Potassium rich rare earth (RE) borates K 3RE(BO 3) 2

NASA Astrophysics Data System (ADS)

Gao, J. H.; Li, R. K.

2008-01-01

A series of new compounds in the K 3RE(BO 3) 2 (RE = Y, Nd, Sm, Gd, Tb, Er and Lu) system were synthesized. Powder X-ray diffraction indicates that structures of the K 3RE(BO 3) 2 series can be separated into two different types with boundary between Gd and Tb. Single crystals of two representative compounds K 3Sm(BO 3) 2 and K 3Y(BO 3) 2 were obtained from a K 2O-B 2O 3 melt. The structure of K 3Y(BO 3) 2, determined from single crystal X-ray diffraction data, belongs to Pnnm space group, with lattice constants of a = 9.3377(9) Å, b = 6.7701(6) Å and c = 5.5058(4) Å. With a larger rare earth element, e.g. Sm 3+, K 3Sm(BO 3) 2 crystallizes in space group Pnma, with cell parameters of a = 9.046(3) Å, b = 7.100(2) Å and c = 11.186(3) Å. The structure of K 3Y(BO 3) 2 can be described as a three-dimensional framework formed by isolated YO 6 octahedra jointed by BO 3 triangles by sharing their apical oxygen atoms. The structure of K 3Sm(BO 3) 2 contains infinite [SmO 4BO 3] ∞ chains formed by corner sharing SmO 7 pentagonal dipyramid and BO 3 group, and those chains are interconnected by the other BO 3 groups.

Structural investigations of vanadyl doped Nb2O5·K2O·B2O3 glasses

NASA Astrophysics Data System (ADS)

Anshu; Sanghi, S.; Agarwal, A.; Lather, M.; Bhatnagar, V.; Khasa, S.

2009-07-01

Pottasium nioborate glasses of composition xNb2O5·(30-x)K2O·69B2O3 containing 1 mol % of V2O5 were prepared by melt quench technique (1473K, 1h). The electron paramagnetic resonance spectra of VO2+ in these glasses have been recorded in X- band (v approx 9.14 GHz) at room temperature (RT). The spin Hamiltonian parameters, dipolar hyperfine coupling parameters, P and Fermi contact interaction parameter, K have been calculated. It is found that V4+ ions in these glasses exist as VO2+ in octahedral coordination with a tetragonal distortion. The tetragonality of V4+O6 complex decreases with increasing Nb2O5: K2O ratio and also there is an expansion of 3dXY orbit of unpaired electron in the vanadium ion. The study of IR transmission spectra over a range 400- 4000 cm-1 depicts the presence of both BO3 and BO4 structural units and Nb5+ ions are incorporated into the glass network as NbO6 octahedra, substituting BO4 groups.

A photoelectron spectroscopy and quantum chemical study on ternary Al-B-O clusters: AlnBO2- and AlnBO2 (n = 2, 3).

PubMed

Ou, Ting; Feng, Yuan; Tian, Wen-Juan; Zhao, Li-Juan; Kong, Xiang-Yu; Xu, Hong-Guang; Zheng, Wei-Jun; Zhai, Hua-Jin

2018-02-14

Both B and Al have high oxygen affinity and their oxidation processes are highly exothermic, hinting at intriguing physical chemistry in ternary Al-B-O clusters. We report a combined photoelectron spectroscopy and density-functional study on the structural, electronic, and bonding properties of Al n BO 2 - and Al n BO 2 (n = 2, 3) clusters. Ground-state vertical detachment energies (VDEs) are measured to be 2.83 and 2.24 eV for Al 2 BO 2 - and Al 3 BO 2 - , respectively. A weak isomer is also observed for Al 3 BO 2 - with a VDE of 1.31 eV. Coalescence-kick global searches allow the identification of candidate structures, confirmed via comparisons with experiment. The Al 2 BO 2 - anion is V-shaped in geometry, C s ( 1 A'), with an Al center connecting to OB and OAl terminals. It can be viewed alternatively as the fusion of BOAl and AlOAl by sharing an Al atom. Al 3 BO 2 - has a C s ( 2 A'') global minimum in which an Al 2 dimer interacts with bridging boronyl (BO) and an OAl unit, as well as a low-lying C 2v ( 2 B 2 ) isomer consisting of boronyl and OAl that are doubly bridged by two Al atoms. The BO 2 block (linear O[double bond, length as m-dash]B[double bond, length as m-dash]O chain) is nonexistent in any of the anion and neutral species. Chemical bonding in these Al-B-O clusters is elucidated via canonical molecular orbitals and adaptive natural density partitioning. The cluster structures are also rationalized using the concept of sequential and competitive oxidation of B versus Al centers in Al n B. The first O atom prefers to oxidize B and form BO, whereas the second O atom has options to interact with a fresh Al/Al n /Al n B unit or a BO group. The former route wins thermodynamically, leading to the observed geometries.

Crystal growth, electronic structure and optical properties of Sr2Mg(BO3)2

NASA Astrophysics Data System (ADS)

Lv, Xianshun; Wei, Lei; Wang, Xuping; Xu, Jianhua; Yu, Huajian; Hu, Yanyan; Zhang, Huadi; Zhang, Cong; Wang, Jiyang; Li, Qinggang

2018-02-01

Single crystals of Sr2Mg(BO3)2 (SMBO) were grown by Kyropoulos method. X-ray powder diffraction (XRD) analysis, transmission spectrum, thermal properties, band structure, density of states and charge distribution as well as Raman spectra of SMBO were described. The as-grown SMBO crystals show wide transparency range with UV cut-off below 180 nm. A direct band gap of 4.66 eV was obtained from the calculated electronic structure results. The calculated band structure and density of states results indicated the top valence band is determined by O 2p states whereas the low conduction band mainly consists of Sr 5s states. Twelve Raman peaks were observed in the experimental spectrum, fewer than the number predicted by the site group analysis. Raman peaks of SMBO were assigned combining first-principle calculation and site group analysis results. The strongest peak at 917 cm-1 in the experimental spectrum is assigned to symmetric stretching mode A1‧(ν1) of free BO3 units. SMBO is a potential Raman crystal which can be used in deep UV laser frequency conversion.

Charge Transfer Salts of BO with Paramagnetic Isothiocyanato Complex Anions: (BO)[ M(isoq) 2(NCS) 4]; M=Cr III or Fe III, isoq=isoquinoline and BO=Bis(ethylenedioxo)tetrathiafulvalene

NASA Astrophysics Data System (ADS)

Setifi, Fatima; Ota, Akira; Ouahab, Lahcéne; Golhen, Stèphane; Yamochi, Hideki; Saito, Gunzi

2002-11-01

The preparation, X-ray structures and magnetic properties of two isostructural new charge transfer salts: (BO)[ M(isoq) 2(NCS) 4]; M=Cr III(1), Fe III(2) and isoq=isoquinoline are reported. Their structure consists of alternate organic and inorganic layers, each layer being formed by mixed columns of BO radical cations and paramagnetic metal complex anions. There are short intermolecular contacts between donor and anion (S2 anion· · ·S4 BO<3.5 Å) and between adjacent BO molecules (O· · · O1<3.2 Å). The two compounds are insulators. ESR measurements show single signal without separating the donor and anion spins. The magnetic measurements obey the Curie-Weiss law and revealed dominant antiferromagnetic interactions between anion spin and donor spin, but long-range magnetic ordering did not occur down to 2 K. This is directly related to structural reasons which were deduced from a comparison of the title compounds with other 1:1 salts containing same anion complexes and different donors.

The Importance of Slag Structure to Boron Removal from Silicon during the Refining Process: Insights from Raman and Nuclear Magnetic Resonance Spectroscopy Study

NASA Astrophysics Data System (ADS)

Qian, Guoyu; Wang, Zhi; Gong, Xuzhong; Sun, Liyuan

2017-12-01

Slag structure plays an important role in determining the relative ease of boron removal from silicon. Correlation between slag structure and boron removal thermodynamics was experimentally studied by Raman and nuclear magnetic resonance (NMR) spectroscopy using CaO-SiO2-Na2O slags with different optical basicities (0.6 to 0.71). Optimization of slag depolymerization leads to efficient removal of boron. The extent of nonbridged oxygen content (NBO/T) and boron removal gradually increased with an increase in optical basicity from 0.6 to 0.66: B2O3 derived from boron oxidation captured nonbridging oxygens of Q 0(Si), Q 1(Si), and Q 2(Si), and was incorporated into the silicate network in the form of Q 3(Si and B). When optical basicity increased to 0.71, NBO/T rapidly increased and boron removal decreased considerably. Quick depolymerization of Q 3(Si and B) deteriorated the stability of boron. Various structural forms of boron in the silicate network were successfully detected: the BO3 trihedrons [3]B-3Si, [3]B-2Si-1NBO, and BO3 (nonring), and the BO4 tetrahedrons BO4 (1B, 3Si) and BO4 (0B, 4Si). BO4 (1B, 3Si) was the main structure contributing to the increase of boron capacity; BO3 (nonring), detected under higher optical basicity conditions, may cause deterioration of boron removal by suppressing its oxidation.

Characterization of a bio-oil from pyrolysis of rice husk by detailed compositional analysis and structural investigation of lignin.

PubMed

Lu, Yao; Wei, Xian-Yong; Cao, Jing-Pei; Li, Peng; Liu, Fang-Jing; Zhao, Yun-Peng; Fan, Xing; Zhao, Wei; Rong, Liang-Ce; Wei, Yan-Bin; Wang, Shou-Ze; Zhou, Jun; Zong, Zhi-Min

2012-07-01

Detailed compositional analysis of a bio-oil (BO) from pyrolysis of rice husk was carried out. The BO was extracted sequentially with n-hexane, CCl(4), CS(2), benzene and CH(2)Cl(2). In total, 167 organic species were identified with GC/MS in the extracts and classified into alkanes, alcohols, hydroxybenzenes, alkoxybenzenes, dioxolanes, aldehydes, ketones, carboxylic acids, esters, nitrogen-containing organic compounds and other species. The benzene ring-containing species (BRCCs) were attributed to the degradation of lignin while most of the rests were derived from the degradation of cellulose and hemicellulose. Along with guaiacyl and p-hydroxyphenyl units as the main components, a new type of linkage was suggested, i.e., C(ar)-CH(2)-C(ar) in 4,4'-methylenebis(2,6-dimethoxyphenol). Based on the species identified, a possible macromolecular structure of the lignin and the mechanism for its pyrolysis are proposed. The BO was also extracted with petroleum ether in ca. 17.8% of the extract yield and about 82.1% of the extracted components are BRCCs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Triple modifier effect on physical, optical and structural properties of boro tellurite zinc lithium glasses

NASA Astrophysics Data System (ADS)

Naresh, P.; Srinivasu, D.; Narsimlu, N.; Ch. Srinivas, Kavitha, B.; Deshpandhe, Uday; Kumar, K. Siva

2018-05-01

To investigate physical, optical and structural properties of glass samples of the Quaternary system (60-x)B2O3-xTeO2-10ZnO-30Li2O with x=0,5,10,15, and 20 mol% were prepared by conventional melt quenching technique. XRD confirmed the amorphous nature of all samples. Physical parameters like density, molar volume, Oxygen packing density and etc. calculated. Density of glass samples increased with the increase of TeO2 concentration due to the replacement of lighter B2O3 with heavier TeO2. Optical properties has studied with the help of UV-Visible spectra. Cut off wavelength is increases whereas Eopt and Urbache energies is decreased except intermediate mole fraction of TeO2 at which the triple modifier effect can be observed. Fourier Transform Infrared spectroscopy reveals that the network consists of TeO3 and TeO6 structural units along with BO3 and BO4 units.

Structure-composition trends in multicomponent borosilicate-based glasses deduced from molecular dynamics simulations with improved B-O and P-O force fields.

PubMed

Stevensson, Baltzar; Yu, Yang; Edén, Mattias

2018-03-28

We present a comprehensive molecular dynamics (MD) simulation study of composition-structure trends in a set of 25 glasses of widely spanning compositions from the following four systems of increasing complexity: Na 2 O-B 2 O 3 , Na 2 O-B 2 O 3 -SiO 2 , Na 2 O-CaO-SiO 2 -P 2 O 5 , and Na 2 O-CaO-B 2 O 3 -SiO 2 -P 2 O 5 . The simulations involved new B-O and P-O potential parameters developed within the polarizable shell-model framework, thereby combining the beneficial features of an overall high accuracy and excellent transferability among different glass systems and compositions: this was confirmed by the good accordance with experimental data on the relative BO 3 /BO 4 populations in borate and boro(phospho)silicate networks, as well as with the orthophosphate fractions in bioactive (boro)phosphosilicate glasses, which is believed to strongly influence their bone-bonding properties. The bearing of the simulated melt-cooling rate on the borate/phosphate speciations is discussed. Each local {BO 3 , BO 4 , SiO 4 , PO 4 } coordination environment remained independent of the precise set of co-existing network formers, while all trends observed in bond-lengths/angles mainly reflected the glass-network polymerization, i.e., the relative amounts of bridging oxygen (BO) and non-bridging oxygen (NBO) species. The structural roles of the Na + /Ca 2+ cations were also probed, targeting their local coordination environments and their relative preferences to associate with the various borate, silicate, and phosphate moieties. We evaluate and discuss the common classification of alkali/alkaline-earth metal ions as charge-compensators of either BO 4 tetrahedra or NBO anions in borosilicate glasses, also encompassing the less explored NBO-rich regime: the Na + /Ca 2+ cations mainly associate with BO/NBO species of SiO 4 /BO 3 groups, with significant relative Na-BO 4 contacts only observed in B-rich glass networks devoid of NBO species, whereas NBO-rich glass networks also reveal substantial amounts of NBO-bearing BO 4 tetrahedra.

Electrical Characteristics of MnO2 Doped Bismuth Borate Glass Systems

NASA Astrophysics Data System (ADS)

Nissar, Umair; Ahmad, Javed; Rana, Anwar Manzoor; Bukhari, S. H.; Jamil, M. T.; Khan, J. Alam; Shakeel, R.; Nadeem, M. Y.

2018-02-01

Transparent glasses have a large number of applications in the industry of electronics as well as optical devices. xMnO2-(25- x) Bi2O3-75H3BO3 (0 ≤ x ≤ 1.5 mol.%) transparent glasses have been prepared via melt-quench technique and characterized using dc electrical measurements, and by analyzing x-ray diffraction and Fourier transform infrared (FTIR) spectra. These characteristics were examined to understand the role of modifier oxides, i.e., Bi2O3 and MnO2 in the B2O3 glass network. Adding MnO2 into a glass network causes structural changes, which are responsible for any variations in electrical characteristics of bismuth borate glasses. Manganese bismuth borate glasses (MBBG) show Ohmic conduction at low fields; however, glasses with higher manganese content seem to conduct through bulk limited Poole-Frenkel mechanism. FTIR spectroscopy analyses depict the presence of BO3 and BO4 groups along with B-O-B and Bi-O-Bi bonding vibrations. Glasses with higher MnO2 content also show Mn-O bond vibrations. The reduction of BO4 groups and increase of BO3 units lead to the formation of non-bridging oxygens (NBOs) which are responsible for the variations in the electrical properties of these glasses.

Identification of Small Molecules against Botulinum Neurotoxin B Binding to Neuronal Cells at Ganglioside GT1b Binding Site with Low to Moderate Affinity

DTIC Science & Technology

2014-10-01

BoNT serotype B (BoNT/B) for the trisaccharide GT1b were identified from the x-ray crystal structure of the BoNT/B/trisaccharide (GT1b) complex ( PDB ...trisaccharide and all the water from the structure and identified four potential binding pockets (Pocket-1, Pocket-2, and Pocket-4) as shown in...four potential binding sites or pockets on BoNT serotype B (BoNT/B) for the trisaccharide GT1b were identified from the x-ray crystal structure of the

Syntheses and crystal structures of two new hydrated borates, Zn{sub 8}[(BO{sub 3}){sub 3}O{sub 2}(OH){sub 3}] and Pb[B{sub 5}O{sub 8}(OH)].1.5H{sub 2}O

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Xuean; Zhao Yinghua; Chang Xinan

Two new hydrated borates, Zn{sub 8}[(BO{sub 3}){sub 3}O{sub 2}(OH){sub 3}] and Pb[B{sub 5}O{sub 8}(OH)].1.5H{sub 2}O, have been prepared by hydrothermal reactions at 170 {sup o}C. Single-crystal X-ray structural analyses showed that Zn{sub 8}[(BO{sub 3}){sub 3}O{sub 2}(OH){sub 3}] crystallizes in a non-centrosymmetric space group R32 with a=8.006(2) A, c=17.751(2) A, Z=3 and Pb[B{sub 5}O{sub 8}(OH)].1.5H{sub 2}O in a triclinic space group P1-bar with a=6.656(2) A, b=6.714(2) A, c=10.701(2) A, {alpha}=99.07(2){sup o}, {beta}=93.67(2){sup o}, {gamma}=118.87(1){sup o}, Z=2. Zn{sub 8}[(BO{sub 3}){sub 3}O{sub 2}(OH){sub 3}] represents a new structure type in which Zn-centered tetrahedra are connected via common vertices leading to helical ribbons {submore » {infinity}} {sup 1}[Zn{sub 8}O{sub 15}(OH){sub 3}]{sup 17-} that pack side by side and are further condensed through sharing oxygen atoms to form a three-dimensional {sub {infinity}} {sup 3}[Zn{sub 8}O{sub 11}(OH){sub 3}]{sup 9-} framework. The boron atoms are incorporated into the channels in the framework to complete the final structure. Pb[B{sub 5}O{sub 8}(OH)].1.5H{sub 2}O is a layered compound containing double ring [B{sub 5}O{sub 8}(OH)]{sup 2-} building units that share exocyclic oxygen atoms to form a two-dimensional layer. Symmetry-center-related layers are stacked along the c-axis and held together by interlayer Pb{sup 2+} ions and water molecules via electrostatic and hydrogen bonding interactions. The IR spectra further confirmed the existence of both triangular BO{sub 3} and OH groups in Zn{sub 8}[(BO{sub 3}){sub 3}O{sub 2}(OH){sub 3}], and BO{sub 3}, BO{sub 4}, OH groups as well as guest water molecules in Pb[B{sub 5}O{sub 8}(OH)].1.5H{sub 2}O. -- Zn{sub 8}[(BO{sub 3}){sub 3}O{sub 2}(OH){sub 3}] represents a new structure type in which Zn-centered tetrahedra are connected via common vertices to form a three-dimensional framework. The boron atoms are incorporated into the channels in the framework to strengen the structure via B-O bonds. Pb[B{sub 5}O{sub 8}(OH)].1.5H{sub 2}O is a new layered material containing double ring [B{sub 5}O{sub 8}(OH)]{sup 2-} building units that share exocyclic oxygen atoms to form a two-dimensional layer.« less

Synthesis, structure, and electronic structure calculation of a new centrosymmetric borate Pb{sub 2}O[BO{sub 2}(OH)] based on anion-centered OPb{sub 4} tetrahedra

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Feng; Wang, Li, E-mail: wangliresearch@163.com; Stoumpos, Constantinos C.

2016-08-15

The synthesis, structure, and characterization of a new centrosymmetric borate Pb{sub 2}O[BO{sub 2}(OH)] based on anion-centered OPb{sub 4} tetrahedra are reported. Pb{sub 2}O[BO{sub 2}(OH)] crystallizes in monoclinic space group C2/m with a=12.725(7) Å, b=5.698(3) Å, c=7.344(4) Å, β=116.277(6)°. The electronic band structure and density of states of Pb{sub 2}O[BO{sub 2}(OH)] have been calculated via the density functional theory (DFT). Electron density difference calculation indicates that lone-pair electrons of Pb{sup 2+} cation should be stereoactive. - Graphical abstract: An indirect gap compound of Pb{sub 2}O[BO{sub 2}(OH)] with 2D inorganic layers motif based on OPb{sub 4} tetrahedra has been synthesized and fullmore » characterized by crystallographic, IR, TG, UV–vis-NIR Diffuse Reflectance, and theoretical calculations. Display Omitted - Highlights: • A centrosymmetric borate Pb{sub 2}O[BO{sub 2}(OH)] was synthesized and characterized. • The crystalstructure, electronic band and density states was analyzed. • The lone-pair electrons of Pb{sup 2+} were proved to be stereoactive.« less

MAS-NMR investigations of the crystallization behaviour of lithium aluminum silicate (LAS) glasses containing P 2O 5 and TiO 2 nucleants

NASA Astrophysics Data System (ADS)

Ananthanarayanan, A.; Kothiyal, G. P.; Montagne, L.; Revel, B.

2010-06-01

Lithium aluminum silicate (LAS) glass of composition (mol%) 20.4Li 2O-4.0Al 2O 3-68.6SiO 2-3.0K 2O-2.6B 2O 3-0.5P 2O 5-0.9TiO 2 was prepared by melt quenching. The glass was then nucleated and crystallized based on differential thermal analysis (DTA) data and was characterized by 29Si, 31P, 11B and 27Al MAS-NMR. XRD and 29Si NMR showed that lithium metasilicate (Li 2SiO 3) is the first phase to c form followed by cristobalite (SiO 2) and lithium disilicate (Li 2Si 2O 5). 29Si MAS-NMR revealed a change in the network structure already for the glasses nucleated at 550 °C. Since crystalline Li 3PO 4, as observed by 31P MAS-NMR, forms concurrently with the silicate phases, we conclude that crystalline Li 3PO 4 does not act as a nucleating agent for lithium silicate phases. Moreover, 31P NMR indicates the formation of M-PO 4 ( M=B, Al or Ti) complexes. The presence of BO 3 and BO 4 structural units in all the glass/glass-ceramic samples is revealed through 11B MAS-NMR. B remains in the residual glass and the crystallization of silicate phases causes a reduction in the number of alkali ions available for charge compensation. As a result, the number of trigonally coordinated B (BO 3) increases at the expense of tetrahedrally coordinated B (BO 4). The 27Al MAS-NMR spectra indicate the presence of tetrahedrally coordinated Al species, which are only slightly perturbed by the crystallization.

Controlling the reaction between boron-containing sealing glass and a lanthanum-containing cathode by adding Nb2O5

NASA Astrophysics Data System (ADS)

Zhao, Dandan; Fang, Lihua; Tang, Dian; Zhang, Teng

2016-09-01

In solid oxide fuel cell (SOFC) stacks, the volatile boron species present in the sealing glass often react with the lanthanum-containing cathode, degrading the activity of the cathode (this phenomenon is known as boron poisoning). In this work, we report that this detrimental reaction can be effectively reduced by doping bismuth-containing borosilicate sealing glass-ceramic with a niobium dopant. The addition of Nb2O5 not only condenses the [SiO4] structural units in the glass network, but also promotes the conversion of [BO3] to [BO4]. Moreover, the Nb2O5 dopant enhances the formation of boron-containing phases (Ca3B2O6 and CaB2Si2O8), which significantly reduces the volatility of boron compounds in the sealing glass, suppressing the formation of LaBO3 in the reaction couple between the glass and the cathode. The reported results provide a new approach to solve the problem of boron poisoning.

Infrared and Raman spectroscopic studies on alkali borate glasses: evidence of mixed alkali effect.

PubMed

Padmaja, G; Kistaiah, P

2009-03-19

A lithium-potassium-borate glass system containing manganese and iron cations has been thoroughly investigated in order to obtain information about the mixed alkali effect and the structural role of both the manganese and iron in such glass hosts. Mixed alkali borate glasses of the (30 - x)Li(2)O - xK(2)O - 10CdO/ZnO - 59B(2)O(3) (x = 0, 10, 15, 20, and 30) doped with 1MnO(2)/1Fe(2)O(3) system were prepared by a melt quench technique. The amorphous phase of the prepared glass samples was confirmed from their X-ray diffraction. The spectroscopic properties of glass samples were studied using infrared (IR) and Raman spectroscopic techniques. The density of all the prepared glasses was measured using Archimedes principle. Molar volumes were estimated from the density data. IR spectra of these glasses revealed a dramatic variation of three- and four-coordinated boron structures as a function of mixed alkali concentration. The vibrations due to Li-O, K-O, and MnO(4)/FeO(4) arrangements are consistent in all the compositions and show a nonlinear variation in the intensity with alkali content. Raman spectra of different alkali combinations with CdO and ZnO present drastic changes in the intensity of various Raman bands. The observation of disappearance and reappearance of IR and Raman bands as a function of various alkali concentrations is an important result pertaining to the mixed alkali effect in borate glasses. Acting as complementary spectroscopic techniques, both types of measurements, IR and Raman, revealed that the network structure of the studied glasses is mainly based on BO(3) and BO(4) units placed in different structural groups, the BO(3) units being dominant. The measured IR and Raman spectra of different glasses are used to clarify the optical properties of the present glasses correlating them with their structure and composition.

Synthesis and Biological Evaluation of Botulinum Neurotoxin A Protease Inhibitors

PubMed Central

Li, Bing; Pai, Ramdas; Cardinale, Steven C.; Butler, Michelle M.; Peet, Norton P.; Moir, Donald T.; Bavari, Sina; Bowlin, Terry L.

2010-01-01

NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogs have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of compounds have also been evaluated for inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor against BoNT/A LC in these two series is compound 12 (IC50 = 2.5 µM, FRET assay), which is 4.4-fold more potent than the lead structure, and 11.2-fold more selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure-activity relationship studies have revealed structural features important to potency and enzyme specificity. PMID:20155918

Structure and method for controlling band offset and alignment at a crystalline oxide-on-semiconductor interface

DOEpatents

McKee, Rodney A.; Walker, Frederick J.

2003-11-25

A crystalline oxide-on-semiconductor structure and a process for constructing the structure involves a substrate of silicon, germanium or a silicon-germanium alloy and an epitaxial thin film overlying the surface of the substrate wherein the thin film consists of a first epitaxial stratum of single atomic plane layers of an alkaline earth oxide designated generally as (AO).sub.n and a second stratum of single unit cell layers of an oxide material designated as (A'BO.sub.3).sub.m so that the multilayer film arranged upon the substrate surface is designated (AO).sub.n (A'BO.sub.3).sub.m wherein n is an integer repeat of single atomic plane layers of the alkaline earth oxide AO and m is an integer repeat of single unit cell layers of the A'BO.sub.3 oxide material. Within the multilayer film, the values of n and m have been selected to provide the structure with a desired electrical structure at the substrate/thin film interface that can be optimized to control band offset and alignment.

Physical, structural and optical characterizations of borate modified bismuth-silicate-tellurite glasses

NASA Astrophysics Data System (ADS)

Berwal, Neelam; Kundu, R. S.; Nanda, Kirti; Punia, R.; Kishore, N.

2015-10-01

Quaternary bismuthate glasses with compositions xB2O3-(80 - x) Bi2O3-15SiO2-5TeO2 have been prepared by melt-quench technique. X-ray diffraction studies were performed to ascertain the amorphous nature of samples. The density, molar volume and crystalline volume decrease with increase in B2O3 content whereas the glass transition temperature shows the reverse trend. The Raman and FTIR spectra of the studied glasses indicate that B2O3 has been found to exist in the form of BO3 trigonal and BO4 tetrahedral structural units and vibrations corresponding to these structural units increase with increase in B2O3 content. SiO2 is present in the form of SiO4 tetrahedral structural units and TeO2 in the form of TeO3 structural units. Bismuth plays the role of network modifier [BiO6 octahedra] as well as network former [BiO3 pyramids] for all the glass compositions. The optical band gap energy has been calculated from the fitting of both Mott and Davis's model and Hydrogenic excitonic model with the experimentally observed absorption spectra. A good fitting of experimental data with HEM indicates the excitonic formation in the studies glass system. The values of optical band gap energy show nonlinear behavior due to the structural changes that take place in the present glass samples. The Urbach energy calculated using Urbach empirical formula for studied glass samples suggest the possibility of reduction in defect concentrations. The metallization criterion of the presently studied samples suggests that the prepared glasses may be potential candidates for nonlinear optical applications.

A taxonomy of apatite frameworks for the crystal chemical design of fuel cell electrolytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pramana, Stevin S.; Klooster, Wim T.; Institute of Materials Research and Engineering, 3 Research Link, Singapore 117602

2008-08-15

Apatite framework taxonomy succinctly rationalises the crystallographic modifications of this structural family as a function of chemical composition. Taking the neutral apatite [La{sub 8}Sr{sub 2}][(GeO{sub 4}){sub 6}]O{sub 2} as a prototype electrolyte, this classification scheme correctly predicted that 'excess' oxygen in La{sub 9}SrGe{sub 6}O{sub 26.5} is tenanted in the framework as [La{sub 9}Sr][(GeO{sub 4}){sub 5.5}(GeO{sub 5}){sub 0.5}]O{sub 2}, rather than the presumptive tunnel location of [La{sub 9}Sr][(GeO{sub 4}){sub 6}]O{sub 2.5}. The implication of this approach is that in addition to the three known apatite genera-A{sub 10}(BO{sub 3}){sub 6}X{sub 2}, A{sub 10}(BO{sub 4}){sub 6}X{sub 2}, A{sub 10}(BO{sub 5}){sub 6}X{sub 2}-hybrid electrolytesmore » of the types A{sub 10}(BO{sub 3}/BO{sub 4}/BO{sub 5}){sub 6}X{sub 2} can be designed, with potentially superior low-temperature ion conduction, mediated by the introduction of oxygen to the framework reservoir. - Graphical abstract: Apatite framework taxonomy succinctly rationalises the crystallographic modifications of this structural family as a function of chemical composition. Neutron diffraction identified that the excess oxygen in La{sub 9}SrGe{sub 6}O{sub 26.5} is tenanted in the framework as [La{sub 9}Sr][(GeO{sub 4}){sub 5.5}(GeO{sub 5}){sub 0.5}]O{sub 2}. The implication of this approach is that in addition to the three known apatite genera-A{sub 10}(BO{sub 3}){sub 6}X{sub 2}, A{sub 10}(BO{sub 4}){sub 6}X{sub 2}, A{sub 10}(BO{sub 5}){sub 6}X{sub 2}-hybrid electrolytes of the types A{sub 10}(BO{sub 3}/BO{sub 4}/BO{sub 5}){sub 6}X{sub 2} can be designed.« less

Thermal analysis and vibrational spectroscopic characterization of the boro silicate mineral datolite - CaBSiO4(OH)

NASA Astrophysics Data System (ADS)

Frost, Ray L.; Xi, Yunfei; Scholz, Ricardo; Lima, Rosa Malena Fernandes; Horta, Laura Frota Campos; Lopez, Andres

2013-11-01

The objective of this work is to determine the thermal stability and vibrational spectra of datolite CaBSiO4(OH) and relate these properties to the structure of the mineral. The thermal analysis of datolite shows a mass loss of 5.83% over a 700-775 °C temperature range. This mass loss corresponds to 1 water (H2O) molecules pfu. A quantitative chemical analysis using electron probe was undertaken. The Raman spectrum of datolite is characterized by bands at 917 and 1077 cm-1 assigned to the symmetric stretching modes of BO and SiO tetrahedra. A very intense Raman band is observed at 3498 cm-1 assigned to the stretching vibration of the OH units in the structure of datolite. BOH out-of-plane vibrations are characterized by the infrared band at 782 cm-1. The vibrational spectra are based upon the structure of datolite based on sheets of four- and eight-membered rings of alternating SiO4 and BO3(OH) tetrahedra with the sheets bonded together by calcium atoms.

