, 5, 660-666).

  4. Interaction study of a novel Macrobrachium rosenbergii effector caspase with B2 and capsid proteins of M. rosenbergii nodavirus reveals their roles in apoptosis.

    Science.gov (United States)

    Youngcharoen, Supak; Senapin, Saengchan; Lertwimol, Tareerat; Longyant, Siwaporn; Sithigorngul, Paisarn; Flegel, Timothy W; Chaivisuthangkura, Parin

    2015-08-01

    Apoptosis is an essential immune response to protect invertebrates from virus infected cells. In shrimp, virus infection has been reported to induce apoptosis. Macrobrachium rosenbergii (Mr) was considered to be a disease-resistant host when compared to penaeid shrimps. Caspase-3 was classified as an executioner caspase which played a key role in virus-induced apoptosis. In this study, an effector caspase gene of M. rosenbergii (Mrcasp) was cloned and characterized. The open reading frame (ORF) of Mrcasp was 957 nucleotide encoding 318 amino acid with a deduced molecular mass of 35.87 kDa. RT-PCR analysis showed the presence of Mrcasp in all examined tissues. The phylogenetic tree indicated that Mrcasp was closely related with caspase 3 of shrimp. The functions of the Mrcasp, B2 and capsid proteins of M. rosenbergii nodavirus (MrNV) were assayed in Sf-9 cells. The results showed that Mrcasp induce apoptotic morphology cells; however, capsid protein of MrNV could inhibit apoptotic cells whereas B2 could neither induce nor inhibit apoptotic cells by DAPI staining. The protein interaction between Mrcasp and viral MrNV structure revealed that Mrcasp did not bind to B2 or capsid protein whereas B2 and capsid proteins could bind directly to each other. This study reported a novel sequence of a full-length Mrcasp and its functional studies indicated that Mrcasp could induce apoptotic cells. Our data is the first report demonstrating the direct protein-protein interaction between capsid protein and B2 protein of MrNV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.

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    Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried

    2010-01-15

    Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

  6. A combined morphological, ultrastructural, molecular, and biochemical study of the peculiar family Gomontiellaceae (Oscillatoriales) reveals a new cylindrospermopsin-producing clade of cyanobacteria.

    Science.gov (United States)

    Bohunická, Markéta; Mareš, Jan; Hrouzek, Pavel; Urajová, Petra; Lukeš, Martin; Šmarda, Jan; Komárek, Jiří; Gaysina, Lira A; Strunecký, Otakar

    2015-12-01

    Members of the morphologically unusual cyanobacterial family Gomontiellaceae were studied using a polyphasic approach. Cultured strains of Hormoscilla pringsheimii, Starria zimbabweënsis, Crinalium magnum, and Crinalium epipsammum were thoroughly examined, and the type specimen of the family, Gomontiella subtubulosa, was investigated. The results of morphological observations using both light microscopy and transmission electron microscopy were consistent with previous reports and provided evidence for the unique morphological and ultrastructural traits of this family. Analysis of the 16S rRNA gene confirmed the monophyletic origin of non-marine repre-sentatives of genera traditionally classified into this family. The family was phylogenetically placed among other groups of filamentous cyanobacterial taxa. The presence of cellulose in the cell wall was analyzed and confirmed in all cultured Gomontiellaceae members using Fourier transform infrared spectroscopy and fluorescence microscopy. Evaluation of toxins produced by the studied strains revealed the hepatotoxin cylindrospermopsin (CYN) in available strains of the genus Hormoscilla. Production of this compound in both Hormoscilla strains was detected using high-performance liquid chromatography in tandem with high resolution mass spectrometry and confirmed by positive PCR amplification of the cyrJ gene from the CYN biosynthetic cluster. To our knowledge, this is the first report of CYN production by soil cyanobacteria, establishing a previously unreported CYN-producing lineage. This study indicates that cyanobacteria of the family Gomontiellaceae form a separate but coherent cluster defined by numerous intriguing morphological, ultrastructural, and biochemical features, and exhibiting a toxic potential worthy of further investigation. © 2015 Phycological Society of America.

  7. Multivariate imaging-genetics study of MRI gray matter volume and SNPs reveals biological pathways correlated with brain structural differences in Attention Deficit Hyperactivity Disorder

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    Sabin Khadka

    2016-07-01

    Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a prevalent neurodevelopmental disorder affecting children, adolescents, and adults. Its etiology is not well-understood, but it is increasingly believed to result from diverse pathophysiologies that affect the structure and function of specific brain circuits. Although one of the best-studied neurobiological abnormalities in ADHD is reduced fronto-striatal-cerebellar gray matter volume, its specific genetic correlates are largely unknown. Methods: In this study, T1-weighted MR images of brain structure were collected from 198 adolescents (63 ADHD-diagnosed. A multivariate parallel independent component analysis technique (Para-ICA identified imaging-genetic relationships between regional gray matter volume and single nucleotide polymorphism data. Results: Para-ICA analyses extracted 14 components from genetic data and 9 from MR data. An iterative cross-validation using randomly-chosen sub-samples indicated acceptable stability of these ICA solutions. A series of partial correlation analyses controlling for age, sex, and ethnicity revealed two genotype-phenotype component pairs significantly differed between ADHD and non-ADHD groups, after a Bonferroni correction for multiple comparisons. The brain phenotype component not only included structures frequently found to have abnormally low volume in previous ADHD studies, but was also significantly associated with ADHD differences in symptom severity and performance on cognitive tests frequently found to be impaired in patients diagnosed with the disorder. Pathway analysis of the genotype component identified several different biological pathways linked to these structural abnormalities in ADHD. Conclusions: Some of these pathways implicate well-known dopaminergic neurotransmission and neurodevelopment hypothesized to be abnormal in ADHD. Other more recently implicated pathways included glutamatergic and GABA-eric physiological systems

  8. A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

    Science.gov (United States)

    Bossini-Castillo, Lara; Martin, Jose-Ezequiel; Broen, Jasper; Gorlova, Olga; Simeón, Carmen P.; Beretta, Lorenzo; Vonk, Madelon C.; Luis Callejas, Jose; Castellví, Ivan; Carreira, Patricia; José García-Hernández, Francisco; Fernández Castro, Mónica; Coenen, Marieke J.H.; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Koeleman, Bobby P.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Palm, Øyvind; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Scorza, Raffaella; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Tan, Filemon K.; Arnett, Frank C.; Agarwal, Sandeep K.; Assassi, Shervin; Fonseca, Carmen; Mayes, Maureen D.; Radstake, Timothy R.D.J.; Martin, Javier

    2012-01-01

    A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [PMH= 1.92 × 10−5 odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (PMH= 4.84 × 10−3 OR = 1.12). The second follow-up phase confirmed this finding (Pχ2 = 2.82 × 10−4 OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (PMH= 2.82 × 10−9 OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis. PMID:22076442

  9. Sound to Language: Different Cortical Processing for First and Second Languages in Elementary School Children as Revealed by a Large-Scale Study Using fNIRS

    Science.gov (United States)

    Ojima, Shiro; Matsuba-Kurita, Hiroko; Dan, Ippeita; Tsuzuki, Daisuke; Katura, Takusige; Hagiwara, Hiroko

    2011-01-01

    A large-scale study of 484 elementary school children (6–10 years) performing word repetition tasks in their native language (L1-Japanese) and a second language (L2-English) was conducted using functional near-infrared spectroscopy. Three factors presumably associated with cortical activation, language (L1/L2), word frequency (high/low), and hemisphere (left/right), were investigated. L1 words elicited significantly greater brain activation than L2 words, regardless of semantic knowledge, particularly in the superior/middle temporal and inferior parietal regions (angular/supramarginal gyri). The greater L1-elicited activation in these regions suggests that they are phonological loci, reflecting processes tuned to the phonology of the native language, while phonologically unfamiliar L2 words were processed like nonword auditory stimuli. The activation was bilateral in the auditory and superior/middle temporal regions. Hemispheric asymmetry was observed in the inferior frontal region (right dominant), and in the inferior parietal region with interactions: low-frequency words elicited more right-hemispheric activation (particularly in the supramarginal gyrus), while high-frequency words elicited more left-hemispheric activation (particularly in the angular gyrus). The present results reveal the strong involvement of a bilateral language network in children’s brains depending more on right-hemispheric processing while acquiring unfamiliar/low-frequency words. A right-to-left shift in laterality should occur in the inferior parietal region, as lexical knowledge increases irrespective of language. PMID:21350046

  10. Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study

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    Subit Barua

    2015-01-01

    Full Text Available Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development.

  11. A Systematic, Integrated Study on the Neuroprotective Effects of Hydroxysafflor Yellow A Revealed by H1 NMR-Based Metabonomics and the NF-κB Pathway

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    Yuanyan Liu

    2013-01-01

    Full Text Available Hydroxysafflor yellow A (HSYA is the main active component of the Chinese herb Carthamus tinctorius L.. Purified HSYA is used as a neuroprotective agent to prevent cerebral ischemia. Injectable safflor yellow (50 mg, containing 35 mg HSYA is widely used to treat patients with ischemic cardiocerebrovascular disease. However, it is unknown how HSYA exerts a protective effect on cerebral ischemia at the molecular level. A systematical integrated study, including histopathological examination, neurological evaluation, blood-brain barrier (BBB, metabonomics, and the nuclear factor-κB (NF-κB pathway, was applied to elucidate the pathophysiological mechanisms of HSYA neuroprotection at the molecular level. HSYA could travel across the BBB, significantly reducing the infarct volume and improving the neurological functions of rats with ischemia. Treatment with HSYA could lead to relative corrections of the impaired metabolic pathways through energy metabolism disruption, excitatory amino acid toxicity, oxidative stress, and membrane disruption revealed by 1H NMR-based metabonomics. Meanwhile, HSYA treatment inhibits the NF-κB pathway via suppressing proinflammatory cytokine expression and p65 translocation and binding activity while upregulating an anti-inflammatory cytokine.

  12. Revealing a cancer diagnosis to patients: attitudes of patients, families, friends, nurses, and physicians in Lebanon—results of a cross-sectional study

    Science.gov (United States)

    Farhat, F.; Othman, A.; el Baba, G.; Kattan, J.

    2015-01-01

    Background Disclosure of a cancer diagnosis to patients is a major problem for physicians in Lebanon. Our survey aimed to identify the attitudes of patients, families and friends, nurses, and physicians regarding disclosure of a cancer diagnosis. Methods Study participants included 343 physicians, nurses, cancer patients, families, and friends from clinics in two major hospitals in Lebanon. All completed a 29-item questionnaire that assessed, by demographic group, the information provided about cancer, opinions about the disclosure of the diagnosis to cancer patients, perceived consequences to patients, and the roles of family, friends, and religion. Results Overall, 7.8% of the patients were convinced that cancer is incurable. Nearly 82% preferred to be informed about their diagnosis. Similarly, 83% of physicians were in favour of disclosing a cancer diagnosis to their patients. However, only 14% of the physicians said that they revealed the truth to the patients themselves, with only 9% doing so immediately after confirmation of the diagnosis. Disclosure of a cancer diagnosis was preferred before the start of the treatment by 59% of the patients and immediately after confirmation of the diagnosis by 72% of the physicians. Overall, 86% of physicians, 51% of nurses, and 69% of patients and their families believed that religion helped with the acceptance of a cancer diagnosis. A role for family in accepting the diagnosis was reported by 74% of the patients, 56% of the nurses, and 88% of the physicians. All participants considered that fear was the most difficult feeling (63%) experienced by cancer patients, followed by pain (29%), pity (8%), and death (1%), with no statistically significant difference between the answers given by the participant groups. Conclusions The social background in Lebanese society is the main obstacle to revealing the truth to cancer patients. Lebanese patients seem to prefer direct communication of the truth, but families take the opposite

  13. Revealing a cancer diagnosis to patients: attitudes of patients, families, friends, nurses, and physicians in Lebanon-results of a cross-sectional study.

    Science.gov (United States)

    Farhat, F; Othman, A; El Baba, G; Kattan, J

    2015-08-01

    Disclosure of a cancer diagnosis to patients is a major problem for physicians in Lebanon. Our survey aimed to identify the attitudes of patients, families and friends, nurses, and physicians regarding disclosure of a cancer diagnosis. Study participants included 343 physicians, nurses, cancer patients, families, and friends from clinics in two major hospitals in Lebanon. All completed a 29-item questionnaire that assessed, by demographic group, the information provided about cancer, opinions about the disclosure of the diagnosis to cancer patients, perceived consequences to patients, and the roles of family, friends, and religion. Overall, 7.8% of the patients were convinced that cancer is incurable. Nearly 82% preferred to be informed about their diagnosis. Similarly, 83% of physicians were in favour of disclosing a cancer diagnosis to their patients. However, only 14% of the physicians said that they revealed the truth to the patients themselves, with only 9% doing so immediately after confirmation of the diagnosis. Disclosure of a cancer diagnosis was preferred before the start of the treatment by 59% of the patients and immediately after confirmation of the diagnosis by 72% of the physicians. Overall, 86% of physicians, 51% of nurses, and 69% of patients and their families believed that religion helped with the acceptance of a cancer diagnosis. A role for family in accepting the diagnosis was reported by 74% of the patients, 56% of the nurses, and 88% of the physicians. All participants considered that fear was the most difficult feeling (63%) experienced by cancer patients, followed by pain (29%), pity (8%), and death (1%), with no statistically significant difference between the answers given by the participant groups. The social background in Lebanese society is the main obstacle to revealing the truth to cancer patients. Lebanese patients seem to prefer direct communication of the truth, but families take the opposite approach. Physicians also prefer to

  14. Pyrosequencing Reveals Bacterial Communities in Unchlorinated Drinking Water Distribution System: An Integral Study of Bulk Water, Suspended Solids, Loose Deposits, and Pipe Wall Biofilm

    KAUST Repository

    Liu, G.

    2014-05-20

    The current understanding of drinking water distribution system (DWDS) microbiology is limited to pipe wall biofilm and bulk water; the contributions of particle-associated bacteria (from suspended solids and loose deposits) have long been neglected. Analyzing the composition and correlation of bacterial communities from different phases helped us to locate where most of the bacteria are and understand the interactions among these phases. In the present study, the bacteria from four critical phases of an unchlorinated DWDS, including bulk water, pipe wall biofilm, suspended solids, and loose deposits, were quantified and identified by adenosine triphosphate analysis and pyrosequencing, respectively. The results showed that the bulk water bacteria (including the contribution of suspended solids) contributed less than 2% of the total bacteria. The bacteria associated with loose deposits and pipe wall biofilm that accumulated in the DWDS accounted for over 98% of the total bacteria, and the contributions of bacteria in loose deposits and pipe wall biofilm were comparable. Depending on the amount of loose deposits, its contribution can be 7-fold higher than the pipe wall biofilm. Pyrosequencing revealed relatively stable bacterial communities in bulk water, pipe wall biofilm, and suspended solids throughout the distribution system; however, the communities present in loose deposits were dependent on the amount of loose deposits locally. Bacteria within the phases of suspended solids, loose deposits, and pipe wall biofilm were similar in phylogenetic composition. The bulk water bacteria (dominated by Polaromonas spp.) were clearly different from the bacteria from the other three phases (dominated by Sphingomonas spp.). This study highlighted that the integral DWDS ecology should include contributions from all of the four phases, especially the bacteria harbored by loose deposits. The accumulation of loose deposits and the aging process create variable microenvironments

  15. Pyrosequencing reveals bacterial communities in unchlorinated drinking water distribution system: an integral study of bulk water, suspended solids, loose deposits, and pipe wall biofilm.

    Science.gov (United States)

    Liu, G; Bakker, G L; Li, S; Vreeburg, J H G; Verberk, J Q J C; Medema, G J; Liu, W T; Van Dijk, J C

    2014-05-20

    The current understanding of drinking water distribution system (DWDS) microbiology is limited to pipe wall biofilm and bulk water; the contributions of particle-associated bacteria (from suspended solids and loose deposits) have long been neglected. Analyzing the composition and correlation of bacterial communities from different phases helped us to locate where most of the bacteria are and understand the interactions among these phases. In the present study, the bacteria from four critical phases of an unchlorinated DWDS, including bulk water, pipe wall biofilm, suspended solids, and loose deposits, were quantified and identified by adenosine triphosphate analysis and pyrosequencing, respectively. The results showed that the bulk water bacteria (including the contribution of suspended solids) contributed less than 2% of the total bacteria. The bacteria associated with loose deposits and pipe wall biofilm that accumulated in the DWDS accounted for over 98% of the total bacteria, and the contributions of bacteria in loose deposits and pipe wall biofilm were comparable. Depending on the amount of loose deposits, its contribution can be 7-fold higher than the pipe wall biofilm. Pyrosequencing revealed relatively stable bacterial communities in bulk water, pipe wall biofilm, and suspended solids throughout the distribution system; however, the communities present in loose deposits were dependent on the amount of loose deposits locally. Bacteria within the phases of suspended solids, loose deposits, and pipe wall biofilm were similar in phylogenetic composition. The bulk water bacteria (dominated by Polaromonas spp.) were clearly different from the bacteria from the other three phases (dominated by Sphingomonas spp.). This study highlighted that the integral DWDS ecology should include contributions from all of the four phases, especially the bacteria harbored by loose deposits. The accumulation of loose deposits and the aging process create variable microenvironments

  16. Ion Torrent PGM as tool for fungal community analysis: a case study of endophytes in Eucalyptus grandis reveals high taxonomic diversity.

    Directory of Open Access Journals (Sweden)

    Martin Kemler

    Full Text Available The Kingdom Fungi adds substantially to the diversity of life, but due to their cryptic morphology and lifestyle, tremendous diversity, paucity of formally described specimens, and the difficulty in isolating environmental strains into culture, fungal communities are difficult to characterize. This is especially true for endophytic communities of fungi living in healthy plant tissue. The developments in next generation sequencing technologies are, however, starting to reveal the true extent of fungal diversity. One of the promising new technologies, namely semiconductor sequencing, has thus far not been used in fungal diversity assessments. In this study we sequenced the internal transcribed spacer 1 (ITS1 nuclear encoded ribosomal RNA of the endophytic community of the economically important tree, Eucalyptus grandis, from South Africa using the Ion Torrent Personal Genome Machine (PGM. We determined the impact of various analysis parameters on the interpretation of the results, namely different sequence quality parameter settings, different sequence similarity cutoffs for clustering and filtering of databases for removal of sequences with incomplete taxonomy. Sequence similarity cutoff values only had a marginal effect on the identified family numbers, whereas different sequence quality filters had a large effect (89 vs. 48 families between least and most stringent filters. Database filtering had a small, but statistically significant, effect on the assignment of sequences to reference sequences. The community was dominated by Ascomycota, and particularly by families in the Dothidiomycetes that harbor well-known plant pathogens. The study demonstrates that semiconductor sequencing is an ideal strategy for environmental sequencing of fungal communities. It also highlights some potential pitfalls in subsequent data analyses when using a technology with relatively short read lengths.

  17. Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a Key Enzyme Regulating Diapause of Haemonchus contortus

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    Yan Huang

    2017-11-01

    Full Text Available Haemonchus contortus (H. contortus is one of the most important parasites of small ruminants, especially goats and sheep. The complex life cycle of this nematode is a main obstacle for the control and prevention of haemonchosis. So far, a special form of arrested development called diapause different from the dauer stage in Caenorhabditis elegans (C. elegans has been found in many parasitic nematodes. In our previous study, we have characterized a novel gene Hc-daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional analysis showed this gene has similar biological function with Ce-daf-22. In this study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and carried out rescue experiments, RNA interference (RNAi experiments and in vitro enzyme activity analysis with the mutants to further explore the precise function site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed in the rescued ok693 worms and the expression positions were mainly in the intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid staining we found that Hc-daf-22 could rescue daf-22 mutant (ok693 from the fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and body length analyses in rescue experiment along with body length and life span analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in effecting the development and capacity of C. elegans and mutants impaired the function of Hc-daf-22. Together with the protease activity assay, this research revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site-directed mutagenesis.

  18. Effects of sex and proficiency in second language processing as revealed by a large-scale fNIRS study of school-aged children.

    Science.gov (United States)

    Sugiura, Lisa; Ojima, Shiro; Matsuba-Kurita, Hiroko; Dan, Ippeita; Tsuzuki, Daisuke; Katura, Takusige; Hagiwara, Hiroko

    2015-10-01

    Previous neuroimaging studies in adults have revealed that first and second languages (L1/L2) share similar neural substrates, and that proficiency is a major determinant of the neural organization of L2 in the lexical-semantic and syntactic domains. However, little is known about neural substrates of children in the phonological domain, or about sex differences. Here, we conducted a large-scale study (n = 484) of school-aged children using functional near-infrared spectroscopy and a word repetition task, which requires a great extent of phonological processing. We investigated cortical activation during word processing, emphasizing sex differences, to clarify similarities and differences between L1 and L2, and proficiency-related differences during early L2 learning. L1 and L2 shared similar neural substrates with decreased activation in L2 compared to L1 in the posterior superior/middle temporal and angular/supramarginal gyri for both sexes. Significant sex differences were found in cortical activation within language areas during high-frequency word but not during low-frequency word processing. During high-frequency word processing, widely distributed areas including the angular/supramarginal gyri were activated in boys, while more restricted areas, excluding the angular/supramarginal gyri were activated in girls. Significant sex differences were also found in L2 proficiency-related activation: activation significantly increased with proficiency in boys, whereas no proficiency-related differences were found in girls. Importantly, cortical sex differences emerged with proficiency. Based on previous research, the present results indicate that sex differences are acquired or enlarged during language development through different cognitive strategies between sexes, possibly reflecting their different memory functions. © 2015 Wiley Periodicals, Inc.

  19. Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a Key Enzyme Regulating Diapause of Haemonchus contortus.

    Science.gov (United States)

    Huang, Yan; Zheng, Xiuping; Zhang, Hongli; Ding, Haojie; Guo, Xiaolu; Yang, Yi; Chen, Xueqiu; Zhou, Qianjin; Du, Aifang

    2017-01-01

    Haemonchus contortus ( H. contortus ) is one of the most important parasites of small ruminants, especially goats and sheep. The complex life cycle of this nematode is a main obstacle for the control and prevention of haemonchosis. So far, a special form of arrested development called diapause different from the dauer stage in Caenorhabditis elegans ( C. elegans ) has been found in many parasitic nematodes. In our previous study, we have characterized a novel gene Hc-daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional analysis showed this gene has similar biological function with Ce-daf-22 . In this study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and carried out rescue experiments, RNA interference (RNAi) experiments and in vitro enzyme activity analysis with the mutants to further explore the precise function site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed in the rescued ok693 worms and the expression positions were mainly in the intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid staining we found that Hc-daf-22 could rescue daf-22 mutant ( ok693 ) from the fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and body length analyses in rescue experiment along with body length and life span analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in effecting the development and capacity of C. elegans and mutants impaired the function of Hc-daf-22 . Together with the protease activity assay, this research revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site-directed mutagenesis.

  20. A new approach for studying GPCR dimers: drug-induced inactivation and reactivation to reveal GPCR dimer function in vitro, in primary culture, and in vivo

    Science.gov (United States)

    Teitler, Milt; Klein, Michael T.