Structural investigation of Zn doped sodium bismuth borate glasses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, V., E-mail: vijetabhatia0712@gmail.com; Kumar, D.; Singh, D.

2016-05-06

A series of Bismuth Borate Oxide Glass samples with composition x(ZnO):(15-x)Na{sub 2}O:15Bi{sub 2}O{sub 3}:70B{sub 2}O{sub 3} (variation in x is from 6 to 12 mole %) have been prepared by conventional melt quenching technique. All the chemicals used were of Analytical Grade. In order to verify the amorphous nature of the prepared samples the X-Ray Diffraction (XRD) was done. The physical and structural properties have been explored by using the techniques such as density, molar volume and FTIR in order to understand the effect of alkali and transition metal ions on the structure of these glasses. The results obtained bymore » these techniques are in good agreement to one another and with literature as well. With the increase in the content of ZnO, the increase in density and some variations in structural coordination (ratio of BO{sub 3} & BO{sub 4} structural units) have been observed.« less

High-pressure synthesis and characterization of the first cerium fluoride borate CeB{sub 2}O{sub 4}F

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinteregger, Ernst; Wurst, Klaus; Tribus, Martina

2013-08-15

CeB{sub 2}O{sub 4}F is the first cerium fluoride borate, which is exclusively built up of one-dimensional, infinite chains of condensed trigonal-planar [BO{sub 3}]{sup 3−} groups. This new cerium fluoride borate was synthesized under high-pressure/high-temperature conditions of 0.9 GPa and 1450 °C in a Walker-type multianvil apparatus. The compound crystallizes in the orthorhombic space group Pbca (No. 61) with eight formula units and the lattice parameters a=821.63(5), b=1257.50(9), c=726.71(6) pm, V=750.84(9) Å{sup 3}, R{sub 1}=0.0698, and wR{sub 2}=0.0682 (all data). The structure exhibits a 9+1 coordinated cerium ion, one three-fold coordinated fluoride ion and a one-dimensional chain of [BO{sub 3}]{sup 3−}more » groups. Furthermore, IR spectroscopy, Electron Micro Probe Analysis and temperature-dependent X-ray powder diffraction measurements were performed. - Graphical abstract: A new rare-earth fluoride borate CeB{sub 2}O{sub 4}F could be synthesized under high-pressure/high-temperature conditions of 0.9 °GPa and 1450 °Cin a Walker-type multianvil apparatus. The crystal structure represents a new structure type in the class of rare-earth fluoride borates. The structure exhibits a 9+1 coordinated cerium ion, one three-fold coordinated fluoride ion and a one-dimensional chain of [BO{sub 3}]{sup 3−} groups. A closer view on the ac-plane shows an interesting wave-like modulation of the borate chains. Highlights: • CeB{sub 2}O{sub 4}F is the first fluoride borate exclusively built up of one-dimensional, infinite chains of condensed trigonal-planar [BO{sub 3}]{sup 3−} groups. • CeB{sub 2}O{sub 4}F is the first cerium fluoride borate. • High-pressure conditions were necessary to synthesize CeB{sub 2}O{sub 4}F.« less

A first-principles study on the B{sub 5}O{sub 5}{sup +/0} and B{sub 5}O{sub 5}{sup −} clusters: The boron oxide analogs of C{sub 6}H{sub 5}{sup +/0} and CH{sub 3}Cl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Wen-Juan; You, Xue-Rui; Ou, Ting

2015-08-14

The concept of boronyl (BO) and the BO/H isolobal analogy build an interesting structural link between boron oxide clusters and hydrocarbons. Based upon global-minimum searches and first-principles electronic structural calculations, we present here the perfectly planar C{sub 2v} B{sub 5}O{sub 5}{sup +} (1, {sup 1}A{sub 1}), C{sub 2v} B{sub 5}O{sub 5} (2, {sup 2}A{sub 1}), and tetrahedral C{sub s} B{sub 5}O{sub 5}{sup −} (3, {sup 1}A′) clusters, which are the global minima of the systems. Structural and molecular orbital analyses indicate that C{sub 2v} B{sub 5}O{sub 5}{sup +} (1) [B{sub 3}O{sub 3}(BO){sub 2}{sup +}] and C{sub 2v} B{sub 5}O{sub 5}more » (2) [B{sub 3}O{sub 3}(BO){sub 2}] feature an aromatic six-membered boroxol (B{sub 3}O{sub 3}) ring as the core with two equivalent boronyl terminals, similar to the recently reported boronyl boroxine D{sub 3h} B{sub 6}O{sub 6} [B{sub 3}O{sub 3}(BO){sub 3}]; whereas C{sub s} B{sub 5}O{sub 5}{sup −} (3) [B(BO){sub 3}(OBO){sup −}] is characterized with a tetrahedral B{sup −} center, terminated with three BO groups and one OBO unit, similar to the previously predicted boronyl methane T{sub d} B{sub 5}O{sub 4}{sup −} [B(BO){sub 4}{sup −}]. Alternatively, the 1–3 clusters can be viewed as the boron oxide analogs of phenyl cation C{sub 6}H{sub 5}{sup +}, phenyl radical C{sub 6}H{sub 5}, and chloromethane CH{sub 3}Cl, respectively. Chemical bonding analyses also reveal a dual three-center four-electron (3c-4e) π hyperbond in C{sub s} B{sub 5}O{sub 5}{sup −} (3). The infrared absorption spectra of B{sub 5}O{sub 5}{sup +} (1), B{sub 5}O{sub 5} (2), and B{sub 5}O{sub 5}{sup −} (3) and anion photoelectron spectrum of B{sub 5}O{sub 5}{sup −} (3) are predicted to facilitate their forthcoming experimental characterizations. The present work completes the B{sub n}O{sub n}{sup +/0/−} series for n = 1–6 and enriches the analogous relationship between boron oxides and hydrocarbons.« less

Tracking BO6 Coupling in Perovskite Superlattices to Engineer Magnetic Interface Behavior

NASA Astrophysics Data System (ADS)

Borisevich, Albina; He, Qian; Ghosh, Saurabh; Moon, Eun Ju; May, Steve; Lupini, Andrew; Pantelides, Sokrates

In the past several years, control of BO6 octahedral coupling at ABO3 perovskite interfaces has emerged as a new tool for engineering of interface properties due to its strong coupling to polar and magnetic properties. High resolution data on tilt transitions at interfaces is instrumental for evaluating the validity of existing theoretical models and developing predictive theories. Recently, we have developed a unique method to investigate BO6 rotation patterns in complex oxides with unit cell resolution. Our method involves column shape analysis in ABF-STEM images of the perovskite heterointerfaces taken in specific orientations. This method will allow us to determine local symmetry between adjacent unit cells, revealing the BO6 coupling behavior at heterointerfaces in 3D. This technique was used to characterize structure and predict properties via a combined STEM and DFT study of magnetic superlattice of La(Ca)MnO3/La(Sr)MnO3 with different periodicities, which exhibit a range of electromagnetic coupling behaviors. We will also discuss the prospects for tilted structure determination using electron ptychography. The correlations among the BO6 rotation, domain size, superlattice periodicity and the electromagnetic coupling will be discussed in detail. Research supported by the MSED of the U.S.DOE, and through a user project at ORNL's CNMS, sponsored by the SUFD of the U.S. DOE.

Structure, crystallization and dielectric resonances in 2-13 GHz of waste-derived glass-ceramic

NASA Astrophysics Data System (ADS)

Yao, Rui; Liao, SongYi; Chen, XiaoYu; Wang, GuangRong; Zheng, Feng

2016-12-01

Structure, kinetics of crystallization, and dielectric resonances of waste-derived glass-ceramic prepared via quench-heating route were studied as a function of dosage of iron ore tailing (IOT) within 20-40 wt% using X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and vector network analyzer (VNA) measurements. The glass-ceramic mainly consisted of ferrite crystals embedded in borosilicate glass matrix. Crystallization kinetics and morphologies of ferrite crystals as well as coordination transformation of boron between [BO4] and [BO3] in glass network were adjustable by changing the amount of IOT. Dielectric resonances in 6-13 GHz were found to be dominated by oscillations of Ca2+ cations in glass network with [SiO4] units on their neighboring sites. Ni2+ ions made a small contribution to those resonances. Diopside formed when IOT exceeded 35 wt%, which led to weakening of the resonances.

Piperidinium bis­(2-oxidobenzoato-κ2 O 1,O 2)borate

PubMed Central

Tang, Zhi-Hua; Huang, Chaojun

2009-01-01

The asymmetric unit of the title compound, C5H12N+·C14H8BO6 − or [C5H12N][BO4(C7H4O)2], contains two piperidinium cations and two bis­(salicylato)borate anions. The coordination geometries around the B atoms are distorted tetra­hedral. In the two mol­ecules, the aromatic rings are oriented at dihedral angles of 76.27 (3) and 83.86 (3)°. The rings containing B atoms have twist-boat conformations, while the two cations adopt chair conformations. In the crystal, the component species are linked by N—H⋯O hydrogen bonds. In the crystal structure, intra- and inter­molecular N—H⋯O hydrogen bonds link the mol­ecules. PMID:21581628

Structural, morphological and optical investigations on electron-beam irradiated PbF2-TeO2-B2O3-Eu2O3 glasses

NASA Astrophysics Data System (ADS)

Wagh, Akshatha; Petwal, Vikash; Dwivedi, Jishnu; Upadhyaya, V.; Raviprakash, Y.; Kamath, Sudha D.

2016-09-01

Combined structural, optical and morphological studies were carried out on Eu2O3 doped PbF2-TeO2-B2O3 glass samples, before and after being subjected to electron beam of energy 7.5 MeV. XRD confirmed the amorphous nature of the glasses even after 150 kGy electron beam irradiation. Densities of the irradiated samples showed slightly greater values when compared to their respective values before irradiation, which proved the increase in the compaction of the network. The intensities of the three prominent bands; B-O-B linkages, BO4 units and BO3 units of FT-IR spectra, of the titled glasses, showed slight decrease after electron beam irradiation. The decrement in the values of energy band gap and shift in cut-off wavelength towards red edge, proved the formation of color centers in the glass network after irradiation. The change in Hunter L values, through color measurement was a proof for the Farbe/color/absorption centers created in the glass sites after irradiation.

Li{sub 2}Sr{sub 4}B{sub 12}O{sub 23}: A new alkali and alkaline-earth metal mixed borate with [B{sub 10}O{sub 18}]{sup 6-} network and isolated [B{sub 2}O{sub 5}]{sup 4-} unit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Min; Graduate University of Chinese Academy of Sciences, Beijing 100049; Pan Shilie, E-mail: slpan@ms.xjb.ac.cn

2012-06-15

A novel ternary lithium strontium borate Li{sub 2}Sr{sub 4}B{sub 12}O{sub 23} crystal with size up to 20 mm Multiplication-Sign 10 mm Multiplication-Sign 4 mm has been grown via the top-seeded solution growth method below 730 Degree-Sign C. Single-crystal XRD analyses showed that Li{sub 2}Sr{sub 4}B{sub 12}O{sub 23} crystallizes in the monoclinic space group P2{sub 1}/c with a=6.4664(4) A, b=8.4878(4) A, c=15.3337(8) A, {beta}=102.02(3) Degree-Sign , Z=2. The crystal structure is composed of [B{sub 10}O{sub 18}]{sup 6-} network and isolated [B{sub 2}O{sub 5}]{sup 4-} unit. The IR spectrum further confirmed the presence of both BO{sub 3} and BO{sub 4} groups. TG-DSCmore » and Transmission spectrum were reported. Band structures and density of states were calculated. - Graphical abstract: A new phase, Li{sub 2}Sr{sub 4}B{sub 12}O{sub 23}, has been discovered in the ternary M{sub 2}O-M Prime O-B{sub 2}O{sub 3} (M=alkali-metal, M Prime =alkalineearth metal) system. The crystal structure consists of [B{sub 10}O{sub 18}]{sup 6-} network and isolated [B{sub 2}O{sub 5}]{sup 4-} unit. Highlights: Black-Right-Pointing-Pointer Li{sub 2}Sr{sub 4}B{sub 12}O{sub 23} is a a novel borate discovered in the M{sub 2}O-M Prime O-B{sub 2}O{sub 3} (M=alkali-metal, M Prime =alkaline-earth metal) system. Black-Right-Pointing-Pointer Li{sub 2}Sr{sub 4}B{sub 12}O{sub 23} crystal structure has a three-dimensional crystal structure with [B{sub 10}O{sub 18}]{sup 6-} network and isolated [B{sub 2}O{sub 5}]{sup 4-} unit. Black-Right-Pointing-Pointer Sr{sub 1} and Sr{sub 2} are located in two different channels constructed by {sup 3}{sub {infinity}}[B{sub 10}O{sub 18}] network.« less

Synthesis and photoluminescence properties of Pb2+ doped inorganic borate phosphor NaSr4(BO3)3

NASA Astrophysics Data System (ADS)

Chauhan, A. O.; Koparkar, K. A.; Bajaj, N. S.; Omanwar, S. K.

2016-05-01

A series of Inorganic borate phosphors NaSr4(BO3)3 doped with Pb2+ was successfully synthesized by modified solid state diffusion method. The crystal structure and the phase purity of sample were characterized by powder X-ray diffraction (XRD). The photoluminescence properties of synthesized materials were investigated using spectrofluorometer at room temperature. The phosphor show strong broad band emission spectra in UVA region maximum at 370 nm under the excitation of 289 nm. The dependence of the emission intensity on the Pb2+ concentration for the NaSr4(BO3)3 were studied in details. The concentration quenching of Pb2+ doped NaSr4(BO3)3 was observed at 0.02 mol. The Stokes shifts of NaSr4(BO3)3: Pb2+ phosphor was calculated to be 7574 cm-1.

Structural insights into the functional role of the Hcn sub-domain of the receptor-binding domain of the botulinum neurotoxin mosaic serotype C/D.

PubMed

Zhang, Yanfeng; Gardberg, Anna S; Edwards, Thomas E; Sankaran, Banumathi; Robinson, Howard; Varnum, Susan M; Buchko, Garry W

2013-07-01

Botulinum neurotoxin (BoNT), the causative agent of the deadly neuroparalytic disease botulism, is the most poisonous protein known for humans. Produced by different strains of the anaerobic bacterium Clostridium botulinum, BoNT effects cellular intoxication via a multistep mechanism executed by the three modules of the activated protein. Endocytosis, the first step of cellular intoxication, is triggered by the ~50 kDa, heavy-chain receptor-binding domain (HCR) that is specific for a ganglioside and a protein receptor on neuronal cell surfaces. This dual receptor recognition mechanism between BoNT and the host cell's membrane is well documented and occurs via specific intermolecular interactions with the C-terminal sub-domain, Hcc, of BoNT-HCR. The N-terminal sub-domain of BoNT-HCR, Hcn, comprises ~50% of BoNT-HCR and adopts a β-sheet jelly roll fold. While suspected in assisting cell surface recognition, no unambiguous function for the Hcn sub-domain in BoNT has been identified. To obtain insights into the potential function of the Hcn sub-domain in BoNT, the first crystal structure of a BoNT with an organic ligand bound to the Hcn sub-domain has been obtained. Here, we describe the crystal structure of BoNT/CD-HCR determined at 1.70 Å resolution with a tetraethylene glycol (PG4) moiety bound in a hydrophobic cleft between β-strands in the β-sheet jelly roll fold of the Hcn sub-domain. The PG4 moiety is completely engulfed in the cleft, making numerous hydrophilic (Y932, S959, W966, and D1042) and hydrophobic (S935, W977, L979, N1013, and I1066) contacts with the protein's side chain and backbone that may mimic in vivo interactions with the phospholipid membranes on neuronal cell surfaces. A sulfate ion was also observed bound to residues T1176, D1177, K1196, and R1243 in the Hcc sub-domain of BoNT/CD-HCR. In the crystal structure of a similar protein, BoNT/D-HCR, a sialic acid molecule was observed bound to the equivalent residues suggesting that residues T1176, D1177, K1196, and R1243 in BoNT/CD may play a role in ganglioside binding. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Structural study of Na2O-B2O3-SiO2 glasses from molecular simulations using a polarizable force field.

PubMed

Pacaud, Fabien; Delaye, Jean-Marc; Charpentier, Thibault; Cormier, Laurent; Salanne, Mathieu

2017-10-28

Sodium borosilicate glasses Na 2 O-B 2 O 3 -SiO 2 (NBS) are complex systems from a structural point of view. Three main building units are present: tetrahedral SiO 4 and BO 4 (B IV ) and triangular BO 3 (B III ). One of the salient features of these compounds is the change of the B III /B IV ratio with the alkali concentration, which is very difficult to capture in force fields-based molecular dynamics simulations. In this work, we develop a polarizable force field that is able to reproduce the boron coordination and more generally the structure of several NBS systems in the glass and in the melt. The parameters of the potential are fitted from density functional theory calculations only, in contrast with the existing empirical potentials for NBS systems. This ensures a strong improvement on the transferability of the parameters from one composition to another. Using this new force field, the structure of NBS systems is validated against neutron diffraction and nuclear magnetic resonance experiments. A special focus is given to the distribution of B III /B IV with respect to the composition and the temperature.

A study of the origin of large magnetic field coupled electric polarization in HoAl(BO3)4

NASA Astrophysics Data System (ADS)

Yu, Tian; Zhang, Han; Tyson, Trevor; Chen, Zhiqiang; Abeykoon, Milinda; Nelson, Christie; Bezmaternykh, Leonard

2015-03-01

The multiferroic system RAl(BO3)4 is known to exhibit a strong coupling of magnetic field to the electrical polarization. Recently a giant magnetoelectric effect was found in HoAl3(BO3)4 system. This phenomenon is considered quite interesting because the value discovered is significantly higher than reported values of linear magnetoelectric or even multiferroic compounds. We are conducting detailed structural measurements to understand the coupling. We are exploring the local and long range structure in these systems using x-ray PDF, XAFS and single crystal diffraction measurement between 10 K and 400 K. Structural parameters including lattice parameters and ADPs are being determined over the full temperature range. This work is supported by DOE Grant DE-FG02-07ER46402.

Photoelectron spectroscopy and density functional calculations of CunBO2(OH)- (n = 1,2) clusters

NASA Astrophysics Data System (ADS)

Feng, Yuan; Hou, Gao-Lei; Xu, Hong-Guang; Zhang, Zeng-Guang; Zheng, Wei-Jun

2012-08-01

CunBO2(OH)- (n = 1, 2) clusters were studied by anion photoelectron spectroscopy and density functional calculations. From the experimental photoelectron spectra, the adiabatic detachment energy (ADE) and vertical detachment energy (VDE) of CuBO2(OH)- are determined to be 4.00 ± 0.08 and 4.26 ± 0.08 eV, and those of Cu2BO2(OH)- to be 2.30 ± 0.08 and 2.58 ± 0.08 eV. The structures of CunBO2(OH)- and their corresponding neutrals are assigned by comparison between theoretical calculations and experimental measurements. Both experiment and theory show that CuBO2(OH) can be viewed as a superhalogen, thus, confirmed that OH can behave like a halogen atom to participate in superhalogen formation.

Unidirectional thermal expansion in edge-sharing BO4 tetrahedra contained KZnB3O6

PubMed Central

Lou, Yanfang; Li, Dandan; Li, Zhilin; Jin, Shifeng; Chen, Xiaolong

2015-01-01

Borates are among a class of compounds that exhibit rich structural diversity and find wide applications. The formation of edge-sharing (es-) BO4 tetrahedra is extremely unfavored according to Pauling’s third and fourth rules. However, as the first and the only es-borate obtained under ambient pressure, es-KZnB3O6 shows an unexpected high thermal stability up to its melting point. The origin of this extraordinary stability is still unclear. Here, we report a novel property in KZnB3O6: unidirectional thermal expansion, which plays a role in preserving es-BO4 from disassociation at elevated temperatures. It is found that this unusual thermal behavior originates from cooperative rotations of rigid groups B6O12 and Zn2O6, driven by anharmonic thermal vibrations of K atoms. Furthermore, a detailed calculation of phonon dispersion in association with this unidirectional expansion predicts the melting initiates with the breakage of the link between BO3 and es-BO4. These findings will broaden our knowledge of the relationship between structure and property and may find applications in future. PMID:26047175

Fusing Benzo[c][1,2,5]oxadiazole Unit with Thiophene for Constructing Wide-bandgap High-performance IDT-based Polymer Solar Cell Donor Material.

PubMed

Song, Xin; Fan, Meijie; Zhang, Kaili; Ding, Dakang; Chen, Weiye; Li, Yonghai; Yu, Liangmin; Sun, Mingliang; Yang, Renqiang

2018-04-01

Benzo[c][1,2,5]oxadiazole (BO) moiety is a strong electron-withdrawing unit compared to benzo[c][1,2,5]thiadiazole (BT). It is usually introduced as an acceptor to construct narrow band-gap donor-acceptor (D-A) materials. Herein, the π-extended conjugated moiety dithieno[3',2':3,4″;2,3″:5,6]benzo[1,2-c][1,2,5]oxadiazole (BOT) was adopted as the acceptor moiety to design D-A polymers. Considering the more extended π-conjugated molecular system of BOT compared to the BO unit, a narrower optical band-gap is expected for BOT-based IDT polymer (PIDT-BOT). Unexpectedly, the UV-vis absorption spectra of PIDT-BOT films display a great hypochromatic shift of about 60 nm compared to a BO-based analog (PIDT-BO). The optical band-gaps of the materials are broadened from 1.63 eV (PIDT-BO) to 2.00 eV (PIDT-BOT) accordingly. Although the range of external quantum efficiency (EQE) of PIDT-BOT-based polymer solar cell (PSC) devices is not as wide as for PIDT-BO-based devices, the EQE response intensities of the PIDT-BOT based device are evidently high. As a result, PSC devices based on PIDT-BOT reveal the best power conversion efficiency at 6.08%. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and photoluminescence properties of Pb{sup 2+} doped inorganic borate phosphor NaSr{sub 4}(BO{sub 3}){sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chauhan, A. O., E-mail: abhi2718@gmail.com; Koparkar, K. A.; Omanwar, S. K.

2016-05-06

A series of Inorganic borate phosphors NaSr{sub 4}(BO{sub 3}){sub 3} doped with Pb{sup 2+} was successfully synthesized by modified solid state diffusion method. The crystal structure and the phase purity of sample were characterized by powder X-ray diffraction (XRD). The photoluminescence properties of synthesized materials were investigated using spectrofluorometer at room temperature. The phosphor show strong broad band emission spectra in UVA region maximum at 370 nm under the excitation of 289 nm. The dependence of the emission intensity on the Pb{sup 2+} concentration for the NaSr{sub 4}(BO{sub 3}){sub 3} were studied in details. The concentration quenching of Pb{sup 2+}more » doped NaSr{sub 4}(BO{sub 3}){sub 3} was observed at 0.02 mol. The Stokes shifts of NaSr{sub 4}(BO{sub 3}){sub 3}: Pb{sup 2+} phosphor was calculated to be 7574 cm{sup −1}.« less

High-temperature heat capacity of YFe3(BO3)4

NASA Astrophysics Data System (ADS)

Denisov, V. M.; Denisova, L. T.; Gudim, I. A.; Temerov, V. L.; Volkov, N. V.; Patrin, G. S.; Chumilina, L. G.

2014-02-01

The molar heat capacity of YFe3(BO3)4 has been measured using differential scanning calorimetry in the temperature range 339-1086 K. It has been found that the dependence C p = f( T) exhibits an extremum at a temperature of 401 K due to the structural transition.

MAS-NMR studies of lithium aluminum silicate (LAS) glasses and glass-ceramics having different Li 2O/Al 2O 3 ratio

NASA Astrophysics Data System (ADS)

Ananthanarayanan, A.; Kothiyal, G. P.; Montagne, L.; Revel, B.

2010-01-01

Emergence of phases in lithium aluminum silicate (LAS) glasses of composition (wt%) xLi 2O-71.7SiO 2-(17.7- x)Al 2O 3-4.9K 2O-3.2B 2O 3-2.5P 2O 5 (5.1≤ x≤12.6) upon heat treatment were studied. 29Si, 27Al, 31P and 11B MAS-NMR were employed for structural characterization of both LAS glasses and glass-ceramics. In glass samples, Al is found in tetrahedral coordination, while P exists mainly in the form of orthophosphate units. B exists as BO 3 and BO 4 units. 27Al NMR spectra show no change with crystallization, ruling out the presence of any Al containing phase. Contrary to X-ray diffraction studies carried out, 11B (high field 18.8 T) and 29Si NMR spectra clearly indicate the unexpected crystallization of a borosilicate phase (Li,K)BSi 2O 6, whose structure is similar to the aluminosilicate virgilite. Also, lithium disilicate (Li 2Si 2O 5), lithium metasilicate (Li 2SiO 3) and quartz (SiO 2) were identified in the 29Si NMR spectra of the glass-ceramics. 31P NMR spectra of the glass-ceramics revealed the presence of Li 3PO 4 and a mixed phase (Li,K) 3PO 4 at low alkali concentrations.

Structure determination and characterization of two rare-earth molybdenum borate compounds: LnMoBO(6) (Ln = La, Ce).

PubMed

Zhao, Dan; Cheng, Wen-Dan; Zhang, Hao; Hang, Shu-Ping; Fang, Ming

2008-07-28

The structural, optical, and electronic properties of two rare-earth molybdenum borate compounds, LnMoBO(6) (Ln = La, Ce), have been investigated by means of single-crystal X-ray diffraction, elemental analyses, and spectral measurements, as well as calculations of energy band structures, density of states, and optical response functions by the density functional method. The title compounds, which crystallize in monoclinic space group P2(1)/c, possess a similar network of interconnected [Ce(2)(MoO(4))(2)](2+) chains and [BO(2)](-) wavy chains. Novel 1D molybdenum oxide chains are contained in their three-dimensional (3D) networks. The calculated results of crystal energy band structure by the density functional theory (DFT) method show that the solid-state compound LaMoBO(6) is a semiconductor with indirect band gaps.

New silicate-germanate Cs2Pb2[(Si0.6Ge0.4)2O7] from the series A2Pb2[B2O7], A = K, Cs, B = Si, Ge with the umbrella-like [PbO3]4- group

NASA Astrophysics Data System (ADS)

Belokoneva, Elena L.; Morozov, Ivan A.; Volkov, Anatoly S.; Dimitrova, Olga V.; Stefanovich, Sergey Yu.

2018-04-01

New silicate-germanate Cs2Pb2[(Si0.6Ge0.4)2O7] was synthesized in multi-components hydrothermal solution with 20 w.% concentration of Cs2CO3 mineralizer, pH = 10. Novel mixed compound belongs to the structure type A2Pb2[B2O7] previously indicated for powders with A = K, B=Si or Ge. Singe crystal structure determination of Cs2Pb2[(Si0.6Ge0.4)2O7] revealed the need for the correction of the space group of the earlier suggested structural model from P-3 to P-3m1, as well as for the splitting of the Pb-atom position. Umbrella-like groups [PbO3]4- are located between [(Si,Ge)O4]4- tetrahedra in mica-like honeycomb layers and play the role of tetrahedra with the Pb-lone-pair as the forth apex. Crystal chemical comparison revealed similarities and differences with the classical structure type of α-celsian Ba[Al2Si2O8] with the tetrahedral double layer. Recently investigated nonlinear optical acentric borates Pb2(BO3)(NO3) and Pb2(BO3)Cl are both related to this structural type, possessing umbrella-like groups [PbO3]4- and honeycomb layers [Pb2(BO3)]+ with the BO3-triangles on the tetrahedral positions.

EPR and FTIR spectroscopic studies of MO-Al2O3-Bi2O3-B2O3-MnO2(M = Pb, Zn and Cd) glasses

NASA Astrophysics Data System (ADS)

Lalitha Phani, A. V.; Sekhar, K. Chandra; Chakradhar, R. P. S.; Narasimha Chary, M.; Shareefuddin, Md

2018-03-01

Glasses of the system (30-x)MO-xAl2O3-15Bi2O3-54.5B2O3-0.5MnO2 [M = Pb, Zn & Cd] (x = 0, 5, 10 & 15 mol%) were prepared by the normal melt quenching method. The amorphous nature of the prepared glasses was confirmed by the XRD studies. The EPR and FTIR studies were carried out at room temperature (RT). The EPR spectra exhibited three resonance signals at g ≈ 2.0 with a hyperfine structure, an absorption around g = 4.3 and a distinct shoulder at g = 3.3. Deconvoluted spectra were drawn for g ≈ 2.0 to resolve the six hyperfine lines. The electron paramagnetic resonance signal at g ≈ 2.0 indicates that the Mn2+ ions are in nearly perfectly octahedral symmetry. The low field signals at g = 3.3 and g = 4.3 are attributed to the Mn2+ ion which are in distorted rhombic symmetries. The hyperfine (HF) splitting constant (A) values suggested that the bonding between Mn2+ ions and its ligands is ionic in nature. The presence of BO3 and BO4 borate units, metal oxide cation units, Mn2+ and Bi-O bond vibrations in BiO3 units were noticed from the FTIR spectra.

Transformation from an easy-plane to an easy-axis antiferromagnetic structure in the mixed rare-earth ferroborates Pr x Y1-x Fe3(BO3)4: magnetic properties and crystal field calculations.

PubMed

Pankrats, A I; Demidov, A A; Ritter, C; Velikanov, D A; Semenov, S V; Tugarinov, V I; Temerov, V L; Gudim, I A

2016-10-05

The magnetic structure of the mixed rare-earth system Pr x Y1-x Fe3(BO3)4 (x  =  0.75, 0.67, 0.55, 0.45, 0.25) was studied via magnetic and resonance measurements. These data evidence the successive spin reorientation from the easy-axis antiferromagnetic structure formed in PrFe3(BO3)4 to the easy-plane one of YFe3(BO3)4 associated with the weakening of the magnetic anisotropy of the Pr subsystem due to its diamagnetic dilution by nonmagnetic Y. This reorientation occurs through the formation of an inclined magnetic structure, as was confirmed by our previous neutron research in the range of x  =  0.67 ÷ 0.45. In the compounds with x  =  0.75 and 0.67 whose magnetic structure is close to the easy-axis one, a two-step spin reorientation takes place in the magnetic field H||c. Such a peculiarity is explained by the formation of an interjacent inclined magnetic structure with magnetic moments of Fe ions located closer to the basal plane than in the initial state, with these intermediate states remaining stable in some ranges of the magnetic field. An approach based on a crystal field model for the Pr(3+) ion and the molecular-field approximation is used to describe the magnetic characteristics of the system Pr x Y1-x Fe3(BO3)4. With the parameters of the d-d and f-d exchange interactions, of the magnetic anisotropy of the iron subsystem and of the crystal field parameters of praseodymium thus determined, it is possible to achieve a good agreement between the experimental and calculated temperature and field dependences of the magnetization curves (up to 90 kOe) and magnetic susceptibilities (2-300 K).

Purification and Characterization of Botulinum Neurotoxin FA from a Genetically Modified Clostridium botulinum Strain

PubMed Central

Pellett, Sabine; Tepp, William H.; Bradshaw, Marite; Kalb, Suzanne R.; Dykes, Janet K.; Lin, Guangyun; Nawrocki, Erin M.; Pier, Christina L.; Barr, John R.; Maslanka, Susan E.

2016-01-01

ABSTRACT Botulinum neurotoxins (BoNTs), produced by neurotoxigenic clostridial species, are the cause of the severe disease botulism in humans and animals. Early research on BoNTs has led to their classification into seven serotypes (serotypes A to G) based upon the selective neutralization of their toxicity in mice by homologous antibodies. Recently, a report of a potential eighth serotype of BoNT, designated “type H,” has been controversial. This novel BoNT was produced together with BoNT/B2 in a dual-toxin-producing Clostridium botulinum strain. The data used to designate this novel toxin as a new serotype were derived from culture supernatant containing both BoNT/B2 and novel toxin and from sequence information, although data from two independent laboratories indicated neutralization by antibodies raised against BoNT/A1, and classification as BoNT/FA was proposed. The sequence data indicate a chimeric structure consisting of a BoNT/A1 receptor binding domain, a BoNT/F5 light-chain domain, and a novel translocation domain most closely related to BoNT/F1. Here, we describe characterization of this toxin purified from the native strain in which expression of the second BoNT (BoNT/B) has been eliminated. Mass spectrometry analysis indicated that the toxin preparation contained only BoNT/FA and confirmed catalytic activity analogous to that of BoNT/F5. The in vivo mouse bioassay indicated a specific activity of this toxin of 3.8 × 107 mouse 50% lethal dose (mLD50) units/mg, whereas activity in cultured human neurons was very high (50% effective concentration [EC50] = 0.02 mLD50/well). Neutralization assays in cells and mice both indicated full neutralization by various antibodies raised against BoNT/A1, although at 16- to 20-fold-lower efficiency than for BoNT/A1. IMPORTANCE Botulinum neurotoxins (BoNTs), produced by anaerobic bacteria, are the cause of the potentially deadly, neuroparalytic disease botulism. BoNTs have been classified into seven serotypes, serotypes A to G, based upon their selective neutralization by homologous antiserum, which is relevant for clinical and diagnostic purposes. Even though supportive care dramatically reduces the death rate of botulism, the only pharmaceutical intervention to reduce symptom severity and recovery time is early administration of antitoxin (antiserum raised against BoNTs). A recent report of a novel BoNT serotype, serotype H, raised concern of a “treatment-resistant” and highly potent toxin. However, the toxin’s chimeric structure and characteristics indicate a chimeric BoNT/FA. Here we describe the first characterization of this novel toxin in purified form. BoNT/FA was neutralized by available antitoxins, supporting classification as BoNT/FA. BoNT/FA required proteolytic activation to achieve full toxicity and had relatively low potency in mice compared to BoNT/A1 but surprisingly high activity in cultured neurons. PMID:27303710

Crystal structures of botulinum neurotoxin DC in complex with its protein receptors synaptotagmin I and II.

PubMed

Berntsson, Ronnie Per-Arne; Peng, Lisheng; Svensson, Linda Marie; Dong, Min; Stenmark, Pål

2013-09-03

Botulinum neurotoxins (BoNTs) can cause paralysis at exceptionally low concentrations and include seven serotypes (BoNT/A-G). The chimeric BoNT/DC toxin has a receptor binding domain similar to the same region in BoNT/C. However, BoNT/DC does not share protein receptor with BoNT/C. Instead, it shares synaptotagmin (Syt) I and II as receptors with BoNT/B, despite their low sequence similarity. Here, we present the crystal structures of the binding domain of BoNT/DC in complex with the recognition domains of its protein receptors, Syt-I and Syt-II. The structures reveal that BoNT/DC possesses a Syt binding site, distinct from the established Syt-II binding site in BoNT/B. Structure-based mutagenesis further shows that hydrophobic interactions play a key role in Syt binding. The structures suggest that the BoNT/DC ganglioside binding sites are independent of the protein receptor binding site. Our results reveal the remarkable versatility in the receptor recognition of the BoNTs. Copyright © 2013 Elsevier Ltd. All rights reserved.

SUMMARY OF 2010 DOE EM INTERNATIONAL PROGRAM STUDIES OF WASTE GLASS STRUCTURE AND PROPERTIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fox, K.; Choi, A.; Marra, J.

2011-02-07

Collaborative work between the Savannah River National Laboratory (SRNL) and SIA Radon in Russia was divided among three tasks for calendar year 2010. The first task focused on the study of simplified high level waste glass compositions with the objective of identifying the compositional drivers that lead to crystallization and poor chemical durability. The second task focused on detailed characterization of more complex waste glass compositions with unexpectedly poor chemical durabilities. The third task focused on determining the structure of select high level waste glasses made with varying frit compositions in order to improve models under development for predicting themore » melt rate of the Defense Waste Processing Facility (DWPF) glasses. The majority of these tasks were carried out at SIA Radon. Selection and fabrication of the glass compositions, along with chemical composition measurements and evaluations of durability were carried out at SRNL and are described in this report. SIA Radon provided three summary reports based on the outcome of the three tasks. These reports are included as appendices to this document. Briefly, the result of characterization of the Task 1 glasses may indicate that glass compositions where iron is predominantly tetrahedrally coordinated have more of a tendency to crystallize nepheline or nepheline-like phases. For the Task 2 glasses, the results suggested that the relatively low fraction of tetrahedrally coordinated boron and the relatively low concentrations of Al{sub 2}O{sub 3} available to form [BO{sub 4/2}]{sup -}Me{sup +} and [AlO{sub 4/2}]{sup -}Me{sup +} tetrahedral units are not sufficient to consume all of the alkali ions, and thus these alkali ions are easily leached from the glasses. All of the twelve Task 3 glass compositions were determined to be mainly amorphous, with some minor spinel phases. Several key structural units such as metasilicate chains and rings were identified, which confirms the current modeling approach for the silicate phase. The coordination of aluminum and iron was found to be mainly tetrahedral, with some octahedral iron ions. In all samples, trigonally-coordinated boron was determined to dominate over tetrahedrally-coordinated boron. The results further suggested that BO{sub 4} tetrahedra and BO{sub 3} triangles form complex borate units and may be present as separate constituents. However, no quantification of tetrahedral-to-trigonal boron ratio was made.« less

Mesoporous LiFeBO3/C hollow spheres for improved stability lithium-ion battery cathodes

NASA Astrophysics Data System (ADS)

Chen, Zhongxue; Cao, Liufei; Chen, Liang; Zhou, Haihui; Zheng, Chunman; Xie, Kai; Kuang, Yafei

2015-12-01

Polyanionic compounds are regarded as one of the most promising cathode materials for the next generation lithium-ion batteries due to their abundant resource and thermal stability. LiFeBO3 has a relatively higher capacity than olivine LiFePO4, however, moisture sensitivity and low conductivity hinder its further development. Here, we design and synthesize mesoporous LiFeBO3/C (LFB/C) hollow spheres to enhance its structural stability and electric conductivity, two LiFeBO3/C electrodes with different carbon content are prepared and tested. The experimental results show that mesoporous LiFeBO3/C hollow spheres with higher carbon content exhibit superior lithium storage capacity, cycling stability and rate capability. Particularly, the LFB/C electrode with higher carbon content demonstrates good structural stability, which can maintain its original crystal structure and Li storage properties even after three months of air exposure at room temperature. The exceptional structural stability and electrochemical performance may justify their potential use as high-performance cathode materials for advanced lithium-ion batteries. In addition, the synthesis strategy demonstrated herein is simple and versatile for the fabrication of other polyanionic cathode materials with mesoporous hollow spherical structure.

Crystal Structure of the Receptor Binding Domain of the botulinum C-D Mosiac Neurotoxin Reveals Potential Roles of Lysines 1118 and 1136 in Membrane Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y Zhang; G Buchko; L Qin

2011-12-31

The botulinum neurotoxins (BoNTs) produced by different strains of the bacterium Clostridium botulinum are responsible for the disease botulism and include a group of immunologically distinct serotypes (A, B, E, and F) that are considered to be the most lethal natural proteins known for humans. Two BoNT serotypes, C and D, while rarely associated with human infection, are responsible for deadly botulism outbreaks afflicting animals. Also associated with animal infections is the BoNT C-D mosaic protein (BoNT/CD), a BoNT subtype that is essentially a hybrid of the BoNT/C ({approx}two-third) and BoNT/D ({approx}one-third) serotypes. While the amino acid sequence of themore » heavy chain receptor binding (HCR) domain of BoNT/CD (BoNT/CD-HCR) is very similar to the corresponding amino acid sequence of BoNT/D, BoNT/CD-HCR binds synaptosome membranes better than BoNT/D-HCR. To obtain structural insights for the different membrane binding properties, the crystal structure of BoNT/CD-HCR (S867-E1280) was determined at 1.56 {angstrom} resolution and compared to previously reported structures for BoNT/D-HCR. Overall, the BoNT/CD-HCR structure is similar to the two sub-domain organization observed for other BoNT HCRs: an N-terminal jellyroll barrel motif and a C-terminal {beta}-trefoil fold. Comparison of the structure of BoNT/CD-HCR with BoNT/D-HCR indicates that K1118 has a similar structural role as the equivalent residue, E1114, in BoNT/D-HCR, while K1136 has a structurally different role than the equivalent residue, G1132, in BoNT/D-HCR. Lysine-1118 forms a salt bridge with E1247 and may enhance membrane interactions by stabilizing the putative membrane binding loop (K1240-N1248). Lysine-1136 is observed on the surface of the protein. A sulfate ion bound to K1136 may mimic a natural interaction with the negatively changed phospholipid membrane surface. Liposome-binding experiments demonstrate that BoNT/CD-HCR binds phosphatidylethanolamine liposomes more tightly than BoNT/D-HCR.« less

Crystal structure of the receptor binding domain of the botulinum C-D mosaic neurotoxin reveals potential roles of lysines 1118 and 1136 in membrane interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yanfeng; Buchko, Garry W.; Qin, Ling

2011-01-07

The botulinum neurotoxins (BoNTs) produced by different strains of the bacterium Clostridium botulinum are responsible for the disease botulism and include a group of immunologically distinct serotypes (A, B, E, and F) that are considered to be the most lethal natural proteins known for humans. Two BoNT serotypes, C and D, while rarely associated with human infection, are responsible for deadly botulism outbreaks afflicting animals. Also associated with animal infections is the BoNT C-D mosaic protein (BoNT/CD), a BoNT subtype that is essentially a hybrid of the BoNT/C (~two-thirds) and BoNT/D (~one-third) serotypes. While the amino acid sequence of themore » heavy chain receptor binding (HCR) domain of BoNT/CD (BoNT/CD-HCR) is very similar to the corresponding amino acid sequence of BoNT/D, BoNT/CD-HCR binds synaptosome membranes better than BoNT/D-HCR. To obtain structural insights for the different membrane binding properties, the crystal structure of BoNT/CD-HCR (S867-E1280) was determined at 1.56 Å resolution and compared to previously reported structures for BoNT/D-HCR. Overall, the BoNT/CD-HCR structure is similar to the two sub-domain organization observed for other BoNT HCRs: an N-terminal jellyroll barrel motif and a C-terminal β-trefoil fold. Comparison of the structure of BoNT/CD-HCR with BoNT/D-HCR indicates that K1118 has a similar structural role as the equivalent residue, E1114, in BoNT/D-HCR, while K1136 has a structurally different role than the equivalent residue, G1132, in BoNT/D-HCR. Lysine-1118 forms a salt bridge with E1247 and may enhance membrane interactions by stabilizing the putative membrane binding loop (K1240-N1248). Lysine-1136 is observed on the surface of the protein. A sulfate ion bound to K1136 may mimic a natural interaction with the negatively changed phospholipid membrane surface. Liposome-binding experiments demonstrate that BoNT/CD-HCR binds phosphatidylethanolamine liposomes more tightly than BoNT/D-HCR« less

Crystal structure of the receptor binding domain of the botulinum C-D mosaic neurotoxin reveals potential roles of lysines 1118 and 1136 in membrane interactions.

PubMed

Zhang, Yanfeng; Buchko, Garry W; Qin, Ling; Robinson, Howard; Varnum, Susan M

2011-01-07

The botulinum neurotoxins (BoNTs) produced by different strains of the bacterium Clostridium botulinum are responsible for the disease botulism and include a group of immunologically distinct serotypes (A, B, E, and F) that are considered to be the most lethal natural proteins known for humans. Two BoNT serotypes, C and D, while rarely associated with human infection, are responsible for deadly botulism outbreaks afflicting animals. Also associated with animal infections is the BoNT C-D mosaic protein (BoNT/CD), a BoNT subtype that is essentially a hybrid of the BoNT/C (∼two-third) and BoNT/D (∼one-third) serotypes. While the amino acid sequence of the heavy chain receptor binding (HCR) domain of BoNT/CD (BoNT/CD-HCR) is very similar to the corresponding amino acid sequence of BoNT/D, BoNT/CD-HCR binds synaptosome membranes better than BoNT/D-HCR. To obtain structural insights for the different membrane binding properties, the crystal structure of BoNT/CD-HCR (S867-E1280) was determined at 1.56 Å resolution and compared to previously reported structures for BoNT/D-HCR. Overall, the BoNT/CD-HCR structure is similar to the two sub-domain organization observed for other BoNT HCRs: an N-terminal jellyroll barrel motif and a C-terminal β-trefoil fold. Comparison of the structure of BoNT/CD-HCR with BoNT/D-HCR indicates that K1118 has a similar structural role as the equivalent residue, E1114, in BoNT/D-HCR, while K1136 has a structurally different role than the equivalent residue, G1132, in BoNT/D-HCR. Lysine-1118 forms a salt bridge with E1247 and may enhance membrane interactions by stabilizing the putative membrane binding loop (K1240-N1248). Lysine-1136 is observed on the surface of the protein. A sulfate ion bound to K1136 may mimic a natural interaction with the negatively changed phospholipid membrane surface. Liposome-binding experiments demonstrate that BoNT/CD-HCR binds phosphatidylethanolamine liposomes more tightly than BoNT/D-HCR. Copyright © 2010 Elsevier Inc. All rights reserved.

Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy.

PubMed

Fischer, Audrey; Garcia-Rodriguez, Consuelo; Geren, Isin; Lou, Jianlong; Marks, James D; Nakagawa, Terunaga; Montal, Mauricio

2008-02-15

Clostridial botulinum neurotoxin (BoNT) causes a neuroparalytic condition recognized as botulism by arresting synaptic vesicle exocytosis. Although the crystal structures of full-length BoNT/A and BoNT/B holotoxins are known, the molecular architecture of the five other serotypes remains elusive. Here, we present the structures of BoNT/A and BoNT/E using single particle electron microscopy. Labeling of the particles with three different monoclonal antibodies raised against BoNT/E revealed the positions of their epitopes in the electron microscopy structure, thereby identifying the three hallmark domains of BoNT (protease, translocation, and receptor binding). Correspondingly, these antibodies selectively inhibit BoNT translocation activity as detected using a single molecule assay. The global structure of BoNT/E is strikingly different from that of BoNT/A despite strong sequence similarity. We postulate that the unique architecture of functionally conserved modules underlies the distinguishing attributes of BoNT/E and contributes to differences with BoNT/A.

A Novel Botulinum Neurotoxin, Previously Reported as Serotype H, Has a Hybrid-Like Structure With Regions of Similarity to the Structures of Serotypes A and F and Is Neutralized With Serotype A Antitoxin

PubMed Central

Maslanka, Susan E.; Lúquez, Carolina; Dykes, Janet K.; Tepp, William H.; Pier, Christina L.; Pellett, Sabine; Raphael, Brian H.; Kalb, Suzanne R.; Barr, John R.; Rao, Agam; Johnson, Eric A.

2016-01-01

Botulism is a potentially fatal paralytic disease caused by the action of botulinum neurotoxin (BoNT) on nerve cells. There are 7 known serotypes (A–G) of BoNT and up to 40 genetic variants. Clostridium botulinum strain IBCA10-7060 was recently reported to produce BoNT serotype B (BoNT/B) and a novel BoNT, designated as BoNT/H. The BoNT gene (bont) sequence of BoNT/H was compared to known bont sequences. Genetic analysis suggested that BoNT/H has a hybrid-like structure containing regions of similarity to the structures of BoNT/A1 and BoNT/F5. This novel BoNT was serologically characterized by the mouse neutralization assay and a neuronal cell–based assay. The toxic effects of this hybrid-like BoNT were completely eliminated by existing serotype A antitoxins, including those contained in multivalent therapeutic antitoxin products that are the mainstay of human botulism treatment. PMID:26068781

Structural Insights into the Functional Role of the Hcn Sub-domain of the Receptor-Binding Domain of the Botulinum Neurotoxin Mosaic Serotype C/D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yanfeng; Gardberg, Anna; Edwards, Tom E.

Botulinum neurotoxin (BoNT), the causative agent of the deadly neuroparalytic disease botulism, is the most poisonous protein known for humans. Produced by different strains of the anaerobic bacterium Clostridium botulinum, BoNT effects cellular intoxication via a multistep mechanism executed by the three modules of the activated protein. Endocytosis, the first step of cellular intoxication, is triggered by the ~50 kDa, heavy-chain receptor-binding module (HCR) that is specific for a ganglioside and a protein receptor on neuronal cell surfaces. This dual receptor recognition mechanism between BoNT and the host cell’s membrane is well documented and occurs via specific intermolecular interactions withmore » the C-terminal sub-domain, Hcc, of BoNT-HCR. The N-terminal sub-domain of BoNT-HCR, Hcn, comprises ~50% of BoNT-HCR and adopts a B-sheet jelly roll fold. While suspected in assisting cell surface recognition, no unambiguous function for the Hcn sub-domain in BoNT has been indentified. To obtain insights into the potential function of the Hcn sub-domain in BoNT, the first crystal structure of a BoNT with an organic ligand bound to the Hcn sub-domain has been obtained. Here, we describe the crystal structure of BoNT/CD-HCR determined at 1.70 Å resolution with a tetraethylene glycol (PG4) molecule bound in an hydrophobic cleft between B-strands in the B-sheet jelly fold roll of the Hcn sub-domain. The molecule is completely engulfed in the cleft, making numerous hydrophobic (Y932, S959, W966, and D1042) and hydrophilic (S935, W977, L979, N1013, and I1066) contacts with the protein’s side chain and backbone that may mimic in vivo interactions with the phospholipid membranes on neuronal cell surfaces. A sulfate ion was also observed bound to residues T1176, D1177, K1196, and R1243 in the Hcc sub-domain of BoNT/CD-HCR. In the crystal structure of a similar protein, BoNT/D-HCR, a sialic acid« less

Microwave synthesis and electrochemical properties of lithium manganese borate as cathode for lithium ion batteries

NASA Astrophysics Data System (ADS)

Ma, Ting; Muslim, Arzugul; Su, Zhi

2015-05-01

Nano structured LiMnBO3/C cathode materials are synthesized by a fast microwave solid-state reaction method using MnCO3, Li2CO3, H3BO3 and glucose as starting materials for the first time. The crystal structure, morphology and electrochemical properties of LiMnBO3/C composites are characterized by X-ray diffraction (XRD), raman spectroscopy (Ramon), scanning electron microscopy (SEM), transmission electron microscopy (TEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and charge-discharge tests. The result shows that not only monoclinic LiMnBO3/C but also hexagonal LiMnBO3/C cathode materials can be successfully synthesized by microwave solid-state method with power of 240 W in different time. Compared with h-LiMnBO3/C and mixed phase LiMnBO3/C, m-LiMnBO3/C displays lower charge-transfer resistance and the Warburg impedance, so it reveals a higher first discharge capacity of 156.3 mAh g-1 at 0.05 C within 1.8V-4.6 V, The value increases up to 173.2 mAh g-1 caused by the activation process. Even after 50 cycles, the discharge capacity of m-LiMnBO3/C still remains at 148.2 mAh g-1.

Optical and physical properties of samarium doped lithium diborate glasses

NASA Astrophysics Data System (ADS)

Hanumantharaju, N.; Sardarpasha, K. R.; Gowda, V. C. Veeranna

2018-05-01

Sm3+ doped lithium di-borate glasses with composition 30Li2O-60B2O3-(10-x) PbO, (where 0 < x < 2 mole. %) were prepared by melt quenching method. The addition of modifier oxide to vitreous B2O3 modifies the glass network by converting three coordinated trigonal boron units (BO3) to weaker anionic four coordinated tetrahedral borons (BO4). The decrease in density and increase in molar volume with samarium ion content indicates the openness of the glass structure. The gradual increase in average separation of boron-boron atoms with VmB clearly indicates deterioration of borate glass network, which in turn leads to decrease in the oxygen packing density. The replacements of Sm2O3 for PbO depolymerise the chain structure and that would increase the concentration of non-bridging oxygens. The marginal increase of optical band gap energy after 1.0 mol.% of Sm2O3 is explained by considering the structural modification in lead-borate. The influence of Sm3+ ion on physical and optical properties in lithium-lead-borate glasses is investigated and the results were discussed in view of the structure of borate glass network.

Crystal Chemistry of the Potassium and Rubidium Uranyl Borate Families Derived from Boric Acid Fluxes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shuao; Alekseev, Evgeny V.; Stritzinger, Jared T.

2010-07-19

The reaction of uranyl nitrate with a large excess of molten boric acid in the presence of potassium or rubidium nitrate results in the formation of three new potassium uranyl borates, K{sub 2}[(UO{sub 2}){sub 2}B{sub 12}O{sub 19}(OH){sub 4}]·0.3H{sub 2}O (KUBO-1), K[(UO{sub 2}){sub 2}B{sub 10}O{sub 15}(OH){sub 5}] (KUBO-2), and K[(UO{sub 2}){sub 2}B{sub 10}O{sub 16}(OH){sub 3}]·0.7H{sub 2}O (KUBO-3) and two new rubidium uranyl borates Rb{sub 2}[(UO{sub 2}){sub 2}B{sub 13}O{sub 20}(OH){sub 5}] (RbUBO-1) and Rb[(UO{sub 2}){sub 2}B{sub 10}O{sub 16}(OH){sub 3}]·0.7H{sub 2}O (RbUBO-2). The latter is isotypic with KUBO-3. These compounds share a common structural motif consisting of a linear uranyl, UO{sub 2}{sup 2+},more » cation surrounded by BO{sub 3} triangles and BO{sub 4} tetrahedra to create an UO{sub 8} hexagonal bipyramidal environment around uranium. The borate anions bridge between uranyl units to create sheets. Additional BO{sub 3} triangles extend from the polyborate layers and are directed approximately perpendicular to the sheets. All of these compounds adopt layered structures. With the exception of KUBO-1, the structures are all centrosymmetric. All of these compounds fluoresce when irradiated with long-wavelength UV light. The fluorescence spectrum yields well-defined vibronically coupled charge-transfer features.« less

Structural analysis of the receptor binding domain of botulinum neurotoxin serotype D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yanfeng; Buchko, Garry W.; Qin, Lin

2010-10-28

Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65 Å resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences aremore » located at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10 Å relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.« less

Structural Analysis of the Receptor Binding Domain of Botulinum Neurotoxin Serotype D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y Zhang; G Buchko; L Qin

2011-12-31

Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65{angstrom} resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences are locatedmore » at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10{angstrom} relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.« less

Synthesis and crystal structure of a novel pentaborate, Na{sub 3}ZnB{sub 5}O{sub 10}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Xuean; Li Ming; Chang Xinan

A novel ternary borate, trisodium zinc pentaborate, Na{sub 3}ZnB{sub 5}O{sub 10}, has been prepared by solid-state reaction at temperature below 750deg. C. The single-crystal X-ray structural analysis showed that Na{sub 3}ZnB{sub 5}O{sub 10} crystallizes in the monoclinic space group P2{sub 1}/n with a=6.6725(7)A, b=18.1730(10)A, c=7.8656(9)A, {beta}=114.604(6){sup o}, Z=4. It represents a new structure type in which double ring [B{sub 5}O{sub 10}]{sup 5-} building units are bridged by ZnO{sub 4} tetrahedra through common O atoms to form a two-dimensional {sub {approx}}{sup 2}[ZnB{sub 5}O{sub 10}]{sup 3-}-layer that affords one-dimensional channels running parallel to the [101] direction. Symmetry-center related {sub {approx}}{sup 2}[ZnB{sub 5}O{submore » 10}]{sup 3-} layers are stacked along the b-axis, with the interlayer void spaces and intralayer open channels filled by Na{sup +} cations to balance charge. The IR spectrum further confirms the presence of both BO{sub 3} and BO{sub 4} groups and UV-vis diffuse reflectance spectrum shows a band gap of about 3.2eV.« less

XRD, Electron Microscopy and Vibrational Spectroscopy Characterization of Simulated SB6 HLW Glasses - 13028

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stefanovsky, S.V.; Institute of Physical Chemistry and Electrochemistry RAS, Leninskii av. 31, Moscow 119991; Nikonov, B.S.

2013-07-01

Sample glasses have been made using SB6 high level waste (HLW) simulant (high in both Al and Fe) with 12 different frit compositions at a constant waste loading of 36 wt.%. As follows from X-ray diffraction (XRD) and optical and scanning electron microscopy (SEM) data, all the samples are composed of primarily glass and minor concentration of spinel phases which form both isometric grains and fine cubic (∼1 μm) crystals. Infrared spectroscopy (IR) spectra of all the glasses within the range of 400-1600 cm{sup -1} consist of the bands due to stretching and bending modes in silicon-oxygen, boron-oxygen, aluminum-oxygen andmore » iron-oxygen structural groups. Raman spectra showed that for the spectra of all the glasses within the range of 850-1200 cm{sup -1} the best fit is achieved by suggestion of overlapping of three major components with maxima at 911-936 cm{sup -1}, 988-996 cm{sup -1} and 1020-1045 cm{sup -1}. The structural network is primarily composed of metasilicate chains and rings with embedded AlO{sub 4} and FeO{sub 4} tetrahedra. Major BO{sub 4} tetrahedra and BO{sub 3} triangles form complex borate units and are present as separate constituents. (authors)« less

Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: Therapeutic implications for migraine and other pains

PubMed Central

Burstein, Rami; Zhang, XiChun; Levy, Dan; Aoki, K Roger

2014-01-01

Background Meningeal and other trigeminal nociceptors are thought to play important roles in the initiation of migraine headache. Currently, the only approved peripherally administered chronic migraine prophylactic drug is onabotulinumtoxinA. The purpose of this study was to determine how botulinum neurotoxin type A (BoNT-A) affects naïve and sensitized meningeal nociceptors. Material and methods Using electrophysiological techniques, we identified 43 C- and 36 Aδ-meningeal nociceptors, and measured their spontaneous and evoked firing before and after BoNT-A administration to intracranial dura and extracranial suture-receptive fields. Results As a rule, BoNT-A inhibited C- but not Aδ-meningeal nociceptors. When applied to nonsensitized C-units, BoNT-A inhibited responses to mechanical stimulation of the dura with suprathreshold forces. When applied to sensitized units, BoNT-A reversed mechanical hypersensitivity. When applied before sensitization, BoNT-A prevented development of mechanical hypersensitivity. When applied extracranially to suture branches of intracranial meningeal nociceptors, BoNT-A inhibited the mechanical responsiveness of the suture branch but not dural axon. In contrast, BoNT-A did not inhibit C-unit responses to mechanical stimulation of the dura with threshold forces, or their spontaneous activity. Discussion The study provides evidence for the ability of BoNT-A to inhibit mechanical nociception in peripheral trigeminovascular neurons. These findings suggest that BoNT-A interferes with neuronal surface expression of high-threshold mechanosensitive ion channels linked preferentially to mechanical pain by preventing their fusion into the nerve terminal membrane. PMID:24694964

Optimization of photoluminescence of GdAl3(BO3)4:Sm3+ phosphors for solid state lighting devices

NASA Astrophysics Data System (ADS)

Jamalaiah, Bungala Chinna

2017-10-01

The GdAl3(BO3)4:Sm3+ phosphors prepared by solid-state reaction method were characterized through thermal, structural and photoluminescence studies at room temperature only. The observed X-ray diffraction peaks were well consistent with JCPDS No. 83-1907. When excited with 406 nm wavelength, the studied phosphors exhibit orange-red luminescence through 4G5/2 → 6H5/2, 4G5/2 → 6H7/2 and 4G5/2 → 6H9/2 transitions. The concentration of Sm3+ ions was optimized to be 0.01 mol% for intense luminescence in GdAl3(BO3)4:Sm3+ phosphors. Beyond 0.01 mol% of Sm3+ ions concentration, luminescence quenching was observed due to energy transfer among the excited Sm3+ ions through cross-relaxation and dipole-dipole interaction mechanisms. The GdAl3(BO3)4:0.01 mol% Sm3+ phosphor was identified as a notable host material to emit intense orange-red luminescence for various solid state lighting devices under 406 nm excitation.

Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

DOE PAGES

Yao, Guorui; Lam, Kwok-ho; Perry, Kay; ...

2017-03-08

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H.

PubMed

Yao, Guorui; Lam, Kwok-Ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

2017-03-08

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A-G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (H C ) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the H C . Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-H C at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.

Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Guorui; Lam, Kwok-ho; Perry, Kay

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

“Ni{sub 5}TiO{sub 7}” is Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nalbandyan, V.B.

2017-05-15

It is shown that the compound known as Ni{sub 5}TiO{sub 7} and considered as a promising catalyst and oxidation product of alloys does not exist and its XRD pattern actually corresponds to Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2} - Graphical abstract: XRD pattern of “Ni{sub 5}TiO{sub 7}” (top) is identical to that for Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2} (bottom) based on single-crystal structural data. - Highlights: • Popular catalyst known as Ni{sub 5}TiO{sub 7} is actually Ni{sub 5}TiO{sub 4}(BO{sub 3}){sub 2}. • B{sub 2}O{sub 3} came from the flux used for crystal growth. • Some authors reporting this phase did notmore » use any boron compounds.« less

Location of the synaptosome-binding regions on botulinum neurotoxin B.

PubMed

Dolimbek, Behzod Z; Steward, Lance E; Aoki, K Roger; Atassi, M Zouhair

2012-01-10

The regions of botulinum neurotoxin B (BoNT/B) involved in binding to mouse brain synaptosomes (snps) were localized. Sixty 19-residue overlapping peptides (peptide C31 consisted of 24 residues) encompassing BoNT/B H chain (residues 442-1291) were synthesized and used to inhibit binding of (125)I-labeled BoNT/B to snps. Synaptosome-binding regions were noncompeting and existed on both H(N) and H(C) domains of neurotoxin. At 37 °C, inhibitory activities on H(N) resided, in decreasing order, in peptides 638-656 (26.7%), 596-614 (18.2%), 512-530 (13.9%), 778-796 (13.8%), and 526-544 (11.6%). On H(C), activity resided in decreasing order in peptides 1170-1188 (44.6%), 1128-1146 (21.6%), 1184-1202 (18.6%), 1156-1174 (13.0%), 946-964 (11.8%), 1114-1132 (11.2%), 1100-1118 (6.2%), 876-894 (6.1%), 1268-1291 (4.6%), and 1226-1244 (4.3%). The 45 remaining H(N) and H(C) peptides had no activity. At 4 °C, peptide C24 (1170-1188) remained quite active (inhibiting, 31.2%), while activities of peptides N15, C21, and C25 were little under 10%. The snp-binding regions contained sites that bind synaptotagmin II and gangliosides. Despite the low degree of sequence homology, BoNT/B and BoNT/A display significant structural homology and appeared to bind in part to the same snp-binding regions. Binding of each labeled toxin to snps was inhibited ~50% by the other toxin, 70-72% by its correlate H(C), and by the H(C) of the other toxin [29% (BoNT/A by H(C) of B) or 32% (BoNT/B by H(C) of A)]. In the three-dimensional structure of BoNT/B, the greater part of H(C), one H(N) face, and part of the belt on the same side interact with snps. Thus, BoNT/B binds to snps through the H(C) head and employs regions on one H(N) face and the belt, reserving flexibility for the belt's unbound part to release the light chain. Most snp-binding regions coincide or overlap with blocking antibody (Ab)-binding regions explaining how such Abs prevent BoNT/B toxicity.

Structure and properties of CdO-B2O3 and CdO-MnO-B2O3 glasses; Criteria of getting the fraction of four coordinated boron atoms from infrared spectra

NASA Astrophysics Data System (ADS)

Doweidar, H.; El-Damrawi, G.; El-Stohy, Sh.

2017-11-01

IR spectra of CdO-B2O3 and xCdO·(50 - x)MnO·50B2O3 glasses (0 ≤ x ≤ 50 mol%) have been analyzed. The fraction N4 of four coordinated boron atoms obtained from the integrated area under the IR spectra of CdO-B2O3 glasses is markedly higher than the reported NMR values. In both cases, N4 does not change with CdO content. The difference between N4 values of both techniques has been correlated with the relative absorption coefficient of BO4 unit with respect to BO3 unit, as suggested by Chryssikos et al. N4 data of xCdO·(50 - x)MnO·50B2O3 glasses could be used to calculate the fraction of modifier and former CdO and MnO in the borate matrix, as a function of composition. There is a linear increase in both the density and molar volume with increasing CdO content. The change has been correlated with the contribution of CdO and MnO. Electric conduction is assumed to take place via hopping of small polarons. There is a decrease in conductivity with increasing CdO concentration, which suggests that the electrons related to Cd sites are more localized than those at Mn sites.

Pharmacological differences and clinical implications of various botulinum toxin preparations: a critical appraisal

PubMed Central

Ferrari, Adriano; Manca, Mario; Tugnoli, Valeria

2018-01-01

Summary Three different type A botulinum neurotoxins (BoNTAs) — onabotulinumtoxinA, abobotulinumtoxinA and incobotulinumtoxinA) — are currently marketed in Europe to treat several conditions. Differences between BoNTA preparations, which depend on their specific biotypes and manufacturing processes, lead to clinically relevant pharmacotherapeutic dissimilarities. All three available products are separately recognized and reviewed in American Academy of Neurology guidelines. The neurotoxin load/100U is likewise different among the different BoNTAs, with the result that the specific potency of the 150kD BoNTA neurotoxin is calculated as 137 units/ng for onabotulinumtoxinA, 154 units/ng for abobotulinumtoxinA, and 227 units/ng for incobotulinumtoxinA. It is important for clinicians to have all three BoNTAs available in order to choose the most suitable preparation for the specific indication in the single patient. Commercially available BoNTAs must be recognized as different from one another, and therefore as non-interchangeable. The essential experience of the clinician is of the utmost importance in choosing the most appropriate treatment. PMID:29633692

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Guorui; Lam, Kwok-ho; Perry, Kay

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures« less

Comparative study of immunological and structural properties of two recombinant vaccine candidates against botulinum neurotoxin type E.

PubMed

Rostamian, Mosayeb; Mousavy, Seyed Jafar; Ebrahimi, Firouz; Ghadami, Seyyed Abolghasem; Sheibani, Nader; Minaei, Mohammad Ebrahim; Arefpour Torabi, Mohammad Ali

2012-01-01

Recently, botulinum neurotoxin (BoNT)-derived recombinant proteins have been suggested as potential botulism vaccines. Here, with concentrating on BoNT type E (BoNT/E), we studied two of these binding domain-based recombinant proteins: a multivalent chimer protein, which is composed of BoNT serotypes A, B and E binding subdomains, and a monovalent recombinant protein, which contains 93 amino acid residues from recombinant C-terminal heavy chain of BoNT/E (rBoNT/E-HCC). Both proteins have an identical region (48 aa) that contains one of the most important BoNT/E epitopes (YLTHMRD sequence). The recombinant protein efficiency in antibody production, their structural differences, and their BoNT/E-epitope location were compared by using ELISA, circular dichroism, computational modeling, and hydrophobicity predictions. Immunological studies indicated that the antibody yield against rBoNT/E-HCC was higher than chimer protein. Cross ELISA confirmed that the antibodies against the chimer protein recognized rBoNT/E-HCC more efficiently. However, both antibody groups (anti-chimer and anti-rBoNT/E-HCC antibodies) were able to recognize other proteins. Structural studies with circular dichroism showed that chimer proteins have slightly more secondary structures than rBoNT/E-HCC. The immunological results suggested that the above-mentioned identical region in rBoNT/E-HCC is more exposed. Circular dichroism, computational protein modeling and hydrophobicity predictions indicated a more exposed location for the identical region in rBoNT/E-HCC than the chimer protein, which is strongly in agreement with immunological results.

X-ray diffraction, crystal structure, and spectral features of the optical susceptibilities of single crystals of the ternary borate oxide lead bismuth tetraoxide, PbBiBO4.

PubMed

Reshak, Ali Hussain; Kityk, I V; Auluck, S; Chen, Xuean

2009-05-14

The all-electron full-potential linearized augmented plane-wave method has been used for an ab initio theoretical study of the band structure, the spectral features of the optical susceptibilities, the density of states, and the electron charge density for PbBiBO4. Our calculations show that the valence-band maximum (VBM) and conduction-band minimum (CBM) are located at the center of the Brillouin zone, resulting in a direct energy gap of about 3.2 eV. We have synthesized the PbBiBO4 crystal by employing a conventional solid-state reaction method. The theoretical calculations in this work are based on the structure built from our measured atomic parameters. We should emphasize that the observed experimental X-ray diffraction (XRD) pattern is in good agreement with the theoretical one, confirming that our structural model is valid. Our calculated bond lengths show excellent agreement with the experimental data. This agreement is attributed to our use of full-potential calculations. The spectral features of the optical susceptibilities show a small positive uniaxial anisotropy.

Whole Genome Sequencing of a Canadian Bovine Gammaherpesvirus 4 Strain and the Possible Link between the Viral Infection and Respiratory and Reproductive Clinical Manifestations in Dairy Cattle

PubMed Central

Gagnon, Carl A.; Traesel, Carolina Kist; Music, Nedzad; Laroche, Jérôme; Tison, Nicolas; Auger, Jean-Philippe; Music, Sanela; Provost, Chantale; Bellehumeur, Christian; Abrahamyan, Levon; Carman, Susy; DesCôteaux, Luc; Charette, Steve J.

2017-01-01

Bovine gammaherpesvirus 4 (BoHV-4) is a herpesvirus widespread in cattle populations, and with no clear disease association. Its genome contains a long unique coding region (LUR) flanked by polyrepetitive DNA and 79 open reading frames (ORFs), with unique 17 ORFs, named Bo1 to Bo17. In 2009, a BoHV-4 strain was isolated (FMV09-1180503: BoHV-4-FMV) from cattle with respiratory disease from Quebec, Canada, and its LUR was sequenced. Despite the overall high similarity, BoHV-4-FMV had the most divergent LUR sequence compared to the two known BoHV-4 reference strain genomes; most of the divergences were in the Bo genes and in the repeat regions. Our phylogenetic analysis based on DNA polymerase and thymidine kinase genes revealed that virus isolate was BoHV-4 gammaherpesvirus and clustered it together with European BoHV-4 strains. Because BoHV-4-FMV was isolated from animals presenting respiratory signs, we have updated the BoHV-4 Canadian cattle seroprevalence data and tried to find out whether there is a link between clinical manifestation and BoHV-4 seropositivity. An indirect immunofluorescence assay (IFA) was performed with nearly 200 randomized sera of dairy cattle from two Canadian provinces, Quebec (n = 100) and Ontario (n = 91). An additional set of sera obtained from Quebec, from the healthy (n = 48) cows or from the animals experiencing respiratory or reproductive problems (n = 75), was also analyzed by IFA. BoHV-4 seroprevalence in Canadian dairy cattle was 7.9% (Quebec: 6% and Ontario: 9.9%). Among animals from the Quebec-based farms, diseased animals showed higher BoHV-4 seropositivity than healthy animals (P < 0.05), with a significant 2.494 odds ratio of being seropositive in sick compared to healthy animals. Although there is no established direct link between BoHV-4 and specific diseases, these seroprevalence data suggest the possible involvement of BoHV-4 in dairy cattle diseases. PMID:28670580

Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.

PubMed

Barbero, Pierangelo; Busso, Marco; Tinivella, Marco; Artusi, Carlo Alberto; De Mercanti, Stefania; Cucci, Angele; Veltri, Andrea; Avagnina, Paolo; Calvo, Andrea; Chio', Adriano; Durelli, Luca; Clerico, Marinella

2015-12-01

Literature provides reports only of a limited follow-up single injection of botulinum toxin-A (BoNT-A) in patients with sialorrhea. The aim of our study is to evaluate the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for severe sialorrhea secondary to neurological dysphagia. We enrolled 38 severe adult sialorrhea patients referred consecutively to the neurology unit and performed bilateral parotid and submandibular gland BoNT-A injections under ultrasound guidance. The outcomes of the study were reduction of sialorrhea, duration of therapeutic effect, and subjective patient- and caregiver-reported satisfaction. A total of 113 BoNT-A administrations were given during the study period with a mean duration of follow-up of 20.2 ± 4.4 months. We observed a significant decrease from baseline in mean number of daily aspirations and a significant improvement in patient- and caregiver-reported outcomes following ultrasound-guided BoNT-A injections (p < 0.001 vs baseline for all comparisons) and the mean duration of the efficacy was 5.6 ± 1 months. No major treatment-related adverse events occurred and a low incidence of minor adverse events was reported. This study confirms the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for sialorrhea, regardless of the causative neurological disorder. These results should encourage the use of BoNT-A in the treatment of severe sialorrhea and highlight the role of ultrasound guidance to obtain optimal results in terms of safety and reproducible outcomes.

Physical and structural properties of Sm3+ ions doped heavy metal oxide containing lanthanum-boro-telluirte glass

NASA Astrophysics Data System (ADS)

Madhu, A.; Eraiah, B.

2018-05-01

The structural studies of Tellurium oxide substituted by samarium oxide in lathanum-lead-boro-tellurite glass are successfully prepared with physical and optical parameters are determined. Due to the effect of increased number of non-bridging oxygen's in the glass samples few physical parameters are observed to be decreased. For the better structural analysis FTIR was carried out and transformation of BO3 → BO4 is observed. Most effective absorption coefficient OH- group was attained in the present work.

A Single-Domain Llama Antibody Potently Inhibits the Enzymatic Activity of Botulinum Neurotoxin by Binding to the Non-Catalytic [alpha]-Exosite Binding Region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Jianbo; Thompson, Aaron A.; Fan, Yongfeng

2010-08-13

Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which, while effective, cannot reverse symptoms once BoNT has entered the neuron. For treatments that can reverse intoxication, interest has focused on developing inhibitors of the enzymatic BoNT light chain (BoNT Lc). Such inhibitors typically mimic substrate and bind in or around the substrate cleavage pocket. To explore the full range of binding sites for serotype A light chain (BoNT/A Lc) inhibitors, we created a library of non-immune llama single-domain VHH (camelid heavy-chain variable region derived from heavy-chain-only antibody)more » antibodies displayed on the surface of the yeast Saccharomyces cerevisiae. Library selection on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation constants (K{sub d}) from 230 to 0.03 nM measured by flow cytometry. Eight of 15 VHH inhibited the cleavage of substrate SNAP25 (synaptosome-associated protein of 25,000 Da) by BoNT/A Lc. The most potent VHH (Aa1) had a solution K{sub d} for BoNT/A Lc of 1.47 x 10{sup -10} M and an IC{sub 50} (50% inhibitory concentration) of 4.7 x 10{sup -10} M and was resistant to heat denaturation and reducing conditions. To understand the mechanism by which Aa1 inhibited catalysis, we solved the X-ray crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 {angstrom} resolution. The structure reveals that the Aa1 VHH binds in the {alpha}-exosite of the BoNT/A Lc, far from the active site for catalysis. The study validates the utility of non-immune llama VHH libraries as a source of enzyme inhibitors and identifies the BoNT/A Lc {alpha}-exosite as a target for inhibitor development.« less

BoNT/AB hybrid maintains similar duration of paresis as BoNT/A wild-type in murine running wheel assay.

PubMed

Kutschenko, Anna; Reinert, Marie-Christine; Krez, Nadja; Liebetanz, David; Rummel, Andreas

2017-03-01

The highly potent Botulinum neurotoxins (BoNT) are successful drugs to treat neuromuscular disorders. Efforts are being made to further reduce the injected BoNT dose and to lengthen the interval between treatments. Detailed knowledge of the BoNT structure-activity relationship (SAR) allows combining the best features of the different BoNT serotypes. Of all seven BoNT serotypes A-G, BoNT/A displays the highest potency despite low neuronal binding affinity, while BoNT/B exhibits much higher affinity. Recently, a new BoNT/AB hybrid (AABB) was constructed comprising the catalytic and translocation domain of BoNT/A and the 50kDa cell binding domain of BoNT/B. Here, we compared BoNT/A wild-type (AAAA) and AABB with regard to ex vivo potency and in vivo potency, efficacy and duration of action using the mouse phrenic nerve hemidiaphragm assay and the murine running wheel assay, respectively. The ex vivo potency of AABB was found to be 8.4-fold higher than that of AAAA. For the latter, two and 5 pg each of AAAA and AABB, respectively, were bilaterally injected into the calf muscles and mouse running wheel performance was automatically monitored during the following weeks to determine potency, efficacy and duration. Mice displayed a dose-dependent impairment of running performance. AABB showed potency, efficacy and duration equal to AAAA demonstrating successful exchange of the cell binding domain. AABB might combine the higher potency and longer duration of BoNT/A with the target specificity for the autonomic nervous system of BoNT/B. AABB might therefore constitute an improved treatment option for acetylcholine-mediated autonomic disorders such as hypersalivation or hyperhidrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of cement kiln dust and gamma irradiation on the ultrasonic parameters of HMO borate glasses

NASA Astrophysics Data System (ADS)

Abd elfadeel, G.; Saddeek, Yasser B.; Mohamed, Gehan Y.; Mostafa, A. M. A.; Shokry Hassan, H.

2017-03-01

Glass samples with the chemical formula x CKD-(100 - x) (5Na2O-65 B2O3-9 Bi2O3-21PbO), (0 ⩽ x ⩽ 32 mol%) were prepared. The density and the ultrasonic estimations of the investigated glasses were analyzed at room temperature before and after the impact of two dosages of gamma irradiation to study the effect of both CKD and gamma radiation. It was found that the density, and the ultrasonic parameters are sensitive to the variety of the content of CKD and the effect of γ-radiation. Replacement of oxides with higher atomic weights such as Bi2O3 and PbO by CKD decreases the density. Analysis of the behavior of the ultrasonic parameters demonstrates that creation of CaO6 and SiO4 on one hand and an alternate transformation between BO4 and BO3 structural units, on the other hand, affect the increase of the ultrasonic velocities and the elastic moduli. Moreover, the density and the ultrasonic parameters decrease somewhat with the increase of the doses of γ-irradiation. The variations of the previous physical parameters can be referred to the creation of radiation imperfections, which occupied the voids inside the glass structure.

Detection of bovine herpesvirus 2 and bovine herpesvirus 4 DNA in trigeminal ganglia of naturally infected cattle by polymerase chain reaction.

PubMed

Campos, F S; Franco, A C; Oliveira, M T; Firpo, R; Strelczuk, G; Fontoura, F E; Kulmann, M I R; Maidana, S; Romera, S A; Spilki, F R; Silva, A D; Hübner, S O; Roehe, P M

2014-06-25

Establishment of latent infection within specific tissues in the host is a common biological feature of the herpesviruses. In the case of bovine herpesvirus 2 (BoHV-2), latency is established in neuronal tissues, while bovine herpesvirus 4 (BoHV-4) and ovine herpesvirus 2 (OvHV-2) latent virus targets on cells of the monocytic lineage. This study was conducted in quest of BoHV-2, BoHV-4 and OvHV-2 DNA in two hundred trigeminal ganglia (TG) specimens, derived from one hundred clinically healthy cattle, majority of them naturally infected with bovine herpesvirus 1 (BoHV-1) and bovine herpesvirus 5 (BoHV-5). Total DNA extracted from ganglia was analyzed by polymerase chain reaction (PCR) designed to amplify part of the genes coding for BoHV-2, and BoHV-4 glycoprotein B and, for OvHV-2, the gene coding for phosphoribosylformylglycinamidine synthase-like protein. BoHV-2 DNA was detected in TG samples of two (2%) and BoHV-4 DNA in nine (9%) of the animals, whereas OvHV-2 DNA could not be detected in any of the TG DNA. The two animals in which BoHV-2 DNA was identified were also co-infected with BoHV-1 and BoHV-5. Within the nine animals in which BoHV-4 DNA was detected, six were also co-infected with BoHV-1 and BoHV-5. This report provides for the first time evidence that viral DNA from BoHV-2 and BoHV-4 can be occasionally detected in TG of naturally infected cattle. Likewise, in this report we provided for the first time evidence that the co-infection of cattle with three distinct bovine herpesviruses might be a naturally occurring phenomenon. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex.

PubMed

Lee, Kwangkook; Zhong, Xiaofen; Gu, Shenyan; Kruel, Anna Magdalena; Dorner, Martin B; Perry, Kay; Rummel, Andreas; Dong, Min; Jin, Rongsheng

2014-06-20

How botulinum neurotoxins (BoNTs) cross the host intestinal epithelial barrier in foodborne botulism is poorly understood. Here, we present the crystal structure of a clostridial hemagglutinin (HA) complex of serotype BoNT/A bound to the cell adhesion protein E-cadherin at 2.4 angstroms. The HA complex recognizes E-cadherin with high specificity involving extensive intermolecular interactions and also binds to carbohydrates on the cell surface. Binding of the HA complex sequesters E-cadherin in the monomeric state, compromising the E-cadherin-mediated intercellular barrier and facilitating paracellular absorption of BoNT/A. We reconstituted the complete 14-subunit BoNT/A complex using recombinantly produced components and demonstrated that abolishing either E-cadherin- or carbohydrate-binding of the HA complex drastically reduces oral toxicity of BoNT/A complex in vivo. Together, these studies establish the molecular mechanism of how HAs contribute to the oral toxicity of BoNT/A. Copyright © 2014, American Association for the Advancement of Science.

Reactive belite stabilization mechanisms by boron-bearing dopants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuesta, Ana; Losilla, Enrique R.; Aranda, Miguel A.G.

2012-04-15

Belite-rich cements hold promise for reduced energy consumption and CO{sub 2} emissions, but their use is hindered by the slow hydration rates of ordinary belites. This drawback may be overcome by activation of belite by doping. Here, the doping mechanism of B and Na/B in belites is reported. For B-doping, three solid solutions have been tested: Ca{sub 2-x/2{open_square}x/2}(SiO{sub 4}){sub 1-x}(BO{sub 3}){sub x}, Ca{sub 2}(SiO{sub 4}){sub 1-x}(BO{sub 3}){sub x}O{sub x/2} and Ca{sub 2-x}B{sub x}(SiO{sub 4}){sub 1-x}(BO{sub 4}){sub x}. The experimental results support the substitution of silicate groups by tetrahedral borate groups with the concomitant substitution of calcium by boron for chargemore » compensation, Ca{sub 2-x}B{sub x}(SiO{sub 4}){sub 1-x}(BO{sub 4}){sub x}. Otherwise, the coupled Na/B-doping of belite has also been investigated and Ca{sub 2-x}Na{sub x}(SiO{sub 4}){sub 1-x}(BO{sub 3}){sub x} series is confirmed to exist for a large range of x values. Along this series, {alpha}'{sub H}-C{sub 2}S is the main phase (for x {>=} 0.10) and is single phase for x = 0.25. Finally, a new structural description for borax doping in belite has been developed for {alpha}'{sub H}-Ca{sub 1.85}Na{sub 0.15}(SiO{sub 4}){sub 0.85}(BO{sub 3}){sub 0.15}, which fits better borax activated belite cements in Rietveld mineralogical analysis.« less

Role of lithium ions on the physical, structural and optical properties of zinc boro tellurite glasses

NASA Astrophysics Data System (ADS)

Rani, S.; Ahlawat, N.; Parmar, R.; Dhankhar, S.; Kundu, R. S.

2018-07-01

Lithium zinc boro tellurite glasses with compositions xLi2O-(100-x) [0.25ZnO-0.15B2O3-0.60TeO2] [where x = 0, 5, 10, 15 and 20 mol%] have been prepared by melt-quench technique. The amorphous nature of the prepared system is ascertained by X-ray diffraction. The density and molar volume are found to decrease with the increase in concentration of Li2O. The differential scanning calorimetry is used to calculate the glass transition temperature (Tg) and the observed values are found to be decreased. The IR and Raman spectra indicate that Li2O acts as a network modifier in the glass matrix. In the present system, tellurium exists as TeO4 and TeO3, B2O3 in the form of BO4 and BO3 and zinc oxide exists as ZnO4 structural units. The values of the optical band gap are estimated from the fitting of Mott and Davis's and model. A better convergence is achieved between experimental observed spectra of absorption coefficient and hydrogenic excitonic model. The optical band gap energy increases, whereas refractive index and molar refractivity follow the reverse trend with Li2O. The range of metallization criterion suggests that these glasses may be a potential candidate for nonlinear optical materials.

Role of lithium ions on the physical, structural and optical properties of zinc boro tellurite glasses

NASA Astrophysics Data System (ADS)

Rani, S.; Ahlawat, N.; Parmar, R.; Dhankhar, S.; Kundu, R. S.

2018-01-01

Lithium zinc boro tellurite glasses with compositions xLi2O-(100-x) [0.25ZnO-0.15B2O3-0.60TeO2] [where x = 0, 5, 10, 15 and 20 mol%] have been prepared by melt-quench technique. The amorphous nature of the prepared system is ascertained by X-ray diffraction. The density and molar volume are found to decrease with the increase in concentration of Li2O. The differential scanning calorimetry is used to calculate the glass transition temperature (Tg) and the observed values are found to be decreased. The IR and Raman spectra indicate that Li2O acts as a network modifier in the glass matrix. In the present system, tellurium exists as TeO4 and TeO3, B2O3 in the form of BO4 and BO3 and zinc oxide exists as ZnO4 structural units. The values of the optical band gap are estimated from the fitting of Mott and Davis's and model. A better convergence is achieved between experimental observed spectra of absorption coefficient and hydrogenic excitonic model. The optical band gap energy increases, whereas refractive index and molar refractivity follow the reverse trend with Li2O. The range of metallization criterion suggests that these glasses may be a potential candidate for nonlinear optical materials.

Search for the genome of bovine herpesvirus types 1, 4 and 5 in bovine semen

PubMed Central

Morán, P.E.; Favier, P.A.; Lomónaco, M.; Catena, M.C.; Chiapparrone, M.L.; Odeón, A.C.; Verna, A.E.; Pérez, S.E.

2013-01-01

Bovine herpesvirus type 1 (BoHV-1) causes respiratory and reproductive disorders in cattle. Recently, bovine herpesvirus type 5 (BoHV-5) and bovine herpesvirus type 4 (BoHV-4) have been identified to be associated with genital disease. In this study, the presence of the genome of BoHV-1, BoHV-4 and BoHV-5 in bovine semen of Argentinean and international origin was analyzed by PCR assays. The most important finding of this study is the detection of the genome of BoHV-1 and BoHV-4 in semen of bulls maintained at artificial insemination centers. It is particularly relevant that BoHV-1 DNA was also identified in one sample of international origin suggesting the need for extensive quality control measures on international transport of bovine semen. PMID:26623325

Cyclopentadienyl-bis(oxazoline) magnesium and zirconium complexes in aminoalkene hydroaminations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eedugurala, Naresh; Hovey, Megan; Ho, Hung -An

Here, a new class of cyclopentadiene-bis(oxazoline) compounds and their piano-stool-type organometallic complexes have been prepared as catalysts for hydroamination of aminoalkenes. The two compounds MeC(Ox Me2) 2C 5H 5 (Bo MCpH; Ox Me2 = 4,4-dimethyl-2-oxazoline) and MeC(Ox Me2) 2C 5Me 4H (Bo MCp tetH) are synthesized from C 5R 4HI (R = H, Me) and MeC(Ox Me2) 2Li. These cyclopentadiene-bis(oxazolines) are converted into ligands that support a variety of metal centers in piano-stool-type geometries, and here we report the preparation of Mg, Tl, Ti, and Zr compounds. Bo MCpH and Bo MCp tetH react with MgMe 2(O 2C 4H 8)more » 2 to give the magnesium methyl complexes {Bo MCp}MgMe and {Bo MCp tet}MgMe. Bo MCpH and Bo MCp tetH are converted to Bo MCpTl and Bo MCp tetTl by reaction with TlOEt. The thallium derivatives react with TiCl 3(THF) 3 to provide [{Bo MCp}TiCl(μ-Cl)] 2 and [{Bo MCptet}TiCl(μ-Cl)] 2, the former of which is crystallographically characterized as a dimeric species. Bo MCpH and Zr(NMe 2) 4 react to eliminate dimethylamine and afford {Bo MCp}Zr(NMe 2) 3, which is crystallographically characterized as a monomeric four-legged piano-stool compound. {Bo MCp}Zr(NMe 2) 3, {Bo MCp}MgMe, and {Bo MCp tet}MgMe are efficient catalysts for the hydroamination/cyclization of aminoalkenes under mild conditions.« less

Cyclopentadienyl-bis(oxazoline) magnesium and zirconium complexes in aminoalkene hydroaminations

DOE PAGES

Eedugurala, Naresh; Hovey, Megan; Ho, Hung -An; ...