    2011-01-01

    GPCRs are a major family of homologous proteins and are key mediators of the effects of numerous endogenous neurotransmitters, hormones, cytokines, therapeutic drugs, and drugs-of-abuse. Despite the enormous amount of research on the pharmacological and biochemical properties of GPCRs, the question as to whether they exist as monomers, dimers, or higher order structures in the body is unanswered. The GPCR dimer field has been dominated by techniques involving recombinant cell lines expressing mutant receptors, often involving the solubilization of the receptors. These techniques cannot be applied in vivo or even to primary cell cultures. This review will focus on a novel approach to exploring the functional properties of homodimers. Studies of the 5-HT7 and 5-HT2A serotonin receptors have revealed that binding of a pseudo-irreversible antagonist (“inactivator”) to one of the orthosteric sites of a homodimer abolishes all receptor activity, and subsequent binding of a competitive antagonist to the orthosteric site of the second protomer releases the inactivator, allowing the receptor to return to an active state. This approach demonstrates allosteric crosstalk between protomers of native GPCR homodimers, indicating that GPCRs do exist and function as homodimers in both recombinant cells and rat primary astrocytes. This technique can be applied universally using intact recombinant or primary cells in culture, membrane homogenate preparations and, potentially, in vivo. The data obtained using the 5-HT7 and 5-HT2A receptors are strongly supportive of a GPCR homodimer structure, with little evidence of monomer involvement in the function of these receptors. PMID:22119169

  1. Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements

    Science.gov (United States)

    Sauer-Heilborn, Annette; Welte, Tobias; Guzman, Carlos A.; Abraham, Wolf-Rainer; Höfle, Manfred G.

    2015-01-01

    The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF. PMID:26135861

  2. Structural and functional studies of the modulator NS9283 reveal agonist-like mechanism of action at α4β2 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Olsen, Jeppe A; Ahring, Philip K; Kastrup, Jette S; Gajhede, Michael; Balle, Thomas

    2014-09-05

    Modulation of Cys loop receptor ion channels is a proven drug discovery strategy, but many underlying mechanisms of the mode of action are poorly understood. We report the x-ray structure of the acetylcholine-binding protein from Lymnaea stagnalis with NS9283, a stoichiometry selective positive modulator that targets the α4-α4 interface of α4β2 nicotinic acetylcholine receptors (nAChRs). Together with homology modeling, mutational data, quantum mechanical calculations, and pharmacological studies on α4β2 nAChRs, the structure reveals a modulator binding mode that overlaps the α4-α4 interface agonist (acetylcholine)-binding site. Analysis of contacts to residues known to govern agonist binding and function suggests that modulation occurs by an agonist-like mechanism. Selectivity for α4-α4 over α4-β2 interfaces is determined mainly by steric restrictions from Val-136 on the β2-subunit and favorable interactions between NS9283 and His-142 at the complementary side of α4. In the concentration ranges where modulation is observed, its selectivity prevents NS9283 from directly activating nAChRs because activation requires coordinated action from more than one interface. However, we demonstrate that in a mutant receptor with one natural and two engineered α4-α4 interfaces, NS9283 is an agonist. Modulation via extracellular binding sites is well known for benzodiazepines acting at γ-aminobutyric acid type A receptors. Like NS9283, benzodiazepines increase the apparent agonist potency with a minimal effect on efficacy. The shared modulatory profile along with a binding site located in an extracellular subunit interface suggest that modulation via an agonist-like mechanism may be a common mechanism of action that potentially could apply to Cys loop receptors beyond the α4β2 nAChRs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. High-Resolution Longitudinal Study of HIV-1 Env Vaccine-Elicited B Cell Responses to the Virus Primary Receptor Binding Site Reveals Affinity Maturation and Clonal Persistence.

    Science.gov (United States)

    Wang, Yimeng; Sundling, Christopher; Wilson, Richard; O'Dell, Sijy; Chen, Yajing; Dai, Kaifan; Phad, Ganesh E; Zhu, Jiang; Xiao, Yongli; Mascola, John R; Karlsson Hedestam, Gunilla B; Wyatt, Richard T; Li, Yuxing

    2016-05-01

    Because of the genetic variability of the HIV-1 envelope glycoproteins (Env), the elicitation of neutralizing Abs to conserved neutralization determinants including the primary receptor binding site, CD4 binding site (CD4bs), is a major focus of vaccine development. To gain insight into the evolution of Env-elicited Ab responses, we used single B cell analysis to interrogate the memory B cell Ig repertoires from two rhesus macaques after five serial immunizations with Env/adjuvant. We observed that the CD4bs-specific repertoire displayed unique features in the third CDR of Ig H chains with minor alterations along the immunization course. Progressive affinity maturation occurred as evidenced by elevated levels of somatic hypermutation (SHM) in Ab sequences isolated at the late immunization time point compared with the early time point. Abs with higher SHM were associated with increased binding affinity and virus neutralization capacity. Moreover, a notable portion of the CD4bs-specific repertoire was maintained between early and late immunization time points, suggesting that persistent clonal lineages were induced by Env vaccination. Furthermore, we found that the predominant persistent CD4bs-specific clonal lineages had larger population sizes and higher affinities than that from the rest of the repertoires, underscoring the critical role of Ag affinity selection in Ab maturation and clonal expansion. Genetic and functional analyses revealed that the accumulation of SHM in both framework regions and CDRs contributed to the clonal affinity and antigenicity evolution. Our longitudinal study provides high-resolution understanding of the dynamically evolving CD4bs-specific B cell response after Env immunization in primates. Copyright © 2016 by The American Association of Immunologists, Inc.

  4. High Resolution Longitudinal Study of HIV-1 Env Vaccine-elicited B Cell Responses to the Virus Primary Receptor Binding Site Reveals Affinity Maturation and Clonal Persistence

    Science.gov (United States)

    Wang, Yimeng; Sundling, Christopher; Wilson, Richard; O’Dell, Sijy; Chen, Yajing; Dai, Kaifan; Phad, Ganesh E.; Zhu, Jiang; Xiao, Yongli; Mascola, John R.; Karlsson Hedestam, Gunilla B.; Wyatt, Richard T.; Li, Yuxing

    2016-01-01

    Due to the genetic variability of the HIV-1 envelope glycoproteins (Env), the elicitation of neutralizing antibodies to conserved neutralization determinants including the primary receptor binding site, CD4 binding site (CD4bs), is a major focus of vaccine development. To gain insight into the evolution of Env-elicited antibody responses, we utilized single B cell analysis to interrogate the memory B cell Ig repertoires from two rhesus macaques following five serial immunizations with Env/adjuvant. We observed that the CD4bs-specific repertoire displayed unique features in the third complementarity determining region (CDR3) of Ig heavy chains with minor alterations along the immunization course. Progressive affinity maturation occurred as evidenced by elevated levels of somatic hypermutation (SHM) in antibody sequences isolated at late immunization time point compared to the early time point. Antibodies with higher SHM were associated with increased binding affinity and virus neutralization capacity. Moreover, a notable portion of the CD4bs-specific repertoire was maintained between early and late immunization time points, suggesting that persistent clonal lineages were induced by Env vaccination. Furthermore, we found that the predominant persistent CD4bs-specific clonal lineages had larger population sizes and higher affinities than that from the rest of the repertoires, underscoring the critical role of antigen affinity selection in antibody maturation and clonal expansion. Genetic and functional analyses revealed that the accumulation of SHM in both framework regions and CDRs contributed to the clonal affinity and antigenicity evolution. Our longitudinal study provides high resolution understanding of the dynamically evolving CD4bs-specific B cell response following Env immunization in primates. PMID:27001953

  5. Syntopic frogs reveal different patterns of interaction with the landscape: A comparative landscape genetic study of Pelophylax nigromaculatus and Fejervarya limnocharis from central China.

    Science.gov (United States)

    Garcia, Vhon Oliver S; Ivy, Catherine; Fu, Jinzhong

    2017-11-01

    Amphibians are often considered excellent environmental indicator species. Natural and man-made landscape features are known to form effective genetic barriers to amphibian populations; however, amphibians with different characteristics may have different species-landscape interaction patterns. We conducted a comparative landscape genetic analysis of two closely related syntopic frog species from central China, Pelophylax nigromaculatus ( PN ) and Fejervarya limnocharis ( FL ). These two species differ in several key life history traits; PN has a larger body size and larger clutch size, and reaches sexual maturity later than FL . Microsatellite DNA data were collected and analyzed using conventional ( F ST , isolation by distance (IBD), AMOVA) and recently developed (Bayesian assignment test, isolation by resistance) landscape genetic methods. As predicted, a higher level of population structure in FL ( F ST ' = 0.401) than in PN ( F ST ' = 0.354) was detected, in addition to FL displaying strong IBD patterns ( r  =   .861) unlike PN ( r  =   .073). A general north-south break in FL populations was detected, consistent with the IBD pattern, while PN exhibited clustering of northern- and southern-most populations, suggestive of altered dispersal patterns. Species-specific resistant landscape features were also identified, with roads and land cover the main cause of resistance to FL , and elevation the main influence on PN . These different species-landscape interactions can be explained mostly by their life history traits, revealing that closely related and ecologically similar species have different responses to the same landscape features. Comparative landscape genetic studies are important in detecting such differences and refining generalizations about amphibians in monitoring environmental changes.

  6. Expression of ERCC1, p53, and class III β-tubulin do not reveal chemoresistance in endometrial cancer: results from an immunohistochemical study.

    Science.gov (United States)

    Vandenput, Ingrid; Capoen, An; Coenegrachts, Lieve; Verbist, Godelieve; Moerman, Philippe; Vergote, Ignace; Amant, Frédéric

    2011-08-01

    In non-small cell lung cancer, expression of excision repair cross-complementation group 1 (ERCC1) and p53 correlates with platinum resistance and class III β-tubulin with resistance to taxanes. The potential to personalize treatment in endometrial cancer remains uninvestigated. Patients received platinum-based chemotherapy, with or without paclitaxel. Patients were divided into 2 groups: group A (n = 33) consisted of patients with early-stage endometrial cancer treated with adjuvant chemotherapy. Group B (n = 116) included cases with primary advanced or recurrent disease. Immunohistochemistry was performed to analyze the expression of ERCC1 and p53, for all cases, and class III β-tubulin for cases treated with paclitaxel. The findings were correlated with response according to Response Criteria in Solid Tumors; recurrence-free, disease-specific survival; and established prognostic markers. The mean age of 149 patients was 64 years (range, 31-84 years). Distribution of histopathologic subtypes was as follows: 44 endometrioid (30%), 92 serous/clear cell (62%), and 13 carcinosarcomas (8%).In group A, 11 (33%) and 19 patients (58%) showed expression for ERCC1 and p53, respectively. Seven (78%) of nine patients receiving paclitaxel were positive for class III β-tubulin. There was no correlation between expression of ERCC1, p53, or class III β-tubulin and recurrence or survival. In group B, 25 (22%) and 61 patients (64%) were positive for ERCC1 and p53, respectively. Fifty-two (74%) of seventy patients receiving paclitaxel were positive for class III β-tubulin. Only p53 expression correlated with survival (P = 0.01). In contrast to theoretical assumptions, the current study did not reveal evidence that the expression of ERCC1 and class III β-tubulin predicts response to cytotoxic treatment and patient outcome in endometrial cancer.

  7. A large cohort study reveals the association of elevated peripheral blood lymphocyte-to-monocyte ratio with favorable prognosis in nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available BACKGROUND: Nasopharyngeal carcinoma (NPC is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20-30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients. METHODS: A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS, disease-free survival (DFS, distant metastasis-free survival (DMFS and loco-regional recurrence-free survival (LRRFS, respectively. RESULTS: Univariate analysis revealed that higher LMR level (≥ 5.220 was significantly associated with superior OS, DFS and DMFS (P values <0.001. The higher lymphocyte count (≥ 2.145 × 10(9/L was significantly associated with better OS (P = 0.002 and DMFS (P = 0.031, respectively, while the lower monocyte count (<0.475 × 10(9/L was associated with better OS (P = 0.012, DFS (P = 0.011 and DMFS (P = 0.003, respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.558, 95% confidence interval or 95% CI = 0.417-0.748; P<0.001, DFS (HR = 0.669, 95% CI = 0.535-0.838; P<0.001 and DMFS (HR = 0.543, 95% CI = 0.403-0.732; P<0.001, respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053 and DMFS (P = 0.080. CONCLUSIONS: The

  8. Structure/Function Studies of the α4 Subunit Reveal Evolutionary Loss of a GlyR Subtype Involved in Startle and Escape Responses

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    Sophie Leacock

    2018-01-01

    Full Text Available Inhibitory glycine receptors (GlyRs are pentameric ligand-gated anion channels with major roles in startle disease/hyperekplexia (GlyR α1, cortical neuronal migration/autism spectrum disorder (GlyR α2, and inflammatory pain sensitization/rhythmic breathing (GlyR α3. However, the role of the GlyR α4 subunit has remained enigmatic, because the corresponding human gene (GLRA4 is thought to be a pseudogene due to an in-frame stop codon at position 390 within the fourth membrane-spanning domain (M4. Despite this, a recent genetic study has implicated GLRA4 in intellectual disability, behavioral problems and craniofacial anomalies. Analyzing data from sequenced genomes, we found that GlyR α4 subunit genes are predicted to be intact and functional in the majority of vertebrate species—with the exception of humans. Cloning of human GlyR α4 cDNAs excluded alternative splicing and RNA editing as mechanisms for restoring a full-length GlyR α4 subunit. Moreover, artificial restoration of the missing conserved arginine (R390 in the human cDNA was not sufficient to restore GlyR α4 function. Further bioinformatic and mutagenesis analysis revealed an additional damaging substitution at K59 that ablates human GlyR α4 function, which is not present in other vertebrate GlyR α4 sequences. The substitutions K59 and X390 were also present in the genome of an ancient Denisovan individual, indicating that GLRA4 has been a pseudogene for at least 30,000–50,000 years. In artificial synapses, we found that both mouse and gorilla α4β GlyRs mediate synaptic currents with unusually slow decay kinetics. Lastly, to gain insights into the biological role of GlyR α4 function, we studied the duplicated genes glra4a and glra4b in zebrafish. While glra4b expression is restricted to the retina, using a novel tol2-GAL4FF gene trap line (SAIGFF16B, we found that the zebrafish GlyR α4a subunit gene (glra4a is strongly expressed in spinal cord and hindbrain commissural

  9. Principal States of Dynamic Functional Connectivity Reveal the Link Between Resting-State and Task-State Brain: An fMRI Study.

    Science.gov (United States)

    Cheng, Lin; Zhu, Yang; Sun, Junfeng; Deng, Lifu; He, Naying; Yang, Yang; Ling, Huawei; Ayaz, Hasan; Fu, Yi; Tong, Shanbao

    2018-01-25

    Task-related reorganization of functional connectivity (FC) has been widely investigated. Under classic static FC analysis, brain networks under task and rest have been demonstrated a general similarity. However, brain activity and cognitive process are believed to be dynamic and adaptive. Since static FC inherently ignores the distinct temporal patterns between rest and task, dynamic FC may be more a suitable technique to characterize the brain's dynamic and adaptive activities. In this study, we adopted [Formula: see text]-means clustering to investigate task-related spatiotemporal reorganization of dynamic brain networks and hypothesized that dynamic FC would be able to reveal the link between resting-state and task-state brain organization, including broadly similar spatial patterns but distinct temporal patterns. In order to test this hypothesis, this study examined the dynamic FC in default-mode network (DMN) and motor-related network (MN) using Blood-Oxygenation-Level-Dependent (BOLD)-fMRI data from 26 healthy subjects during rest (REST) and a hand closing-and-opening (HCO) task. Two principal FC states in REST and one principal FC state in HCO were identified. The first principal FC state in REST was found similar to that in HCO, which appeared to represent intrinsic network architecture and validated the broadly similar spatial patterns between REST and HCO. However, the second FC principal state in REST with much shorter "dwell time" implied the transient functional relationship between DMN and MN during REST. In addition, a more frequent shifting between two principal FC states indicated that brain network dynamically maintained a "default mode" in the motor system during REST, whereas the presence of a single principal FC state and reduced FC variability implied a more temporally stable connectivity during HCO, validating the distinct temporal patterns between REST and HCO. Our results further demonstrated that dynamic FC analysis could offer unique

  10. Lectin histochemical study on the olfactory organ of the newt, Cynops pyrrhogaster, revealed heterogeneous mucous environments in a single nasal cavity.

    Science.gov (United States)

    Saito, Shouichiro; Matsui, Toshiyasu; Kobayashi, Naoto; Wakisaka, Hiroyuki; Mominoki, Katsumi; Matsuda, Seiji; Taniguchi, Kazuyuki

    2003-04-01

    Expression patterns of glycoconjugates were examined by lectin histochemistry in the nasal cavity of the Japanese red-bellied newt, Cynops pyrrhogaster. Its nasal cavity consisted of two components, a flattened chamber, which was the main nasal chamber (MNC), and a lateral diverticulum called the lateral nasal sinus (LNS), which communicated medially with the MNC. The MNC was lined with the olfactory epithelium (OE), while the diverticulum constituting the LNS was lined with the vomeronasal epithelium (VNE). Nasal glands were observed beneath the OE but not beneath the VNE. In addition, a secretory epithelium was revealed on the dorsal boundary between the MNC and the LNS, which we refer to as the boundary secretory epithelium (BSE) in this study. The BSE seemed to play an important role in the construction of the mucous composition of the VNE. Among 21 lectins used in this study, DBA, SBA and Jacalin showed different staining patterns between the OE and the VNE. DBA staining showed remarkable differences between the OE and the VNE; there was intense staining in the free border and the supporting cells of the VNE, whereas there was no staining or weak staining in the cells of the OE. SBA and Jacalin showed different stainings in the receptor neurons for the OE and the VNE. Furthermore, UEA-I and Con A showed different stainings for the nasal glands. UEA-I showed intense staining in the BSE and in the nasal glands located in the ventral wall of the MNC (VNG), whereas Con A showed intense staining in the BSE and in the nasal glands located in the dorsal and medial wall of the MNC (DMNG). The DMNG were observed to send their excretory ducts into the OE, whereas no excretory ducts were observed from the VNG to the OE or the VNE. These results suggested that the secretion by the supporting cells as well as the BSE and the DMNG establishes that there are heterogeneous mucous environments in the OE and the VNE, although both epithelia are situated in the same nasal cavity.

  11. Study of Mycobacterium tuberculosis complex genotypic diversity in Malaysia reveals a predominance of ancestral East-African-Indian lineage with a Malaysia-specific signature.

    Science.gov (United States)

    Ismail, Fazli; Couvin, David; Farakhin, Izzah; Abdul Rahman, Zaidah; Rastogi, Nalin; Suraiya, Siti

    2014-01-01

    Tuberculosis (TB) still constitutes a major public health problem in Malaysia. The identification and genotyping based characterization of Mycobacterium tuberculosis complex (MTBC) isolates causing the disease is important to determine the effectiveness of the control and surveillance programs. This study intended a first assessment of spoligotyping-based MTBC genotypic diversity in Malaysia followed by a comparison of strains with those prevailing in neighboring countries by comparison with an international MTBC genotyping database. Spoligotyping was performed on a total of 220 M. tuberculosis clinical isolates collected in Kelantan and Kuala Lumpur. The results were compared with the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Spoligotyping revealed 77 different patterns: 22 corresponded to orphan patterns while 55 patterns containing 198 isolates were assigned a Spoligo International Type (SIT) designation in the database (the latter included 6 newly created SITs). The eight most common SITs grouped 141 isolates (5 to 56 strains per cluster) as follows: SIT1/Beijing, n = 56, 25.5%; SIT745/EAI1-SOM, n = 33, 15.0%; SIT591/EAI6-BGD1, n = 13, 5.9%; SIT256/EAI5, n = 12, 5.5%; SIT236/EAI5, n = 10, 4.6%; SIT19/EAI2-Manila, n = 9, 4.1%; SIT89/EAI2-Nonthaburi, n = 5, 2.3%; and SIT50/H3, n = 3, 1.4%. The association between city of isolation and lineages was statistically significant; Haarlem and T lineages being higher in Kuala Lumpur (p<0.01). However, no statistically significant differences were noted when comparing drug resistance vs. major lineages, nor between gender and clades. The ancestral East-African-Indian (EAI) lineage was most predominant followed by the Beijing lineage. A comparison of strains with those prevailing in neighboring countries in South Asia, East Asia and South East Asia underlined the phylogeographical specificity of SIT745 for Malaysia, and its probable ongoing evolution with locally

  12. Study of Mycobacterium tuberculosis complex genotypic diversity in Malaysia reveals a predominance of ancestral East-African-Indian lineage with a Malaysia-specific signature.

    Directory of Open Access Journals (Sweden)

    Fazli Ismail

    Full Text Available Tuberculosis (TB still constitutes a major public health problem in Malaysia. The identification and genotyping based characterization of Mycobacterium tuberculosis complex (MTBC isolates causing the disease is important to determine the effectiveness of the control and surveillance programs.This study intended a first assessment of spoligotyping-based MTBC genotypic diversity in Malaysia followed by a comparison of strains with those prevailing in neighboring countries by comparison with an international MTBC genotyping database.Spoligotyping was performed on a total of 220 M. tuberculosis clinical isolates collected in Kelantan and Kuala Lumpur. The results were compared with the SITVIT2 international database of the Pasteur Institute of Guadeloupe.Spoligotyping revealed 77 different patterns: 22 corresponded to orphan patterns while 55 patterns containing 198 isolates were assigned a Spoligo International Type (SIT designation in the database (the latter included 6 newly created SITs. The eight most common SITs grouped 141 isolates (5 to 56 strains per cluster as follows: SIT1/Beijing, n = 56, 25.5%; SIT745/EAI1-SOM, n = 33, 15.0%; SIT591/EAI6-BGD1, n = 13, 5.9%; SIT256/EAI5, n = 12, 5.5%; SIT236/EAI5, n = 10, 4.6%; SIT19/EAI2-Manila, n = 9, 4.1%; SIT89/EAI2-Nonthaburi, n = 5, 2.3%; and SIT50/H3, n = 3, 1.4%. The association between city of isolation and lineages was statistically significant; Haarlem and T lineages being higher in Kuala Lumpur (p<0.01. However, no statistically significant differences were noted when comparing drug resistance vs. major lineages, nor between gender and clades.The ancestral East-African-Indian (EAI lineage was most predominant followed by the Beijing lineage. A comparison of strains with those prevailing in neighboring countries in South Asia, East Asia and South East Asia underlined the phylogeographical specificity of SIT745 for Malaysia, and its probable ongoing evolution

  13. Outer Membrane Permeability of Cyanobacterium Synechocystis sp. Strain PCC 6803: Studies of Passive Diffusion of Small Organic Nutrients Reveal the Absence of Classical Porins and Intrinsically Low Permeability

    Science.gov (United States)

    Kowata, Hikaru; Tochigi, Saeko; Takahashi, Hideyuki

    2017-01-01

    ABSTRACT The outer membrane of heterotrophic Gram-negative bacteria plays the role of a selective permeability barrier that prevents the influx of toxic compounds while allowing the nonspecific passage of small hydrophilic nutrients through porin channels. Compared with heterotrophic Gram-negative bacteria, the outer membrane properties of cyanobacteria, which are Gram-negative photoautotrophs, are not clearly understood. In this study, using small carbohydrates, amino acids, and inorganic ions as permeation probes, we determined the outer membrane permeability of Synechocystis sp. strain PCC 6803 in intact cells and in proteoliposomes reconstituted with outer membrane proteins. The permeability of this cyanobacterium was >20-fold lower than that of Escherichia coli. The predominant outer membrane proteins Slr1841, Slr1908, and Slr0042 were not permeable to organic nutrients and allowed only the passage of inorganic ions. Only the less abundant outer membrane protein Slr1270, a homolog of the E. coli export channel TolC, was permeable to organic solutes. The activity of Slr1270 as a channel was verified in a recombinant Slr1270-producing E. coli outer membrane. The lack of putative porins and the low outer membrane permeability appear to suit the cyanobacterial autotrophic lifestyle; the highly impermeable outer membrane would be advantageous to cellular survival by protecting the cell from toxic compounds, especially when the cellular physiology is not dependent on the uptake of organic nutrients. IMPORTANCE Because the outer membrane of Gram-negative bacteria affects the flux rates for various substances into and out of the cell, its permeability is closely associated with cellular physiology. The outer membrane properties of cyanobacteria, which are photoautotrophic Gram-negative bacteria, are not clearly understood. Here, we examined the outer membrane of Synechocystis sp. strain PCC 6803. We revealed that it is relatively permeable to inorganic ions but is

  14. Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype-anti-idiotype Fab complex.