2015-11-25

Here, a new class of cyclopentadiene-bis(oxazoline) compounds and their piano-stool-type organometallic complexes have been prepared as catalysts for hydroamination of aminoalkenes. The two compounds MeC(Ox Me2) 2C 5H 5 (Bo MCpH; Ox Me2 = 4,4-dimethyl-2-oxazoline) and MeC(Ox Me2) 2C 5Me 4H (Bo MCp tetH) are synthesized from C 5R 4HI (R = H, Me) and MeC(Ox Me2) 2Li. These cyclopentadiene-bis(oxazolines) are converted into ligands that support a variety of metal centers in piano-stool-type geometries, and here we report the preparation of Mg, Tl, Ti, and Zr compounds. Bo MCpH and Bo MCp tetH react with MgMe 2(O 2C 4H 8)more » 2 to give the magnesium methyl complexes {Bo MCp}MgMe and {Bo MCp tet}MgMe. Bo MCpH and Bo MCp tetH are converted to Bo MCpTl and Bo MCp tetTl by reaction with TlOEt. The thallium derivatives react with TiCl 3(THF) 3 to provide [{Bo MCp}TiCl(μ-Cl)] 2 and [{Bo MCptet}TiCl(μ-Cl)] 2, the former of which is crystallographically characterized as a dimeric species. Bo MCpH and Zr(NMe 2) 4 react to eliminate dimethylamine and afford {Bo MCp}Zr(NMe 2) 3, which is crystallographically characterized as a monomeric four-legged piano-stool compound. {Bo MCp}Zr(NMe 2) 3, {Bo MCp}MgMe, and {Bo MCp tet}MgMe are efficient catalysts for the hydroamination/cyclization of aminoalkenes under mild conditions.« less

The new silver borate Ag{sub 3}B{sub 5}O{sub 9}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sohr, Gerhard; Falkowski, Viktoria; Huppertz, Hubert, E-mail: hubert.huppertz@uibk.ac.at

2015-05-15

Single crystals of Ag{sub 3}B{sub 5}O{sub 9} were obtained via high-pressure synthesis at 3 GPa and 600 °C, using a Walker-type multianvil high-pressure device. Ag{sub 3}B{sub 5}O{sub 9} crystalizes with a=674.7(2), b=943.5(2), c=1103.5(2) pm, V=0.7025(2) nm{sup 3}, and Z=4 in the noncentrosymmetric space group P2{sub 1}2{sub 1}2{sub 1} (no. 19). The orthorhombic structure was refined from 3740 independent reflections with R1=0.0496 and wR2=0.587 (all data). It is built up from infinite corner-sharing chains of BO{sub 4} tetrahedra along the a axis, which are interconnected by BO{sub 3} groups to form a network. In the structure, three crystallographically independent sites aremore » occupied with Ag{sup +} cations exhibiting argentophillic interactions. The synthetic conditions as well as the results of the single crystal structure analysis are presented. - Graphical abstract: Noncentrosymmetric silver borate: During investigations in the system Ag–B–O, a new noncentrosymmetric silver borate Ag{sub 3}B{sub 5}O{sub 9} was discovered. The new structure type is built up from corner-sharing BO{sub 3} and BO{sub 4} groups, forming a network. Argentophillic interactions are clearly indicated by the Ag{sup +}⋯Ag{sup +} distances present in the structure. - Highlights: • A noncentrosymmetric borate Ag{sub 3}B{sub 5}O{sub 9} is accessible via high-pressure synthesis. • Ag{sub 3}B{sub 5}O{sub 9} is the second high-pressure silver borate. • Ag{sup +}⋯Ag{sup +} distances in Ag3B5O9 clearly indicate the presence of argentophillic interactions.« less

Structural Analysis of Botulinum Neurotoxin Type G Receptor Binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmitt, John; Karalewitz, Andrew; Benefield, Desire A.

2010-10-19

Botulinum neurotoxin (BoNT) binds peripheral neurons at the neuromuscular junction through a dual-receptor mechanism that includes interactions with ganglioside and protein receptors. The receptor identities vary depending on BoNT serotype (A-G). BoNT/B and BoNT/G bind the luminal domains of synaptotagmin I and II, homologous synaptic vesicle proteins. We observe conditions under which BoNT/B binds both Syt isoforms, but BoNT/G binds only SytI. Both serotypes bind ganglioside G{sub T1b}. The BoNT/G receptor-binding domain crystal structure provides a context for examining these binding interactions and a platform for understanding the physiological relevance of different Syt receptor isoforms in vivo.

Crystal structures and magnetic properties of lanthanide containing borates LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doi, Yoshihiro, E-mail: doi@sci.hokudai.ac.jp; Satou, Tatsuya; Hinatsu, Yukio

2013-10-15

The synthesis, crystal structures and magnetic properties of LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr) were investigated. The LnCr(BO{sub 3}){sub 2} compounds crystallize in the dolomite-type structure with space group R3{sup ¯}, in which the Ln and Cr ions occupy two octahedral sites. From the result of structural analysis, it was found that there is an anti-site disorder between these two sites and its chemical formula is more exactly Ln{sub 1−r}Cr{sub r}[Cr{sub 1−r}Ln{sub r}](BO{sub 3}){sub 2}. On the other hand, the LnSc(BO{sub 3}){sub 2} adopt the calcite-type structure with space group R3{sup ¯}c. The Ln and Sc ions randomly occupymore » an octahedral site and the chemical formula is represented as (Ln{sub 0.5}Sc{sub 0.5})BO{sub 3}. From the magnetic susceptibility and specific heat measurements, we found that all the LnCr(BO{sub 3}){sub 2} show an antiferromagnetic transition at 6.1–8.1 K. This transition is mainly due to the ordering of Cr{sup 3+} magnetic moments. Among the compounds with magnetic Ln{sup 3+} ions, only YbCr(BO{sub 3}){sub 2} shows an antiferromagnetic ordering of Ln{sup 3+} ion at 2.1 K. - Graphical abstract: The lanthanide containing borates LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr) have the dolomite-type (Ln=Cr) and calcite-type (Ln=Sc) structures. Both structures are similar to each other except for the difference in the partially or fully disordered arrangements of octahedral sites. At low temperatures, the LnCr(BO{sub 3}){sub 2} compounds show an antiferromagnetic transition due to a long-range ordering of Cr{sup 3+} moments. Among them only YbCr(BO{sub 3}){sub 2} shows an antiferromagnetic ordering of Ln{sup 3+} ion at 2.1 K. Display Omitted - Highlights: • Lanthanide containing borates LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr) have been synthesized. • LnCr(BO{sub 3}){sub 2} has the dolomite-type structure with an anti-site disorder between Ln and Cr sites. • LnSc(BO{sub 3}){sub 2} has the calcite-type structure in which the Ln and Cr randomly occupy the same site. • LnCr(BO{sub 3}){sub 2} shows an antiferromagnetic transition at 6.1–8.1 K due to the long-range magnetic ordering of Cr{sup 3+} moments. • Only YbCr(BO{sub 3}){sub 2} shows the two-step antiferromagnetic ordering: Cr{sup 3+} (6.1 K) and Yb{sup 3+} (2.1 K)« less

Composition dependent structural and optical properties of PbF₂-TeO₂-B₂O₃-Eu₂O₃ glasses.

PubMed

Wagh, Akshatha; Raviprakash, Y; Upadhyaya, Vyasa; Kamath, Sudha D

2015-12-05

Boric oxide based quaternary glasses in the system PbF2-TeO2-B2O3-Eu2O3 have been prepared by melt quenching technique. Density, molar volume, FTIR, UV-Vis techniques were used to probe the structural modifications with incorporation of europium ions in the glass network. An increase in glass density & decrease in molar volume (Vm) values proved the structural changes occurring in coordination of boron atom [conversion of BO3 units to BO4]. This resulted in the increase of the compaction of the prepared glasses with increase in Eu2O3 contents. The amorphous natures of the samples were ascertained by XRD and metallization criterion (M) studies. XPS study showed the values of core-level binding energy [O1s, Eu3d, Eu4d, Te3d, Te4d, Pd4f, Pb5d, O1s, and F1s] of (PbF2-TeO2-B2O3-Eu2O3) the glass matrix. The frequency and temperature dependence of dielectric properties of present glasses were investigated in the frequency range of 1 Hz-10 MHz and temperature range of 313-773K. The study of dielectric measurements proved good insulating and thermal stability of the prepared glasses. At room temperature, dielectric loss [tanδ] values were negligibly small for prepared glasses and increased with increase in temperature. FTIR spectroscopy results were in good agreement with optical band energy gap, density, molar volume and hardness values revealing network modifications caused by europium ions in the glass structure. Copyright © 2015 Elsevier B.V. All rights reserved.

Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain: Insight into Cell Surface Binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenmark, Pål; Dong, Min; Dupuy, Jérôme

2011-11-02

Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-{angstrom} X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantlymore » reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.« less

Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding.

PubMed

Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R; Stevens, Raymond C

2010-04-16

Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent. Copyright (c) 2010. Published by Elsevier Ltd.

The structural studies of vanadium substituted lithium-bismuth-boro-tellurite glass

NASA Astrophysics Data System (ADS)

Madhu, A.; Eraiah, B.

2018-05-01

The structural studies of vanadium substituted lithium-bismuth-boro-tellurite glass is successfully prepared and certain analysis like XRD,FTIR,DTA/TGA with density, molar volume are done. The amorphous phase has been identified based on X-ray diffraction analysis. The vanadium oxide plays the role as a glass-modifier and influences on BO3 ↔ BO4 conversion. The observed nonlinear variation in Tg with vanadium oxide increase, it reflects structural changes. The nonlinear variation of density and molar volume can be attributed to vanadium oxide incorporation have increased the number of Non-bridging oxygen (NBO'S).

Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Zhuji; Chen, Chen; Barbieri, Joseph T.

2010-02-22

Botulinum neurotoxin causes rapid flaccid paralysis through the inhibition of acetylcholine release at the neuromuscular junction. The seven BoNT serotypes (A-G) have been proposed to bind motor neurons via ganglioside-protein dual receptors. To date, the structure-function properties of BoNT/F host receptor interactions have not been resolved. Here, we report the crystal structures of the receptor binding domains (HCR) of BoNT/A and BoNT/F and the characterization of the dual receptors for BoNT/F. The overall polypeptide fold of HCR/A is essentially identical to the receptor binding domain of the BoNT/A holotoxin, and the structure of HCR/F is very similar to that ofmore » HCR/A, except for two regions implicated in neuronal binding. Solid phase array analysis identified two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core. Using affinity chromatography, HCR/F bound native synaptic vesicle glycoproteins as part of a protein complex. Deglycosylation of glycoproteins using {alpha}(1-3,4)-fucosidase, endo-{beta}-galactosidase, and PNGase F disrupted the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, was unaffected. These data indicate that the HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2. The interaction of HCR/F with gangliosides was also investigated. HCR/F bound specifically to gangliosides that contain {alpha}2,3-linked sialic acid on the terminal galactose of a neutral saccharide core (binding order GT1b = GD1a GM3; no binding to GD1b and GM1a). Mutations within the putative ganglioside binding pocket of HCR/F decreased binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons. Thus, BoNT/F neuronal discrimination involves the recognition of ganglioside and protein (glycosylated SV2) carbohydrate moieties, providing a structural basis for the high affinity and specificity of BoNT/F for neurons.« less

Catalytic Properties of Botulinum Neurotoxins Subtypes A3 and A4

PubMed Central

Henkel, James S.; Jacobson, Mark; Tepp, William; Pier, Christina; Johnson, Eric A.; Barbieri, Joseph T.

2009-01-01

Botulinum toxins (BoNT) are zinc proteases (serotypes A-G) which cause flaccid paralysis through the cleavage of SNARE proteins within motor neurons. BoNT/A was originally organized into two subtypes: BoNT/A1 and BoNT/A2, which are ~ 95 % homologous and possess similar catalytic activities. Subsequently, two additional subtypes were identified; BoNT/A3 (Loch Maree), and BoNT/A4 (657Ba), which have 81 and 88% homology with BoNT/A1, respectively. Alignment studies predicted that BoNT/A3 and BoNT/A4 were sufficiently different to BoNT/A1 to affect SNAP25 binding and cleavage. Recombinant Light Chain (LC) of BoNT/A3 (LC/A3) and BoNT/A4 (LC/A4) were subjected to biochemical analysis. LC/A3 cleaved SNAP25 at 50% the rate of LC/A1, but cleaved SNAPtide® at a faster rate than LC/A1, while LC/A4 cleaved SNAP25 and SNAPtide® at slower rates than LC/A1. LC/A3 and LC/A4 had similar Kms for SNAP25 relative to LC/A1, while the kcat for LC/A4 was 10- fold slower than LC/A1, suggesting a defect in substrate cleavage. Neither LC/A3 nor LC/A4 possessed autocatalytic activity, a property of LC/A1 and LC/A2. Thus, the four subtypes of BoNT/A bind SNAP25 with similar affinity but have different catalytic capacities for SNAP25 cleavage, SNAPtide® cleavage, and autocatalysis. The catalytic properties identified among the subtypes of LC/A may influence strategies for the development of small molecule- or peptide- inhibitors as therapies against botulism. PMID:19256469

Domain Organization in Clostridium botulinum Neurotoxin Type E is Unique: Its Implication in Faster Translocation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumaran, D.; Eswaramoorthy, S; Furey, W

2009-01-01

Clostridium botulinum produces seven antigenically distinct neurotoxins [C. botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based on sequence and functional similarity, it was believed that their three-dimensional structures will also be similar. Indeed, the crystal structures of BoNTs A and B exhibit similar fold and domain association where the translocation domain is flanked on either side by binding and catalytic domains. Here, we report the crystal structure of BoNT E holotoxin and show that the domain association is different and unique, although the individual domains are similar to those of BoNTs A and B. In BoNT E, bothmore » the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation. We propose that the translocation domain in other BoNTs follows a two-step process to attain translocation-competent conformation as in BoNT E. We also suggest that this translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A. However, this needs further experimental elucidation.« less

In vivo image analysis of BoHV-4-based vector in mice.

PubMed

Franceschi, Valentina; Stellari, Fabio Franco; Mangia, Carlo; Jacca, Sarah; Lavrentiadou, Sophia; Cavirani, Sandro; Heikenwalder, Mathias; Donofrio, Gaetano

2014-01-01

Due to its biological characteristics bovine herpesvirus 4 (BoHV-4) has been considered as an appropriate gene delivery vector. Its genomic clone, modified as a bacterial artificial chromosome (BAC), is better genetically manipulable and can be used as an efficient gene delivery and vaccine vector. Although a large amount of data have been accumulated in vitro on this specific aspect, the same cannot be asserted for the in vivo condition. Therefore, here we investigated the fate of a recombinant BoHV-4 strain expressing luciferase (BoHV-4-A-CMVlucΔTK) after intraperitoneal or intravenous inoculation in mice, by generating a novel recombinant BoHV-4 expressing luciferase (BoHV-4-A-CMVlucΔTK) and by following the virus replication through in vivo imaging analysis. BoHV-4-A-CMVlucΔTK was first characterized in vitro where it was shown, on one hand that its replication properties are identical to those of the parental virus, and on the other that the transduced/infected cells strongly express luciferase. When BoHV-4-A-CMVlucΔTK was inoculated in mice, either intraperitoneally or intravenously, BoHV-4-A-CMVlucΔTK infection/transduction was exclusively localized to the liver, as detected by in vivo image analysis, and in particular almost exclusively in the hepatocytes, as determined by immuno-histochemistry. These data, that add a new insight on the biology of BoHV-4 in vivo, provide the first indication for the potential use of a BoHV-4-based vector in gene-transfer in the liver.

Point defect disorder in high-temperature solution grown Sr6Tb0.94Fe1.06(BO3)6 single crystals

NASA Astrophysics Data System (ADS)

Velázquez, M.; Péchev, S.; Duttine, M.; Wattiaux, A.; Labrugère, C.; Veber, Ph.; Buffière, S.; Denux, D.

2018-08-01

New Sr6Tb0.94Fe1.06(BO3)6 single crystals were obtained from lithium borate high-temperature solution growth under controlled atmosphere. Their average crystal structure was found to adopt the trigonal R-3 space group with lattice parameters a = 12.2164 Å and c = 9.1934 Å. A combined multiscale characterization approach, involving diffuse reflectance, X-ray photoelectron (XPS) and Mössbauer spectroscopies, was undertaken to establish the exact nature of the point defect disorder in this crystal structure. The FeTb× antisite disorder in the Sr6Tb0.94Fe1.06(BO3)6 single crystals is different from the kind of point defect disorder known to exist in the powder phase material counterpart. The absence of Tb4+ cations in the crystal lattice was established by XPS, and that of any phase transition down to 4 K was checked by specific heat measurements. The magnetic susceptibility curve was found to follow a Curie-Weiss behaviour in the 4-354 K temperature range.

The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems.

PubMed

Kumar, Raj; Dhaliwal, Harkiran Preet; Kukreja, Roshan Vijay; Singh, Bal Ram

2016-02-01

Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

High-pressure studies on electronic and mechanical properties of FeBO3 (B = Ti, Mn, Cr) ceramics - a first-principles study

NASA Astrophysics Data System (ADS)

Kishore, N.; Nagarajan, V.; Chandiramouli, R.

2018-04-01

Using the density functional theory (DFT) method, the electronic and mechanical properties of perovskites FeBO3 (B = Ti, Mn, Cr) nanostructures were studied in the pressure range of 0-100 GPa. The band structure studies show the change in the band structure upon substitution of different B cation in FeBO3 perovskite structure. The density of states spectrum gives the perception of change in the electronic properties of FeBO3 with the substitution of B cation. The bulk, shear and Young's moduli were calculated and an increase in the moduli is noticed. Moreover, the hardness increases under high pressure. The high-pressure studies of FeBO3 perovskite nanostructures are explored at atomistic level. The findings show that ductility and hardness of FeBO3 get increased upon an increase in the applied pressure. The substitution of Ti, Mn and Cr on FeBO3 shows a significant change in the electronic and mechanical properties.

Botulinum neurotoxin structure, engineering, and novel cellular trafficking and targeting.

PubMed

Singh, B R

2006-04-01

Botulinum neurotoxins are multifaceted molecules, which are truly unique not only in their mode of action, but also their utility as a drug carrier either across the gut wall or to the nerve terminals. The molecule is divided in clear functional domains that can operate independently. This feature can be used to employ them as cargo carrier by linking other drugs or vaccines with the binding and translocation domains of BoNT. While the domain structures are largely independent of each other, the dynamic structure of these domains, especially that of the enzymatic domain (L chain), is quite different from the reported crystal structures for several BoNT serotypes and their enzymatic domain. This review discusses the comparative structures of BoNT in crystal and solution for their relevance to the molecular mechanism of BoNT action, especially in view of our recent discovery that the enzymatically active structure of the BoNT exists as a molten-globule and that of the endopeptidase domain as a novel PRIME conformation. Finally, a non-exhaustive discussion has been included to explain the long-lasting biological effects of certain serotypes of BoNT, based on the current knowledge of the structure-function of different serotypes of botulinum neurotoxins.

Botulinum neurotoxins: new questions arising from structural biology.

PubMed

Kammerer, Richard A; Benoit, Roger M

2014-11-01

Botulinum neurotoxins (BoNTs) are the most toxic substances known and cause botulism in vertebrates. They have also emerged as effective and powerful reagents for cosmetic and medical applications. One important prerequisite for understanding BoNT function in disease, and the further development of the toxins for cosmetic and medical applications, is a detailed knowledge of BoNT interactions with non-toxic neurotoxin-associated proteins and cell surface receptors. Based on the substantial recent progress in obtaining high-resolution crystal structures of key BoNT complexes, we summarize the major advances in understanding BoNT interactions and discuss the resulting potential implications, in particular those relating to BoNT serotype A. Copyright © 2014 Elsevier Ltd. All rights reserved.

CaB2 S4 O16 : A Borosulfate Exhibiting a New Structure Type with Phyllosilicate Analogue Topology.

PubMed

Bruns, Jörn; Podewitz, Maren; Schauperl, Michael; Joachim, Bastian; Liedl, Klaus R; Huppertz, Hubert

2017-11-27

The reaction of Ca(CO 3 ) with H 3 BO 3 in oleum (20 % SO 3 ) yielded colorless single-crystals of CaB 2 S 4 O 16 (monoclinic, P2 1 /c, a=5.5188(2), b=15.1288(6), c=13.2660(6) Å, β=92.88(1)°, V=1106.22(8) Å 3 ). X-ray single-crystal structure analysis revealed a phyllosilicate-analogue anionic sub-structure, forming 2D infinite anionic layers, which exhibit an unprecedented arrangement of condensed twelve-membered (zwölfer) and four-membered (vierer) rings of corner-shared (SO 4 ) and (BO 4 ) tetrahedra. Charge compensation is achieved by Ca 2+ cations, residing exclusively above the centers of the twelve-membered rings. DFT investigations on the solid-state structure corroborate the experimental findings and allow for a detailed valuation of charge distribution within the anionic network and an assignment of vibrational frequencies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A vibrational spectroscopic study of the borate mineral ezcurrite Na4B10O17·7H2O - Implications for the molecular structure

NASA Astrophysics Data System (ADS)

Frost, Ray L.; López, Andrés; Theiss, Frederick L.; Scholz, Ricardo; Belotti, Fernanda M.

2014-07-01

We have studied the boron containing mineral ezcurrite Na4B10O17·7H2O using electron microscopy and vibrational spectroscopy. Both tetrahedral and trigonal boron units are observed. The nominal resolution of the Raman spectrometer is of the order of 2 cm-1 and as such is sufficient enough to identify separate bands for the stretching bands of the two boron isotopes. The Raman band at 1037 cm-1 is assigned to BO stretching vibration. Raman bands at 1129, 1163, 1193 cm-1 are attributed to BO stretching vibration of the tetrahedral units. The Raman band at 947 cm-1 is attributed to the antisymmetric stretching modes of tetrahedral boron. The sharp Raman peak at 1037 cm-1 is from the 11-B component such a mode, then it should have a smaller 10-B satellite near (1.03) × (1037) = 1048 cm-1, and indeed a small peak at 1048 is observed. The broad Raman bands at 3186, 3329, 3431, 3509, 3547 and 3576 cm-1 are assigned to water stretching vibrations. Broad infrared bands at 3170, 3322, 3419, 3450, 3493, 3542, 3577 and 3597 cm-1 are also assigned to water stretching vibrations. Infrared bands at 1330, 1352, 1389, 1407, 1421 and 1457 cm-1 are assigned to the antisymmetric stretching vibrations of trigonal boron. The observation of so many bands suggests that there is considerable variation in the structure of ezcurrite. Infrared bands at 1634, 1646 and 1681 cm-1 are assigned to water bending modes. The number of water bending modes is in harmony with the number of water stretching vibrations.

Characterization of the regulatory network of BoMYB2 in controlling anthocyanin biosynthesis in purple cauliflower.

PubMed

Chiu, Li-Wei; Li, Li

2012-10-01

Purple cauliflower (Brassica oleracea L. var. botrytis) Graffiti represents a unique mutant in conferring ectopic anthocyanin biosynthesis, which is caused by the tissue-specific activation of BoMYB2, an ortholog of Arabidopsis PAP2 or MYB113. To gain a better understanding of the regulatory network of anthocyanin biosynthesis, we investigated the interaction among cauliflower MYB-bHLH-WD40 network proteins and examined the interplay of BoMYB2 with various bHLH transcription factors in planta. Yeast two-hybrid studies revealed that cauliflower BoMYBs along with the other regulators formed the MYB-bHLH-WD40 complexes and BobHLH1 acted as a bridge between BoMYB and BoWD40-1 proteins. Different BoMYBs exhibited different binding activity to BobHLH1. Examination of the BoMYB2 transgenic lines in Arabidopsis bHLH mutant backgrounds demonstrated that TT8, EGL3, and GL3 were all involved in the BoMYB2-mediated anthocyanin biosynthesis. Expression of BoMYB2 in Arabidopsis caused up-regulation of AtTT8 and AtEGL3 as well as a subset of anthocyanin structural genes encoding flavonoid 3'-hydroxylase, dihydroflavonol 4-reductase, and leucoanthocyanidin dioxygenase. Taken together, our results show that MYB-bHLH-WD40 network transcription factors regulated the bHLH gene expression, which may represent a critical feature in the control of anthocyanin biosynthesis. BoMYB2 together with various BobHLHs specifically regulated the late anthocyanin biosynthetic pathway genes for anthocyanin biosynthesis. Our findings provide additional information for the complicated regulatory network of anthocyanin biosynthesis and the transcriptional regulation of transcription factors in vegetable crops.

Pegram Nuclear Physics Laboratories Progress Report for January 1969 through December 1969 to the United States Atomic Energy Commission

DTIC Science & Technology

1969-12-01

1 +1 4J. Lr) x 0 ra4 -4 Lr) C1 U4)) -I Cd Cd -1 ~ 0 r-4 Nn 0 >- C N u ~~~) +1 +1 +1 ct w +1 a) 0O u 4.-44- L"A ~ - r-5- a) Ln Ln) o +1 +1 +1 + 10 b4... 10 - 10 -7 seconds). These isomers have been observed and so were intermediate structures in the sub-threshold fission of 2 37Np, 2 34U etc., which...bo- Un n C4 1 . 0) 1.4 M) V4-1 aj ) t.) Eq 0 9d ’-4 ;:a. 0 U co 4- d H. 4) a) ,q a) 41 u 4J -rq a) ) .p4 (D 0 ’-4 o 0 D U)29. 10 1 1 Neutron TOF

Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA.

PubMed

Lam, Kwok-Ho; Sikorra, Stefan; Weisemann, Jasmin; Maatsch, Hannah; Perry, Kay; Rummel, Andreas; Binz, Thomas; Jin, Rongsheng

2018-04-23

The extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a ∼2.09 Å resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites. When compared to BoNT/F5 that cleaves VAMP-2 at the same site as BoNT/HA, LC/HA displays higher affinity for VAMP-2, which could be caused by their different surface charge properties surrounding a VAMP-2 exosite-binding cleft. Furthermore, systematic mutagenesis studies on VAMP-2 and structural modeling demonstrate that residues R47 to K59 spanning the cleavage site in VAMP-2 may adopt a novel extended conformation when interacting with LC/HA and LC/F5. Taken together, our structure provides new insights into substrate-recognition of BoNT/HA and paves the way for rational design of small molecule or peptide inhibitors against LC/HA.

Silurian and Devonian in Vietnam—Stratigraphy and facies

NASA Astrophysics Data System (ADS)

Thanh, Tống Duy; Phương, Tạ Hoàng; Janvier, Philippe; Hùng, Nguyễn Hữu; Cúc, Nguyễn Thị Thu; Dương, Nguyễn Thùy

2013-09-01

Silurian and Devonian deposits in Viet Nam are present in several zones and regions, including Quang Ninh, East Bac Bo, and West Bac Bo Zones of the Bac Bo Region, the Dien Bien-Nghe An and Binh Tri Thien Zones of the Viet-Lao Region, and the South Trung Bo, and Western Nam Bo Zones of the South Viet Nam Region (Fig. 1). The main lithological features and faunal composition of the Silurian and Devonian Units in all these zones are briefly described. The Silurian consists of deep-water deposits of the upper parts of the Co To and Tan Mai Formations in the Quang Ninh Zone, the upper parts of the Phu Ngu Formation in the East Bac Bo Zone and the upper parts of the Long Dai and Song Ca Formations in the Viet-Lao Region. Shallow water facies Silurian units containing benthic faunas are more widely distributed, including the upper part of the Sinh Vinh and Bo Hieng Formations in the West Bac Bo Zone, the Kien An Formation in the Quang Ninh Zone, and, in the Viet-Lao Region, the Dai Giang Formation and the upper part of the Tay Trang Formation. No Lower and Middle Devonian deposits indicate deep water facies, but they are characterized by different shallow water facies. Continental to near shore, deltaic facies characterize the Lower Devonian Song Cau Group in the East Bac Bo Zone, the Van Canh Formation in the Quang Ninh Zone, and the A Choc Formation in the Binh Tri Thien Zone. Similar facies also occur in the Givetian Do Son Formation of the Quang Ninh Zone, and the Tan Lap Formation in the East Bac Bo Zone, and consist of coarse terrigenous deposits—cross-bedded conglomerates, sandstone, etc. Most Devonian units are characterized by shallow marine shelf facies. Carbonate and terrigenous-carbonate facies dominate, and terrigenous facies occur in the Lower and Middle Devonian sections in some areas only. The deep-water-like facies is characteriztic for some Upper Devonian formations in the Bac Bo (Bang Ca and Toc Tat Formations) and Viet-Lao Regions (Thien Nhan and Xom Nha Formations). These formations contain cherty shale or siliceous limestone, and fossils consist of conodonts, but there are also brachiopods and other benthos. They were possibly deposited in a deep water environment on the slope of the continental shelf. Most Devonian units distributed in the North and the Central Viet Nam consist of self shallow water sediments, and apparently they were deposited in a passive marginal marine environment. The coarse clastic continental or subcontinental deposits are distributed only in some areas of the East Bac Bo and of the Quang Ninh zones of the Bac Bo Region, and in the south of the Binh Tri Thien Zone. This situation suggests the influence of the Caledonian movement at the end of the Silurian period that called the Guangxi movement in South China.

A new promising nonlinear optical (NLO) crystal for visible and ultraviolet (UV) regions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gheorghe, L.; Achim, A.; Voicu, F.

Different La{sub 1−x}Gd{sub x}Sc{sub 3}(BO{sub 3}){sub 4} compounds with 0 ≤ x ≤ 0.5 were synthesized by solid-state reaction method. The X-ray diffraction studies revealed that the compounds containing more than 30 at.% Gd{sup 3+} ions have non-centrosymmetric trigonal structure (space group R32) and, consequently they are optically nonlinear. A crystal of La{sub x}Gd{sub y}Sc{sub z}(BO{sub 3}){sub 4} (x+y+z = 4) – LGSB with La{sub 0.75}Gd{sub 0.5}Sc{sub 2.75}(BO{sub 3}){sub 4} starting melt composition and relatively small dimensions (about 10 mm in diameter and 25 mm in length) was grown by the Czochralski method. In order to confirm the NLO property, the as-grownmore » crystal was subjected to second-harmonic generation (SHG) test. The nonlinear coefficient d{sub 11} of LGSB crystal has been preliminary estimated to be about 1.9 pm/V, which is larger than that of YAl{sub 3}(BO{sub 3}){sub 4} (YAB) crystal. This article has been formally retracted, please refer to the article PDF for the full retraction notice.« less

Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H

PubMed Central

Fan, Yongfeng; Barash, Jason R.; Lou, Jianlong; Conrad, Fraser; Marks, James D.; Arnon, Stephen S.

2016-01-01

Background. Only Clostridium botulinum strain IBCA10-7060 produces the recently described novel botulinum neurotoxin type H (BoNT/H). BoNT/H (N-terminal two-thirds most homologous to BoNT/F and C-terminal one-third most homologous to BoNT/A) requires antitoxin to toxin ratios ≥1190:1 for neutralization by existing antitoxins. Hence, more potent and safer antitoxins against BoNT/H are needed. Methods. We therefore evaluated our existing monoclonal antibodies (mAbs) to BoNT/A and BoNT/F for BoNT/H binding, created yeast-displayed mutants to select for higher-affinity-binding mAbs by using flow cytometry, and evaluated the mAbs' ability to neutralize BoNT/H in the standard mouse bioassay. Results. Anti-BoNT/A HCC-binding mAbs RAZ1 and CR2 bound BoNT/H with high affinity. However, only 1 of 6 BoNT/F mAbs (4E17.2A) bound BoNT/H but with an affinity >800-fold lower (equilibrium dissociation binding constant [KD] = 7.56 × 10−8 M) than its BoNT/F affinity (KD = 9.1 × 10−11 M), indicating that the N-terminal two-thirds of BoNT/H is immunologically unique. The affinity of 4E17.2A for BoNT/H was increased >500-fold to KD = 1.48 × 10−10 M (mAb 4E17.2D). A combination of mAbs RAZ1, CR2, and 4E17.2D completely protected mice challenged with 280 mouse median lethal doses of BoNT/H at a mAb dose as low as 5 µg of total antibody. Conclusions. This 3-mAb combination potently neutralized BoNT/H and represents a potential human antitoxin that could be developed for the prevention and treatment of type H botulism. PMID:26936913

Prediction on electronic structure of CH3NH3PbI3/Fe3O4 interfaces

NASA Astrophysics Data System (ADS)

Hou, Xueyao; Wang, Xiaocha; Mi, Wenbo; Du, Zunfeng

2018-01-01

The interfacial electronic structures of CH3NH3PbI3(MAPbI3)/Fe3O4 heterostructures are predicted by density functional theory. Four models (MAI/FeBO, PbI2/FeBO, MAI/FeA and PbI2/FeA) are included. Especially, a half-metal to semiconductor transition of Fe3O4 appears in PbI2/FeA model. A series of electric field is added to PbI2/FeA model, and a direct-indirect bandgap transition of Fe3O4 appears at a 500-kV/cm field. The electric field can control the bandgap of Fe3O4 in PbI2/FeA model by modulating the hybridization. The prediction of spin-related bandgap characteristic in MAPbI3/Fe3O4 is meaningful for further study.

Interfacial layer thickness dependent electrical characteristics of Au/(Zn-doped PVA)/n-4H-SiC (MPS) structures at room temperature

NASA Astrophysics Data System (ADS)

Lapa, Havva Elif; Kökce, Ali; Al-Dharob, Mohammed; Orak, İkram; Özdemir, Ahmet Faruk; Altındal, Semsettin

2017-10-01

Au/(Zn-doped PVA)/n-4H-SiC metal/polymer/semiconductor (MPS) structures with different interfacial layer thickness values (50, 150, 500 nm) were fabricated and their electrical characteristics were compared. Their electrical parameters (i.e. reverse-bias saturation current (Io), ideality factor (n), zero-bias barrier height (BH) (Φbo), series and shunt resistances (Rs, Rsh)) were calculated from the forward bias current-voltage (IF-VF) data whereas other parameters (i.e. Fermi energy level (EF), BH (Vb) and donor concentration (Nd)) were calculated from the linear part of C-2-V characteristics at room temperature. Obtained results confirmed that the values of n, Φbo, Rs and Rsh increase with increasing interlayer thickness, and linear correlation between n and Φbo was observed. The high values of n for three structures can be ascribed to the presence of an interlayer, surface states (Nss) and barrier inhomogeneities. The energy density distribution profile of Nss was obtained from the IF-VF data by taking into account voltage-dependent effective BH (Ve) and n for each structure. The Ri vs V plot for these structures was obtained using both Ohm's law and Nicollian-Brews method. All these experimental results show that the interfacial layer and its thickness play an important role in main electric parameters of these structures.

Anomalous property of Ag(BO2)2 hyperhalogen: does spin-orbit coupling matter?

PubMed

Chen, Hui; Kong, Xiang-Yu; Zheng, Weijun; Yao, Jiannian; Kandalam, Anil K; Jena, Puru

2013-10-07

Hyperhalogens were recently identified as a new class of highly electronagative species which are composed of metals and superhalogens. In this work, high-level theoretical calculations and photoelectron spectroscopy experiments are systematically conducted to investigate a series of coinage-metal-containing hyperhalogen anions, Cu(BO(2))(2)(-), Ag(BO(2))(2)(-), and Au(BO(2))(2)(-). The vertical electron detachment energy (VDE) of Ag(BO(2))(2)(-) is anomalously higher than those of Au(BO(2))(2)(-) and Cu(BO(2))(2)(-). In quantitative agreement with the experiment, high-level ab initio calculations reveal that spin-orbit coupling (SOC) lowers the VDE of Au(BO(2))(2)(-) significantly. The sizable magnitude of about 0.5 eV of SOC effect on the VDE of Au(BO(2))(2)(-) demonstrates that SOC plays an important role in the electronic structure of gold hyperhalogens. This study represents a new paradigm for relativistic electronic structure calculations for the one-electron-removal process of ionic Au(I)L(2) complexes, which is characterized by a substantial SOC effect. Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

High-level Expression Purification Crystallization and Preliminary X-ray Crystallographic Studies of the Receptor Binding Domain of botulinum neurotoxin Serotype D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y Zhang; X Gao; G Buchko

2011-12-31

Botulinum neurotoxins (BoNTs) are highly toxic proteins for humans and animals that are responsible for the deadly neuroparalytic disease botulism. Here, details of the expression and purification of the receptor-binding domain (HCR) of BoNT/D in Escherichia coli are presented. Using a codon-optimized cDNA, BoNT/D{_}HCR was expressed at a high level (150-200 mg per litre of culture) in the soluble fraction. Following a three-step purification protocol, very pure (>98%) BoNT/D{_}HCR was obtained. The recombinant BoNT/D{_}HCR was crystallized and the crystals diffracted to 1.65 {angstrom} resolution. The crystals belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 60.8,more » b = 89.7, c = 93.9 {angstrom}. Preliminary crystallographic data analysis revealed the presence of one molecule in the asymmetric unit.« less

High-level expression, purification, crystallization and preliminary X-ray crystallographic studies of the receptor-binding domain of botulinum neurotoxin serotype D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Y.; Robinson, H.; Gao, X.

2010-12-01

Botulinum neurotoxins (BoNTs) are highly toxic proteins for humans and animals that are responsible for the deadly neuroparalytic disease botulism. Here, details of the expression and purification of the receptor-binding domain (HCR) of BoNT/D in Escherichia coli are presented. Using a codon-optimized cDNA, BoNT/D{_}HCR was expressed at a high level (150-200 mg per litre of culture) in the soluble fraction. Following a three-step purification protocol, very pure (>98%) BoNT/D{_}HCR was obtained. The recombinant BoNT/D{_}HCR was crystallized and the crystals diffracted to 1.65 {angstrom} resolution. The crystals belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 60.8,more » b = 89.7, c = 93.9 {angstrom}. Preliminary crystallographic data analysis revealed the presence of one molecule in the asymmetric unit.« less

A novel single-phase white phosphor NaBaBO{sub 3}:Dy{sup 3+},K{sup +} for near-UV white light-emitting diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Jianghui; Cheng, Qijin; Wu, Jieyang

Highlights: • A white phosphor NaBaBO{sub 3}:Dy{sup 3+},K{sup +} with CIE coordinate (0.301, 0.308) was synthesized. • The optimum doping concentration of Dy{sup 3+} ions was found. • The effect and mechanism of K{sup +} ion as a charge compensator were discussed. • Temperature-dependent PL property of NaBaBO{sub 3}:Dy{sup 3+},K{sup +} was studied. • PL decay and quantum efficiency behaviors of the samples were investigated. - Abstract: A novel Dy{sup 3+}-doped NaBaBO{sub 3} white-emitting phosphor has been prepared by high temperature solid-state reaction method. The phase structure and luminescence properties of NaBaBO{sub 3}:Dy{sup 3+},K{sup +} samples were investigated. Photoluminescence resultsmore » show that the as-prepared samples could be effectively excited by near-ultraviolet (NUV) light and generate white light emission due to the {sup 4}F{sub 9/2} → {sup 6}H{sub 15/2} (blue) transition and {sup 4}F{sub 9/2} → {sup 6}H{sub 13/2} (yellow) transition of Dy{sup 3+} ions, respectively. The optimum doping concentration of Dy{sup 3+} ions in the NaBaBO{sub 3} host was determined to be 5.0 mol% and the CIE chromaticity of the sample was determined to be (0.301, 0.308). Moreover, the mechanism of K{sup +} ion as a charge compensator on the improvement of photoluminescence property and the effect of temperature on the photoluminescence property of NaBaBO{sub 3}:Dy{sup 3+},K{sup +} were investigated. Furthermore, photoluminescence decay and quantum efficiency behaviors of NaBaBO{sub 3}:Dy{sup 3+},K{sup +} were also studied. The present work demonstrates that the NaBaBO{sub 3}:Dy{sup 3+},K{sup +} phosphor is a potential candidate for NUV white light emitting diodes.« less

Novel Small-Molecule Antibacterial Agents

DTIC Science & Technology

2014-07-01

post-exposure protection of mice against 5 LD50 BoNTA. HAB also showed significant 4-hour-post-exposure protection of zebrafish against 5 LD50 BoNTA...protection of mice against 5 LD50 BoNTA. HAB also showed significant 4-hour-post-exposure protection of zebrafish against 5 LD50 BoNTA. Our kinetics...significant 4-hour-post-exposure protection of zebrafish against 5 LD50 BoNTA. Our kinetics and affinity analyses using the surface plasmon resonance

Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, Shenyan; Rumpel, Sophie; Zhou, Jie

2012-03-28

Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it uponmore » entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.« less

Effect of the tetrahedral groups on the optical properties of LaBRO{sub 5} (R = Si and Ge): A first-principles study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Linping; School of Physics Science and Technology, Xinjiang University, Urumqi 830046; Jing, Qun

2015-09-21

As potential candidates for deep-UV nonlinear optical (NLO) crystals, borosilicates and borogermanates, which contain NLO-active groups such as B-O, Si-O, and Ge-O groups, have fascinated many material scientists' research enthusiasm. In this paper, the electronic structures and optical properties of two isostructural noncentrosymmetric crystals LaBRO{sub 5} (R = Si and Ge) have been studied by the first-principles method. Combined with the analyses of the SHG-density and the localized electron-density difference, contributions of the constituent tetrahedra to the total NLO responses are investigated. Eventually, BO{sub 4} and GeO{sub 4} groups give nearly equal contributions to the SHG effect of LaBGeO{sub 5}, but formore » LaBSiO{sub 5}, SiO{sub 4} groups express stronger SHG response than that of BO{sub 4}. Such interesting conclusion is consistent with the distortion index analyses and dipole moment.« less

Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin.

PubMed

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M; Das, Samir; Nag, Arundhati; Agnew, Heather D; Heath, James R

2015-06-08

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Raman Spectroscopic Study of Kernite to 25 GPa

NASA Astrophysics Data System (ADS)

Silva, M. E.; O'Bannon, E. F., III; Williams, Q. C.

2015-12-01

A Raman spectroscopic study of kernite to 25 GPaMarcus Silva, Earl O'Bannon III, and Quentin Williams Department of Earth & Planetary Sciences, University of California Santa Cruz The Raman spectrum of kernite (Na2B4O6(OH)2·3(H2O)) has been characterized up to ~25 GPa in order to explore pressure-induced changes in a structurally novel mineral that contains mixed coordination borate groups (three- and four-fold), and both hydroxyl units and water. During compression, all of the ~30 modes monitored shift positively and monotonically until ~2.2 GPa where a few low frequency modes disappear and tetrahedral borate modes merge. The low frequency modes that disappear at ~2.2 GPa are likely associated with Na vibrations, and their disappearance suggests that dramatic changes occur in the Na sites at ~2.2 GPa. The merging of the boron bending and stretching modes at ~2.2 GPa suggests that the local symmetry of the BO4 tetrahedra changes at this pressure, and likely becomes more symmetric. The remaining modes shift positively up to ~7.4 GPa where a second notable change occurs. All but 5 modes (with initial frequencies of 150, 166, 289, 307, and 525 cm-1) disappear at ~7.4 GPa. This indicates that a second phase transition has occurred which affects both the BO3H and BO4­ groups: based on the loss of modes, this transition may be associated with disordering of the crystal. These 5 modes persist and shift monotonically up to ~25 GPa. On decompression, the 5 modes shift smoothly down to ~2.0 GPa where a few new modes appear in the spectrum. When fully decompressed to room pressure, the Raman spectrum of the recovered sample is significantly different from the ambient spectrum of the initial sample. Thus, our results are suggest a phase transition occurring at 2.2 GPa with changes in the Na and tetrahedral boron sites, followed by an additional transition at 7.4 GPa that may involve disordering of the crystal. In the latter transition, at least the BO3H groups appear to be destabilized, implying that the three-fold coordination of boron groups is, in contrast to the case of carbon, unstable in crystalline phases at relatively modest pressure conditions.

Bovine herpes virus-1 (BoHV-1) in cattle–a review with emphasis on reproductive impacts and the emergence of infection in Ireland and the United Kingdom

PubMed Central

2013-01-01

Bovine reproductive disease attributable to bovine herpes virus-1 (BoHV-1) was first described in Germany in the 19th century, being recognised primarily as the cause of infectious vulvovaginitis and balanoposthitis until the mid-1950s when a more virulent strain of the virus (BoHV-1.1) associated with respiratory disease (infectious bovine rhinotracheitis; IBR) emerged in the western United States. Subsequently, IBR emerged as a clinical condition in Europe, from the 1970s onward. While the ability of BoHV-1 to produce respiratory disease is now well recognised, the potential negative outcomes of infection on fertility and reproduction are less frequently considered. This review was conducted against the background of the prioritization of disease caused by BoHV-1 as one of several diseases to be addressed by Animal Health Ireland, with the twin goals of summarizing the published literature on the potential outcomes of infection at different stages of breeding and pregnancy, and of describing the emergence of BoHV-1 as a significant pathogen in Ireland and the UK. PMID:23916092

Influence of Li3BO3 additives on the Li+ conductivity and stability of Ca/Ta-substituted Li6.55(La2.95Ca0.05)(Zr1.5Ta0.5)O12 electrolytes

NASA Astrophysics Data System (ADS)

Zhang, L. C.; Yang, J. F.; Gao, Y. X.; Wang, X. P.; Fang, Q. F.; Chen, C. H.

2017-07-01

The cubic Ca/Ta-substituted Li6.55(La2.95Ca0.05)(Zr1.5Ta0.5)O12 (LLCZTO) electrolytes were synthesized at 800 °C with Li3BO3 as additives. The optimal amount of Li3BO3 and its influences on the microstructure, crystal structures, Li+ conductivity and the stability of the Li6.55(La2.95Ca0.05)(Zr1.5Ta0.5)O12 were studied by SEM, XRD and EIS. Among all the samples, when the molar ratio of Li3BO3 to the Li6.55(La2.95Ca0.05)(Zr1.5Ta0.5)O12 is 4:5, the highest Li+ conductivity of 1.33 × 10-4 S cm-1 at 30 °C is obtained. When the LLCZTO samples are exposed in air, the Li+ conductivity is deteriorated possibly owing to the side reactions between the LLCZTO and the H2O or CO2 in the air. The Li3BO3 addition can alleviate such deterioration of the Li+ conductivity.

Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A

NASA Astrophysics Data System (ADS)

Benoit, Roger M.; Frey, Daniel; Hilbert, Manuel; Kevenaar, Josta T.; Wieser, Mara M.; Stirnimann, Christian U.; McMillan, David; Ceska, Tom; Lebon, Florence; Jaussi, Rolf; Steinmetz, Michel O.; Schertler, Gebhard F. X.; Hoogenraad, Casper C.; Capitani, Guido; Kammerer, Richard A.

2014-01-01

Botulinum neurotoxin A (BoNT/A) belongs to the most dangerous class of bioweapons. Despite this, BoNT/A is used to treat a wide range of common medical conditions such as migraines and a variety of ocular motility and movement disorders. BoNT/A is probably best known for its use as an antiwrinkle agent in cosmetic applications (including Botox and Dysport). BoNT/A application causes long-lasting flaccid paralysis of muscles through inhibiting the release of the neurotransmitter acetylcholine by cleaving synaptosomal-associated protein 25 (SNAP-25) within presynaptic nerve terminals. Two types of BoNT/A receptor have been identified, both of which are required for BoNT/A toxicity and are therefore likely to cooperate with each other: gangliosides and members of the synaptic vesicle glycoprotein 2 (SV2) family, which are putative transporter proteins that are predicted to have 12 transmembrane domains, associate with the receptor-binding domain of the toxin. Recently, fibroblast growth factor receptor 3 (FGFR3) has also been reported to be a potential BoNT/A receptor. In SV2 proteins, the BoNT/A-binding site has been mapped to the luminal domain, but the molecular details of the interaction between BoNT/A and SV2 are unknown. Here we determined the high-resolution crystal structure of the BoNT/A receptor-binding domain (BoNT/A-RBD) in complex with the SV2C luminal domain (SV2C-LD). SV2C-LD consists of a right-handed, quadrilateral β-helix that associates with BoNT/A-RBD mainly through backbone-to-backbone interactions at open β-strand edges, in a manner that resembles the inter-strand interactions in amyloid structures. Competition experiments identified a peptide that inhibits the formation of the complex. Our findings provide a strong platform for the development of novel antitoxin agents and for the rational design of BoNT/A variants with improved therapeutic properties.

4-Amino-7-chloroquinolines: probing ligand efficiency provides botulinum neurotoxin serotype A light chain inhibitors with significant antiprotozoal activity

PubMed Central

Opsenica, Igor M.; Tot, Mikloš; Gomba, Laura; Nuss, Jonathan E.; Sciotti, Richard J.; Bavari, Sina; Burnett, James C.; Šolaja, Bogdan A.

2013-01-01

Structurally simplified analogs of dual antimalarial and botulinum neurotoxin serotype A light chain (BoNT/A LC) inhibitor bis-aminoquinoline (1) were prepared. New compounds were designed to improve ligand efficiency while maintaining or exceeding the inhibitory potency of 1. Three of the new compounds are more active than 1 against both indications. Metabolically, the new inhibitors are relatively stable and non-toxic. Twelve, 14, and 15 are more potent BoNT/A LC inhibitors than 1. Additionally, 15 has excellent in vitro antimalarial efficacy, with IC90 values ranging from 4.45-12.11 nM against five Plasmodium falciparum (P.f.) strains: W2, D6, C235, C2A, C2B. The results indicate that the same level of inhibitory efficacy provided by 1 can be retained/exceeded with less structural complexity. Twelve, 14, and 15 provide new platforms for the development of more potent dual BoNT/A LC and P.f. inhibitors adhering to generally accepted chemical properties associated with the druggability of synthetic molecules. PMID:23815186

Crystal structure, phase transition and structural deformations in iron borate (Y0.95Bi0.05)Fe3(BO3)4 in the temperature range 90-500 K.

PubMed

Smirnova, Ekaterina S; Alekseeva, Olga A; Dudka, Alexander P; Artemov, Vladimir V; Zubavichus, Yan V; Gudim, Irina A; Bezmaterhykh, Leonard N; Frolov, Kirill V; Lyubutin, Igor S

2018-04-01

An accurate X-ray diffraction study of (Y 0.95 Bi 0.05 )Fe 3 (BO 3 ) 4 single crystals in the temperature range 90-500 K was performed on a laboratory diffractometer and used synchrotron radiation. It was established that the crystal undergoes a diffuse structural phase transition in the temperature range 350-380 K. The complexity of localization of such a transition over temperature was overcome by means of special analysis of systematic extinction reflections by symmetry. The transition temperature can be considered to be T str ≃ 370 K. The crystal has a trigonal structure in the space group P3 1 21 at temperatures of 90-370 K, and it has a trigonal structure in the space group R32 at 375-500 K. There is one type of chain formed by the FeO 6 octahedra along the c axis in the R32 phase. When going into the P3 1 21 phase, two types of nonequivalent chains arise, in which Fe atoms are separated from the Y atoms by a different distance. Upon lowering the temperature from 500 to 90 K, a distortion of the Y(Bi)O 6 , FeO 6 , B(2,3)O 3 coordination polyhedra is observed. The distances between atoms in helical Fe chains and Fe-O-Fe angles change non-uniformly. A sharp jump in the equivalent isotropic displacement parameters of O1 and O2 atoms within the Fe-Fe chains and fluctuations of the equivalent isotropic displacement parameters of B2 and B3 atoms were observed in the region of structural transition as well as noticeable elongation of O1, O2, B2, B3, Fe1, Fe2 atomic displacement ellipsoids. It was established that the helices of electron density formed by Fe, O1 and O2 atoms may be structural elements determining chirality, optical activity and multiferroicity of rare-earth iron borates. Compression and stretching of these helices account for the symmetry change and for the manifestation of a number of properties, whose geometry is controlled by an indirect exchange interaction between iron cations that compete with the thermal motion of atoms in the structure. Structural analysis detected these changes as variations of a number of structural characteristics in the c unit-cell direction, that is, the direction of the helices. Structural results for the local surrounding of the atoms in (Y 0.95 Bi 0.05 )Fe 3 (BO 3 ) 4 were confirmed by EXAFS and Mössbauer spectroscopies.

Bovine herpesvirus 1 abortion: current prevalence in the United Kingdom and evidence of hematogenous spread within the fetus in natural cases.

PubMed

Crook, Tara; Benavides, Julio; Russell, George; Gilray, Janice; Maley, Maddy; Willoughby, Kim

2012-07-01

While Bovine herpesvirus 1 (BoHV-1) has been known as a cause of bovine abortion for nearly 50 years, information is limited on the current prevalence of BoHV-1 abortion in the United Kingdom, or about the mode of virus dissemination to cause infection of the fetus. The present study aimed to investigate these issues by surveying the prevalence of BoHV-1 in abortion cases in the United Kingdom, and comparing diagnostic methods to determine which are most efficient in BoHV-1-induced abortion. Where BoHV-1 DNA was detected, viral load was compared in fetal tissues, using real-time polymerase chain reaction (PCR), supported by histopathology and immunohistochemistry (IHC) to investigate virus dissemination in bovine abortions. A total of 400 U.K. bovine abortion cases were studied; PCR detected BoHV-1 nucleic acids in 10 cases, suggestive histopathological lesions were observed in 8, and positive IHC staining was observed in 9. In routine diagnosis, BoHV-1 was identified in 2 of these cases, highlighting the utility of using molecular diagnostic tests such as real-time PCR to achieve high sensitivity in potentially autolyzed tissues. The study of different fetal samples showed the highest viral load in the liver, along with severe multifocal necrotic hepatitis, suggesting either a clear tropism of the virus for this organ or that it is the first location to be reached in the fetus. Presence of viral antigen in endothelial cells of the placenta, brain, or heart suggest a hematogenous spread of virus from placenta to the liver, through the umbilical vein, and then to the rest of the organs via fetal blood vessels.

Fabrication of a Novel Highly Sensitive and Selective Immunosensor for Botulinum Neurotoxin Serotype A Based on an Effective Platform of Electrosynthesized Gold Nanodendrites/Chitosan Nanoparticles.

PubMed

Sorouri, Rahim; Bagheri, Hasan; Afkhami, Abbas; Salimian, Jafar

2017-05-09

In this work, a novel nanocomposite consisting of electrosynthesized gold nanodendrites and chitosan nanoparticles (AuNDs/CSNPs) has been prepared to fabricate an impedimetric immunosensor based on a screen printed carbon electrode (SPCE) for the rapid and sensitive immunoassay of botulinum neurotoxin A (BoNT/A). BoNT/A polyclonal antibody was immobilized on the nanocomposite-modified SPCE for the signal amplification. The structure of the prepared nanocomposite was investigated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The charge transfer resistance (R CT ) changes were used to detect BoNT/A as the specific immuno-interactions at the immunosensor surface that efficiently limited the electron transfer of Fe(CN)₆ 3-/4- as a redox probe at pH = 7.4. A linear relationship was observed between the %∆ R CT and the concentration logarithm of BoNT/A within the range of 0.2 to 230 pg·mL -1 with a detection limit (S/N = 3) of 0.15 pg·mL -1 . The practical applicability of the proposed sensor was examined by evaluating the detection of BoNT/A in milk and serum samples with satisfactory recoveries. Therefore, the prepared immunosensor holds great promise for the fast, simple and sensitive detection of BoNT/A in various real samples.

Fabrication of a Novel Highly Sensitive and Selective Immunosensor for Botulinum Neurotoxin Serotype A Based on an Effective Platform of Electrosynthesized Gold Nanodendrites/Chitosan Nanoparticles

PubMed Central

Sorouri, Rahim; Bagheri, Hasan; Afkhami, Abbas; Salimian, Jafar

2017-01-01

In this work, a novel nanocomposite consisting of electrosynthesized gold nanodendrites and chitosan nanoparticles (AuNDs/CSNPs) has been prepared to fabricate an impedimetric immunosensor based on a screen printed carbon electrode (SPCE) for the rapid and sensitive immunoassay of botulinum neurotoxin A (BoNT/A). BoNT/A polyclonal antibody was immobilized on the nanocomposite-modified SPCE for the signal amplification. The structure of the prepared nanocomposite was investigated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The charge transfer resistance (RCT) changes were used to detect BoNT/A as the specific immuno-interactions at the immunosensor surface that efficiently limited the electron transfer of Fe(CN)63−/4− as a redox probe at pH = 7.4. A linear relationship was observed between the %∆RCT and the concentration logarithm of BoNT/A within the range of 0.2 to 230 pg·mL−1 with a detection limit (S/N = 3) of 0.15 pg·mL−1. The practical applicability of the proposed sensor was examined by evaluating the detection of BoNT/A in milk and serum samples with satisfactory recoveries. Therefore, the prepared immunosensor holds great promise for the fast, simple and sensitive detection of BoNT/A in various real samples. PMID:28486408

Structural Studies on Intact Clostridium botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design

DTIC Science & Technology

2009-02-01

compounds via virtual screening. These compounds include small molecules – transition state analogues and benzimidazoles . Since there is a commonality in...Crystal structure of BoNT/E has been determined helping us to understand the faster action of BoNT/E compared to BoNT/A. • A subset of benzimidazole

Lead apatites: structural variations among Pb 5( BO 4) 3 Cl with B = P (pyromorphite), As (mimetite) and V (vanadinite)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antao, Sytle M.; Dhaliwal, Inayat

The crystal structure of four Pb apatite samples, Pb 5(BO 4) 3Cl, was refined with synchrotron high-resolution powder X-ray diffraction data, Rietveld refinements, space groupP6 3/mandZ= 2. For this isotypic series,B= P 5+ is pyromorphite,B= As 5+is mimetite andB= V 5+is vanadinite. The ionic radius for As 5+(0.355 Å) is similar to that of V 5+(0.335 Å), and this is twice as large as that for P 5+(0.170 Å). However, thecunit-cell parameter for mimetite is surprisingly different from that of vanadinite, although their unit-cell volumes,V, are almost equal to each other. No explanation was available for this peculiarc-axis value for mimetite. Structural parameters such as averagemore » $$\\langle$$B—O$$\\rangle$$ [4], $$\\langle$$Pb1—O 9$$\\rangle$$ [9] and $$\\langle$$Pb2—O 6Cl 2$$\\rangle$$ [8] distances increase linearly withV (the coordination numbers for the cations are given in square brackets). Mimetite has a short Pb2—O1 distance, so the O1 oxygen atom interacts with the 6s 2lone-pair electrons of the Pb 2+ cation that causes the Cl—Cl distance (=c/2) to increase to the largest value in the series because of repulsion, which causes thec-axis to increase anomalously. Although Pb apatite minerals occur naturally in ore deposits, they are also formed as scaly deposits in lead water pipes that give rise to lead in tap water, as was found recently in Flint, Michigan, USA. It is important to identify Pb-containing phases in water-pipe deposits.« less

Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A.