    Science.gov (United States)

    Wong, Yee Hwa; Goh, Boon Chong; Lim, She Yah; Teo, En Wei; Lim, Angeline P C; Dedon, Pete C; Hanson, Brendon J; MacAry, Paul A; Lescar, Julien

    2017-06-21

    A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic Flaviviruses such as Dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idiotype antibody (E1) specific for a potent, fully human DENV serotype 1-specific antibody termed HM14c10, derived from a recovered patient. The crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 provides the first detailed molecular comparison of an anti-idiotype paratope specific for a human antibody with its analogous epitope- a discontinuous quaternary structure located at the surface of the viral particle that spans adjacent envelope (E) proteins. This comparison reveals that the footprints left by E1 and E on HM14c10 largely overlap, explaining why formation of the binary complexes are mutually exclusive. Structural mimicry of the DENV E epitope by the E1 combining site is achieved via the formation of numerous interactions with heavy chain CDRs of HM14c10, while fewer interactions are observed with its light chain, compared to the E protein. We show that E1 can be utilized to detect HM14c10-like antibodies in sera from patients recovered from a DENV-1 infection suggesting that this is a public (common) idiotype. These data demonstrate the utility of employing an anti-idiotype antibody to monitor a patient's specific immune responses and suggest routes for improvement of E 'mimicry' by E1 through increasing its recognition of the FabHM14c10 light chain CDRs. IMPORTANCE A chimeric yellow fever/dengue live-attenuated tetravalent vaccine is now marketed. Dengue remains a significant public health problem, because protection conferred by this vaccine is uneven against the four circulating serotypes. Reliable tools must be developed to measure the immune response of individuals exposed to DENV, either via viral infection

  15. A comparative study of ancient sedimentary DNA, pollen and macrofossils from permafrost sediments of northern Siberia reveals long-term vegetational stability

    DEFF Research Database (Denmark)

    Jørgensen, Tina; Haile, James Seymour; Möller, Per

    2012-01-01

    approach. SedaDNA and macrofossils share greater overlap in plant identifications than with pollen, suggesting that sedaDNA is local in origin. These two proxies also permit identification to lower taxonomic levels than pollen, enabling investigation into temporal changes in species composition...... and the determination of indicator species to describe environmental changes. Combining data from all three proxies reveals an area continually dominated by a mosaic vegetation of tundra-steppe, pioneer and wet-indicator plants. Such vegetational stability is unexpected, given the severe climate changes taking place...

  16. Increase of sodium current after pyrethroid insecticides in mouse neuroblastoma cells

    NARCIS (Netherlands)

    Ruigt, G.S.F.; Neyt, H.C.; Zalm, J.M. van der; Bercken, J. van der

    1987-01-01

    The effects of 4 different pyrethroid insecticides on sodium channel gating in internally perfused, cultured mouse neuroblastoma cells (N1E-115) were studied using the suction pipette, voltage clamp technique. Pyrethroids increased the amplitude of the sodium current, sometimes by more than 200%.

  17. Chloride channels in toad skin

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Rasmussen, B E

    1982-01-01

    A study of the voltage and time dependence of a transepithelial Cl- current in toad skin (Bufo bufo) by the voltage-clamp method leads to the conclusion that potential has a dual role for Cl- transport. One is to control the permeability of an apical membrane Cl-pathway, the other is to drive Cl...

  18. Advanced patch-clamp techniques and single-channel analysis

    NARCIS (Netherlands)

    Biskup, B; Elzenga, JTM; Homann, U; Thiel, G; Wissing, F; Maathuis, FJM

    Much of our knowledge of ion-transport mechanisms in plant cell membranes comes from experiments using voltage-clamp. This technique allows the measurement of ionic currents across the membrane, whilst the voltage is held under experimental control. The patch-clamp technique was developed to study

  19. Proteomic study of serum using gel chromatography and MALDI-TOF MS reveals diagnostic biomarkers in male patients with liver-cancer

    Science.gov (United States)

    Zeng, Xin-Hua; Huang, He-Qing; Chen, Dong-Shi; Jin, Hong-Wei; Huang, Hui-Ying

    2007-03-01

    Human serum has been widely employed clinically for diagnosing various fatal diseases. However, the concentration of most proteins in human serum is too low to be directly measured using normal analytical methods. In order to obtain reliable analytical results from proteomic analysis of human serum, appropriate sample preparation is essential. A combined off-line analytical technique of gel chromatography and matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) has been successfully established to separate proteins for MS analysis. Using these combined techniques, 176 mass signal peaks of proteins/peptides were found in 6 of 18 fractions from normal male serum (NMS) in the presence of buffer consisting of NH4HCO3 and acetonitrile. A simple gel chromatography column packed with Sephadex G-50 removed most signal-suppressing compounds such as salts and high abundance proteins (HAP). The molecular mass to charge (m/z) ratios of differential peptides revealed in serum of male patient with liver-cancer (LCMPS) compared to NMS were 5365, 5644 and 6462, and these peptides can be used as biomarkers to clinically diagnose liver-cancer. The simple and convenient chromatographic method described here is not only superior to recently described HPLC separation for MS analysis, but also reveals many novel and significant serum biomarkers for the clinical diagnosis of various diseases.

  20. TypeScript revealed

    CERN Document Server

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  1. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...

  2. NMR studies of the fifth transmembrane segment of Na+,K+-ATPase reveals a non-helical ion-binding region

    DEFF Research Database (Denmark)

    Underhaug, Jarl; Jakobsen, Louise Odgaard; Esmann, Mikael

    2006-01-01

    The structure of a synthetic peptide corresponding to the fifth membrane-spanning segment (M5) in Na(+),K(+)-ATPase in sodium dodecyl sulfate (SDS) micelles was determined using liquid-state nuclear magnetic resonance (NMR) spectroscopy. The spectra reveal that this peptide is substantially less...... transmembrane element of the Ca(2+)-ATPase. Furthermore, this region spans the residues implicated in Na(+) and K(+) transport, where they are likely to offer the flexibility needed to coordinate Na(+) as well as K(+) during active transport....... alpha-helical than the corresponding M5 peptide of Ca(2+)-ATPase. A well-defined alpha-helix is shown in the C-terminal half of the peptide. Apart from a short helical stretch at the N-terminus, the N-terminal half contains a non-helical region with two proline residues and sequence similarity to a non-structured...

  3. Genome-wide association study in breast cancer survivors reveals SNPs associated with gene expression of genes belonging to MHC class I and II.

    Science.gov (United States)

    Landmark-Høyvik, Hege; Dumeaux, Vanessa; Nebdal, Daniel; Lund, Eiliv; Tost, Jörg; Kamatani, Yoichiro; Renault, Victor; Børresen-Dale, Anne-Lise; Kristensen, Vessela; Edvardsen, Hege

    2013-10-01

    We investigated the effect of genetic variation on gene expression in blood from a cohort of BC survivors. Further, we investigated the associations that were specific for BC survivors by performing identical analyses for a group of healthy women and comparing the results. eQTL analysis was performed for 288 BC survivors (full data set). Further, using a subset of the data, eQTL analyses were performed on 288 BC survivors and on 81 healthy women separately and results were compared. A large number of associations were observed for the BC survivors, and the expression of human leukocyte antigen genes was found associated with SNPs in 100 genes. The comparison analyses with healthy women revealed associations occurring specifically in BC survivors, and the genes showed enrichment for immune system processes. The results suggest that the immune system has a different constitution in BC survivors compared to healthy women. © 2013 Elsevier Inc. All rights reserved.

  4. The crystal structure, mutagenesis, and activity studies reveal that patatin is a lipid acyl hydrolase with a Ser-Asp catalytic dyad.

    Science.gov (United States)

    Rydel, Timothy J; Williams, Jennifer M; Krieger, Elysia; Moshiri, Farhad; Stallings, William C; Brown, Sherri M; Pershing, Jay C; Purcell, John P; Alibhai, Murtaza F

    2003-06-10

    Patatin is a nonspecific lipid acyl hydrolase that accounts for approximately 40% of the total soluble protein in mature potato tubers, and it has potent insecticidal activity against the corn rootworm. We determined the X-ray crystal structure of a His-tagged variant of an isozyme of patatin, Pat17, to 2.2 A resolution, employing SeMet multiwavelength anomalous dispersion (MAD) phasing methods. The patatin crystal structure has three molecules in the asymmetric unit, an R-factor of 22.0%, and an R(free) of 27.2% (for 10% of the data not included in the refinement) and includes 498 water molecules. The structure notably revealed that patatin has a Ser-Asp catalytic dyad and an active site like that of human cytosolic phospholipase A(2) (cPLA(2)) [Dessen, A., et al. (1999) Cell 97, 349-360]. In addition, patatin has a folding topology related to that of the catalytic domain of cPLA(2) and unlike the canonical alpha/beta-hydrolase fold. The structure confirms our site-directed mutagenesis and bioactivity data that initially suggested patatin possessed a Ser-Asp catalytic dyad. Alanine-scanning mutagenesis revealed that Ser77 and Asp215 were critical for both esterase and bioactivity, consistent with prior work implicating a Ser residue [Strickland, J. H., et al. (1995) Plant Physiol. 109, 667-674] and a Ser-Asp dyad [Hirschberg, H. J. H. B., et al. (2001) Eur. J. Biochem. 268, 5037-5044] in patatin's catalytic activity. The crystal structure aids the understanding of other structure-function relationships in patatin. Patatin does not display interfacial activation, a hallmark feature of lipases, and this is likely due to the fact that it lacks a flexible lid that can shield the active site.

  5. Dysregulation of the descending pain system in temporomandibular disorders revealed by low-frequency sensory transcutaneous electrical nerve stimulation: a pupillometric study.

    Directory of Open Access Journals (Sweden)

    Annalisa Monaco

    Full Text Available Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS is dysregulated in patients suffering from temporomandibular disorders (TMDs, suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation and long after (recovery period sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired

  6. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test...... in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even...

  7. Urinary Loss of Tricarboxylic Acid Cycle Intermediates As Revealed by Metabolomics Studies: An Underlying Mechanism to Reduce Lipid Accretion by Whey Protein Ingestion?

    Science.gov (United States)

    2015-01-01

    Whey protein intake is associated with the modulation of energy metabolism and altered body composition both in human subjects and in animals, but the underlying mechanisms are not yet elucidated. We fed obesity-prone C57BL/6J mice high-fat diets with either casein (HF casein) or whey (HF whey) for 6 weeks. At equal energy intake and apparent fat and nitrogen digestibility, mice fed HF whey stored less energy as lipids, evident both as lower white adipose tissue mass and as reduced liver lipids, compared with HF-casein-fed mice. Explorative analyses of 48 h urine, both by 1H NMR and LC–MS metabolomic platforms, demonstrated higher urinary excretion of tricarboxylic acid (TCA) cycle intermediates citric acid and succinic acid (identified by both platforms), and cis-aconitic acid and isocitric acid (identified by LC–MS platform) in the HF whey, relative to in the HF-casein-fed mice. Targeted LC–MS analyses revealed higher citric acid and cis-aconitic acid concentrations in fed state plasma, but not in liver of HF-whey-fed mice. We propose that enhanced urinary loss of TCA cycle metabolites drain available substrates for anabolic processes, such as lipogenesis, thereby leading to reduced lipid accretion in HF-whey-fed compared to HF-casein-fed mice. PMID:24702026

  8. An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism.

    Science.gov (United States)

    Mélade, Julien; Wieseke, Nicolas; Ramasindrazana, Beza; Flores, Olivier; Lagadec, Erwan; Gomard, Yann; Goodman, Steven M; Dellagi, Koussay; Pascalis, Hervé

    2016-04-12

    An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.

  9. An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism

    Science.gov (United States)

    Mélade, Julien; Wieseke, Nicolas; Ramasindrazana, Beza; Flores, Olivier; Lagadec, Erwan; Gomard, Yann; Goodman, Steven M.; Dellagi, Koussay; Pascalis, Hervé

    2016-01-01

    An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats. PMID:27068130

  10. A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: A comparative study of human psychophysics and rat behaviour.

    Science.gov (United States)

    Dunham, James P; Hulse, Richard P; Donaldson, Lucy F

    2015-07-15

    Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents. We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured. Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: -11.3 °C to -11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours. Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients. Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain. Copyright © 2015. Published by Elsevier B.V.

  11. Impact of Erasmus mobility for study on the development of Tuning Europe generic competences, as assessed by outgoing and incoming students in a large university: a revealing analysis

    Directory of Open Access Journals (Sweden)

    Luigi F. Donà dalle Rose

    2015-12-01

    Full Text Available We explore on the basis of a simple survey tool the perceived impact of the Erasmus mobility experience on the improvement of the thirty generic competences of the Tuning Europe list. We rely on a self-assessment procedure, i.e. on data collected by the Erasmus Office of the University of Padova, Italy, through end-of-stay questionnaires, as returned by both outgoing and incoming Erasmus students. Processed data yield the percentage number of ticks, by which a given competence was chosen by the answering samples. We introduce a quantity “importance of improvement”, which measures the perceived degree of development of a given generic competence during the mobility experience and allows a consistent comparison among different samples. On this basis, we can order the thirty competences according to decreasing perceived importance of improvement in the two above samples. From a general point of view, Erasmus students perceive the most important improvement in instrumental competences. We can then carry out meaningful comparisons between the profiles of competences’ improvement of outgoing and incoming students, both in qualitative and in quantitative terms. Such a comparison reveals interesting features linked to the academic and human environments of mobile students. A further step in the analysis describes how country effects give more insight into the previous results. In such a context, we analyze the country impact on each given competence for both outgoing (visiting the country and incoming (from the country students, on the country subgroup  competences’ profile and on the exchange of competences, which occurs between paired country subgroups.

  12. Six Month In Situ High-Resolution Carbonate Chemistry and Temperature Study on a Coral Reef Flat Reveals Asynchronous pH and Temperature Anomalies.

    Directory of Open Access Journals (Sweden)

    David I Kline

    Full Text Available Understanding the temporal dynamics of present thermal and pH exposure on coral reefs is crucial for elucidating reef response to future global change. Diel ranges in temperature and carbonate chemistry parameters coupled with seasonal changes in the mean conditions define periods during the year when a reef habitat is exposed to anomalous thermal and/or pH exposure. Anomalous conditions are defined as values that exceed an empirically estimated threshold for each variable. We present a 200-day time series from June through December 2010 of carbonate chemistry and environmental parameters measured on the Heron Island reef flat. These data reveal that aragonite saturation state, pH, and pCO2 were primarily modulated by biologically-driven changes in dissolved organic carbon (DIC and total alkalinity (TA, rather than salinity and temperature. The largest diel temperature ranges occurred in austral spring, in October (1.5 - 6.6°C and lowest diel ranges (0.9 - 3.2°C were observed in July, at the peak of winter. We observed large diel total pH variability, with a maximum range of 7.7 - 8.5 total pH units, with minimum diel average pH values occurring during spring and maximum during fall. As with many other reefs, the nighttime pH minima on the reef flat were far lower than pH values predicted for the open ocean by 2100. DIC and TA both increased from June (end of Fall to December (end of Spring. Using this high-resolution dataset, we developed exposure metrics of pH and temperature individually for intensity, duration, and severity of low pH and high temperature events, as well as a combined metric. Periods of anomalous temperature and pH exposure were asynchronous on the Heron Island reef flat, which underlines the importance of understanding the dynamics of co-occurrence of multiple stressors on coastal ecosystems.

  13. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  14. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

    2012-01-01

    BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

  15. Uncovering the secret lives of sewer rats (Rattus norvegicus): Movements, distribution and population dynamics revealed by a capture-mark-recapture study

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte; Sluydts, Vincent; Leirs, Herwig E.l.

    2012-01-01

    and behaviour of these populations. Aims.: The study aimed to uncover the population dynamics, movements and distribution of rats in populations living in sewers. Methods.: We studied rats in a capture–mark–recapture study in two adjacent but separate sewer systems in suburban Copenhagen, Denmark, covering......-to-day movements took place over shorter distances. There were no movements of rats between sewer systems and no sewer rats were observed to be active on the surface. The rat populations seemed to be substructured in smaller groups. Conclusions.: Sewer rat populations vary irregularly in abundance. Pipe dimensions...

  16. A proteomics study reveals a predominant change in MaoB expression in platelets of healthy volunteers after high protein meat diet

    DEFF Research Database (Denmark)

    Zellner, Maria; Babeluk, Rita; Jakobsen, Lene Holm

    2011-01-01

    Studies investigating the impact of high meat intake on cognition have yielded contradictory results as some show improved cognitive performance, whereas others report an increase of risk factors for dementia. However, few studies were designed to directly assess the effect of a high protein (HP)...... showed improved cognitive function and counteract well-known dementia biomarkers such as platelet MaoB and components of the methylation cycle such as vitamin B(12) and homocysteine....

  17. Label-free solution-based kinetic study of aptamer-small molecule interactions by kinetic capillary electrophoresis with UV detection revealing how kinetics control equilibrium.

    Science.gov (United States)

    Bao, Jiayin; Krylova, Svetlana M; Reinstein, Oren; Johnson, Philip E; Krylov, Sergey N

    2011-11-15

    Here we demonstrate a label-free solution-based approach for studying the kinetics of biopolymer-small molecule interactions. The approach utilizes kinetic capillary electrophoresis (KCE) separation and UV light absorption detection of the unlabeled small molecule. In this proof-of-concept work, we applied KCE-UV to study kinetics of interaction between a small molecule and a DNA aptamer. From the kinetic analysis of a series of aptamers, we found that dissociation rather than binding controls the stability of the complex. Because of its label-free features and generic nature, KCE-UV promises to become a practical tool for challenging kinetic studies of biopolymer-small molecule interactions.

  18. Isolation of novel microsatellites using FIASCO by dual probe enrichment from Jatropha curcas L. and study on genetic equilibrium and diversity of Indian population revealed by isolated microsatellites

    KAUST Repository

    Pamidimarri, D. V N N Sudheer

    2010-03-11

    Jatropha curcas L. belongs to family Euphorbiaceae, native to South America attained significant importance for its seed oil which can be converted to biodiesel, a renewable energy source alternative to conventional petrodiesel. Very few attempts were made to isolate novel microsatellite markers and assessment of the extent of genetic equilibrium and diversity that exists in J. curcas. Therefore, the present investigation was undertaken to isolate the novel microsatellites and access genetic equilibrium, diversity that exists among 44 diverse germplasm collected from distinct geographical areas in India using isolated microsatellites. The overall efficiency of the enrichment of microsatellite by dual probe in the present study found to be 54% and among the sequences obtained the percentage of sequences having suitable flanking regions for the primer designing was found to be 89.58%. The mean co-efficient of genetic similarity (CGS) was found to be 0.97. The overall diversity obtained by microsatellites was found to be low in comparison with the diversity reported by multilocus markers systems observed in earlier studies; however, the good allele polymorphism was observed. The overall dendrogram of microsatellite analysis resulted in random clustering of germplasm and not in accordance to geographical area of collection. The present study, diversity analysis using microsatellite markers concludes the low genetic diversity and genetic disequlibrium of J. curcas in India and will provide pavement for further intra-population studies on narrow geographical areas to understand the population genetic structure, phylogeography and molecular ecological studies. The germplasm characterized, and the microsatellite markers isolated and characterized in the present study can be employed efficiently in breeding programs for genetic improvement of the species through marker assisted selection and QTL analysis, for further genetic resource management and help in making the J

  19. A comparative study of APLI and APCI in IMS at atmospheric pressure to reveal and explain peak broadening effects by the use of APLI.

    Science.gov (United States)

    Ihlenborg, Marvin; Raupers, Björn; Gunzer, Frank; Grotemeyer, Jürgen

    2015-11-21

    The details of the ionization mechanism in atmospheric pressure are still not completely known. In order to obtain further insight into the occurring processes in atmospheric pressure laser ionization (APLI) a comparative study of atmospheric pressure chemical ionization (APCI) and APLI is presented in this paper. This study is carried out using similar experimental condition at atmospheric pressure employing a commercial ion mobility spectrometer (IMS). Two different peak broadening mechanisms can then be assigned, one related to a range of different species generated and detected, and furthermore for the first time a power broadening effect on the signals can be identified.

  20. Revealing Conceptual Understanding of International Business

    Science.gov (United States)

    Ashley, Sue; Schaap, Harmen; de Bruijn, Elly

    2017-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students' conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual understanding in higher education. Essays and concept…

  1. All SNPs Are Not Created Equal: Genome-Wide Association Studies Reveal a Consistent Pattern of Enrichment among Functionally Annotated SNPs

    NARCIS (Netherlands)

    Schork, Andrew J.; Thompson, Wesley K.; Pham, Phillip; Torkamani, Ali; Roddey, J. Cooper; Sullivan, Patrick F.; Kelsoe, John R.; O'Donovan, Michael C.; Furberg, Helena; Schork, Nicholas J.; Andreassen, Ole A.; Dale, Anders M.; Absher, Devin; Agudo, Antonio; Almgren, Peter; Ardissino, Diego; Assimes, Themistocles L.; Bandinelli, Stephania; Barzan, Luigi; Bencko, Vladimir; Benhamou, Simone; Benjamin, Emelia J.; Bernardinelli, Luisa; Bis, Joshua; Boehnke, Michael; Boerwinkle, Eric; Boomsma, Dorret I.; Brennan, Paul; Canova, Cristina; Castellsagué, Xavier; Chanock, Stephen; Chasman, Daniel; Conway, David I.; Dackor, Jennifer; de Geus, Eco J. C.; Duan, Jubao; Elosua, Roberto; Everett, Brendan; Fabianova, Eleonora; Ferrucci, Luigi; Foretova, Lenka; Fortmann, Stephen P.; Franceschini, Nora; Frayling, Timothy; Furberg, Curt; Gejman, Pablo V.; Groop, Leif; Gu, Fangyi; Guralnik, Jack; Hankinson, Susan E.; Haritunians, Talin; Healy, Claire; Hofman, Albert; Holcátová, Ivana; Hunter, David J.; Hwang, Shih-Jen; Ioannidis, John P. A.; Iribarren, Carlos; Jackson, Anne U.; Janout, Vladimir; Kaprio, Jaakko; Kim, Yunjung; Kjaerheim, Kristina; Knowles, Joshua W.; Kraft, Peter; Ladenvall, Claes; Lagiou, Pagona; Lanthrop, Mark; Lerman, Caryn; Levinson, Douglas F.; Levy, Daniel; Li, Ming D.; Lin, Dan Yu; Lips, Esther H.; Lissowska, Jolanta; Lowry, Ray; Lucas, Gavin; Macfarlane, Tatiana V.; Maes, Hermine; Mannucci, Pier Mannuccio; Mates, Dana; Mauri, Francesco; McGovern, Janet Audrain; McKay, James D.; McKnight, Barbara; Melander, Olle; Merlini, Piera Angelica; Milaneschi, Yuri; Mohlke, Karen L.; O'Donnell, Christopher J.; Pare, Guillaume; Penninx, Brenda W.; Perry, John; Posthuma, Danielle; Preis, Sarah Rosner; Psaty, Bruce; Quertermous, Thomas; Ramachandran, Vasan S.; Richiardi, Lorenzo; Ridker, Paul; Rose, Jed; Rudnai, Peter; Salomaa, Veikko; Sanders, Alan R.; Schwartz, Stephen M.; Shi, Jianxin; Smit, Johannes H.; Stringham, Heather M.; Szeszenia-Dabrowska, Neonilia; Tanaka, Toshiko; Taylor, Kent; Thacker, Evan; Thornton, Laura; Tiemeier, Henning; Tuomilehto, Jaakko; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Vink, Jacqueline M.; Vogelzangs, Nicole; Voight, Benjamin F.; Walter, Stefan; Willemsen, Gonneke; Zaridze, David; Znaor, Ariana; Akil, Huda; Anjorin, Adebayo; Backlund, Lena; Badner, Judith A.; Barchas, Jack D.; Barrett, Thomas B.; Bass, Nick; Bauer, Michael; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Blackwood, Douglas; Bloss, Cinnamon S.; Breen, Gerome; Breuer, René; Bunner, William E.; Burmeister, Margit; Byerley, William; Caesar, Sian; Chambert, Kim; Cichon, Sven; St Clair, David; Collier, David A.; Corvin, Aiden; Coryell, William H.; Craddock, Nicholas; Craig, David W.; Daly, Mark; Day, Richard; Degenhardt, Franziska; Djurovic, Srdjan; Dudbridge, Frank; Edenberg, Howard J.; Elkin, Amanda; Etain, Bruno; Farmer, Anne E.; Ferreira, Manuel A.; Ferrier, I. Nicol; Flickinger, Matthew; Foroud, Tatiana; Frank, Josef; Fraser, Christine; Frisén, Louise; Gershon, Elliot S.; Gill, Michael; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; Gustafsson, Ómar; Hamshere, Marian L.; Hautzinger, Martin; Herms, Stefan; Hipolito, Maria; Holmans, Peter A.; Hultman, Christina M.; Jamain, Stéphane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Kandaswamy, Radhika; Kennedy, James L.; Kirov, George K.; Koller, Daniel L.; Kwan, Phoenix; Landén, Mikael; Langstrom, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Lee, Phil H.; Li, Jun; Lichtenstein, Paul; Lin, Danyu; Liu, Chunyu; Lohoff, Falk W.; Lucae, Susanne; Mahon, Pamela B.; Maier, Wolfgang; Martin, Nicholas G.; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McGhee, Kevin A.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McQuillin, Andrew; Meier, Sandra; Melle, Ingrid; Meng, Fan; Mitchell, Philip B.; Montgomery, Grant W.; Moran, Jennifer; Morken, Gunnar; Morris, Derek W.; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W.; Muir, Walter J.; Müller-Myhsok, Bertram; Myers, Richard M.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nöthen, Markus M.; Nurnberger, John I.; Nwulia, Evaristus A.; O'Dushlaine, Colm; Osby, Urban; Óskarsson, Högni; Owen, Michael J.; Petursson, Hannes; Pickard, Benjamin S.; Porgeirsson, Porgeir; Potash, James B.; Propping, Peter; Purcell, Shaun M.; Quinn, Emma; Raychaudhuri, Soumya; Rice, John; Rietschel, Marcella; Ruderfer, Douglas; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schofield, Peter R.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus M.; Scolnick, Ed; Scott, Laura J.; Shilling, Paul D.; Sigurdsson, Engilbert; Sklar, Pamela; Smith, Erin N.; Stefansson, Hreinn; Stefansson, Kari; Steffens, Michael; Steinberg, Stacy; Strauss, John; Strohmaier, Jana; Szelinger, Szabocls; Thompson, Robert C.; Tozzi, Federica; Treutlein, Jens; Vincent, John B.; Watson, Stanley J.; Wienker, Thomas F.; Williamson, Richard; Witt, Stephanie H.; Wright, Adam; Xu, Wei; Young, Allan H.; Zandi, Peter P.; Zhang, Peng; Zöllner, Sebastian; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bitter, István; Black, Donald W.; Børglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Danoy, Patrick A.; Datta, Susmita; DeHert, Marc; Demontis, Ditte; Dikeos, Dimitris; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fanous, Ayman; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Glenthøj, Birte; Godard, Stephanie; Golimbet, Vera; de Haan, Lieuwe; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Ingason, Andrés; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Jönsson, Erik G.; Jürgens, Gesche; Kahn, René S.; Keller, Matthew C.; Kendler, Kenneth S.; Kenis, Gunter; Kenny, Elaine; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lencz, Todd; Lerer, F. Bernard; Liang, Kung-Yee; Lieberman, Jeffrey A.; Linszen, Don H.; Lönnqvist, Jouko; Loughland, Carmel M.; Maclean, Alan W.; Maher, Brion S.; Malhotra, Anil K.; Mallet, Jacques; Malloy, Pat; McGrath, John J.; McLean, Duncan E.; Michie, Patricia T.; Milanova, Vihra; Mors, Ole; Mortensen, Preben B.; Mowry, Bryan J.; Myin-Germeys, Inez; Neale, Benjamin; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nordentoft, Merete; Norton, Nadine; O'Neill, F. Anthony; Olincy, Ann; Olsen, Line; Ophoff, Roel A.; Ørntoft, Torben F.; van Os, Jim; Pantelis, Christos; Papadimitriou, George; Pato, Carlos N.; Pato, Michele T.; Peltonen, Leena; Pickard, Ben; Pietiläinen, Olli P. H.; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Rasmussen, Henrik B.; Réthelyi, János M.; Ribble, Robert; Riley, Brien P.; Rossin, Lizzy; Ruggeri, Mirella; Rujescu, Dan; Schall, Ulrich; Schwab, Sibylle G.; Scolnick, Edward; Scott, Rodney J.; Silverman, Jeremy M.; Spencer, Chris C. A.; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Timm, Sally; Toncheva, Draga; Tosato, Sarah; van den Oord, Edwin J. C. G.; Veldink, Jan; Visscher, Peter M.; Walsh, Dermot; Wang, August G.; Werge, Thomas; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; van Winkel, Ruud; Wormley, Brandon; Zammit, Stan

    2013-01-01

    Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery

  2. NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high-fibre rye bread

    DEFF Research Database (Denmark)

    Bertram, Hanne C; Bach Knudsen, Knud E; Serena, Anja

    2006-01-01

    This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegra...

  3. Toxic pyrene metabolism in Mycobacterium gilvum PYR-GCK results in the expression of mammalian cell entry genes as revealed by transcriptomics study.

    Science.gov (United States)

    Badejo, Abimbola Comfort; Chung, Won Hyong; Kim, Nam Shin; Kim, Se Kye; Chai, Jin Choul; Lee, Young Seek; Jung, Kyoung Hwa; Kim, Hyo Joon; Chai, Young Gyu

    2014-09-01

    Mycobacterium gilvum PYR-GCK is a bacterial strain under study for its bioremediation use on heavy hydrocarbon pollutants in the environment. During the course of our study, mammalian cell entry (mce) genes, known to facilitate pathogenicity in M. tuberculosis, were highly expressed during a comparative and substrate-related cultural global transcriptomic study. RNA sequencing of the global transcriptome of the test strain in two different substrates, pyrene and glucose, showed high expression of the mce genes based on the differential results. After validating the expression of these genes with quantitative real-time PCR, we arrived at the conclusion that the genes were expressed based on the pyrene substrate (a phytosterol compound), and sterol metabolism is said to activate the expression of the mce genes in some actinomycetes bacteria, M. gilvum PYR-GCK in this case. This study is believed to be important based on the fact that some mycobacterial strains are undergoing a continuous research as a result of their use in practical bioremediation of anthropogenic exposure of toxic organic wastes in the environment.

  4. Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality

    NARCIS (Netherlands)

    Seppala, I.; Kleber, M.E.; Lyytikainen, L.P.; Hernesniemi, J.A.; Makela, K.M.; Oksala, N.; Laaksonen, R.; Pilz, S.; Tomaschitz, A.; Silbernagel, G.; Boehm, B.O.; Grammer, T.B.; Koskinen, T.; Juonala, M.; Hutri-Kahonen, N.; Alfthan, G.; Viikari, J.S.A.; Kahonen, M.; Raitakari, O.T.; Marz, W.; Meinitzer, A.; Lehtimaki, T.

    2014-01-01

    AimsThe purpose of this study was to identify novel genetic variants influencing circulating asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels and to evaluate whether they have a prognostic value on cardiovascular mortality.Methods and resultsWe conducted a genome-wide

  5. NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high-fibre rye bread

    DEFF Research Database (Denmark)

    Bertram, Hanne C; Bach Knudsen, Knud E; Serena, Anja

    2006-01-01

    This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegrain...... disclosed biochemical effects of a wholegrain diet on plasma betaine content and excretion of betaine and creatinine....

  6. Small angle x-ray studies reveal that Aspergillus niger glucoamylase has a defined extended conformation and can form dimers in solution

    DEFF Research Database (Denmark)

    Jørgensen, Anders Dysted; Nøhr, Jane; Kastrup, Jette Sandholm

    2008-01-01

    is poorly understood and structurally undescribed, and data regarding domain organization and intramolecular functional cooperativity are conflicting or non-comprehensive. Here, we report a combined small angle x-ray scattering and calorimetry study of Aspergillus niger glucoamylase 1, glucoamylase 2, which...

  7. Do our talks with patients meet their expectations? Yes, for the most part they do. Results of this study, however, reveal specific areas that require greater attention.

    NARCIS (Netherlands)

    Brink-Muinen, A. van den; Dulmen, A.M. van; Jung, H.P.; Bensing, J.M.

    2007-01-01

    While it's encouraging that physicians by and large understand their patients and communicate with them meaningfully, we wondered whether communication could improve further. Our purpose in this study was to gain detailed insight into patients' preferences in physician communication and, through

  8. Delta Plots in the study of individual differences: New tools reveal response inhibition deficits in AD/HD that are eliminated by methylphenidate treatment

    NARCIS (Netherlands)

    Ridderinkhof, K.R.; Scheres, A.; Oosterlaan, J.; Sergeant, J.A.

    2005-01-01

    The authors highlight the utility of distribution-analytical techniques in the study of individual differences and clinical disorders. Cognitive deficits associated with attention-deficit/hyperactivity disorder (AD/HD) were examined by using delta-plot analyses of performance data (reaction time and

  9. Comparative activity of tigecycline and tetracycline on Gram-negative and Gram-positive bacteria revealed by a multicentre study in four North European countries

    DEFF Research Database (Denmark)

    Nilsson, Lennart E; Frimodt-Møller, Niels; Vaara, Martti

    2011-01-01

    This study involves a multicentre surveillance of tigecycline and tetracycline activity against Gram-negative and Gram-positive bacteria from primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs) in Denmark (n = 9), Finland (n = 10), Norway (n = 7) and Sweden (n...

  10. All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs

    DEFF Research Database (Denmark)

    Schork, Andrew J; Thompson, Wesley K; Pham, Phillip

    2013-01-01

    Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discov...

  11. Impact of the whole-cell patch-clamp configuration on the pharmacological assessment of the hERG channel: trazodone as a case example.

    Science.gov (United States)

    Rodriguez-Menchaca, Aldo A; Ferrer, Tania; Navarro-Polanco, Ricardo A; Sanchez-Chapula, Jose A; Moreno-Galindo, Eloy G

    2014-01-01

    Voltage- and state-dependent blocks are important mechanisms by which drugs affect voltage-gated ionic channels. However, spontaneous (i.e. drug-free) time-dependent changes in the activation and inactivation of hERG and Na(+) channels have been reported when using conventional whole-cell patch-clamp in HEK-293 cells. hERG channels were heterologously expressed in HEK-293 cells and in Xenopus laevis oocytes. hERG current (IhERG) was recorded using both conventional and perforated whole-cell patch-clamp (HEK-293 cells), and two microelectrode voltage-clamp (Xenopus oocytes) in drug-free solution, and in the presence of the drug trazodone. In conventional whole-cell setup, we observed a spontaneous time-dependent hyperpolarizing shift in the activation curve of IhERG. Conversely, in perforated patch whole-cell (HEK-293 cells) or in two microelectrode voltage-clamp (Xenopus oocytes) activation curves of IhERG were very stable for periods ~50min. Voltage-dependent inactivation of IhERG was not significantly altered in the three voltage clamp configurations tested. When comparing voltage- and state-dependent effects of the antidepressant drug trazodone on IhERG, similar changes between the three voltage clamp configurations were observed as under drug-free conditions. The comparative analysis performed in this work showed that only under conventional whole-cell voltage-clamp conditions, a leftward shift in the activation curve of IhERG occurred, both in the presence and absence of drugs. These spontaneous time-dependent changes in the voltage activation gate of IhERG are a potential confounder in pharmacological studies on hERG channels expressed in HEK-293 cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Bio-functions and molecular carbohydrate structure association study in forage with different source origins revealed using non-destructive vibrational molecular spectroscopy techniques.

    Science.gov (United States)

    Ji, Cuiying; Zhang, Xuewei; Yan, Xiaogang; Mostafizar Rahman, M; Prates, Luciana L; Yu, Peiqiang

    2017-08-05

    The objectives of this study were to: 1) investigate forage carbohydrate molecular structure profiles; 2) bio-functions in terms of CHO rumen degradation characteristics and hourly effective degradation ratio of N to OM (HED N/OM ), and 3) quantify interactive association between molecular structures, bio-functions and nutrient availability. The vibrational molecular spectroscopy was applied to investigate the structure feature on a molecular basis. Two sourced-origin alfalfa forages were used as modeled forages. The results showed that the carbohydrate molecular structure profiles were highly linked to the bio-functions in terms of rumen degradation characteristics and hourly effective degradation ratio. The molecular spectroscopic technique can be used to detect forage carbohydrate structure features on a molecular basis and can be used to study interactive association between forage molecular structure and bio-functions. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Bio-functions and molecular carbohydrate structure association study in forage with different source origins revealed using non-destructive vibrational molecular spectroscopy techniques

    Science.gov (United States)

    Ji, Cuiying; Zhang, Xuewei; Yan, Xiaogang; Mostafizar Rahman, M.; Prates, Luciana L.; Yu, Peiqiang

    2017-08-01

    The objectives of this study were to: 1) investigate forage carbohydrate molecular structure profiles; 2) bio-functions in terms of CHO rumen degradation characteristics and hourly effective degradation ratio of N to OM (HEDN/OM), and 3) quantify interactive association between molecular structures, bio-functions and nutrient availability. The vibrational molecular spectroscopy was applied to investigate the structure feature on a molecular basis. Two sourced-origin alfalfa forages were used as modeled forages. The results showed that the carbohydrate molecular structure profiles were highly linked to the bio-functions in terms of rumen degradation characteristics and hourly effective degradation ratio. The molecular spectroscopic technique can be used to detect forage carbohydrate structure features on a molecular basis and can be used to study interactive association between forage molecular structure and bio-functions.

  14. Revealing the effect of angular correlation in the ground-state He wavefunction: a coincidence study of the transfer ionization process

    International Nuclear Information System (INIS)

    Schoeffler, M; Godunov, A L; Whelan, Colm T; Walters, H R J; Schipakov, V S; Mergel, V; Doerner, R; Jagutzki, O; Schmidt, L Ph H; Titze, J; Weigold, E; Schmidt-Boecking, H

    2005-01-01

    A joint theoretical-experimental study of the transfer ionization process p + He → H 0 + He 2+ + e - is presented. For the first time all particles in the final state have been detected in triple coincidence. This fully differential measurement is in good agreement with a theoretical model where the target is described by a wavefunction containing both radial and angular correlation terms. (letter to the editor)

  15. Cellobiose as a model system to reveal cellulose dissolution mechanism in acetate-based ionic liquids: Density functional theory study substantiated by NMR spectra.

    Science.gov (United States)

    Cao, Bobo; Du, Jiuyao; Du, Dongmei; Sun, Haitao; Zhu, Xiao; Fu, Hui

    2016-09-20

    Cellulose dissolution mechanism in acetate-based ionic liquids was systematically studied in Nuclear Magnetic Resonance (NMR) spectra and Density Functional Theory (DFT) methods by using cellobiose and 1-butyl-3-methylimidazolium acetate (BmimAc) as a model system. The solubility of cellulose in ionic liquid increased with temperature increase in the range of 90-140°C. NMR spectra suggested OAc(-) preferred to form stronger hydrogen bonds with hydrogen of hydroxyl in cellulose. Electrostatic potential method was employed to predict the most possible reaction sites and locate the most stable configuration. Atoms in molecules (AIM) theory was used to study the features of bonds at bond critical points and the variations of bond types. Simultaneously, noncovalent interactions were characterized and visualized by employing reduced density gradient analysis combined with Visual Molecular Dynamics (VMD) program. Natural bond orbital (NBO) theory was applied to study the noncovalent nature and characterize the orbital interactions between cellobiose and Bmim[OAc]. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Urinary1H Nuclear Magnetic Resonance Metabolomic Fingerprinting Reveals Biomarkers of Pulse Consumption Related to Energy-Metabolism Modulation in a Subcohort from the PREDIMED study.

    Science.gov (United States)

    Madrid-Gambin, Francisco; Llorach, Rafael; Vázquez-Fresno, Rosa; Urpi-Sarda, Mireia; Almanza-Aguilera, Enrique; Garcia-Aloy, Mar; Estruch, Ramon; Corella, Dolores; Andres-Lacueva, Cristina

    2017-04-07

    Little is known about the metabolome fingerprint of pulse consumption. The study of robust and accurate biomarkers for pulse dietary assessment has great value for nutritional epidemiology regarding health benefits and their mechanisms. To characterize the fingerprinting of dietary pulses (chickpeas, lentils, and beans), spot urine samples from a subcohort from the PREDIMED study were stratified using a validated food frequency questionnaire. Urine samples of nonpulse consumers (≤4 g/day of pulse intake) and habitual pulse consumers (≥25 g/day of pulse intake) were analyzed using a 1 H nuclear magnetic resonance (NMR) metabolomics approach combined with multi- and univariate data analysis. Pulse consumption showed differences through 16 metabolites coming from (i) choline metabolism, (ii) protein-related compounds, and (iii) energy metabolism (including lower urinary glucose). Stepwise logistic regression analysis was applied to design a combined model of pulse exposure, which resulted in glutamine, dimethylamine, and 3-methylhistidine. This model was evaluated by a receiver operating characteristic curve (AUC > 90% in both training and validation sets). The application of NMR-based metabolomics to reported pulse exposure highlighted new candidates for biomarkers of pulse consumption and the impact on energy metabolism, generating new hypotheses on energy modulation. Further intervention studies will confirm these findings.

  17. A global proteome study of Mycobacterium gilvum PYR-GCK grown on pyrene and glucose reveals the activation of glyoxylate, shikimate and gluconeogenetic pathways through the central carbon metabolism highway.

    Science.gov (United States)

    Badejo, Abimbola Comfort; Choi, Chi-Won; Badejo, Adegoke Olugboyega; Shin, Kyung-Hoon; Hyun, Jung-Ho; Lee, Yeol-Gyun; Kim, Seung-Il; Park, Kang-Sik; Kim, Sang Hoon; Jung, Kyoung Hwa; Chung, Young-Ho; Chai, Young Gyu

    2013-11-01

    Various hydrocarbons have been released into the environment as a result of industrialization. An effective way of removing these materials without further environmental contamination is microbial bioremediation. Mycobacterium gilvum PYR-GCK, a bacteria isolated from a PAH polluted estuary, was studied using comparative shotgun proteomics to gain insight on its molecular activity while using pyrene and glucose as sole carbon and energy sources. Based on annotated genomic information, a confirmation analysis was first performed to confirm its pyrene degradation activity, using gas chromatography-mass spectrometry technology. One dimensional gel electrophoresis and liquid chromatography-mass spectrometry technologies employed in the proteomics analysis revealed the expression of pyrene degrading gene products along with upregulated expression of proteins functioning in the glyoxylate and shikimate pathways, in the pyrene-induced cells. The study also revealed the pathway of pyrene degraded intermediates, via partial gluconeogenesis, into the pentose phosphate pathway to produce precursors for nucleotides and amino acids biosynthesis.

  18. A comparative study of ripening among berries of the grape cluster reveals an altered transcriptional programme and enhanced ripening rate in delayed berries.

    Science.gov (United States)

    Gouthu, Satyanarayana; O'Neil, Shawn T; Di, Yanming; Ansarolia, Mitra; Megraw, Molly; Deluc, Laurent G

    2014-11-01

    Transcriptional studies in relation to fruit ripening generally aim to identify the transcriptional states associated with physiological ripening stages and the transcriptional changes between stages within the ripening programme. In non-climacteric fruits such as grape, all ripening-related genes involved in this programme have not been identified, mainly due to the lack of mutants for comparative transcriptomic studies. A feature in grape cluster ripening (Vitis vinifera cv. Pinot noir), where all berries do not initiate the ripening at the same time, was exploited to study their shifted ripening programmes in parallel. Berries that showed marked ripening state differences in a véraison-stage cluster (ripening onset) ultimately reached similar ripeness states toward maturity, indicating the flexibility of the ripening programme. The expression variance between these véraison-stage berry classes, where 11% of the genes were found to be differentially expressed, was reduced significantly toward maturity, resulting in the synchronization of their transcriptional states. Defined quantitative expression changes (transcriptional distances) not only existed between the véraison transitional stages, but also between the véraison to maturity stages, regardless of the berry class. It was observed that lagging berries complete their transcriptional programme in a shorter time through altered gene expressions and ripening-related hormone dynamics, and enhance the rate of physiological ripening progression. Finally, the reduction in expression variance of genes can identify new genes directly associated with ripening and also assess the relevance of gene activity to the phase of the ripening programme. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  19. Smartphone application for rheumatoid arthritis self-management: cross-sectional study revealed the usefulness, willingness to use and patients' needs.