PubMed

Masuyer, Geoffrey; Thiyagarajan, Nethaji; James, Peter L; Marks, Philip M H; Chaddock, John A; Acharya, K Ravi

2009-03-27

Botulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.

NEUTRON SHIELDING STRUCTURE

DOEpatents

Mattingly, J.T.

1962-09-25

A lightweight neutron shielding structure comprises a honeycomb core which is filled with a neutron absorbing powder. The honeycomb core is faced with parallel planar facing sheets to form a lightweight rigid unit. Suitable absorber powders are selected from among the following: B, B/sub 4/C, B/sub 2/O/ sub 3/, CaB/sub 6/, Li/sub 2/CO3, LiOH, LiBO/sub 2/, Li/s ub 2/O. The facing sheets are constructed of a neutron moderating material, so that fast neutrons will be moderated while traversing the facing sheets, and ultimately be absorbed by the absorber powder in the honeycomb. Beryllium is a preferred moderator material for use in the facing sheets. The advantage of the structure is that it combines the rigidity and light weight of a honeycomb construction with the neutron absorption properties of boron and lithium. (AEC)

Functional, textural and sensory properties of dry pasta supplemented with lyophilized tomato matrix or with durum wheat bran extracts produced by supercritical carbon dioxide or ultrasound.

PubMed

Pasqualone, Antonella; Gambacorta, Giuseppe; Summo, Carmine; Caponio, Francesco; Di Miceli, Giuseppe; Flagella, Zina; Marrese, Pier Paolo; Piro, Gabriella; Perrotta, Carla; De Bellis, Luigi; Lenucci, Marcello Salvatore

2016-12-15

A study was carried out to produce functional pasta by adding bran aqueous extract (BW) and bran oleoresin (BO) obtained using ultrasound and supercritical CO2, respectively, or a powdery lyophilized tomato matrix (LT). The bioactive compounds, hydrophilic and lipophilic antioxidant activity (HAA and LAA) in vitro, were evaluated. BW supplementation did not improve antioxidant activity, whilst LT pasta showed unconventional taste and odor. BO pasta had good levels of tocochromanols (2551μg/100g pasta f.w.) and carotenoids (40.2μg/100g pasta f.w.), and the highest HAA and LAA. The oleoresin altered starch swelling and gluten network, as evidenced by scanning electron microscopy, therefore BO pasta had structural characteristics poor compared with the control (4.8% vs. 3.2% cooking loss), although this difference did not affect significantly overall sensory judgment (74 vs. 79 for BO and control, respectively). BO supplementation was most effective for increasing antioxidant activity without jeopardizing pasta quality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Crystal structure and magnetic properties of Mn substituted ludwigite Co 3O 2BO 3

NASA Astrophysics Data System (ADS)

Knyazev, Yu. V.; Ivanova, N. B.; Kazak, N. V.; Platunov, M. S.; Bezmaternykh, L. N.; Velikanov, D. А.; Vasiliev, А. D.; Ovchinnikov, S. G.; Yurkin, G. Yu.

2012-03-01

The needle shape single crystals Co3-x MnxO2BO3 with ludwigite structure have been prepared. According to the X-ray diffraction data the preferable character of distinct crystallographic positions occupation by Mn ions is established. Magnetization field and temperature dependencies are measured. Paramagnetic Curie temperature value Θ=-100 K points out the predominance of antiferromagnetic interactions. Spin-glass magnetic ordering takes the onset at TN=41 K. The crystallographic and magnetic properties of Co3O2BO3:Mn are compared with the same for the isostructural analogs Co3O2BO3 and CoO2BO3:Fe.

BoS: a large and diverse family of short interspersed elements (SINEs) in Brassica oleracea.

PubMed

Zhang, Xiaoyu; Wessler, Susan R

2005-05-01

Short interspersed elements (SINEs) are nonautonomous non-LTR retrotransposons that populate eukaryotic genomes. Numerous SINE families have been identified in animals, whereas only a few have been described in plants. Here we describe a new family of SINEs, named BoS, that is widespread in Brassicaceae and present at approximately 2000 copies in Brassica oleracea. In addition to sharing a modular structure and target site preference with previously described SINEs, BoS elements have several unusual features. First, the head regions of BoS RNAs can adopt a distinct hairpin-like secondary structure. Second, with 15 distinct subfamilies, BoS represents one of the most diverse SINE families described to date. Third, several of the subfamilies have a mosaic structure that has arisen through the exchange of sequences between existing subfamilies, possibly during retrotransposition. Analysis of BoS subfamilies indicate that they were active during various time periods through the evolution of Brassicaceae and that active elements may still reside in some Brassica species. As such, BoS elements may be a valuable tool as phylogenetic makers for resolving outstanding issues in the evolution of species in the Brassicaceae family.

Understanding peptide competitive inhibition of botulinum neurotoxin A binding to SV2 protein via molecular dynamics simulations.

PubMed

Chang, Shan; He, Hong-Qiu; Shen, Lin; Wan, Hua

2015-10-01

Botulinum neurotoxins (BoNTs) are known as the most toxic natural substances. Synaptic vesicle protein 2 (SV2) has been proposed to be a protein receptor for BoNT/A. Recently, two short peptides (BoNT/A-A2 and SV2C-A3) were designed to inhibit complex formation between the BoNT/A receptor-binding domain (BoNT/A-RBD) and the synaptic vesicle protein 2C luminal domain (SV2C-LD). In this article, the two peptide complex systems are studied by molecular dynamics (MD) simulations. The structural stability analysis indicates that BoNT/A-A2 system is more stable than SV2C-A3 system. The conformational analysis implies that the β-sheet in BoNT/A-A2 system maintains its secondary structure but the two β-strands in SV2C-A3 system have remarkable conformational changes. Based on the calculation of hydrogen bonds, hydrophobic interactions and cation-π interactions, it is found that the internal hydrogen bonds play crucial roles in the structural stability of the peptides. Because of the stable secondary structure, the β-sheet in BoNT/A-A2 system establishes effective interactions at the interface and inhibits BoNT/A-RBD binding to SV2C-LD. In contrast, without other β-strands forming internal hydrogen bonds, the two isolated β-strands in SV2C-A3 system become the random coil. This conformational change breaks important hydrogen bonds and weakens cation-π interaction in the interface, so the complex formation is only partially inhibited by the two β-strands. These results are consistent with experimental studies and may be helpful in understanding the inhibition mechanisms of peptide inhibitors. © 2015 Wiley Periodicals, Inc.

δ18O and salinity variability from the Last Glacial Maximum to Recent in the Bay of Bengal and Andaman Sea

NASA Astrophysics Data System (ADS)

Sijinkumar, A. V.; Clemens, Steven; Nath, B. Nagender; Prell, Warren; Benshila, Rachid; Lengaigne, Matthieu

2016-03-01

Oxygen isotopes of surface, thermocline and bottom dwelling foraminifera were analysed from two well-dated Andaman Sea cores and combined with nine previously published records from the Bay of Bengal (BoB) and Andaman Sea to create a transect spanning 20°N to 5°N. Combined with temperature estimates and the observed seawater δ18O-salinity relationship, these data are used to estimate past changes in BoB salinity structure. Compared to modern, mid-Holocene (9-6 cal ka BP) surface waters in the northern BoB were 2.5 psμ (8%) fresher, Andaman Sea were 3.8 psμ (12%) fresher, and southern BoB were 1.2 psμ (3.5%) fresher. Conversely, during the last glacial maximum (LGM), surface waters in the northern BoB were 2.9 psμ (9%) more saline while Andaman Sea were essentially unchanged and southern BoB were 1.7 psμ (4.9%) more saline compared to modern. The relative freshness of the Andaman during the last glacial maximum is likely the result of basin morphology during sea level low stand, resulting in reduced surface water mixing with the open BoB as well as shelf emergence, causing increased proximity of the core locations to river outflow. Sensitivity experiments using a regional ocean model indicate that the increased mid-Holocene north to south (20°N to 5°N) salinity gradient can be achieved with a ∼50% increase in precipitation/runoff while the decreased glacial age gradient can be achieved with a ∼50% reduction in precipitation/runoff. During the deglaciation, both surface and thermocline-dwelling species in the Andaman and northern BoB exhibit depleted δ18O within the Younger Dryas (YD), indicating colder and/or more saline conditions. None of the records from the southern BoB site have clear YD structure, possibly due to the combined effects of bioturbation and low sedimentation rates.

Molecular Characterization of the First Bovine Herpesvirus 4 (BoHV-4) Strains Isolated from In Vitro Bovine Embryos production in Argentina.

PubMed

González Altamiranda, Erika; Manrique, Julieta M; Pérez, Sandra E; Ríos, Glenda L; Odeón, Anselmo C; Leunda, María R; Jones, Leandro R; Verna, Andrea

2015-01-01

Bovine herpesvirus 4 (BoHV-4) is increasingly considered as responsible for various problems of the reproductive tract. The virus infects mainly blood mononuclear cells and displays specific tropism for vascular endothelia, reproductive and fetal tissues. Epidemiological studies suggest its impact on reproductive performance, and its presence in various sites in the reproductive tract highlights its potential transmission in transfer-stage embryos. This work describes the biological and genetic characterization of BoHV-4 strains isolated from an in vitro bovine embryo production system. BoHV-4 strains were isolated in 2011 and 2013 from granulosa cells and bovine oocytes from ovary batches collected at a local abattoir, used as "starting material" for in vitro production of bovine embryos. Compatible BoHV-4-CPE was observed in the co-culture of granulosa cells and oocytes with MDBK cells. The identity of the isolates was confirmed by PCR assays targeting three ORFs of the viral genome. The phylogenetic analyses of the strains suggest that they were evolutionary unlinked. Therefore it is possible that BoHV-4 ovary infections occurred regularly along the evolution of the virus, at least in Argentina, which can have implications in the systems of in vitro embryo production. Thus, although BoHV-4 does not appear to be a frequent risk factor for in vitro embryo production, data are still limited. This study reveals the potential of BoHV-4 transmission via embryo transfer. Moreover, the high variability among the BoHV-4 strains isolated from aborted cows in Argentina highlights the importance of further research on the role of this virus as an agent with the potential to cause reproductive disease in cattle. The genetic characterization of the isolated strains provides data to better understand the pathogenesis of BoHV-4 infections. Furthermore, it will lead to fundamental insights into the molecular aspects of the virus and the means by which these strains circulate in the herds.

Identification of a Unique Ganglioside Binding Loop within Botulinum Neurotoxins C and D-SA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karalewitz, Andrew P.-A.; Kroken, Abby R.; Fu, Zhuji

2010-09-22

The botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. There are seven serotypes of BoNTs (A-G) based on a lack of cross antiserum neutralization. BoNTs utilize gangliosides as components of the host receptors for binding and entry into neurons. Members of BoNT/C and BoNT/D serotypes include mosaic toxins that are organized in D/C and C/D toxins. One D/C mosaic toxin, BoNT/D-South Africa (BoNT/D-SA), was not fully neutralized by immunization with BoNT serotype C or D, which stimulated this study. Here the crystal structures of the receptor binding domains of BoNT/C, BoNT/D, and BoNT/D-SA are presented. Biochemical andmore » cell binding studies show that BoNT/C and BoNT/D-SA possess unique mechanisms for ganglioside binding. These studies provide new information about how the BoNTs can enter host cells as well as a basis for understanding the immunological diversity of these neurotoxins.« less

Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

PubMed

Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

2014-04-01

Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

The role of boric acid in the synthesis of Eni Carbon Silicates.

PubMed

Zanardi, Stefano; Bellussi, Giuseppe; Parker, Wallace O'Neil; Montanari, Erica; Bellettato, Michela; Cruciani, Giuseppe; Carati, Angela; Guidetti, Stefania; Rizzo, Caterina; Millini, Roberto

2014-07-21

The influence of H3BO3 on the crystallization of hybrid organic-inorganic aluminosilicates denoted as Eni Carbon Silicates (ECS's) was investigated. Syntheses were carried out at 100 °C under different experimental conditions, using bridged silsesquioxanes of general formula (EtO)3Si-R-Si(OEt)3 (R = -C6H4- (BTEB), -C10H6- (BTEN) and -C6H4-C6H4- (BTEBP)), in the presence of equimolar concentrations of NaAlO2 and H3BO3. The study, involving the synthesis of three different but structurally related phases (ECS-14 from BTEB, ECS-13 here described for the first time from BTEN, and ECS-5 from BTEBP), confirmed a catalytic role for H3BO3 which in general increased the crystallization rate and improved the product quality in terms of amount of crystallized phase (crystallinity), size of the crystallites and phase purity, while it was weakly incorporated in trace amounts in the framework of ECS's.

Clinical Protection of Goats against CpHV-1 Induced Genital Disease with a BoHV-4-Based Vector Expressing CpHV-1 gD

PubMed Central

Donofrio, Gaetano; Franceschi, Valentina; Lovero, Angela; Capocefalo, Antonio; Camero, Michele; Losurdo, Michele; Cavirani, Sandro; Marinaro, Mariarosaria; Grandolfo, Erika; Buonavoglia, Canio; Tempesta, Maria

2013-01-01

Caprine herpesvirus type 1 (CpHV-1) is an alphaherpesvirus causing genital disease leading to abortion in adult pregnant goats and a systemic disease with high morbility and mortality in kids. Further, Caprine herpesvirus 1 infection represents a valuable large animal model for human herpesvirus induced genital disease, exploitable for pathogenic studies, new vaccines and antiviral molecules testing. Here, the bovine herpesvirus 4 (BoHV-4) based vector derived from an apathogenic isolate of BoHV-4 and expressing the immunodominant CpHV-1 glycoprotein D (BoHV-4-A-gDcpgD106ΔTK) was constructed and its ability to protect goats against CpHV-1 induced genital disease evaluated. The subcutaneous route of recombinant BoHV-4 administration was first tested in vivo/ex vivo by in vivo image analysis and in vitro by goat skin primary cultures preparation and transduction. Next, an exploratory immunization and safety study in goats was performed with two recombinant BoHV4, BoHV-4-A-gDcpgD106ΔTK or BoHV-4-CMV-IgK-gE2gD-TM. In both cases no clinical signs were evident but a good titer of serum neutralizing antibodies was produced in all inoculated animals. When a challenge experiment was performed in a new group of animals using a highly pathogenic dose of CpHV-1, all the vaccinated goats with BoHV-4-A-gDcpgD106ΔTK were protected toward CpHV-1 induced genital disease respect to the unvaccinated control which showed typical vaginal lesions with a high grade of clinical score as well as a long lasting viral shedding. In summary, the data acquired in the present study validate BoHV-4-based vector as a safe and effective viral vector for goat vaccination against CpHV-1 induced genital disease and pave the way for further applications. PMID:23300989

Botulinum Neurotoxin Serotype A Recognizes Its Protein Receptor SV2 by a Different Mechanism than Botulinum Neurotoxin B Synaptotagmin

PubMed Central

Weisemann, Jasmin; Stern, Daniel; Mahrhold, Stefan; Dorner, Brigitte G.; Rummel, Andreas

2016-01-01

Botulinum neurotoxins (BoNTs) exhibit extraordinary potency due to their exquisite neurospecificity, which is achieved by dual binding to complex polysialo-gangliosides and synaptic vesicle proteins. The luminal domain 4 (LD4) of the three synaptic vesicle glycoprotein 2 isoforms, SV2A‐C, identified as protein receptors for the most relevant serotype BoNT/A, binds within the 50 kDa cell binding domain HC of BoNT/A. Here, we deciphered the BoNT/A‐SV2 interactions in more detail. In pull down assays, the binding of HCA to SV2-LD4 isoforms decreases from SV2C >> SV2A > SV2B. A binding constant of 200 nM was determined for BoNT/A to rat SV2C-LD4 in GST pull down assay. A similar binding constant was determined by surface plasmon resonance for HCA to rat SV2C and to human SV2C, the latter being slightly lower due to the substitution L563F in LD4. At pH 5, as measured in acidic synaptic vesicles, the binding constant of HCA to hSV2C is increased more than 10-fold. Circular dichroism spectroscopy reveals that the quadrilateral helix of SV2C-LD4 already exists in solution prior to BoNT/A binding. Hence, the BoNT/A‐SV2C interaction is of different nature compared to BoNT/B‐Syt-II. In particular, the preexistence of the quadrilateral β-sheet helix of SV2 and its pH-dependent binding to BoNT/A via backbone–backbone interactions constitute major differences. Knowledge of the molecular details of BoNT/A‐SV2 interactions drives the development of high affinity peptides to counteract BoNT/A intoxications or to capture functional BoNT/A variants in innovative detection systems for botulism diagnostic. PMID:27196927

Effect of Fe-substitution on the structure and magnetism of single crystals Mn2-xFexBO4

NASA Astrophysics Data System (ADS)

Platunov, M. S.; Kazak, N. V.; Knyazev, Yu. V.; Bezmaternykh, L. N.; Moshkina, E. M.; Trigub, A. L.; Veligzhanin, A. A.; Zubavichus, Y. V.; Solovyov, L. A.; Velikanov, D. A.; Ovchinnikov, S. G.

2017-10-01

Single crystalline Mn2-xFexBO4 with x = 0.3, 0.5, 0.7 grown by the flux method have been studied by means of X-ray diffraction and X-ray absorption spectroscopy at both Mn and Fe K edges. The compounds were found to crystallize in an orthorhombic warwickite structure (sp. gr. Pnam). The lattice parameters change linearly with x thus obeying the Vegard's law. The Fe3+ substitution for Mn3+ has been deduced from the X-ray absorption near-edge structure (XANES) spectra. Two energy positions of the absorption edges have been observed in Mn K-edge XANES spectra indicating the presence of manganese in two different oxidation states. Extended X-ray absorption fine structure (EXAFS) analysis has shown the reduction of local structural distortions upon Fe substitution. The magnetization data have revealed a spin-glass transition at TSG = 11, 14 and 18 K for x = 0.3, 0.5 and 0.7, respectively.

AbobotulinumtoxinA: A 25-Year History

PubMed Central

Pickett, Andy

2017-01-01

Abstract During the late 1960s and early 1970s, Alan Scott showed that intramuscular injections of botulinum toxin (BoNT) corrected nonaccommodative strabismus without resorting to surgery. The UK doctors who trained with Scott soon realized the significant potential offered by BoNT type A as a therapeutic option for several difficult-to-treat diseases. This led to a collaboration between these pioneering clinicians and the Centre for Applied Microbiology and Research at Porton Down, United Kingdom, and, in turn, to the development and commercialization of abobotulinumtoxinA as Dysport (Dystonia/Porton Down; Ipsen Biopharm Ltd., Wrexham, UK). Dysport was approved in Europe for the treatment of specific dystonias in December 1990 and now has marketing authorizations in 75 countries. Since then, the use of BoNT in therapeutic and aesthetic indications has grown year-on-year, and continues to expand well beyond Scott’s initial aim. For example, ongoing trials are assessing potential new indications for BoNT-A, including acne and psoriasis. Furthermore, a growing number of other BoNT products, often termed “biosimilars,” together with innovative formulations of well-established BoNT types, are likely to reach the market over the next few years. This review focuses on the history of Dysport to mark the 25th anniversary of its first launch in the United Kingdom. PMID:28388718

The interaction between cations and anionic groups inducing SHG enhancement in a series of apatite-like crystals: A first-principles study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jing, Qun; University of Chinese Academy of Sciences, Beijing 100049; Department of Physics, School of Science, Shihezi University, Shihezi 832000

2014-11-15

It is an interesting topic to reveal the origin of the SHG intensity enhancement after substitution from alkali and alkali-earth metal atoms to cadmium in a series of apatite-like borates KSr{sub 4}(BO{sub 3}){sub 3}, Ca{sub 5}(BO{sub 3}){sub 3}F, Cd{sub 5}(BO{sub 3}){sub 3}F. Combined with the first-principles method, SHG-density method and real-space atom-cutting method, the electronic structure, the optical properties and the contribution of respective ion and ion groups have been investigated. Second harmonic generation (SHG) responses are mainly attributed to BO{sub 3} groups with π conjugated configuration and their alignment framework. The contributions of A site are more important inmore » CaBOF and CdBOF compounds than in KSrBO. It is also demonstrated that the strong covalent interactions between the boron–oxygen groups and the cadmium atoms contribute the enhancement of SHG responses after substitution from alkali and alkali-earth metal atoms. - graphical abstract: Combined with the first-principles method, SHG-density method and real-space atom-cutting method, the enhancement of SHG response are attributed to the interaction between cadmium and BO{sub 3} groups. - Highlights: • SHG response on a series of apatite-like borates was studied by a SHG-density method. • SHG responses are mainly attributed to BO{sub 3} groups and their alignment framework. • The contributions of A site are more important in CaBOF and CdBOF than in KSrBO. • Covalent interaction between BO and Cd is responsible for SHG of CdBOF.« less

Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kroken, Abby R.; Karalewitz, Andrew P.-A.; Fu, Zhuji

2012-02-07

Botulinum Neurotoxins (BoNTs) are organized into seven serotypes, A-G. Although several BoNT serotypes enter neurons through synaptic vesicle cycling utilizing dual receptors (a ganglioside and a synaptic vesicle-associated protein), the entry pathway of BoNT/D is less well understood. Although BoNT/D entry is ganglioside-dependent, alignment and structural studies show that BoNT/D lacks key residues within a conserved ganglioside binding pocket that are present in BoNT serotypes A, B, E, F, and G, which indicate that BoNT/D-ganglioside interactions may be unique. In this study BoNT/D is shown to have a unique association with ganglioside relative to the other BoNT serotypes, utilizing amore » ganglioside binding loop (GBL, residues Tyr-1235-Ala-1245) within the receptor binding domain of BoNT/D (HCR/D) via b-series gangliosides, including GT1b, GD1b, and GD2. HCR/D bound gangliosides and entered neurons dependent upon the aromatic ring of Phe-1240 within the GBL. This is the first BoNT-ganglioside interaction that is mediated by a phenylalanine. In contrast, Trp-1238, located near the N terminus of the ganglioside binding loop, was mostly solvent-inaccessible and appeared to contribute to maintaining the loop structure. BoNT/D entry and intoxication were enhanced by membrane depolarization via synaptic vesicle cycling, where HCR/D colocalized with synaptophysin, a synaptic vesicle marker, but immunoprecipitation experiments did not detect direct association with synaptic vesicle protein 2. Thus, BoNT/D utilizes unique associations with gangliosides and synaptic vesicles to enter neurons, which may facilitate new neurotoxin therapies.« less

Properties of blue emitting CaAl2O4:Eu2+, Nd3+ phosphor by optimizing the amount of flux and fuel

NASA Astrophysics Data System (ADS)

Wako, A. H.; Dejene, B. F.; Swart, H. C.

2014-04-01

Long afterglow CaAl2O4:0.03Eu2+, 0.03Nd3+ phosphor was prepared by solution-combustion synthesis. The active role of boric acid (H3BO3) as a flux in enhancing the Eu2+ photoluminescence and the effect of a varied amount of urea (CO (NH2)2) as a fuel on the morphological, structural and photoluminescent (PL) properties of the CaAl2O4:0.03Eu2+, 0.03Nd3+ systems were investigated. The results of X-ray diffraction, scanning electron microscopy, and PL spectra revealed the influence of the dosage of urea and hence the heated process on the crystallinity, morphology, and luminescence of the phosphor. The addition of H3BO3 favoured the formation of a monoclinic CaAl2O4 phase while the variation of the amount of CO (NH2)2 showed mixed phases although still predominantly monoclinic. Both H3BO3 and CO(NH2)2 to some extent influence the luminescence intensity of the obtained phosphor but unlike the case of CO(NH2)2, the presence of H3BO3 did not evidently shift the emission peak due to no obvious change in the energy level difference of the 4f-5d levels. The broad blue emissions consisting mainly of symmetrical bands having maxima between 440 and 445 nm originate from the energy transitions between the ground state (4f7) and the excited state (4f65d1) of the Eu2+ ions while the narrow emissions in the red region (600-630 nm) arise from the 5D0→7F2 transitions of the remnant unreduced Eu3+ions. Higher concentrations of H3BO3 (0.228 mol and 0.285 mol) reduce both intensity and lifetime of the phosphor. The optimized content of H3BO3 was 0.171 mol for the obtained phosphor with the best optical properties.

Understanding of the mechanical and structural changes induced by alpha particles and heavy ions in the French simulated nuclear waste glass

NASA Astrophysics Data System (ADS)

Karakurt, G.; Abdelouas, A.; Guin, J.-P.; Nivard, M.; Sauvage, T.; Paris, M.; Bardeau, J.-F.

2016-07-01

Borosilicate glasses are considered for the long-term confinement of high-level nuclear wastes. External irradiations with 1 MeV He+ ions and 7 MeV Au5+ ions were performed to simulate effects produced by alpha particles and by recoil nuclei in the simulated SON68 nuclear waste glass. To better understand the structural modifications, irradiations were also carried out on a 6-oxides borosilicate glass, a simplified version of the SON68 glass (ISG glass). The mechanical and macroscopic properties of the glasses were studied as function of the deposited electronic and nuclear energies. Alpha particles and gold ions induced a volume change up to -0.7% and -2.7%, respectively, depending on the glass composition. Nano-indentations tests were used to determine the mechanical properties of the irradiated glasses. A decrease of about -22% to -38% of the hardness and a decrease of the reduced Young's modulus by -8% were measured after irradiations. The evolution of the glass structure was studied by Raman spectroscopy, and also 11B and 27Al Nuclear Magnetic Resonance (MAS-NMR) on a 20 MeV Kr irradiated ISG glass powder. A decrease of the silica network connectivity after irradiation with alpha particles and gold ions is deduced from the structural changes observations. NMR spectra revealed a partial conversion of BO4 to BO3 units but also a formation of AlO5 and AlO6 species after irradiation with Kr ions. The relationships between the mechanical and structural changes are also discussed.

Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea).

PubMed

Xiao, Zhiliang; Hu, Yang; Zhang, Xiaoli; Xue, Yuqian; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Liu, Yumei; Li, Zhansheng; Liu, Xing; Liu, Zezhou; Lv, Honghao; Zhuang, Mu

2017-06-05

Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage ( Brassica oleracea ) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2 , respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1 , seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380 ) were found, whereas in the region of BoHL2 , two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810 ) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.

Proteomic Characterization of Bovine Herpesvirus 4 Extracellular Virions

PubMed Central

Lété, Céline; Palmeira, Leonor; Leroy, Baptiste; Mast, Jan; Machiels, Bénédicte; Wattiez, Ruddy; Vanderplasschen, Alain

2012-01-01

Gammaherpesviruses are important pathogens in human and animal populations. During early events of infection, these viruses manipulate preexisting host cell signaling pathways to allow successful infection. The different proteins that compose viral particles are therefore likely to have critical functions not only in viral structures and in entry into target cell but also in evasion of the host's antiviral response. In this study, we analyzed the protein composition of bovine herpesvirus 4 (BoHV-4), a close relative of the human Kaposi's sarcoma-associated herpesvirus. Using mass spectrometry-based approaches, we identified 37 viral proteins associated with extracellular virions, among which 24 were resistant to proteinase K treatment of intact virions. Analysis of proteins associated with purified capsid-tegument preparations allowed us to define protein localization. In parallel, in order to identify some previously undefined open reading frames, we mapped peptides detected in whole virion lysates onto the six frames of the BoHV-4 genome to generate a proteogenomic map of BoHV-4 virions. Furthermore, we detected important glycosylation of three envelope proteins: gB, gH, and gp180. Finally, we identified 38 host proteins associated with BoHV-4 virions; 15 of these proteins were resistant to proteinase K treatment of intact virions. Many of these have important functions in different cellular pathways involved in virus infection. This study extends our knowledge of gammaherpesvirus virions composition and provides new insights for understanding the life cycle of these viruses. PMID:22896609

Electric field effect on chemical and phase equilibria in nano-TiB 2–TiO 2–TiBO 3 system at <650 °C: an in situ time-resolved energy dispersive x-ray diffraction study with an ultrahigh energy synchrotron probe

DOE PAGES

Özdemir, Tevfik E.; Akdoğan, Enver Koray; Şavklıyıldız, İlyas; ...

2016-12-19

Nano-TiB 2 powder of 58 nm size with TiO 2 and TiBO 3 as secondary phases was heated with 20 °C to <650 °C in argon while applying an electric field. The powder became conductive at 520 and 305 °C (T onset) for 16 and 40 V/cm, respectively, at which point current bursts of 4.5 and 10.0 A (peak value) were observed. Current bursts were accompanied by >1% TiB 2 unit cell expansion, exceeding zero field thermally induced expansion. The current bursts also induced nonisothermal reaction between TiB 2 and TiO 2, yielding TiBO 3 that is absent with nomore » field. Increase from 16 to 40 V/cm shifts the TiB 2 → TiBO 3 reaction forward, decreases T onset but increases reaction rate. Analysis using Van’t Hoff relation, including electrochemical effects, precluded possibility of appreciable Joule heating, which was supported with adiabatic internal temperature calculations. In conclusion, the observed low temperature oxidation of TiB 2 to TiBO 3 that is electrochemically driven and is mediated by the TiO 2 solid electrolyte.« less

Effect of Onabotulinum Toxin A on Substance P and Receptor Neurokinin 1 in the Rat Ventral Prostate

PubMed Central

Cakir, Omer Onur; Podlasek, Carol A.; Wood, Douglas; McKenna, Kevin E.; McVary, Kevin T.