    Science.gov (United States)

    Azevedo, Rita; Bernardes, Miguel; Fonseca, João; Lima, Aurea

    2015-10-01

    Patient-centered smartphone applications have potential to support rheumatoid arthritis (RA) self-management but remain almost unexplored in literature. Therefore, this study evaluated the usefulness of a smartphone application to support RA self-management, the willingness of RA patients to use and pay for it and the features the application should have. In this cross-sectional study, a questionnaire was developed to collect information on population, device ownership, usefulness and willingness to use and pay for a RA self-management application and application features. Descriptive statistics, Chi-square, Fisher's exact test, t test or Mann-Whitney's test and multivariate analysis were used. One hundred RA patients answered the questionnaire. Patients' mean age was 57 ± 11.9 years, most were females (91 %), with multiple drug regimens and a 40 % treatment non-compliance rate. Most patients believed that could have a more active role in self-management (94 %) and reported it would be useful to develop a RA self-management application (86 %). Patients willing to use an application (83 %) were younger, with a possible more active role in self-management, with access to a smartphone, and using short message service, electronic mail and Internet. Multivariate analysis confirmed these results, except the associations regarding access to a smartphone and use of electronic mail and Internet. Fifty-eight patients (82 %) were willing to pay for a RA self-management application and the most requested feature for it was information in a simple format. This study suggested the usefulness and patients' willingness to use and pay for a RA self-management application and provided insight on patients' needs.

  20. A network pharmacology study of Chinese medicine QiShenYiQi to reveal its underlying multi-compound, multi-target, multi-pathway mode of action.

    Directory of Open Access Journals (Sweden)

    Xiang Li

    Full Text Available Chinese medicine is a complex system guided by traditional Chinese medicine (TCM theories, which has proven to be especially effective in treating chronic and complex diseases. However, the underlying modes of action (MOA are not always systematically investigated. Herein, a systematic study was designed to elucidate the multi-compound, multi-target and multi-pathway MOA of a Chinese medicine, QiShenYiQi (QSYQ, on myocardial infarction. QSYQ is composed of Astragalus membranaceus (Huangqi, Salvia miltiorrhiza (Danshen, Panax notoginseng (Sanqi, and Dalbergia odorifera (Jiangxiang. Male Sprague Dawley rat model of myocardial infarction were administered QSYQ intragastrically for 7 days while the control group was not treated. The differentially expressed genes (DEGs were identified from myocardial infarction rat model treated with QSYQ, followed by constructing a cardiovascular disease (CVD-related multilevel compound-target-pathway network connecting main compounds to those DEGs supported by literature evidences and the pathways that are functionally enriched in ArrayTrack. 55 potential targets of QSYQ were identified, of which 14 were confirmed in CVD-related literatures with experimental supporting evidences. Furthermore, three sesquiterpene components of QSYQ, Trans-nerolidol, (3S,6S,7R-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol and (3S,6R,7R-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol from Dalbergia odorifera T. Chen, were validated experimentally in this study. Their anti-inflammatory effects and potential targets including extracellular signal-regulated kinase-1/2, peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 were identified. Finally, through a three-level compound-target-pathway network with experimental analysis, our study depicts a complex MOA of QSYQ on myocardial infarction.

  1. NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high fibre rye bread

    DEFF Research Database (Denmark)

    Bertram, Hanne C.; Bach Knudsen, Knud E.; Serena, Anja

    2006-01-01

    This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegrain...... diet (WGD)) and non-wholegrain wheat (non-wholegrain diet (NWD)) and fed to four pigs in a crossover design. Plasma samples were collected after 7 d on each diet, and 1H NMR spectra were acquired on these. Partial least squares regression discriminant analysis (PLS-DA) on spectra obtained for plasma...

  2. First plastid phylogenomic study reveals potential cyto-nuclear discordance in the evolutionary history of Ficus L. (Moraceae)

    DEFF Research Database (Denmark)

    Bruun-Lund, Sam; Clement, Wendy; Kjellberg, Finn

    2017-01-01

    , combinations of low copy nuclear, nuclear ribosomal and chloroplast regions have not been able to confidently resolve relationships among major groups of figs. Using a high throughput sequencing approach we attempted to resolve the major lineages of Ficus based on plastome data. In this study, we show...... that the use of a de novo assembled plastome from within the genus provides less ambiguity and higher coverage across the 59 Ficus and 6 outgroup plastome assemblies compared to using the nearest available reference plastome outside the genus resulting in improved resolution and higher support...

  3. Quantum Model of Catalysis Based on a Mobile Proton Revealed by Subatomic X-ray and Neutron Diffraction Studies of h-aldose Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Blakeley, M. P. [European Molecular Biology Laboratory (EMBL), France; Ruiz, Fredrico [Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, ULP, INSER; Cachau, Raul [SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD; Hazemann, I. [Institut Laue-Langevin (ILL); Meilleur, Flora [Institut Laue-Langevin (ILL); Mitschler, A. [IGBMC; Ginell, Stephan [Argonne National Laboratory (ANL); Afonine, Pavel [Lawrence Berkeley National Laboratory (LBNL); Ventura, Oscar [Computational Chemical Physics Group, DETEMA, Facultad de Quimica, UdelaR, C.C.1; Cousido-Siah, Alexandra [Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, ULP, INSER; Haertlein, M. [Institut Laue-Langevin (ILL); Joachimiak, Andrzej [Argonne National Laboratory (ANL); Myles, Dean A A [ORNL; Podjarny, A. [IGBMC

    2008-01-01

    We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 Angstroms, 100K; 0.80 Angstroms, 15K; 1.75 Angstroms, 293K), neutron Laue data (2.2 Angstroms, 293K), and quantum mechanical modeling. These complementary techniques unveil the internal organization and mobility of the hydrogen bond network that defines the properties of the catalytic engine, explaining how this promiscuous enzyme overcomes the simultaneous requirements of efficiency and promiscuity offering a general mechanistic view for this class of enzymes.

  4. A High Incidence of Intussusception Revealed by a Retrospective Hospital-Based Study in Nha Trang, Vietnam between 2009 and 2011

    Science.gov (United States)

    Tran, Lan Anh T.; Yoshida, Lay Myint; Nakagomi, Toyoko; Gauchan, Punita; Ariyoshi, Koya; Anh, Dang Duc; Nakagomi, Osamu; Thiem, Vu Dinh

    2013-01-01

    Rotavirus is a leading cause of severe diarrhea among children worldwide. Thus, the World Health Organization recommended including rotavirus vaccines in national immunization programs. One concern about rotavirus vaccine, however, is a possible association with intussusception. Thus, it is crucial to know the baseline incidence of intussusception in the first year of life. A study conducted in Hanoi, Vietnam showed that the incidence of intussusception was the highest in the world. This retrospective cross-sectional study was undertaken to determine the incidence of intussusception among children Khanh Hoa Provincial General Hospital where virtually all cases of intussusception occurring in the city were assumed to have been encountered. The incidence of intussusception among children <1 year of age was 296 per 100,000 person-years (95% confidence interval [CI]: 225–382), and that among children <5 years of age was 196 per 100,000 person-years (95% CI: 169–226), confirming the high incidence of intussusception in Vietnam. Nevertheless, there was no intussusception in the first three months of life. We therefore recommend that the first dose of any rotavirus vaccine be administered to infants between 6 and 12 weeks of age. PMID:24155653

  5. In Silico and Wet Lab Studies Reveal the Cholesterol Lowering Efficacy of Lauric Acid, a Medium Chain Fat of Coconut Oil.

    Science.gov (United States)

    Lekshmi Sheela, Devi; Nazeem, Puthiyaveetil Abdulla; Narayanankutty, Arunaksharan; Manalil, Jeksy Jos; Raghavamenon, Achuthan C

    2016-12-01

    The coconut oil (CO) contains 91 % of saturated fatty acids in which 72 % are medium chain fatty acids (MCFAs) like lauric, capric and caprylic acids. In contrast to animal fat, coconut oil has no cholesterol. Despite this fact, CO is sidelined among other vegetable oils due to the health hazards attributed to the saturated fatty acids. Though various medicinal effects of CO have been reported including the hypolipidemic activity, people are still confused in the consumption of this natural oil. In silico analyses and wet lab experiments have been carried out to identify the hypolipidemic properties of MCFAs and phenolic acids in CO by using different protein targets involved in cholesterol synthesis. The molecular docking studies were carried out using CDOCKER protocol in Accelery's Discovery Studio, by taking different proteins like HMG- CoA reductase and cholesterol esterase as targets and the different phytocompounds in coconut as ligands. Molecular docking highlighted the potential of lauric acid in inhibiting the protein targets involved in hyperlipidemics. Further, validation of in silico results was carried out through in vivo studies. The activity of key enzymes HMG- CoA reductase and lipoprotein lipase were found reduced in animals fed with lauric acid and CO.

  6. Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

    Science.gov (United States)

    Yanes, Julio A; Riedel, Michael C; Ray, Kimberly L; Kirkland, Anna E; Bird, Ryan T; Boeving, Emily R; Reid, Meredith A; Gonzalez, Raul; Robinson, Jennifer L; Laird, Angela R; Sutherland, Matthew T

    2018-03-01

    Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

  7. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells

    Science.gov (United States)

    Zhu, Xiaohua; Badawi, Mohamed; Pomeroy, Steven; Sutaria, Dhruvitkumar S.; Xie, Zhiliang; Baek, Alice; Jiang, Jinmai; Elgamal, Ola A.; Mo, Xiaokui; Perle, Krista La; Chalmers, Jeffrey; Schmittgen, Thomas D.; Phelps, Mitch A.

    2017-01-01

    ABSTRACT Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV-induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks. EVs were harvested from wild type or engineered HEK293T cells which were modified to produce EVs loaded with miR-199a-3p and chimeric proteins. Blood was collected to assess hematology, blood chemistry, and immune markers. Spleen cells were immunophenotyped, and tissues were harvested for gross necropsy and histopathological examination. No signs of toxicity were observed, and minimal evidence of changes in immune markers were noted in mice dosed with engineered, but not with wild type EVs. This study provides a framework for assessment of immunogenicity and toxicity that will be required as EVs from varying cell sources are tested within numerous animal models and eventually in humans. PMID:28717420

  8. Revealing the relationship between microbial community structure in natural biofilms and the pollution level in urban rivers: a case study in the Qinhuai River basin, Yangtze River Delta.

    Science.gov (United States)

    Cai, Wei; Li, Yi; Wang, Peifang; Niu, Lihua; Zhang, Wenlong; Wang, Chao

    River pollution is one of the most challenging environmental issues, but the effect of river pollution levels on the biofilm communities has not been well-studied. Spatial and temporal distribution characteristics of environmental parameters and the biofilm communities were investigated in the Qinhuai River basin, Nanjing, China. Water samples were grouped into three clusters reflecting their varying pollution levels of relatively slight pollution, moderated pollution, and high pollution by hierarchical cluster analysis. In different clusters, the biofilm communities mainly differed in the proportion of Actinobacteria, Firmicutes, and Proteobacteria. As the dominant classes of Proteobacteria, Alpha-, Beta- and Gammaproteobacteria seemed to show an upward trend followed by a small fluctuation in the abundance with the escalation of water pollution level. Results of redundancy analysis demonstrated that temperature, total nitrogen to total phosphorus ratios (TN/TP) and concentrations of ammonia nitrogen (NH3-N) and TN were mainly responsible for the variation in bacterial community structure. The occurrences of Alpha-, Beta- and Gammaproteobacteria were closely associated with higher temperature, higher concentrations of NH3-N and TN and a lower TN/TP ratio. This study may provide a theoretical basis for the water pollution control and ecological restoration in urban rivers under different pollution levels.

  9. Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.

    Science.gov (United States)

    Ding, Wei-na; Sun, Jin-hua; Sun, Ya-Wen; Chen, Xue; Zhou, Yan; Zhuang, Zhi-guo; Li, Lei; Zhang, Yong; Xu, Jian-rong; Du, Ya-song

    2014-05-30

    Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents. Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness Scale (BIS)-11 was used to assess impulsivity. There were no differences in the behavioral performance on the Go/No-Go task between the groups. However, the IGA group was significantly hyperactive during No-Go trials in the left superior medial frontal gyrus, right anterior cingulate cortex, right superior/middle frontal gyrus, left inferior parietal lobule, left precentral gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were significantly hypoactive during No-Go trials. Activation of the left superior medial frontal gyrus was positively associated with BIS-11 and Chen Internet Addiction Scale (CIAS) total score across IGA participants. Our data suggest that the prefrontal cortex may be involved in the circuit modulating impulsivity, while its impaired function may relate to high impulsivity in adolescents with IGA, which may contribute directly to the Internet addiction process.

  10. Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Mendichovszky, I.A.; Lomas, D.J. [Addenbrooke' s Hospital, Department of Radiology, Cambridge (United Kingdom); University of Cambridge, Department of Radiology, Cambridge (United Kingdom); Priest, A.N.; Bowden, D.J.; Hunter, S.; Joubert, I.; Hilborne, S.; Graves, M.J. [Addenbrooke' s Hospital, Department of Radiology, Cambridge (United Kingdom); Baglin, T. [Addenbrooke' s Hospital, Department of Haematology, Cambridge (United Kingdom)

    2017-06-15

    Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. (orig.)

  11. Integrative species delimitation in photosynthetic sea slugs reveals twenty candidate species in three nominal taxa studied for drug discovery, plastid symbiosis or biological control.

    Science.gov (United States)

    Krug, Patrick J; Vendetti, Jann E; Rodriguez, Albert K; Retana, Jennifer N; Hirano, Yayoi M; Trowbridge, Cynthia D

    2013-12-01

    DNA barcoding can highlight taxa in which conventional taxonomy underestimates species richness, identifying mitochondrial lineages that may correspond to unrecognized species. However, key assumptions of barcoding remain untested for many groups of soft-bodied marine invertebrates with poorly resolved taxonomy. Here, we applied an integrative approach for species delimitation to herbivorous sea slugs in clade Sacoglossa, in which unrecognized diversity may complicate studies of drug discovery, plastid endosymbiosis, and biological control. Using the mitochondrial barcoding COI gene and the nuclear histone 3 gene, we tested the hypothesis that three widely distributed "species" each comprised a complex of independently evolving lineages. Morphological and reproductive characters were then used to evaluate whether each lineage was distinguishable as a candidate species. The "circumtropical" Elysia ornata comprised a Caribbean species and four Indo-Pacific candidate species that are potential sources of kahalalides, anti-cancer compounds. The "monotypic" and highly photosynthetic Plakobranchus ocellatus, used for over 60 years to study chloroplast symbiosis, comprised 10 candidate species. Finally, six candidate species were distinguished in the Elysia tomentosa complex, including potential biological control agents for invasive green algae (Caulerpa spp.). We show that a candidate species approach developed for vertebrates effectively categorizes cryptic diversity in marine invertebrates, and that integrating threshold COI distances with non-molecular character data can delimit species even when common assumptions of DNA barcoding are violated. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition

    Directory of Open Access Journals (Sweden)

    Laura Ordovás

    2015-11-01

    Full Text Available Tools for rapid and efficient transgenesis in “safe harbor” loci in an isogenic context remain important to exploit the possibilities of human pluripotent stem cells (hPSCs. We created hPSC master cell lines suitable for FLPe recombinase-mediated cassette exchange (RMCE in the AAVS1 locus that allow generation of transgenic lines within 15 days with 100% efficiency and without random integrations. Using RMCE, we successfully incorporated several transgenes useful for lineage identification, cell toxicity studies, and gene overexpression to study the hepatocyte lineage. However, we observed unexpected and variable transgene expression inhibition in vitro, due to DNA methylation and other unknown mechanisms, both in undifferentiated hESC and differentiating hepatocytes. Therefore, the AAVS1 locus cannot be considered a universally safe harbor locus for reliable transgene expression in vitro, and using it for transgenesis in hPSC will require careful assessment of the function of individual transgenes.

  13. Functional and structural studies of the disulfide isomerase DsbC from the plant pathogen Xylella fastidiosa reveals a redox-dependent oligomeric modulation in vitro.

    Science.gov (United States)

    Santos, Clelton A; Toledo, Marcelo A S; Trivella, Daniela B B; Beloti, Lilian L; Schneider, Dilaine R S; Saraiva, Antonio M; Crucello, Aline; Azzoni, Adriano R; Souza, Alessandra A; Aparicio, Ricardo; Souza, Anete P

    2012-10-01

    Xylella fastidiosa is a Gram-negative bacterium that grows as a biofilm inside the xylem vessels of susceptible plants and causes several economically relevant crop diseases. In the present study, we report the functional and low-resolution structural characterization of the X. fastidiosa disulfide isomerase DsbC (XfDsbC). DsbC is part of the disulfide bond reduction/isomerization pathway in the bacterial periplasm and plays an important role in oxidative protein folding. In the present study, we demonstrate the presence of XfDsbC during different stages of X. fastidiosa biofilm development. XfDsbC was not detected during X. fastidiosa planktonic growth; however, after administering a sublethal copper shock, we observed an overexpression of XfDsbC that also occurred during planktonic growth. These results suggest that X. fastidiosa can use XfDsbC in vivo under oxidative stress conditions similar to those induced by copper. In addition, using dynamic light scattering and small-angle X-ray scattering, we observed that the oligomeric state of XfDsbC in vitro may be dependent on the redox environment. Under reducing conditions, XfDsbC is present as a dimer, whereas a putative tetrameric form was observed under nonreducing conditions. Taken together, our findings demonstrate the overexpression of XfDsbC during biofilm formation and provide the first structural model of a bacterial disulfide isomerase in solution. © 2012 The Authors Journal compilation © 2012 FEBS.

  14. Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans.

    Directory of Open Access Journals (Sweden)

    Célia Dos Santos

    Full Text Available Dermaseptin-B2 (DRS-B2 is a multifunctional cationic antimicrobial peptide (CAP isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0-DRS-B2 shows that in sensitive human tumor cells (PC3, DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG, DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all D-amino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C. Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts an α-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity.

  15. Assessment of synchronous neural activities revealed by regional homogeneity in individuals with acute eye pain: a resting-state functional magnetic resonance imaging study

    Directory of Open Access Journals (Sweden)

    Tang L

    2018-04-01

    Full Text Available Li-Yuan Tang,1,* Hai-Jun Li,2,* Xin Huang,1 Jing Bao,1 Zubin Sethi,3 Lei Ye,1 Qing Yuan,1 Pei-Wen Zhu,1 Nan Jiang,1 Gui-Ping Gao,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; 2Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; 3The Department of Medicine, University of Miami, Coral Gables, FL, USA *These authors contributed equally to this work Objective: Previous neuroimaging studies have demonstrated that pain-related diseases are associated with brain function and anatomical abnormalities, whereas altered synchronous neural activity in acute eye pain (EP patients has not been investigated. The purpose of this study was to explore whether or not synchronous neural activity changes were measured with the regional homogeneity (ReHo method in acute EP patients.Methods: A total of 20 patients (15 males and 5 females with EP and 20 healthy controls (HCs consisting of 15 and 5 age-, sex-, and education-matched males and females, respectively, underwent resting-state functional magnetic resonance imaging. The ReHo method was applied to assess synchronous neural activity changes.Results: Compared with HCs, acute EP patients had significantly lower ReHo values in the left precentral/postcentral gyrus (Brodmann area [BA]3/4, right precentral/postcentral gyrus (BA3/4, and left middle frontal gyrus (BA6. In contrast, higher ReHo values in acute EP patients were observed in the left superior frontal gyrus (BA11, right inferior parietal lobule (BA39/40, and left precuneus (BA7. However, no relationship was found between the mean ReHo signal values of the different areas and clinical manifestations, which included both the duration and degree of pain in EP patients.Conclusion: Our study highlighted that acute EP patients showed altered synchronous neural activities in many brain regions, including somatosensory regions. These

  16. Meta-analysis of sequence-based association studies across three cattle breeds reveals 25 QTL for fat and protein percentages in milk at nucleotide resolution.

    Science.gov (United States)

    Pausch, Hubert; Emmerling, Reiner; Gredler-Grandl, Birgit; Fries, Ruedi; Daetwyler, Hans D; Goddard, Michael E

    2017-11-09

    Genotyping and whole-genome sequencing data have been generated for hundreds of thousands of cattle. International consortia used these data to compile imputation reference panels that facilitate the imputation of sequence variant genotypes for animals that have been genotyped using dense microarrays. Association studies with imputed sequence variant genotypes allow for the characterization of quantitative trait loci (QTL) at nucleotide resolution particularly when individuals from several breeds are included in the mapping populations. We imputed genotypes for 28 million sequence variants in 17,229 cattle of the Braunvieh, Fleckvieh and Holstein breeds in order to compile large mapping populations that provide high power to identify QTL for milk production traits. Association tests between imputed sequence variant genotypes and fat and protein percentages in milk uncovered between six and thirteen QTL (P < 1e-8) per breed. Eight of the detected QTL were significant in more than one breed. We combined the results across breeds using meta-analysis and identified a total of 25 QTL including six that were not significant in the within-breed association studies. Two missense mutations in the ABCG2 (p.Y581S, rs43702337, P = 4.3e-34) and GHR (p.F279Y, rs385640152, P = 1.6e-74) genes were the top variants at QTL on chromosomes 6 and 20. Another known causal missense mutation in the DGAT1 gene (p.A232K, rs109326954, P = 8.4e-1436) was the second top variant at a QTL on chromosome 14 but its allelic substitution effects were inconsistent across breeds. It turned out that the conflicting allelic substitution effects resulted from flaws in the imputed genotypes due to the use of a multi-breed reference population for genotype imputation. Many QTL for milk production traits segregate across breeds and across-breed meta-analysis has greater power to detect such QTL than within-breed association testing. Association testing between imputed sequence variant genotypes and

  17. Low-field EPR studies of levels near the top of the barrier in Mn 12-acetate reveal a new magnetization relaxation pathway

    Science.gov (United States)

    Rakvin, Boris; Žilić, Dijana; Dalal, Naresh S.; Harter, Andrew; Sanakis, Yiannis

    2006-07-01

    We show that X-band electron paramagnetic resonance (EPR) measurements using a dual-mode resonance cavity can directly probe the levels near the top of the magnetization reversal barrier in the single-molecule magnet (SMM) Mn 12-acetate. The observed transitions are much sharper than those reported in high-field EPR studies. The observed temperature dependence of the line positions points to the presence of a spin-diffusional mode. The correlation time for such fluctuations is of the order of 6×10 -8 s at 10 K, and follows an Arrhenius activation energy of 35-40 K. These results open a new avenue for understanding the mechanism of tunneling and spin-lattice relaxations in these SMMs.

  18. Rise of CC398 Lineage of Staphylococcus aureus among Infective Endocarditis Isolates Revealed by Two Consecutive Population-Based Studies in France

    Science.gov (United States)

    Tristan, Anne; Rasigade, Jean-Philippe; Ruizendaal, Esmée; Laurent, Frédéric; Bes, Michèle; Meugnier, Hélène; Lina, Gérard; Etienne, Jerome; Celard, Marie; Tattevin, Pierre; Monecke, Stefan; Le Moing, Vincent; Vandenesch, François

    2012-01-01

    Staphylococcus aureus isolates from two prospective studies on infective endocarditis (IE) conducted in 1999 and 2008 and isolated from non-IE bacteremia collected in 2006 were spa-typed and their virulence factors were analyzed with a microarray. Both populations were genetically diverse, with no virulence factors or genotypes significantly more associated with the IE isolates compared with the non-IE isolates. The population structure of the IE isolates did not change much between 1999 and 2008, with the exception of the appearance of CC398 methicillin-susceptible Staphylococcus aureus (MSSA) isolates responsible for 5.6% of all cases in 2008. In 1999, this lineage was responsible for no cases. The increasing prevalence of S. aureus in IE is apparently not the result of a major change in staphylococcal population structure over time, with the exception of the emerging CC398 MSSA lineage. PMID:23272091

  19. Structural organizations of yeast RNase P and RNase MRP holoenzymes as revealed by UV-crosslinking studies of RNA–protein interactions

    Science.gov (United States)

    Khanova, Elena; Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S.

    2012-01-01

    Eukaryotic ribonuclease (RNase) P and RNase MRP are closely related ribonucleoprotein complexes involved in the metabolism of various RNA molecules including tRNA, rRNA, and some mRNAs. While evolutionarily related to bacterial RNase P, eukaryotic enzymes of the RNase P/MRP family are much more complex. Saccharomyces cerevisiae RNase P consists of a catalytic RNA component and nine essential proteins; yeast RNase MRP has an RNA component resembling that in RNase P and 10 essential proteins, most of which are shared with RNase P. The structural organizations of eukaryotic RNases P/MRP are not clear. Here we present the results of RNA–protein UV crosslinking studies performed on RNase P and RNase MRP holoenzymes isolated from yeast. The results indicate locations of specific protein-binding sites in the RNA components of RNase P and RNase MRP and shed light on the structural organizations of these large ribonucleoprotein complexes. PMID:22332141

  20. Structural organizations of yeast RNase P and RNase MRP holoenzymes as revealed by UV-crosslinking studies of RNA-protein interactions.

    Science.gov (United States)

    Khanova, Elena; Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2012-04-01

    Eukaryotic ribonuclease (RNase) P and RNase MRP are closely related ribonucleoprotein complexes involved in the metabolism of various RNA molecules including tRNA, rRNA, and some mRNAs. While evolutionarily related to bacterial RNase P, eukaryotic enzymes of the RNase P/MRP family are much more complex. Saccharomyces cerevisiae RNase P consists of a catalytic RNA component and nine essential proteins; yeast RNase MRP has an RNA component resembling that in RNase P and 10 essential proteins, most of which are shared with RNase P. The structural organizations of eukaryotic RNases P/MRP are not clear. Here we present the results of RNA-protein UV crosslinking studies performed on RNase P and RNase MRP holoenzymes isolated from yeast. The results indicate locations of specific protein-binding sites in the RNA components of RNase P and RNase MRP and shed light on the structural organizations of these large ribonucleoprotein complexes.

  1. Why is seed production so variable among individuals? A ten-year study with oaks reveals the importance of soil environment.

    Directory of Open Access Journals (Sweden)

    Ignacio M Pérez-Ramos

    Full Text Available Mast-seeding species exhibit not only a large inter-annual variability in seed production but also considerable variability among individuals within the same year. However, very little is known about the causes and consequences for population dynamics of this potentially large between-individual variability. Here, we quantified seed production over ten consecutive years in two Mediterranean oak species - the deciduous Quercus canariensis and the evergreen Q. suber - that coexist in forests of southern Spain. First, we calibrated likelihood models to identify which abiotic and biotic variables best explain the magnitude (hereafter seed productivity and temporal variation of seed production at the individual level (hereafter CVi, and infer whether reproductive effort results from the available soil resources for the plant or is primarily determined by selectively favoured strategies. Second, we explored the contribution of between-individual variability in seed production as a potential mechanism of satiation for predispersal seed predators. We found that Q. canariensis trees inhabiting moister and more fertile soils were more productive than those growing in more resource-limited sites. Regarding temporal variation, individuals of the two studied oak species inhabiting these resource-rich environments also exhibited larger values of CVi. Interestingly, we detected a satiating effect on granivorous insects at the tree level in Q. suber, which was evident in those years where between-individual variability in acorn production was higher. These findings suggest that individual seed production (both in terms of seed productivity and inter-annual variability is strongly dependent on soil resource heterogeneity (at least for one of the two studied oak species with potential repercussions for recruitment and population dynamics. However, other external factors (such as soil heterogeneity in pathogen abundance or certain inherent characteristics of the

  2. Selectivity of primary events in the radiation chemistry of organic solids and polymers as revealed by model studies of ionized molecules

    International Nuclear Information System (INIS)

    Feldman, V.

    2006-01-01

    Selectivity of the primary chemical events induced by ionizing radiation in molecular systems is the key issue of basic radiation chemistry, which is crucially important for controlling the radiation sensitivity of various-type organic and polymeric materials and designing new effective approaches to the radiation modification. In the past decade we have demonstrated that many features of selective localization of the radiation-induced effects in molecular solids can be understood on the basis of model studies of the primary ionized molecules in rigid low-temperature matrices. This talk will outline the key results of these studies and possible implications for radiation chemistry of vatious systems. In particular, the following aspects will be considered: (1) Spectroscopic characteristics of ustable ionized molecules in low-temperature matrices and their correlations with the site-selective reactivity. (2) Experimental modeling of the effect of excess energy on the properties of primary ionized molecules in condensed phases. (3) Intramolecular long-range effects with particular impact on the properties of ionized bifunctional molecules of X-(CH 2 ) n -X and X-(CH 2 ) n -Y types. (4) Modeling of intermolecular long-range positive hole transfer between molecular traps with close ionization energy and manifestations of 'fine tuning' effects resulting from conformation variations and intermolecular interactions. Several illustrative examples of correlation between the properties of primary ionized molecules and selectivity of the radiation-chemical transformations in organic solids and macromolecules will be presented. Finally, the problem of prediction of the radiation-chemical behaviour of complex organic systems on the basis of limited spectroscopic information and quantum-chemical data obtained for model systems will be addressed. This work was supported by the Russian Foundation for Basic Research (Project No. 06-03-33104) and the Russian Academy of Sciences

  3. Co-operative intra-protein structural response due to protein-protein complexation revealed through thermodynamic quantification: study of MDM2-p53 binding

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-10-01

    The p53 protein activation protects the organism from propagation of cells with damaged DNA having oncogenic mutations. In normal cells, activity of p53 is controlled by interaction with MDM2. The well understood p53-MDM2 interaction facilitates design of ligands that could potentially disrupt or prevent the complexation owing to its emergence as an important objective for cancer therapy. However, thermodynamic quantification of the p53-peptide induced structural changes of the MDM2-protein remains an area to be explored. This study attempts to understand the conformational free energy and entropy costs due to this complex formation from the histograms of dihedral angles generated from molecular dynamics simulations. Residue-specific quantification illustrates that, hydrophobic residues of the protein contribute maximum to the conformational thermodynamic changes. Thermodynamic quantification of structural changes of the protein unfold the fact that, p53 binding provides a source of inter-element cooperativity among the protein secondary structural elements, where the highest affected structural elements (α2 and α4) found at the binding site of the protein affects faraway structural elements (β1 and Loop1) of the protein. The communication perhaps involves water mediated hydrogen bonded network formation. Further, we infer that in inhibitory F19A mutation of P53, though Phe19 is important in the recognition process, it has less prominent contribution in the stability of the complex. Collectively, this study provides vivid microscopic understanding of the interaction within the protein complex along with exploring mutation sites, which will contribute further to engineer the protein function and binding affinity.

  4. Antibody complement-mediated hemolytic studies with kodecytes reveal that human complement utilized in the classical pathway is more stable than generally accepted.

    Science.gov (United States)

    Perry, Holly; Bovin, Nicolai; Henry, Stephen

    2016-10-01

    Complement has significant status in the field of transfusion medicine. The accepted stability profile of complement is based on historical studies of diluted human serum hemolyzing rabbit heterophile antibody-sensitized sheep red blood cells (RBCs). Contemporary tools are available to reevaluate these historical observations using human heterophile antibodies, undiluted serum, and antigen-modified human RBCs. Human RBCs were made into "animal-like" kodecytes with heterophile Galα3Galβ4GlcNAcβ function-spacer-lipid constructs. These α-Gal-kodecytes were prepared with an antigen dilution capable of consistently producing 50% antibody-mediated hemolysis against human α1-3galactose heterophile antibodies and undiluted standardized serum. Standardized human serum aliquots from a two-donor pool stored at -85, -20, 4, 22, and 37°C for durations of up to 150 days were evaluated for loss of hemolytic activity. Where practical methodologic procedures were aligned with historical studies. Comparison of the historical assay with the α-Gal-kodecyte assay against complement activity standards showed concordance. However, in most scenarios complement was found to be more than twice as stable as generally accepted. At least 60% of complement hemolytic activity was observed in serum stored at 22°C for 1 week or 2 months at 4°C. No loss of hemolytic activity was observed after 5 months' storage at temperatures below -20°C. An alternative method using undiluted serum and modified human RBCs observed that classical-pathway complement hemolytic activity in stored human serum is at least twice as stable as previously accepted. © 2016 AABB.

  5. Co-operative intra-protein structural response due to protein-protein complexation revealed through thermodynamic quantification: study of MDM2-p53 binding.

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-10-01

    The p53 protein activation protects the organism from propagation of cells with damaged DNA having oncogenic mutations. In normal cells, activity of p53 is controlled by interaction with MDM2. The well understood p53-MDM2 interaction facilitates design of ligands that could potentially disrupt or prevent the complexation owing to its emergence as an important objective for cancer therapy. However, thermodynamic quantification of the p53-peptide induced structural changes of the MDM2-protein remains an area to be explored. This study attempts to understand the conformational free energy and entropy costs due to this complex formation from the histograms of dihedral angles generated from molecular dynamics simulations. Residue-specific quantification illustrates that, hydrophobic residues of the protein contribute maximum to the conformational thermodynamic changes. Thermodynamic quantification of structural changes of the protein unfold the fact that, p53 binding provides a source of inter-element cooperativity among the protein secondary structural elements, where the highest affected structural elements (α2 and α4) found at the binding site of the protein affects faraway structural elements (β1 and Loop1) of the protein. The communication perhaps involves water mediated hydrogen bonded network formation. Further, we infer that in inhibitory F19A mutation of P53, though Phe19 is important in the recognition process, it has less prominent contribution in the stability of the complex. Collectively, this study provides vivid microscopic understanding of the interaction within the protein complex along with exploring mutation sites, which will contribute further to engineer the protein function and binding affinity.

  6. Fast voltage gating of Ca2+ release in frog skeletal muscle revealed by supercharging pulses.

    Science.gov (United States)

    Kim, A M; Vergara, J L

    1998-09-01

    1. In single frog skeletal muscle fibres, we utilized supercharging voltage clamp command pulses to boost the rate of depolarization in the transverse tubular system (T-system) such that 95 % of steady-state potential is achieved in muscle fibres indicate that peripheral regions of the T-system are not significantly overcompensated under these conditions. 2. We explored the impact of accelerating T-system depolarization on voltage-dependent events of excitation-contraction (E-C) coupling by measuring charge movement currents (CMCs) and Ca2+ fluorescence transients in response to both supercharging and conventional step pulses. 3. When compared with CMCs elicited by step pulses, supercharging CMCs are larger, and their kinetics more closely resemble those of gating current records reported for ionic channels. Furthermore, they decay bi-exponentially (tau fast range, 1.3-1.8 ms; tau slow range, 7.3-11.9 ms), whereas step CMCs fall with a single exponential time course (tau range, 12.5-26.7 ms). 4. Similarly, supercharging produces a distinct acceleration in Ca2+ release transients, which show little evidence of the voltage-dependent onset latencies previously encountered using step pulses. 5. The use of this novel methodology in skeletal muscle unveils a previously undetected component of charge movement, the rapid, voltage-dependent recruitment of which may provide the basis for understanding the fast gating of physiological E-C coupling.

  7. Comparison of spatially matched airways reveals thinner airway walls in COPD. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS).

    Science.gov (United States)

    Smith, Benjamin M; Hoffman, Eric A; Rabinowitz, Dan; Bleecker, Eugene; Christenson, Stephanie; Couper, David; Donohue, Kathleen M; Han, Meilan K; Hansel, Nadia N; Kanner, Richard E; Kleerup, Eric; Rennard, Stephen; Barr, R Graham

    2014-11-01

    COPD is characterised by reduced airway lumen dimensions and fewer peripheral airways. Most studies of airway properties sample airways based upon lumen dimension or at random, which may bias comparisons given reduced airway lumen dimensions and number in COPD. We sought to compare central airway wall dimensions on CT in COPD and controls using spatially matched airways, thereby avoiding selection bias of airways in the lung. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) recruited smokers with COPD and controls aged 50-79 years and 40-80 years, respectively. COPD was defined by current guidelines. Using CT image data, airway dimensions were measured for all central airway segments (generations 0-6) following 5 standardised paths into the lungs. Case-control airway comparisons were spatially matched by generation and adjusted for demographics, body size, smoking, CT dose, per cent emphysema, airway length and lung volume. Among 311 MESA COPD participants, airway wall areas at generations 3-6 were smaller in COPD compared with controls (all pcentral airways. Other approaches to airway sampling result in comparisons of more proximal to more distal airways and potentially biased assessment of airway properties in COPD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Enhanced virulence of sheep-passaged bovine spongiform encephalopathy agent is revealed by decreased polymorphism barriers in prion protein conversion studies.

    Science.gov (United States)

    Priem, Jan; Langeveld, Jan P M; van Keulen, Lucien J M; van Zijderveld, Fred G; Andreoletti, Olivier; Bossers, Alex

    2014-03-01

    variety of hosts, including sheep and humans. Based on the typical BSE agent strain signatures and epidemiological data, the occurrence of a novel variant of CJD in humans was linked to BSE occurrence in the United Kingdom. Measures, including genetic selection of sheep toward less susceptible PrP genotypes, have been implemented to lower the risk of BSE transmission into sheep, since the disease could potentially spread into a natural reservoir. In this study, we demonstrated using molecular PrP conversion studies that when BSE is first transmitted through sheep, the host range is modified significantly and the PrP converting potency increased, allowing the ovine BSE to transmit more efficiently than cow BSE into supposedly less susceptible hosts.

  9. Quantitative Phosphoproteomic Study Reveals that Protein Kinase A Regulates Neural Stem Cell Differentiation Through Phosphorylation of Catenin Beta-1 and Glycogen Synthase Kinase 3β.

    Science.gov (United States)

    Wang, Shuxin; Li, Zheyi; Shen, Hongyan; Zhang, Zhong; Yin, Yuxin; Wang, Qingsong; Zhao, Xuyang; Ji, Jianguo

    2016-08-01

    Protein phosphorylation is central to the understanding of multiple cellular signaling pathways responsible for regulating the self-renewal and differentiation of neural stem cells (NSCs). Here we performed a large-scale phosphoproteomic analysis of rat fetal NSCs using strong cation exchange chromatography prefractionation and citric acid-assisted two-step enrichment with TiO2 strategy followed by nanoLC-MS/MS analysis. Totally we identified 32,546 phosphosites on 5,091 phosphoproteins, among which 23,945 were class I phosphosites, and quantified 16,000 sites during NSC differentiation. More than 65% of class I phosphosites were novel when compared with PhosphoSitePlus database. Quantification results showed that the early and late stage of NSC differentiation differ greatly. We mapped 69 changed phosphosites on 20 proteins involved in Wnt signaling pathway, including S552 on catenin beta-1 (Ctnnb1) and S9 on glycogen synthase kinase 3β (Gsk3β). Western blotting and real-time PCR results proved that Wnt signaling pathway plays critical roles in NSC fate determination. Furthermore, inhibition and activation of PKA dramatically affected the phosphorylation state of Ctnnb1 and Gsk3β, which regulates the differentiation of NSCs. Our data provides a valuable resource for studying the self-renewal and differentiation of NSCs. Stem Cells 2016;34:2090-2101. © 2016 AlphaMed Press.

  10. Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

    Directory of Open Access Journals (Sweden)

    F. Balazard

    2016-09-01

    Full Text Available Abstract Background The incidence of childhood type 1 diabetes (T1D incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D. Methods Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods. Results We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age. Conclusions The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas. Trial registration Clinical-Trial.gov NCT02212522 . Registered August 6, 2014. 

  11. Genome-wide association study reveals constant and specific loci for hematological traits at three time stages in a White Duroc × Erhualian F2 resource population.

    Directory of Open Access Journals (Sweden)

    Zhiyan Zhang

    Full Text Available Hematological traits are important indicators of immune function and have been commonly examined as biomarkers of disease and disease severity in humans. Pig is an ideal biomedical model for human diseases due to its high degree of similarity with human physiological characteristics. Here, we conducted genome-wide association studies (GWAS for 18 hematological traits at three growth stages (days 18, 46 and 240 in a White Duroc × Erhualian F2 intercross. In total, we identified 38 genome-wide significant regions containing 185 genome-wide significant SNPs by single-marker GWAS or LONG-GWAS. The significant regions are distributed on pig chromosomes (SSC 1, 4, 5, 7, 8, 10, 11, 12, 13, 17 and 18, and most of significant SNPs reside on SSC7 and SSC8. Of the 38 significant regions, 7 show constant effects on hematological traits across the whole life stages, and 6 regions have time-specific effects on the measured traits at early or late stages. The most prominent locus is the genomic region between 32.36 and 84.49 Mb on SSC8 that is associated with multiple erythroid traits. The KIT gene in this region appears to be a promising candidate gene. The findings improve our understanding of the genetic architecture of hematological traits in pigs. Further investigations are warranted to characterize the responsible gene(s and causal variant(s especially for the major loci on SSC7 and SSC8.

  12. Longevity of a small shield volcano revealed by crypto-tephra studies (Rangitoto volcano, New Zealand): Change in eruptive behavior of a basaltic field

    Science.gov (United States)

    Shane, Phil; Gehrels, Maria; Zawalna-Geer, Aleksandra; Augustinus, Paul; Lindsay, Jan; Chaillou, Isabelle

    2013-05-01

    The life-span of small volcanoes in terrestrial basaltic fields, commonly considered 'monogenetic', can be difficult to assess due to a paucity of datable materials capable of providing a 102-103-year age resolution. We have used microscopic tephra layers (crypto-tephra) in lake sediments to determine the longevity of Rangitoto volcano, a small shield that represents the most recent volcanism in the Auckland Volcanic Field (AVF), New Zealand. Previous studies suggested construction in a relatively short interval at ~ 550-500 cal yrs BP. In contrast, the tephra record shows evidence of intermittent activity from 1498 ± 140 to (at least) 504 ± 6 cal yrs BP, a longevity of ~ 1000 years. Rangitoto volcano is thought to represent about half the magma erupted in the 250-ka-history of AVF. Thus, the AVF has experienced a dramatic shift to prolonged and voluminous central-vent volcanism in its most recent history. This demonstrates the difficulty in determining time-erupted volume relationships in such fields. Previous AVF hazard-risk modeling based on isolated, short-lived (< 1 year) phenomena at sites that have not experienced activity needs to be revisited in light of the new Rangitoto chronology.

  13. In Silico Biology of H1N1: Molecular Modelling of Novel Receptors and Docking Studies of Inhibitors to Reveal New Insight in Flu Treatment

    Directory of Open Access Journals (Sweden)

    Deepak Kumar Behera

    2012-01-01

    Full Text Available Influenza is an infectious disease caused by RNA viruses of the family Orthomyxoviridae. The new influenza H1N1 viral stain has emerged by the genetic combination of genes from human, pig, and bird’s H1N1 virus. The influenza virus is roughly spherical and is enveloped by a lipid membrane. There are two glycoproteins in this lipid membrane; namely, hemagglutinin (HA which helps in attachment of the viral strain on the host cell surface and neuraminidase (NA that is responsible for initiation of viral infection. We have developed homology models of both Hemagglutinin and Neuraminidase receptors from H1N1 strains in eastern India. The docking studies of B-Sialic acid and O-Sialic acid in the optimized and energy-minimized homology models show important H-bonding interactions with ALA142, ASP230, GLN231, GLU232, and THR141. This information can be used for structure-based and pharmacophore-based new drug design. We have also calculated ADME properties (Human Oral Absorption (HOA and % HOA for Oseltamivir which have been subject of debate for long.

  14. Molecular study on the carAB operon reveals that carB gene is required for swimming and biofilm formation in Xanthomonas citri subsp. citri.

    Science.gov (United States)

    Zhuo, Tao; Rou, Wei; Song, Xue; Guo, Jing; Fan, Xiaojing; Kamau, Gicharu Gibson; Zou, Huasong

    2015-10-23

    The carA and carB genes code the small and large subunits of carbamoyl-phosphate synthase (CPS) that responsible for arginine and pyrimidine production. The purpose of this work was to study the gene organization and expression pattern of carAB operon, and the biological functions of carA and carB genes in Xanthomonas citri subsp. citri. RT-PCR method was employed to identify the full length of carAB operon transcript in X. citri subsp. citri. The promoter of carAB operon was predicted and analyzed its activity by fusing a GUS reporter gene. The swimming motility was tested on 0.25% agar NY plates with 1% glucose. Biofilm was measured by cell adhesion to polyvinyl chloride 96-well plate. The results indicated that carAB operon was composed of five gene members carA-orf-carB-greA-rpfE. A single promoter was predicted from the nucleotide sequence upstream of carAB operon, and its sensitivity to glutamic acid, uracil and arginine was confirmed by fusing a GUS reporter gene. Deletion mutagenesis of carB gene resulted in reduced abilities in swimming on soft solid media and in forming biofilm on polystyrene microtiter plates. From these results, we concluded that carAB operon was involved in multiple biological processes in X. citri subsp. citri.

  15. An Atomic Force Microscope Study Revealed Two Mechanisms in the Effect of Anticancer Drugs on Rate-Dependent Young's Modulus of Human Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Juan Ren

    Full Text Available Mechanical properties of cells have been recognized as a biomarker for cellular cytoskeletal organization. As chemical treatments lead to cell cytoskeletal rearrangements, thereby, modifications of cellular mechanical properties, investigating cellular mechanical property variations provides insightful knowledge to effects of chemical treatments on cancer cells. In this study, the effects of eight different anticancer drugs on the mechanical properties of human prostate cancer cell (PC-3 are investigated using a recently developed control-based nanoindentation measurement (CNM protocol on atomic force microscope (AFM. The CNM protocol overcomes the limits of other existing methods to in-liquid nanoindentation measurement of live cells on AFM, particularly for measuring mechanical properties of live cells. The Young's modulus of PC-3 cells treated by the eight drugs was measured by varying force loading rates over three orders of magnitude, and compared to the values of the control. The results showed that the Young's modulus of the PC-3 cells increased substantially by the eight drugs tested, and became much more pronounced as the force load rate increased. Moreover, two distinct trends were clearly expressed, where under the treatment of Disulfiram, paclitaxel, and MK-2206, the exponent coefficient of the frequency- modulus function remained almost unchanged, while with Celebrex, BAY, Totamine, TPA, and Vaproic acid, the exponential rate was significantly increased.

  16. First study on gene expression of cement proteins and potential adhesion-related genes of a membranous-based barnacle as revealed from Next-Generation Sequencing technology

    KAUST Repository

    Lin, Hsiu Chin

    2013-12-12

    This is the first study applying Next-Generation Sequencing (NGS) technology to survey the kinds, expression location, and pattern of adhesion-related genes in a membranous-based barnacle. A total of 77,528,326 and 59,244,468 raw sequence reads of total RNA were generated from the prosoma and the basis of Tetraclita japonica formosana, respectively. In addition, 55,441 and 67,774 genes were further assembled and analyzed. The combined sequence data from both body parts generates a total of 79,833 genes of which 47.7% were shared. Homologues of barnacle cement proteins - CP-19K, -52K, and -100K - were found and all were dominantly expressed at the basis where the cement gland complex is located. This is the main area where transcripts of cement proteins and other potential adhesion-related genes were detected. The absence of another common barnacle cement protein, CP-20K, in the adult transcriptome suggested a possible life-stage restricted gene function and/or a different mechanism in adhesion between membranous-based and calcareous-based barnacles. © 2013 © 2013 Taylor & Francis.

  17. A molecular epidemiology study based on VP2 gene sequences reveals that a new genotype of infectious bursal disease virus is dominantly prevalent in Italy.

    Science.gov (United States)

    Lupini, Caterina; Giovanardi, Davide; Pesente, Patrizia; Bonci, Michela; Felice, Viviana; Rossi, Giulia; Morandini, Emilio; Cecchinato, Mattia; Catelli, Elena

    2016-08-01

    A distinctive infectious bursal disease (IBD) virus genotype (ITA) was detected in IBD-live vaccinated broilers in Italy without clinical signs of IBD. It was isolated in specific-pathogen-free eggs and molecularly characterized in the hypervariable region of the virus protein (VP) 2. Phylogenetic analysis showed that ITA strains clustered separately from other homologous reference sequences of IBDVs, either classical or very virulent, retrieved from GenBank or previously reported in Italy, and from vaccine strains. The new genotype shows peculiar molecular characteristics in key positions of the VP2 hypervariable region, which affect charged or potentially glycosylated amino acids virtually associated with important changes in virus properties. Characterization of 41 IBDV strains detected in Italy between 2013 and 2014 showed that ITA is emergent in densely populated poultry areas of Italy, being 68% of the IBDV detections made during routine diagnostic activity over a two-year period, in spite of the immunity induced by large-scale vaccination. Four very virulent strains (DV86) and one classical strain (HPR2), together with eight vaccine strains, were also detected. The currently available epidemiological and clinical data do not allow the degree of pathogenicity of the ITA genotype to be defined. Only in vivo experimental pathogenicity studies conducted in secure isolation conditions, through the evaluation of clinical signs and macro/microscopic lesions, will clarify conclusively the virulence of the new Italian genotype.

  18. Uptake and distribution of combined nitrogen and its incorporation into seeds of nodulated soybean plants as revealed by 15N studies

    International Nuclear Information System (INIS)

    Rabie, R.K.; Arima, Yasuhiro; Kumazawa, Kikuo

    1980-01-01

    Pot experiments were carried out with soybean plants grown with N-free solution, then supplied with NO 3 - or NH 4 + before 15 N administration, in order to study the uptake, distribution and redistribution of absorbed nitrogen. To determine the utilization and incorporation of combined nitrogen to the yield of seeds, as influenced by the form of N and application time, another series of experiments was carried out, in which the plants were grown with N-free solution, then 15 N was fed as 15 NO 3 - or 15 NH 4 + at pod setting stage (PS) or initial pod filling stage (IPF). By comparing the nitrate-treated plants (Nt plants) with the ammonia-treated ones (Am plants), and the treatment at PS with that at IPF, the following results were obtained. Nt plants accumulated larger amount of dry matters in respective plant parts than Am plants, particularly in the pods, and it was proved that the pods were the active sinks for newly metabolized nitrate. Both 15 N abundance and 15 N incorporation in the whole plants were much higher in Nt plants, and those in respective plant parts except nodules were also higher in Nt plants. Large part of the 15 N in roots was redistributed to the top parts in Nt plants, while large part of the absorbed N was distributed to the nodules in Am plants. Some more results are reported. (Kako, I.)

  19. Mechanistic and Structural Studies of Protein-Only RNase P Compared to Ribonucleoproteins Reveal the Two Faces of the Same Enzymatic Activity

    Directory of Open Access Journals (Sweden)

    Cédric Schelcher

    2016-06-01

    Full Text Available RNase P, the essential activity that performs the 5′ maturation of tRNA precursors, can be achieved either by ribonucleoproteins containing a ribozyme present in the three domains of life or by protein-only enzymes called protein-only RNase P (PRORP that occur in eukaryote nuclei and organelles. A fast growing list of studies has investigated three-dimensional structures and mode of action of PRORP proteins. Results suggest that similar to ribozymes, PRORP proteins have two main domains. A clear functional analogy can be drawn between the specificity domain of the RNase P ribozyme and PRORP pentatricopeptide repeat domain, and between the ribozyme catalytic domain and PRORP N4BP1, YacP-like Nuclease domain. Moreover, both types of enzymes appear to dock with the acceptor arm of tRNA precursors and make specific contacts with the corner of pre-tRNAs. While some clear differences can still be delineated between PRORP and ribonucleoprotein (RNP RNase P, the two types of enzymes seem to use, fundamentally, the same catalytic mechanism involving two metal ions. The occurrence of PRORP and RNP RNase P represents a remarkable example of convergent evolution. It might be the unique witness of an ongoing replacement of catalytic RNAs by proteins for enzymatic activities.

  20. Kinetic and Structural Studies of Aldehyde Oxidoreductase from Desulfovibrio gigas Reveal a Dithiolene-Based Chemistry for Enzyme Activation and Inhibition by H2O2

    Science.gov (United States)

    Brondino, Carlos D.; Moura, José J. G.; Romão, Maria J.; González, Pablo J.; Santos-Silva, Teresa

    2013-01-01

    Mononuclear Mo-containing enzymes of the xanthine oxidase (XO) family catalyze the oxidative hydroxylation of aldehydes and heterocyclic compounds. The molybdenum active site shows a distorted square-pyramidal geometry in which two ligands, a hydroxyl/water molecule (the catalytic labile site) and a sulfido ligand, have been shown to be essential for catalysis. The XO family member aldehyde oxidoreductase from Desulfovibrio gigas (DgAOR) is an exception as presents in its catalytically competent form an equatorial oxo ligand instead of the sulfido ligand. Despite this structural difference, inactive samples of DgAOR can be activated upon incubation with dithionite plus sulfide, a procedure similar to that used for activation of desulfo-XO. The fact that DgAOR does not need a sulfido ligand for catalysis indicates that the process leading to the activation of inactive DgAOR samples is different to that of desulfo-XO. We now report a combined kinetic and X-ray crystallographic study to unveil the enzyme modification responsible for the inactivation and the chemistry that occurs at the Mo site when DgAOR is activated. In contrast to XO, which is activated by resulfuration of the Mo site, DgAOR activation/inactivation is governed by the oxidation state of the dithiolene moiety of the pyranopterin cofactor, which demonstrates the non-innocent behavior of the pyranopterin in enzyme activity. We also showed that DgAOR incubation with dithionite plus sulfide in the presence of dioxygen produces hydrogen peroxide not associated with the enzyme activation. The peroxide molecule coordinates to molybdenum in a η2 fashion inhibiting the enzyme activity. PMID:24391748

  1. Kinetic and structural studies of aldehyde oxidoreductase from Desulfovibrio gigas reveal a dithiolene-based chemistry for enzyme activation and inhibition by H(2O(2.

    Directory of Open Access Journals (Sweden)

    Jacopo Marangon

    Full Text Available Mononuclear Mo-containing enzymes of the xanthine oxidase (XO family catalyze the oxidative hydroxylation of aldehydes and heterocyclic compounds. The molybdenum active site shows a distorted square-pyramidal geometry in which two ligands, a hydroxyl/water molecule (the catalytic labile site and a sulfido ligand, have been shown to be essential for catalysis. The XO family member aldehyde oxidoreductase from Desulfovibrio gigas (DgAOR is an exception as presents in its catalytically competent form an equatorial oxo ligand instead of the sulfido ligand. Despite this structural difference, inactive samples of DgAOR can be activated upon incubation with dithionite plus sulfide, a procedure similar to that used for activation of desulfo-XO. The fact that DgAOR does not need a sulfido ligand for catalysis indicates that the process leading to the activation of inactive DgAOR samples is different to that of desulfo-XO. We now report a combined kinetic and X-ray crystallographic study to unveil the enzyme modification responsible for the inactivation and the chemistry that occurs at the Mo site when DgAOR is activated. In contrast to XO, which is activated by resulfuration of the Mo site, DgAOR activation/inactivation is governed by the oxidation state of the dithiolene moiety of the pyranopterin cofactor, which demonstrates the non-innocent behavior of the pyranopterin in enzyme activity. We also showed that DgAOR incubation with dithionite plus sulfide in the presence of dioxygen produces hydrogen peroxide not associated with the enzyme activation. The peroxide molecule coordinates to molybdenum in a η(2 fashion inhibiting the enzyme activity.

  2. Kinetic and structural studies of aldehyde oxidoreductase from Desulfovibrio gigas reveal a dithiolene-based chemistry for enzyme activation and inhibition by H(2)O(2).

    Science.gov (United States)

    Marangon, Jacopo; Correia, Hugo D; Brondino, Carlos D; Moura, José J G; Romão, Maria J; González, Pablo J; Santos-Silva, Teresa

    2013-01-01

    Mononuclear Mo-containing enzymes of the xanthine oxidase (XO) family catalyze the oxidative hydroxylation of aldehydes and heterocyclic compounds. The molybdenum active site shows a distorted square-pyramidal geometry in which two ligands, a hydroxyl/water molecule (the catalytic labile site) and a sulfido ligand, have been shown to be essential for catalysis. The XO family member aldehyde oxidoreductase from Desulfovibrio gigas (DgAOR) is an exception as presents in its catalytically competent form an equatorial oxo ligand instead of the sulfido ligand. Despite this structural difference, inactive samples of DgAOR can be activated upon incubation with dithionite plus sulfide, a procedure similar to that used for activation of desulfo-XO. The fact that DgAOR does not need a sulfido ligand for catalysis indicates that the process leading to the activation of inactive DgAOR samples is different to that of desulfo-XO. We now report a combined kinetic and X-ray crystallographic study to unveil the enzyme modification responsible for the inactivation and the chemistry that occurs at the Mo site when DgAOR is activated. In contrast to XO, which is activated by resulfuration of the Mo site, DgAOR activation/inactivation is governed by the oxidation state of the dithiolene moiety of the pyranopterin cofactor, which demonstrates the non-innocent behavior of the pyranopterin in enzyme activity. We also showed that DgAOR incubation with dithionite plus sulfide in the presence of dioxygen produces hydrogen peroxide not associated with the enzyme activation. The peroxide molecule coordinates to molybdenum in a η(2) fashion inhibiting the enzyme activity.

  3. LOFAR reveals the giant: a low-frequency radio continuum study of the outflow in the nearby FR I radio galaxy 3C 31

    Science.gov (United States)

    Heesen, V.; Croston, J. H.; Morganti, R.; Hardcastle, M. J.; Stewart, A. J.; Best, P. N.; Broderick, J. W.; Brüggen, M.; Brunetti, G.; ChyŻy, K. T.; Harwood, J. J.; Haverkorn, M.; Hess, K. M.; Intema, H. T.; Jamrozy, M.; Kunert-Bajraszewska, M.; McKean, J. P.; Orrú, E.; Röttgering, H. J. A.; Shimwell, T. W.; Shulevski, A.; White, G. J.; Wilcots, E. M.; Williams, W. L.

    2018-03-01

    We present a deep, low-frequency radio continuum study of the nearby Fanaroff-Riley class I (FR I) radio galaxy 3C 31 using a combination of LOw Frequency ARray (LOFAR; 30-85 and 115-178 MHz), Very Large Array (VLA; 290-420 MHz), Westerbork Synthesis Radio Telescope (WSRT; 609 MHz) and Giant Metre Radio Telescope (GMRT; 615 MHz) observations. Our new LOFAR 145-MHz map shows that 3C 31 has a largest physical size of 1.1 Mpc in projection, which means 3C 31 now falls in the class of giant radio galaxies. We model the radio continuum intensities with advective cosmic ray transport, evolving the cosmic ray electron population and magnetic field strength in the tails as functions of distance to the nucleus. We find that if there is no in situ particle acceleration in the tails, then decelerating flows are required that depend on radius r as v∝rβ (β ≈ -1). This then compensates for the strong adiabatic losses due to the lateral expansion of the tails. We are able to find self-consistent solutions in agreement with the entrainment model of Croston & Hardcastle, where the magnetic field provides ≈1/3 of the pressure needed for equilibrium with the surrounding intracluster medium. We obtain an advective time-scale of ≈190 Myr, which, if equated to the source age, would require an average expansion Mach number M ≈ 5 over the source lifetime. Dynamical arguments suggest that instead either the outer tail material does not represent the oldest jet plasma or else the particle ages are underestimated due to the effects of particle acceleration on large scales.

  4. Revealing the complexity of quitting smoking: a qualitative grounded theory study of the natural history of quitting in Australian ex-smokers.

    Science.gov (United States)

    Smith, Andrea L; Carter, Stacy M; Dunlop, Sally M; Freeman, Becky; Chapman, Simon

    2017-11-23

    To explore the quitting histories of Australian ex-smokers in order to develop an understanding of the varied contribution of smoking cessation assistance (either pharmacotherapy or professionally mediated behavioural support) to the process of quitting. Qualitative grounded theory study; in-depth interviews. 37 Australian adult ex-smokers (24-68 years; 15 men, 22 women) who quit in the past 6-24 months. Although participants' individual quitting histories and their overall experiences of quitting were unique, when the 37 quitting histories were compared it was clear two experiences were common to almost all participants: almost no one quit at their first quit attempt and almost everyone started out quitting unassisted. Furthermore, distinct patterns existed in the timing and use of assistance, in particular the age at which assistance was first used, how some participants were resolutely uninterested in assistance, and how assistance might have contributed to the process of successful quitting even if not used on the final quit attempt. Importantly, three patterns in use of assistance were identified: (1) only ever tried to quit unassisted (n=13); (2) started unassisted, tried assistance but reverted back to unassisted (n=13); (3) started unassisted, tried assistance and quit with assistance (n=11). For most participants, insight into what quitting would require was only gained through prior quitting experiences with and without assistance. For a number of participants, interest in assistance was at its lowest when the participant was most ready to quit. Quitting should be viewed as a process drawing on elements of assisted and unassisted quitting rather than a stand-alone event that can be labelled as strictly assisted or unassisted. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. A camera-phone based study reveals erratic eating pattern and disrupted daily eating-fasting cycle among adults in India.

    Directory of Open Access Journals (Sweden)

    Neelu Jain Gupta

    Full Text Available The daily rhythm of feeding-fasting and meal-timing are emerging as important determinants of health. Circadian rhythm research in animal models and retrospective analyses of human nutrition data have shown that reduced length of overnight fasting or increased late night eating increases risk for metabolic diseases including obesity and diabetes. However, the daily rhythm in eating pattern in humans is rarely measured. Traditional methods to collect nutrition information through food diary and food log pay little attention to the timing of eating which may also change from day to day. We adopted a novel cell-phone based approach to longitudinally record all events of food and beverage intake in adults. In a feasibility study daily food-eating patterns of 93 healthy individuals were recorded for 21 days using camera phones. Analysis of the daily eating patterns of these individuals indicates deviation from conventional assumption that people eat three meals-a-day within a 12 h interval. We found that eating events are widespread throughout the day, with 30% consumed in evening and late night hours. There was little difference in eating pattern between weekdays and weekends. In this cohort more than 50% of people spread their caloric intake events over 15 h or longer. One decile of the cohort who were spouses of shift-workers or had flexible work schedule spread their caloric intake over 20 h. Although the nutrition quality and diversity of food consumed is different between South-East Asian and Western countries, such overall disruption of daily eating-fasting rhythm is similar. Therefore, in view of hypothesis that disrupted daily eating pattern may contribute to the global increase in metabolic diseases and modification of daily eating pattern is a potential modifiable behavior to contain these diseases, monitoring eating pattern is an important aspect of lifestyle.

  6. Natural history-driven, plant-mediated RNAi-based study reveals CYP6B46’s role in a nicotine-mediated antipredator herbivore defense

    Science.gov (United States)

    Kumar, Pavan; Pandit, Sagar S.; Steppuhn, Anke; Baldwin, Ian T.

    2014-01-01

    Manduca sexta (Ms) larvae are known to efficiently excrete ingested nicotine when feeding on their nicotine-producing native hostplant, Nicotiana attenuata. Here we describe how ingested nicotine is co-opted for larval defense by a unique mechanism. Plant-mediated RNAi was used to silence a midgut-expressed, nicotine-induced cytochrome P450 6B46 (CYP6B46) in larvae consuming transgenic N. attenuata plants producing MsCYP6B46 dsRNA. These and transgenic nicotine-deficient plants were planted into native habitats to study the phenotypes of larvae feeding on these plants and the behavior of their predators. The attack-behavior of a native wolf spider (Camptocosa parallela), a major nocturnal predator, provided the key to understanding MsCYP6B46’s function: spiders clearly preferred CYP6B46-silenced larvae, just as they had preferred larvae fed nicotine-deficient plants. MsCYP6B46 redirects a small amount (0.65%) of ingested nicotine from the midgut into hemolymph, from which nicotine is exhaled through the spiracles as an antispider signal. CYP6B46-silenced larvae were more susceptible to spider-attack because they exhaled less nicotine because of lower hemolymph nicotine concentrations. CYP6B46-silenced larvae were impaired in distributing ingested nicotine from midgut to hemolymph, but not in the clearing of hemolymph nicotine or in the exhalation of nicotine from hemolymph. MsCYP6B46 could be a component of a previously hypothesized pump that converts nicotine to a short-lived, transportable, metabolite. Other predators, big-eyed bugs, and antlion larvae were insensitive to this defense. Thus, chemical defenses, too toxic to sequester, can be repurposed for defensive functions through respiration as a form of defensive halitosis, and predators can assist the functional elucidation of herbivore genes. PMID:24379363

  7. A feasibility study of NIR fluorescent image-guided surgery in head and neck cancer based on the assessment of optimum surgical time as revealed through dynamic imaging

    Directory of Open Access Journals (Sweden)

    Yokoyama J

    2013-04-01

    Full Text Available Junkichi Yokoyama,* Mitsuhisa Fujimaki,* Shinichi Ohba, Takashi Anzai, Ryota Yoshii, Shin Ito, Masataka Kojima, Katsuhisa IkedaDepartment of Otolaryngology-Head and Neck Surgery, Juntendo University School of Medicine, Tokyo, Japan *These authors contributed equally to this study Background: In order to minimize surgical stress and preserve organs, endoscopic or robotic surgery is often performed when conducting head and neck surgery. However, it is impossible to physically touch tumors or to observe diffusely invaded deep organs through the procedure of endoscopic or robotic surgery. In order to visualize and safely resect tumors even in these cases, we propose using an indocyanine green (ICG fluorescence method for navigation surgery in head and neck cancer. Objective: To determine the optimum surgical time for tumor resection after the administration of ICG based on the investigation of dynamic ICG fluorescence imaging. Methods: Nine patients underwent dynamic ICG fluorescence imaging for 360 minutes, assessing tumor visibility at 10, 30, 60, 120, 180, and 360 minutes. All cases were scored according to near-infrared (NIR fluorescence imaging visibility scored from 0 to 5. Results: Dynamic NIR fluorescence imaging under the HyperEye Medical System indicated that the greatest contrast in fluorescent images between tumor and normal tissue could be observed from 30 minutes to 1 hour after the administration of ICG. The optimum surgical time was determined to be between 30 minutes to 2 hours after ICG injection. These findings are particularly useful for detection and safe resection of tumors invading the parapharyngeal space. Conclusion: ICG fluorescence imaging is effective for the detection of head and neck cancer. Preliminary findings suggest that the optimum timing for surgery is from 30 minutes to 2 hours after the ICG injection. Keywords: indocyanine green (ICG, navigation surgery, robotic surgery, endoscopic surgery, minimally invasive

  8. Multiple gene genealogies and phenotypic data reveal cryptic species of the Botryosphaeriaceae: a case study on the Neofusicoccum parvum/N. ribis complex.

    Science.gov (United States)

    Pavlic, Draginja; Slippers, Bernard; Coutinho, Teresa A; Wingfield, Michael J

    2009-05-01

    Neofusicoccum parvum and N. ribis (Botryosphaeriaceae, Ascomycetes) are closely related, plant pathogenic fungi with a world-wide distribution on a wide range of woody hosts. Species boundaries in the N. parvum/N. ribis complex have eluded definition, despite the application of various tools for characterisation. In this study, we test the hypothesis that only one species exists amongst isolates from the N. parvum/N. ribis complex, identified from Syzygiumcordatum trees across their native distribution in South Africa. Genealogical concordance phylogenetic species recognition (GCPSR) was applied based on concordance of genealogies obtained from DNA sequence data for five nuclear loci. These data showed that the single species hypothesis must be rejected. Rather, all analyses support the existence of three previously unrecognised, cryptic species within the N. parvum/N.ribis complex from S. cordatum, in addition to N. parvum and N. ribis. The three lineages reflecting these cryptic taxa are sympatric across their geographical range, indicating barriers to gene flow other than geographic isolation. Phenotypic characters failed to detect all the species uncovered by the GCPSR. Sequence data of the Internal Transcribed Spacer (ITS) of the ribosomal DNA locus, which is thought to be useful for barcoding in fungi, did not distinguish all the species with confidence. RNA polymerase II subunit (RPB2) was the most informative to distinguish all the species a posteriori to the application of GCPSR. The results reflect the critical importance of using multiple gene genealogies and adequate sampling to identify cryptic species and to characterise the true diversity within the Botryosphaeriaceae.

  9. Structural and molecular dynamics studies of a C1-oxidizing lytic polysaccharide monooxygenase from Heterobasidion irregulare reveal amino acids important for substrate recognition.

    Science.gov (United States)

    Liu, Bing; Kognole, Abhishek A; Wu, Miao; Westereng, Bjørge; Crowley, Michael F; Kim, Seonah; Dimarogona, Maria; Payne, Christina M; Sandgren, Mats

    2018-04-16

    Lytic polysaccharide monooxygenases (LPMOs) are a group of recently discovered enzymes that play important roles in the decomposition of recalcitrant polysaccharides. Here, we report the biochemical, structural and computational characterization of an LPMO from the white-rot fungus Heterobasidion irregulare (HiLPMO9B). This enzyme oxidizes cellulose at the C1 carbon of glycosidic linkages. The crystal structure of HiLPMO9B was determined at 2.1 Å resolution using X-ray crystallography. Unlike the majority of the currently available C1-specific LPMO structures, the HiLPMO9B structure contains an extended L2 loop, connecting β-strands β2 and β3 of the β-sandwich structure. Molecular dynamics (MD) simulations suggest roles for both aromatic and acidic residues in the substrate binding of HiLPMO9B, with the main contribution from the residues located on the extended region of the L2 loop (Tyr20) and the LC loop (Asp205, Tyr207 and Glu210). Asp205 and Glu210 were found to be involved in the hydrogen bonding with the hydroxyl group of the C6 carbon of glucose moieties directly or via a water molecule. Two different binding orientations were observed over the course of the MD simulations. In each orientation, the active-site copper of this LPMO preferentially skewed toward the pyranose C1 of the glycosidic linkage over the targeted glycosidic bond. This study provides additional insight into cellulose binding by C1-specific LPMOs, giving a molecular-level picture of active site substrate interactions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Structure-function analysis of porcine cytochrome P450 3A29 in the hydroxylation of T-2 toxin as revealed by docking and mutagenesis studies.

    Directory of Open Access Journals (Sweden)

    Guyue Cheng

    Full Text Available T-2 toxin, one of the type A trichothecenes, presents a potential hazard to human and animal health. Our previous work demonstrated that porcine cytochrome P450 3A29 (CYP3A29 played an important role in the hydroxylation of T-2 toxin. To identify amino acids involved in this metabolic process, T-2 toxin was docked into a homology model of CYP3A29 based on a crystal structure of CYP3A4 using AutoDock 4.0. Nine residues of CYP3A29, Arg105, Arg106, Phe108, Ser119, Lys212, Phe213, Phe215, Arg372 and Glu374, which were found within 5 Å around T-2 toxin were subjected to site-directed mutagenesis. In the oxidation of nifedipine, the CLint value of R106A was increased by nearly two-folds compared with the wild-type CYP3A29, while the substrate affinities and CLint values of S119A and K212A were significantly reduced. In the hydroxylation of T-2 toxin, the generation of 3'-OH-T-2 by R105A, S119A and K212A was significantly less than that by the wild-type, whereas R106A slightly increased the generation of 3'-OH-T-2. These results were further confirmed by isothermal titration calorimetry analysis, suggesting that these four residues are important in the hydroxylation of T-2 toxin and Arg105 may be a specific recognition site for the toxin. Our study suggests a possible structure-function relationship of CYP3A29 in the hydroxylation of T-2 toxin, providing with new insights into the mechanism of CYP3A enzymes in the biotransformation of T-2 toxin.

  11. Natural history-driven, plant-mediated RNAi-based study reveals CYP6B46's role in a nicotine-mediated antipredator herbivore defense.

    Science.gov (United States)

    Kumar, Pavan; Pandit, Sagar S; Steppuhn, Anke; Baldwin, Ian T

    2014-01-28

    Manduca sexta (Ms) larvae are known to efficiently excrete ingested nicotine when feeding on their nicotine-producing native hostplant, Nicotiana attenuata. Here we describe how ingested nicotine is co-opted for larval defense by a unique mechanism. Plant-mediated RNAi was used to silence a midgut-expressed, nicotine-induced cytochrome P450 6B46 (CYP6B46) in larvae consuming transgenic N. attenuata plants producing MsCYP6B46 dsRNA. These and transgenic nicotine-deficient plants were planted into native habitats to study the phenotypes of larvae feeding on these plants and the behavior of their predators. The attack-behavior of a native wolf spider (Camptocosa parallela), a major nocturnal predator, provided the key to understanding MsCYP6B46's function: spiders clearly preferred CYP6B46-silenced larvae, just as they had preferred larvae fed nicotine-deficient plants. MsCYP6B46 redirects a small amount (0.65%) of ingested nicotine from the midgut into hemolymph, from which nicotine is exhaled through the spiracles as an antispider signal. CYP6B46-silenced larvae were more susceptible to spider-attack because they exhaled less nicotine because of lower hemolymph nicotine concentrations. CYP6B46-silenced larvae were impaired in distributing ingested nicotine from midgut to hemolymph, but not in the clearing of hemolymph nicotine or in the exhalation of nicotine from hemolymph. MsCYP6B46 could be a component of a previously hypothesized pump that converts nicotine to a short-lived, transportable, metabolite. Other predators, big-eyed bugs, and antlion larvae were insensitive to this defense. Thus, chemical defenses, too toxic to sequester, can be repurposed for defensive functions through respiration as a form of defensive halitosis, and predators can assist the functional elucidation of herbivore genes.

  12. A verification protocol for the probe sequences of Affymetrix genome arrays reveals high probe accuracy for studies in mouse, human and rat

    Directory of Open Access Journals (Sweden)

    Nap Jan-Peter

    2007-04-01

    Full Text Available Abstract Background The Affymetrix GeneChip technology uses multiple probes per gene to measure its expression level. Individual probe signals can vary widely, which hampers proper interpretation. This variation can be caused by probes that do not properly match their target gene or that match multiple genes. To determine the accuracy of Affymetrix arrays, we developed an extensive verification protocol, for mouse arrays incorporating the NCBI RefSeq, NCBI UniGene Unique, NIA Mouse Gene Index, and UCSC mouse genome databases. Results Applying this protocol to Affymetrix Mouse Genome arrays (the earlier U74Av2 and the newer 430 2.0 array, the number of sequence-verified probes with perfect matches was no less than 85% and 95%, respectively; and for 74% and 85% of the probe sets all probes were sequence verified. The latter percentages increased to 80% and 94% after discarding one or two unverifiable probes per probe set, and even further to 84% and 97% when, in addition, allowing for one or two mismatches between probe and target gene. Similar results were obtained for other mouse arrays, as well as for human and rat arrays. Based on these data, refined chip definition files for all arrays are provided online. Researchers can choose the version appropriate for their study to (reanalyze expression data. Conclusion The accuracy of Affymetrix probe sequences is higher than previously reported, particularly on newer arrays. Yet, refined probe set definitions have clear effects on the detection of differentially expressed genes. We demonstrate that the interpretation of the results of Affymetrix arrays is improved when the new chip definition files are used.

  13. To Reveal Thy Heart Perchance to Reveal the World

    Directory of Open Access Journals (Sweden)

    Robert B. Faux

    2005-05-01

    Full Text Available Ronald PELIAS, a professor of speech communications, employs a variety of writing methods as examples of alternative ways to do research and to share with the reader a seldom seen and seldom considered aspect of academic life: Heart. In the early chapters of the book, PELIAS sets out to establish a way to place his Heart in the foreground; baring his emotional vulnerability, his humanness, his being in the world. Later chapters of the book encompass an autoethnographic study of academic life in which the previously revealed Heart is placed in context. In this review essay I discuss PELIAS' book in relation to the larger literature on autoethnography and subjectivist research; I follow this by discussing the need for and usefulness of such alternative methods using PELIAS' autoethnography of academic life as a context. URN: urn:nbn:de:0114-fqs050279

  14. A genome-wide association study in a large F2-cross of laying hens reveals novel genomic regions associated with feather pecking and aggressive pecking behavior.

    Science.gov (United States)

    Lutz, Vanessa; Stratz, Patrick; Preuß, Siegfried; Tetens, Jens; Grashorn, Michael A; Bessei, Werner; Bennewitz, Jörn

    2017-02-03

    Feather pecking and aggressive pecking in laying hens are serious economic and welfare issues. In spite of extensive research on feather pecking during the last decades, the motivation for this behavior is still not clear. A small to moderate heritability has frequently been reported for these traits. Recently, we identified several single-nucleotide polymorphisms (SNPs) associated with feather pecking by mapping selection signatures in two divergent feather pecking lines. Here, we performed a genome-wide association analysis (GWAS) for feather pecking and aggressive pecking behavior, then combined the results with those from the recent selection signature experiment, and linked them to those obtained from a differential gene expression study. A large F2 cross of 960 F2 hens was generated using the divergent lines as founders. Hens were phenotyped for feather pecks delivered (FPD), aggressive pecks delivered (APD), and aggressive pecks received (APR). Individuals were genotyped with the Illumina 60K chicken Infinium iSelect chip. After data filtering, 29,376 SNPs remained for analyses. Single-marker GWAS was performed using a Poisson model. The results were combined with those from the selection signature experiment using Fisher's combined probability test. Numerous significant SNPs were identified for all traits but with low false discovery rates. Nearly all significant SNPs were located in clusters that spanned a maximum of 3 Mb and included at least two significant SNPs. For FPD, four clusters were identified, which increased to 13 based on the meta-analysis (FPD meta ). Seven clusters were identified for APD and three for APR. Eight genes (of the 750 investigated genes located in the FPD meta clusters) were significantly differentially-expressed in the brain of hens from both lines. One gene, SLC12A9, and the positional candidate gene for APD, GNG2, may be linked to the monomanine signaling pathway, which is involved in feather pecking and aggressive behavior

  15. Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Agniswamy, Johnson; Louis, John M.; Roche, Julien; Harrison, Robert W.; Weber, Irene T. (GSU); (NIH); (Iowa State)

    2016-12-16

    We report structural analysis of HIV protease variant PRS17 which was rationally selected by machine learning to represent wide classes of highly drug-resistant variants. Crystal structures were solved of PRS17 in the inhibitor-free form and in complex with antiviral inhibitor, darunavir. Despite its 17 mutations, PRS17 has only one mutation (V82S) in the inhibitor/substrate binding cavity, yet exhibits high resistance to all clinical inhibitors. PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with darunavir resistance, but has 10,000-fold weaker binding affinity relative to the wild type PR. Comparable binding affinity of 8000-fold weaker than PR is seen for drug resistant mutant PR20, which bears 3 mutations associated with major resistance to darunavir (I47V, I54L and I84V). Inhibitor-free PRS17 shows an open flap conformation with a curled tip correlating with G48V flap mutation. NMR studies on inactive PRS17 D25N unambiguously confirm that the flaps adopt mainly an open conformation in solution very similar to that in the inhibitor-free crystal structure. In PRS17, the hinge loop cluster of mutations, E35D, M36I and S37D, contributes to the altered flap dynamics by a mechanism similar to that of PR20. An additional K20R mutation anchors an altered conformation of the hinge loop. Flap mutations M46L and G48V in PRS17/DRV complex alter the Phe53 conformation by steric hindrance between the side chains. Unlike the L10F mutation in PR20, L10I in PRS17 does not break the inter-subunit ion pair or diminish the dimer stability, consistent with a very low dimer dissociation constant comparable to that of wild type PR. Distal mutations A71V, L90M and I93L propagate alterations to the catalytic site of PRS17. PRS17 exhibits a molecular mechanism whereby mutations act synergistically to alter the flap dynamics resulting in significantly weaker binding yet maintaining active site contacts with darunavir.

  16. Epidemiological and entomological studies of a malaria outbreak among French armed forces deployed at illegal gold mining sites reveal new aspects of the disease's transmission in French Guiana.

    Science.gov (United States)

    Pommier de Santi, Vincent; Girod, Romain; Mura, Marie; Dia, Aissata; Briolant, Sébastien; Djossou, Félix; Dusfour, Isabelle; Mendibil, Alexandre; Simon, Fabrice; Deparis, Xavier; Pagès, Frédéric

    2016-01-22

    In December 2010, a Plasmodium vivax malaria outbreak occurred among French forces involved in a mission to control illegal gold mining in French Guiana. The findings of epidemiological and entomological investigations conducted after this outbreak are presented here. Data related to malaria cases reported to the French armed forces epidemiological surveillance system were collected during the epidemic period from December 2010 to April 2011. A retrospective cohort study was conducted to identify presumed contamination sites. Anopheles mosquitoes were sampled at the identified sites using Mosquito Magnet and CDC light traps. Specimens were identified morphologically and confirmed using molecular methods (sequencing of ITS2 gene and/or barcoding). Anopheles infections with Plasmodium falciparum and P. vivax were tested by both enzyme-linked immunosorbent assay and real-time PCR. Seventy-two P. vivax malaria cases were reported (three were mixed P. falciparum/P. vivax infections), leading to a global attack rate of 26.5% (72/272). Lack of compliance with vector control measures and doxycycline chemoprophylaxis was reported by patients. Two illegal gold mining sites located in remote areas in the primary forest were identified as places of contamination. In all, 595 Anopheles females were caught and 528 specimens were formally identified: 305 Anopheles darlingi, 145 Anopheles nuneztovari s.l., 63 Anopheles marajoara and 15 Anopheles triannulatus s.l. Three An. darlingi were infected by P. falciparum (infection rate: 1.1%) and four An. marajoara by P. vivax (infection rate: 6.4%). The main drivers of the outbreak were the lack of adherence by military personnel to malaria prevention measures and the high level of malaria transmission at illegal gold mining sites. Anopheles marajoara was clearly implicated in malaria transmission for the first time in French Guiana. The high infection rates observed confirm that illegal gold mining sites must be considered as high level

  17. A Genome-Wide Association Study for Culm Cellulose Content in Barley Reveals Candidate Genes Co-Expressed with Members of the CELLULOSE SYNTHASE A Gene Family

    Science.gov (United States)

    Houston, Kelly; Burton, Rachel A.; Sznajder, Beata; Rafalski, Antoni J.; Dhugga, Kanwarpal S.; Mather, Diane E.; Taylor, Jillian; Steffenson, Brian J.; Waugh, Robbie; Fincher, Geoffrey B.

    2015-01-01

    Cellulose is a fundamentally important component of cell walls of higher plants. It provides a scaffold that allows the development and growth of the plant to occur in an ordered fashion. Cellulose also provides mechanical strength, which is crucial for both normal development and to enable the plant to withstand both abiotic and biotic stresses. We quantified the cellulose concentration in the culm of 288 two – rowed and 288 six – rowed spring type barley accessions that were part of the USDA funded barley Coordinated Agricultural Project (CAP) program in the USA. When the population structure of these accessions was analysed we identified six distinct populations, four of which we considered to be comprised of a sufficient number of accessions to be suitable for genome-wide association studies (GWAS). These lines had been genotyped with 3072 SNPs so we combined the trait and genetic data to carry out GWAS. The analysis allowed us to identify regions of the genome containing significant associations between molecular markers and cellulose concentration data, including one region cross-validated in multiple populations. To identify candidate genes we assembled the gene content of these regions and used these to query a comprehensive RNA-seq based gene expression atlas. This provided us with gene annotations and associated expression data across multiple tissues, which allowed us to formulate a supported list of candidate genes that regulate cellulose biosynthesis. Several regions identified by our analysis contain genes that are co-expressed with CELLULOSE SYNTHASE A (HvCesA) across a range of tissues and developmental stages. These genes are involved in both primary and secondary cell wall development. In addition, genes that have been previously linked with cellulose synthesis by biochemical methods, such as HvCOBRA, a gene of unknown function, were also associated with cellulose levels in the association panel. Our analyses provide new insights into the

  18. Changes in host-mycorrhiza relationships revealed by stable isotopes after naturally-induced thinning of the stand: case study on Tuber aestivum.

    Science.gov (United States)

    Gavrichkova, Olga; Lauteri, Marco; Ciolfi, Marco; Chiocchini, Francesca; Paris, Pierluigi; Pisanelli, Andrea; Portarena, Silvia; Brugnoli, Enrico

    2016-04-01

    Terrestrial plants overcome nutrients and water limitations by forming mutualistic associations with mycorrhizal fungi. Fungi, in return, take advantage from the carbohydrates supplied by the host. Some mycorrhizal fruit bodies, like that of Tuber spp., have a peculiar gastronomic value with many efforts being undertaken to predict and enhance their productivity. However, many issues of truffle-producing mycorrhizal ecology are still poorly understood, in particular optimal conditions favoring fruit formation, potential host plants and host-mycorrhiza relationships. In this study, we tested the applicability of stable isotope measurements under natural abundance to identify the plants which likely host the mycorrhiza of Tuber aestivum and to characterize host-mycorrhizal nutrient, water and carbohydrate exchange under plant natural growing conditions and with the change of the forest cover after naturally occurred thinning. For these purposes, sampling of the fruit bodies of T. aestivum was performed during the growing season 2011 in a mixed broadleaved-coniferous forest in central Italy (initially the site was a manmade pine plantation). Nine truffle-producing parcels were identified with five being composed of the original Pinus pinaster -dominated vegetation and four in which pine was replaced by broadleaf species after both wind-induced thinning and natural dieback of pine trees. Seasonal variation of δ13C, δ15N and δ18O were analyzed in the fungal material, in the surrounding soil and in the plant material of the potential host species (xylem water in the trunk, branches and leaves, recently assimilated carbohydrates in phloem and leaves). The results showed a possibility of the identification of the mycorrhizal host species applying isotope analyses, with mycorrhiza receiving most part of the carbohydrates from the pine in pine-dominated parcels. Interestingly, in thinned parcels, the truffle bodies maintained isotope composition similar to bodies gathered

  19. Cosmic Flasher Reveals All!

    Science.gov (United States)

    1998-09-01

    For more information on magnetars and soft gamma-ray repeaters, see the Background Information which includes a "movie" of the flashing magnetar nebula, as seen by the VLA. Astronomers have found evidence for the most powerful magnetic field ever seen in the universe. They found it by observing a long-sought, short-lived "afterglow" of subatomic particles ejected from a magnetar -- a neutron star with a magnetic field billions of times stronger than any on Earth and 100 times stronger than any other previously known in the Universe. The afterglow is believed to be the aftermath of a massive starquake on the neutron star's surface. "And where there's smoke, there's fire, and we've seen the 'smoke' that tells us there's a magnetar out there," says Dale Frail, who used the National Science Foundation's Very Large Array (VLA) radio telescope to make the discovery. "Nature has created a unique laboratory where there are magnetic fields far stronger than anything that can be created here on Earth. As a result, the study of these objects enables us to study the effects of extraordinarily intense magnetic fields on matter," explains Dr. Morris L. Aizenman, Executive Officer in the Division of Astronomy at the National Science Foundation. Frail, an astronomer at the National Radio Astronomy Observatory (NRAO) in Socorro, New Mexico, along with Shri Kulkarni and Josh Bloom, astronomers at Caltech, discovered radio emission coming from a strange object 15,000 light-years away in our own Milky Way Galaxy. The radio emission was seen after the object experienced an outburst of gamma-rays and X-rays in late August. "This emission comes from particles ejected at nearly the speed of light from the surface of the neutron star interacting with the extremely powerful magnetic field," said Kulkarni. This is the first time this phenomenon, predicted by theorists, has been seen so clearly from a suspected magnetar. "Magnetars are expected to behave in certain ways. Astronomers have seen

  20. Communication Games Reveal Preparation Contextuality

    Science.gov (United States)

    Hameedi, Alley; Tavakoli, Armin; Marques, Breno; Bourennane, Mohamed

    2017-12-01

    A communication game consists of distributed parties attempting to jointly complete a task with restricted communication. Such games are useful tools for studying limitations of physical theories. A theory exhibits preparation contextuality whenever its predictions cannot be explained by a preparation noncontextual model. Here, we show that communication games performed in operational theories reveal the preparation contextuality of that theory. For statistics obtained in a particular family of communication games, we show a direct correspondence with correlations in spacelike separated events obeying the no-signaling principle. Using this, we prove that all mixed quantum states of any finite dimension are preparation contextual. We report on an experimental realization of a communication game involving three-level quantum systems from which we observe a strong violation of the constraints of preparation noncontextuality.

  1. Communication Games Reveal Preparation Contextuality.

    Science.gov (United States)

    Hameedi, Alley; Tavakoli, Armin; Marques, Breno; Bourennane, Mohamed

    2017-12-01

    A communication game consists of distributed parties attempting to jointly complete a task with restricted communication. Such games are useful tools for studying limitations of physical theories. A theory exhibits preparation contextuality whenever its predictions cannot be explained by a preparation noncontextual model. Here, we show that communication games performed in operational theories reveal the preparation contextuality of that theory. For statistics obtained in a particular family of communication games, we show a direct correspondence with correlations in spacelike separated events obeying the no-signaling principle. Using this, we prove that all mixed quantum states of any finite dimension are preparation contextual. We report on an experimental realization of a communication game involving three-level quantum systems from which we observe a strong violation of the constraints of preparation noncontextuality.

  2. The chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1990-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. Important insights were obtained from tracer experiments, but the full complexity of plutonium chemistry was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were aqueous solution based, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, it was found that an equilibrium was rapidly established among the four aqueous oxidation states while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element will be reported

  3. Omics strategies for revealing Yersinia pestis virulence

    Science.gov (United States)

    Yang, Ruifu; Du, Zongmin; Han, Yanping; Zhou, Lei; Song, Yajun; Zhou, Dongsheng; Cui, Yujun

    2012-01-01

    Omics has remarkably changed the way we investigate and understand life. Omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. Mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. In this review, we summarize omics-driven studies to reveal the virulence features of Yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. These studies serve as foundations for further hypothesis-driven research and help us gain insight into Y. pestis pathogenesis. PMID:23248778

  4. Tanzania's Revealed Comparative Advantage and Structural ...

    African Journals Online (AJOL)

    This study examines Tanzania's structural transformation by using the revealed comparative approach using export data for 2001, 2002 and 2011, at the second level of the Harmonised. System (HS). Using global data, the study finds that for 2002 and 2011, agricultural products, fish and minerals have comparative ...

  5. Ultra-high-resolution C-arm flat-detector CT angiography evaluation reveals 3-fold higher association rate for sporadic intracranial cavernous malformations and developmental venous anomalies: a retrospective study in consecutive 58 patients with 60 cavernous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Kocak, Burak [Aksaray State Hospital, Department of Radiology, Aksaray (Turkey); Kizilkilic, Osman; Kocer, Naci; Islak, Civan [Istanbul University, Department of Radiology, Cerrahpasa Medical Faculty, Istanbul (Turkey); Oz, Buge; Bakkaloglu, Dogu Vuralli [Istanbul University, Department of Pathology, Cerrahpasa Medical Faculty, Istanbul (Turkey); Isler, Cihan [Istanbul University, Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul (Turkey)

    2017-06-15

    The imaging and surgical literature has confusing association rates for the association between sporadic intracranial cavernous malformations (CMs) and developmental venous anomalies (DVAs). In this study, our purpose was to determine the association rate using ultra-high-resolution C-arm flat-detector CT angiography (FDCTA) and compare it with literature. Fifty-eight patients with 60 sporadic intracranial CMs that underwent an FDCTA study were included in our retrospective study. Re-evaluation of radiological data was performed based on the criteria defined by authors. Isotropic volumetric reconstructions with ultra-high resolution (voxel size of 102 μm{sup 3} for initial; 67 μm{sup 3} and 32 μm{sup 3} for further evaluation) were used for assessment. Sixteen patients underwent surgery for excision of their CMs. Fifty-one of all patients (87.9 %) were associated with a DVA. Undefined local venous structures (UD-LVSs) were observed in the remaining 7 patients (12.1 %). The strength of interobserver agreement was excellent [kappa(k) coefficient = 0.923]. Ultra-high-resolution FDCTA evaluation of CMs and DVAs reveals 3-fold higher association rate compared to the literature. FDCTA for patients with sporadic CMs could help identify the a