2016-01-01

Introduction The objective of this work is to examine if sensory innervation impacts lower urinary tract symptoms (LUTS). Onabotulinum toxin A (BoNTA) has been used for the treatment of overactive and neurogenic bladder and as a treatment for LUTS secondary to benign prostatic hyperplasia (BPH). The mechanism of how BoNTA impacts LUTS/BPH is unclear. In rats, BoNTA injection causes prostate denervation, apoptosis and atrophy. In clinical trials reduced prostate size and LUTS are observed inconsistently, suggesting a neurologic component. We will examine if BoNTA treatment inhibits substance P production in sensory nerve fibers in the rat prostate. Methods Twenty Sprague Dawley rats were divided into four groups including 1X PBS (control, n=6), 2.5 units Onabotulinum toxin A (BoNTA, n=6), 5 units BoNTA (n=6) injected into both lobes of the ventral prostate (VP) and sham surgery (n=2). Rats were Euthanized after one week. Substance P and its receptor neurokinin 1 localization and quantification were performed by counting the number of stained neurons and nerve bundles, by semi-quantitative immunohistochemical analysis and by western analysis. Results Substance P was localized in neuronal axons and bundles in the stroma of the VP but not in the epithelium. Receptor neurokinin 1 was identified in neuronal bundles of the stroma and in columnar epithelium of the VP ducts. Substance P decreased ~90% after BoNTA treatment (p=0.0001) while receptor neurokinin 1 did not change by IHC (p=0.213) or Western (p=0.3675). Conclusions BoNTA treatment decreases substance P in the rat VP. PMID:27144785

Molecular Characterization of the First Bovine Herpesvirus 4 (BoHV-4) Strains Isolated from In Vitro Bovine Embryos production in Argentina

PubMed Central

González Altamiranda, Erika; Manrique, Julieta M.; Pérez, Sandra E.; Ríos, Glenda L.; Odeón, Anselmo C.; Leunda, María R.; Jones, Leandro R.; Verna, Andrea

2015-01-01

Bovine herpesvirus 4 (BoHV-4) is increasingly considered as responsible for various problems of the reproductive tract. The virus infects mainly blood mononuclear cells and displays specific tropism for vascular endothelia, reproductive and fetal tissues. Epidemiological studies suggest its impact on reproductive performance, and its presence in various sites in the reproductive tract highlights its potential transmission in transfer-stage embryos. This work describes the biological and genetic characterization of BoHV-4 strains isolated from an in vitro bovine embryo production system. BoHV-4 strains were isolated in 2011 and 2013 from granulosa cells and bovine oocytes from ovary batches collected at a local abattoir, used as “starting material” for in vitro production of bovine embryos. Compatible BoHV-4-CPE was observed in the co-culture of granulosa cells and oocytes with MDBK cells. The identity of the isolates was confirmed by PCR assays targeting three ORFs of the viral genome. The phylogenetic analyses of the strains suggest that they were evolutionary unlinked. Therefore it is possible that BoHV-4 ovary infections occurred regularly along the evolution of the virus, at least in Argentina, which can have implications in the systems of in vitro embryo production. Thus, although BoHV-4 does not appear to be a frequent risk factor for in vitro embryo production, data are still limited. This study reveals the potential of BoHV-4 transmission via embryo transfer. Moreover, the high variability among the BoHV-4 strains isolated from aborted cows in Argentina highlights the importance of further research on the role of this virus as an agent with the potential to cause reproductive disease in cattle. The genetic characterization of the isolated strains provides data to better understand the pathogenesis of BoHV-4 infections. Furthermore, it will lead to fundamental insights into the molecular aspects of the virus and the means by which these strains circulate in the herds. PMID:26177382

Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle.

PubMed

Tsai, Feng-Chou; Hsieh, Ming-Shium; Chou, Chih-Ming

2010-08-01

Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 +/- 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p < 0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

Clostridium botulinum strains producing BoNT/F4 or BoNT/F5.

PubMed

Raphael, Brian H; Bradshaw, Marite; Kalb, Suzanne R; Joseph, Lavin A; Lúquez, Carolina; Barr, John R; Johnson, Eric A; Maslanka, Susan E

2014-05-01

Botulinum neurotoxin type F (BoNT/F) may be produced by Clostridium botulinum alone or in combination with another toxin type such as BoNT/A or BoNT/B. Type F neurotoxin gene sequences have been further classified into seven toxin subtypes. Recently, the genome sequence of one strain of C. botulinum (Af84) was shown to contain three neurotoxin genes (bont/F4, bont/F5, and bont/A2). In this study, eight strains containing bont/F4 and seven strains containing bont/F5 were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis, allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containing bont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboring bont/F5. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring either bont/F4 or bont/F5 are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously, suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of a bont/F5-carrying plasmid among strains of diverse genomic backgrounds.

Iron-based magnetic superhalogens with pseudohalogens as ligands: An unbiased structure search

PubMed Central

Ping Ding, Li; Shao, Peng; Lu, Cheng; Hui Zhang, Fang; Wang, Li Ya

2017-01-01

We have performed an unbiased structure search for a series of neutral and anionic FeL4 (L = BO2, CN, NO2, NO3, OH, CH3, NH2, BH4 and Li2H3) clusters using the CALYPSO (Crystal structure Analysis by Particle Swarm Optimization) structure search method. To probe the superhalogen properties of neutral and anionic FeL4 clusters, we used density-functional theory with the B3LYP functional to examine three factors, including distribution of extra electron, pattern of bonding and the nature of the ligands. Theoretical results show that Fe(BO2)4, Fe(NO3)4 and Fe(NO2)4 can be classified as magnetic superhalogen due to that their electron affinities even exceed those of the constituent ligands. The magnetic moment of Fe atom is almost entirly maintained when it is decorated with various ligands except for neutral and anionic (Li2H3)4. Moreover, the current work is also extended to the salt moieties formed by hyperhalogen/superhalogen anion and Na+ ion. It is found that these salts against dissociation into Na + FeL4 are thermodynamic stable except for Na[Fe(OH)4]. These results provides a wealth of electronic structure information about FeL4 magnetic superhalogens and offer insights into the synthesis mechanisms. PMID:28327547

Kale BoRACK1 is involved in the plant response to salt stress and Peronospora brassicae Gaumann.

PubMed

Li, Da-Hong; Shen, Fu-Jia; Li, Hong-Yan; Li, Wei

2017-06-01

The receptor for activated C kinase 1 (RACK1) belongs to a protein subfamily containing a tryptophan-aspartic acid-domain (WD) repeat structure. Compelling evidence indicates that RACK1 can interact with many signal molecules and affect different signal transduction pathways. In this study, a kale (Brassica oleracea var. acephala f.tricolor) RACK1 gene (BoRACK1) was cloned by RT-PCR. The amino acid sequence of BoRACK1 had seven WD repeats in which there were typical GH (glycine-histidine) and WD dipeptides. Comparison with AtRACK1 from Arabidopsis revealed 87.1% identity at the amino acid level. Expression pattern analysis by RT-PCR showed that BoRACK1 was expressed in all analyzed tissues of kale and that its transcription in leaves was down-regulated by salt, abscisic acid, and H 2 O 2 at a high concentration. Overexpression of BoRACK1 in kale led to a reduction in symptoms caused by Peronospora brassicae Gaumann on kale leaves. The expression levels of the pathogenesis-related protein genes, PR-1 and PRB-1, increased 2.5-4-fold in transgenic kale, and reactive oxygen species production was more active than in the wild-type. They also exhibited increased tolerance to salt stress in seed germination. H 2 O 2 may also be involved in the regulation of BoRACK1 during seed germination under salt stress. Quantitative real-time PCR analyses showed that the transcript levels of BoRbohs genes were significantly higher in overexpression of BoRACK1 transgenic lines. Yeast two-hybrid assays showed that BoRACK1 could interact with WNK8, eIF6, RAR1, and SGT1. This study and previous work lead us to believe that BoRACK1 may form a complex with regulators of plant salt and disease resistance to coordinate kale reactions to pathogens. Copyright © 2017 Elsevier GmbH. All rights reserved.

Synthesis and characterization of γ-irradiated cadmium-borate glasses doped V2O5

NASA Astrophysics Data System (ADS)

Bahammam, S.; Abd El Al, S.; Ezz-Eldin, F. M.

In this work, we study the relationship between the optical and magnetic properties for the irradiated and unirradiated V2O5-doped cadmium borate glasses and examined their optical band energy that has compromise of non-bridging oxygen (NBO) and bridging oxygen (BO), V3+, V4+ and V5+, and BO3 units and BO4 units. The induced defects created by γ-rays were characterized by optical and EPR spectroscopy. The dependability of the defects and the tendency for recombination or conversion of the defects besides the environment of optically dynamic V centers was also discussed. It is concluded that the development of both optical and magnetic intensity is related to V4+ ions at tetrahedral sites whereas the decrease in their intensity is recognized to the ligand-metal charge transfer transitions of V4+ ions coupled to V5+. The optical band gap energy (Eg) has been observed to decrease with increasing either V2O5 content or γ-doses. High γ-dose reduces the values of the allowed direct optical band gap Eg of 0.5 Mol% V2O5 glass up to 45 kGy after which Eg increases, but remain lower than that of un-irradiated glass. Borate glasses under this study showed linear optical absorption response over the dose range of 5-80 kG. Fading under dark and room light in 2 h after exposure in the course of 30 days have been studied in detail and presented. Our results and findings indicate that, the investigated samples may be seemed to be a good candidate for radiation processing purposes.

Assembly and function of the botulinum neurotoxin progenitor complex.

PubMed

Gu, Shenyan; Jin, Rongsheng

2013-01-01

Botulinum neurotoxins (BoNTs) are among the most poisonous substances known to man, but paradoxically, BoNT-containing medicines and cosmetics have been used with great success in the clinic. Accidental BoNT poisoning mainly occurs through oral ingestion of food contaminated with Clostridium botulinum. BoNTs are naturally produced in the form of progenitor toxin complexes (PTCs), which are high molecular weight (up to ~900 kDa) multiprotein complexes composed of BoNT and several non-toxic neurotoxin-associated proteins (NAPs). NAPs protect the inherently fragile BoNTs against the hostile environment of the gastrointestinal (GI) tract and help BoNTs pass through the intestinal epithelial barrier before they are released into the general circulation. These events are essential for ingested BoNTs to gain access to motoneurons, where they inhibit neurotransmitter release and cause muscle paralysis. In this review, we discuss the structural basis for assembly of NAPs and BoNT into the PTC that protects BoNT and facilitate its delivery into the bloodstream.

Molecular biology of botulinum neurotoxin serotype A: a cosmetic perspective.

PubMed

Eapen, Bell Raj

2008-09-01

Cosmetic use of botulinum neurotoxin serotype A (BoNT/A) involves low doses of toxin administered for facial wrinkles and hyperhidrosis. The structural and functional properties of BoNT/A can affect the degree and duration of effect. Actively using the injected muscle is favorable as it exposes more receptors to BoNT/A. Divided doses of BoNT/A at an interval of more than 3 days may be longer lasting than single dose by blocking nascent neuronal sprouts. Antibodies are unlikely to be effective in BoNT/A neutralization because of the large area of receptor interaction. Several commonly used drugs including zinc and chloroquine can interact with BoNT/A, necessitating dosage adjustment for optimum effect. Serotype E (BoNT/E) can emerge as an antidote for BoNT/A for cosmetic use.

Electrical properties of crystallized 30B2O3-70V2O5 glass

NASA Astrophysics Data System (ADS)

Gwoo, Donggun; Kim, Taehee; Han, Kyungseok; Choi, Wongyu; Kim, Jonghwan; Ryu, Bongki

2013-05-01

30B2O3-70V2O5 binary-system glass was prepared, and variations in structural and electrical property were examined using crystallization. While different related research studies exist, few have evaluated the variations in the structure and properties with changes in the crystallization rate. 30B2O3-70V2O5 glass was annealed in the graphite mold above the glass transition temperature for 2 h and heat-treated at each crystallization temperature for 3 h. 30B2O3-70V2O5 glass showed predominantly electronic conductive characteristic. FTIR was preferentially used for analyzing the structural changes of B-O bond after crystallization, while XRD was utilized to verify the inferred changes in the structure array (BO3 + V2O5 ↔ BO4 + 2VO2). Structural changes induced by heat treatment were confirmed by analyzing the molecular volume determined from the sample density, and conductance was measured to correlate structural and property changes. Conductivity is discussed based on the migration of vanadate ions with different valence states because of the increase in VO2 crystallinity at 130°C, which, however, was not observed at 170°C. After VO2 structures were reinforced, a 1.8-fold increase in conductance was observed (as compared to the annealed sample) after crystallization at 130°C for 3 h.

Effects of the synthetic corticosteroid dexamethasone on bovine herpesvirus 1 productive infection.

PubMed

Zhu, Liqian; Thompson, Jesse; Ma, Fangrui; Eudy, James; Jones, Clinton

2017-05-01

Sensory neurons are a primary site for life-long latency of bovine herpesvirus 1 (BoHV-1). The synthetic corticosteroid dexamethasone induces reactivation from latency and productive infection, in part because the BoHV-1 genome contains more than 100 glucocorticoid receptor (GR) responsive elements (GREs). Two GREs in the immediate early transcription unit 1 promoter are required for dexamethasone induction. Recent studies also demonstrated that the serum and glucocorticoid receptor protein kinase (SGK) family stimulated BoHV-1 replication. Consequently, we hypothesized that dexamethasone influences several aspects of productive infection. In this study, we demonstrated that dexamethasone increased expression of the immediate early protein bICP4, certain late transcripts, and UL23 (thymidine kinase) by four hours after infection. SGK1 expression and Akt phosphorylation were also stimulated during early stages of infection and dexamethasone treatment further increased this effect. These studies suggest that stress, as mimicked by dexamethasone treatment, has the potential to stimulate productive infection by multiple pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Proconvulsant Actions of Intrahippocampal Botulinum Neurotoxin B in the Rat

PubMed Central

Bröer, Sonja; Zolkowska, Dorota; Gernert, Manuela; Rogawski, Michael A.

2013-01-01

Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target SNAP-25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 unit) by convection-enhanced delivery caused a reduction in myoclonic twitch and clonic seizure thresholds in response to intravenous PTZ beginning about 6 days after the infusion. Handling-evoked and spontaneous convulsive seizures were observed in many BoNT/B-treated animals but not in vehicle-treated controls. Spontaneous electrographic seizure discharges were recorded in the dentate gyrus of animals that received local BoNT/B infusion. In addition, there was an increased frequency of interictal epileptiform spikes and sharp waves at the same recording site. BoNT/B treated animals also exhibited tactile hyperresponsivity in comparison with vehicle-treated controls. This is the first demonstration that BoNT/B causes a delayed proconvulsant action when infused into the hippocampus. Local infusion of BoNT/B could be useful as a focal epilepsy model. PMID:23906638

Asymmetric angular dependence of spin-transfer torques in CoFe/Mg-B-O/CoFe magnetic tunnel junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Ling, E-mail: lingtang@zjut.edu.cn; Xu, Zhi-Jun, E-mail: xzj@zjut.edu.cn; Zuo, Xian-Jun

Using a first-principles noncollinear wave-function-matching method, we studied the spin-transfer torques (STTs) in CoFe/Mg-B-O/CoFe(001) magnetic tunnel junctions (MTJs), where three different types of B-doped MgO in the spacer are considered, including B atoms replacing Mg atoms (Mg{sub 3}BO{sub 4}), B atoms replacing O atoms (Mg{sub 4}BO{sub 3}), and B atoms occupying interstitial positions (Mg{sub 4}BO{sub 4}) in MgO. A strong asymmetric angular dependence of STT can be obtained both in ballistic CoFe/Mg{sub 3}BO{sub 4} and CoFe/Mg{sub 4}BO{sub 4} based MTJs, whereas a nearly symmetric STT curve is observed in the junctions based on CoFe/Mg{sub 4}BO{sub 3}. Furthermore, the asymmetry ofmore » the angular dependence of STT can be suppressed significantly by the disorder of B distribution. Such skewness of STTs in the CoFe/Mg-B-O/CoFe MTJs could be attributed to the interfacial resonance states induced by the B diffusion into MgO spacer.« less

Structural And Biochemical Studies of Botulinum Neurotoxin Serotype C1 Light Chain Protease: Implications for Dual Substrate Specificity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, R.; Sikorra, S.; Stegmann, C.M.

2009-06-01

Clostridial neurotoxins are the causative agents of the neuroparalytic disease botulism and tetanus. They block neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs) SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery. The catalytic component of the clostridial neurotoxins is their light chain (LC), a Zn2+ endopeptidase. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), termed serotype A to G, and tetanus neurotoxin (TeNT). Each of them exhibits unique specificity for their target SNAREs and peptide bond(s) they cleave. The mechanisms of action for substrate recognitionmore » and target cleavage are largely unknown. Here, we report structural and biochemical studies of BoNT/C1-LC, which is unique among BoNTs in that it exhibits dual specificity toward both syntaxin and SNAP-25. A distinct pocket (S1') near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin. Mutations of this SNAP-25 residue dramatically reduce enzymatic activity. The remote a-exosite that was previously identified in the complex of BoNT/A-LC and SNAP-25 is structurally conserved in BoNT/C1. However, mutagenesis experiments show that the a-exosite of BoNT/C1 plays a less stringent role in substrate discrimination in comparison to that of BoNT/A, which could account for its dual substrate specificity.« less

A novel subunit structure of Clostridium botulinum serotype D toxin complex with three extended arms.

PubMed

Hasegawa, Kimiko; Watanabe, Toshihiro; Suzuki, Tomonori; Yamano, Akihito; Oikawa, Tetsuo; Sato, Yasuhiko; Kouguchi, Hirokazu; Yoneyama, Tohru; Niwa, Koichi; Ikeda, Toshihiko; Ohyama, Tohru

2007-08-24

The botulinum neurotoxins (BoNTs) are the most potent toxins known in nature, causing the lethal disease known as botulism in humans and animals. The BoNTs act by inhibiting neurotransmitter release from cholinergic synapses. Clostridium botulinum strains produce large BoNTs toxin complexes, which include auxiliary non-toxic proteins that appear not only to protect BoNTs from the hostile environment of the digestive tract but also to assist BoNT translocation across the intestinal mucosal layer. In this study, we visualize for the first time a series of botulinum serotype D toxin complexes using negative stain transmission electron microscopy (TEM). The complexes consist of the 150-kDa BoNT, 130-kDa non-toxic non-hemagglutinin (NTNHA), and three kinds of hemagglutinin (HA) subcomponents: 70-kDa HA-70, 33-kDa HA-33, and 17-kDa HA-17. These components assemble sequentially to form the complex. A novel TEM image of the mature L-TC revealed an ellipsoidal-shaped structure with "three arms" attached. The "body" section was comprised of a single BoNT, a single NTNHA and three HA-70 molecules. The arm section consisted of a complex of HA-33 and HA-17 molecules. We determined the x-ray crystal structure of the complex formed by two HA-33 plus one HA-17. On the basis of the TEM image and biochemical results, we propose a novel 14-mer subunit model for the botulinum toxin complex. This unique model suggests how non-toxic components make up a "delivery vehicle" for BoNT.

Face-capping μ3-BO in B6(BO)7-: boron oxide analogue of B6H7- with rhombic 4c-2e bonds.

PubMed

Guo, Jin-Chang; Lu, Hai-Gang; Zhai, Hua-Jin; Li, Si-Dian

2013-11-14

Using the first-principle approaches, we predict a B6(BO)7(-) cluster with a face-capping μ(3)-BO, which is the boron oxide analogue of closo-B6H7(-) with a face-capping μ(3)-H. Detailed topological analysis of electron density clearly reveals the existence of three rhombic 4c-2e bonds around the B/H apex in both C3v B6(BO)7(-) and C3v B6H7(-), which possesses similar electron densities at their bond and ring critical points. The adaptive natural density partitioning (AdNDP) analysis provides a direct and visual picture of the B-B-B-B/H 4c-2e bonds for the first time. Adiabatic and vertical electron detachment energies of the concerned monoanions are calculated to facilitate their future photoelectron spectroscopy measurements and characterizations. The presence of the B6(BO)7(-) and B6H7(-) clusters extends the BO/H isolobal analogy to the whole μ(n)-BO/H series (n = 1, 2, and 3) and enriches the chemistry of boronyl.

Tunable Yellow-Red Photoluminescence and Persistent Afterglow in Phosphors Ca4LaO(BO3)3:Eu3+ and Ca4EuO(BO3)3.

PubMed

Chen, Zhen; Pan, Yuexiao; Xi, Luqing; Pang, Ran; Huang, Shaoming; Liu, Guokui

2016-11-07

In most Eu 3+ activated phosphors, only red luminescence from the 5 D 0 is obtainable, and efficiency is limited by concentration quenching. Herein we report a new phosphor of Ca 4 LaO(BO 3 ) 3 :Eu 3+ (CLBO:Eu) with advanced photoluminescence properties. The yellow luminescence emitted from the 5 D 1,2 states is not thermally quenched at room temperature. The relative intensities of the yellow and red emission bands depend strongly on the Eu 3+ doping concentration. More importantly, concentration quenching of Eu 3+ photoluminescence is absent in this phosphor, and the stoichiometric compound of Ca 4 EuO(BO 3 ) 3 emits stronger luminescence than the Eu 3+ doped compounds of CLBO:Eu; it is three times stronger than that of a commercial red phosphor of Y 2 O 3 :Eu 3+ . Another beneficial phenomenon is that ligand-to-metal charge transfer (CT) transitions occur in the long UV region with the lowest charge transfer band (CTB) stretched down to about 3.67 eV (∼330 nm). The CT transitions significantly enhance Eu 3+ excitation, and thus result in stronger photoluminescence and promote trapping of excitons for persistent afterglow emission. Along with structure characterization, optical spectra and luminescence dynamics measured under various conditions as a function of Eu 3+ doping, temperature, and excitation wavelength are analyzed for a fundamental understanding of electronic interactions and for potential applications.

Hygroscopic growth of particles nebulized from water-soluble extracts of PM2.5 aerosols over the Bay of Bengal: Influence of heterogeneity in air masses and formation pathways.

PubMed

Boreddy, S K R; Kawamura, Kimitaka; Bikkina, Srinivas; Sarin, M M

2016-02-15

Hygroscopic properties of water-soluble matter (WSM) extracted from fine-mode aerosols (PM2.5) in the marine atmospheric boundary layer of the Bay of Bengal (BoB) have been investigated during a cruise from 27th December 2008 to 30th January 2009. Hygroscopic growth factors were measured on particles generated from the WSM using an H-TDMA system with an initial dry size of 100 nm in the range of 5-95% relative humidity (RH). The measured hygroscopic growth of WSM at 90% RH, g(90%)WSM, were ranged from 1.11 to 1.74 (mean: 1.43 ± 0.19) over the northern BoB and 1.12 to 1.38 (mean: 1.25 ± 0.09) over the southern BoB. A key finding is that distinct hygroscopic growth factors are associated with the air masses from the Indo-Gangetic plains (IGP), which are clearly distinguishable from those associated with air masses from Southeast Asia (SEA). We found higher (lower) g(90%)WSM over the northern (southern) BoB, which were associated with an IGP (SEA) air masses, probably due the formation of high hygroscopic salts such as (NH4)2SO4. On the other hand, biomass burning influenced SEA air masses confer the low hygroscopic salts such as K2SO4, MgSO4, and organic salts over the southern BoB. Interestingly, mass fractions of water-soluble organic matter (WSOM) showed negative and positive correlations with g(90%)WSM over the northern and southern BoB, respectively, suggesting that the mixing state of organic and inorganic fractions could play a major role on the g(90%)WSM over the BoB. Further, WSOM/SO4(2-) mass ratios suggest that SO4(2-) dominates the g(90%)WSM over the northern BoB whereas WSOM fractions were important over the southern BoB. The present study also suggests that aging process could significantly alter the hygroscopic growth of aerosol particles over the BoB, especially over the southern BoB. Copyright © 2015 Elsevier B.V. All rights reserved.

Spinel, YbFe2O4, and Yb2Fe3O7 types of structure for compounds in the In2O3 and Sc2O3-A2O3-BO systems (A: Fe, Ga, or Al; B: Mg, Mn, Fe, Ni, Cu, or Zn) at temperatures over 1000C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimizuka, N.; Mohri, T.

In the Sc2O3-Ga2O3-CuO, Sc2O3-Ga2O3-ZnO, and Sc2O3-Al2O3-CuO systems, ScGaCuO4, ScGaZnO4, and ScAlCuO4 with the YbFe2O4-type structure and Sc2Ga2CuO7 with the Yb2Fe3O7-type structure were obtained. In the In2O3-A2O3-BO systems (A: Fe, Ga, or Al; B: Mg, Mn, Fe, Ni, or Zn), InGaFeO4, InGaNiO4, and InFeT MgO4 with the spinel structure, InGaZnO4, InGaMgO4, and InAl-CuO4 with the YbFe2O4-type structure, and In2Ga2MnO7 and In2Ga2ZnO7 with the Yb2Fe3O7-type structure were obtained. InGaMnO4 and InFe2O4 had both the YbFe2O4-type and spinel-type structures. The revised classification for the crystal structures of AB2O4 compounds is presented, based upon the coordination numbers of constituent A and B cations. 5more » references, 2 tables.« less

Pilot cohort study of endoscopic botulinum neurotoxin injection in Parkinson's disease.

PubMed

Triadafilopoulos, George; Gandhy, Rita; Barlow, Carrolee

2017-11-01

Gastrointestinal symptoms, such as dysphagia, postprandial bloating, and defecatory straining are common in Parkinson's Disease (PD) and they impact quality of life. Endoscopic botulinum neurotoxin (BoNT) injection has been used in the treatment of dysphagia, gastroparesis and chronic anismus. To examine the feasibility, safety and efficacy of endoscopically delivered BoNT injection to distal esophagus, pylorus or anal canal aiming at relieving regional gastrointestinal symptoms in patients with PD. This is a retrospective open cohort pilot study to assess the clinical response to endoscopic BoNT injection on selected PD patients with symptoms and identifiable abnormalities on high-resolution manometry and wireless motility capsule, to generate early uncontrolled data on feasibility, tolerability, safety and efficacy. Baseline symptoms and response to therapy were assessed by questionnaires. Fourteen PD patients (10 M:4 F), mean age 73 (range: 62-93) were treated. Three patients had esophageal Botox for ineffective esophageal motility (IEM) (n = 1), esophago-gastric junction outlet obstruction (EGJOO) & IEM (n = 1), and diffuse esophageal spasm (DES) (n = 1). Nine patients were treated with pyloric BoNT injection for gastroparesis with mean gastric transit time of 21.2 h; range 5.2-44.2 h. Two patients received anal Botox for defecatory dyssynergia ((Type I) (n = 1) and overlap (slow-transit and dyssynergic) constipation (n = 1). Endoscopic BoNT injection (100-200 units) was well tolerated and there were no significant adverse events. Endoscopic BoNT injection to esophagus, pylorus or anal canal is safe, well-tolerated and leads to symptomatic improvement that lasts up to several months. The procedure can be repeated as needed and combined with other therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural, thermal and optical investigations of Dy3+ ions doped lead containing lithium fluoroborate glasses for simulation of white light

NASA Astrophysics Data System (ADS)

Zulfiqar Ali Ahamed, Sd.; Madhukar Reddy, C.; Deva Prasad Raju, B.

2013-05-01

Lead containing barium zinc lithium fluoroborate (LBZLFB) glasses doped with different concentrations of trivalent dysprosium ions were synthesized by conventional melt quenching method and characterized through the XRD, DSC, FTIR, FT-Raman, optical absorption, photoluminescence and decay curve analysis. X-ray diffraction studies revealed amorphous nature of the studied glass matrices. The thermal behavior has been reported by recording DSC thermograms. Coexistence of trigonal BO3 and tetrahedral BO4 units was evidenced by IR and Raman spectroscopy. Judd-Ofelt intensity parameters have been evaluated for 1.0 mol% Dy3+ ions doped LBZLFB glass. The measuring branching ratios are reasonably high for transitions 4F9/2 → 6H15/2 and 6H13/2 suggesting that the emission at 486 and 577 nm, respectively can give rise to lasing action in the visible region. From the visible emission spectra, the yellow to blue (Y/B) intensity ratios and chromaticity color coordinates were estimated. A combination of blue and yellow emissions has emerged in the glasses, which allows the observation of white light when the glasses are excited by the ultraviolet/blue light. These Dy3+ doped glasses are studied for their utility for white light generation under 454 nm excitation and the present LBZLFB glass is more suitable for generation of white light for blue LED chips.

Thermal, spectroscopic properties and laser performance at 1.06 and 1.33 μm of Nd : Ca 4YO(BO 3) 3 and Nd : Ca 4GdO(BO 3) 3 crystals

NASA Astrophysics Data System (ADS)

Wang, Changqing; Zhang, Huaijin; Meng, Xianlin; Zhu, Li; Chow, Y. T.; Liu, Xuesong; Cheng, Ruiping; Yang, Zhaohe; Zhang, Shaojun; Sun, Lianke

2000-11-01

Nd : Ca 4YO(BO 3) 3 (Nd : YCOB) and Nd : Ca 4GdO(BO 3) 3 (Nd : GdCOB) crystals were grown by Czochralski method. Thermal expansion and specific heat of these two crystals were experimentally determined. Their fluorescence spectra were measured within the range from 1000 to 1500 nm. Laser output experiments at 1.06 and 1.33 μm of Nd : YCOB and Nd : GdCOB crystals were performed with a cw Ti : sapphire laser as the pump source.

Spin-wave dynamics and exchange interactions in multiferroic NdFe3(BO3)4 explored by inelastic neutron scattering

NASA Astrophysics Data System (ADS)

Golosovsky, I. V.; Ovsyanikov, A. K.; Aristov, D. N.; Matveeva, P. G.; Mukhin, A. A.; Boehm, M.; Regnault, L.-P.; Bezmaternykh, L. N.

2018-04-01

Magnetic excitations and exchange interactions in multiferroic NdFe3(BO3)4 were studied by inelastic neutron scattering in the phase with commensurate antiferromagnetic structure. The observed spectra were analyzed in the frame of the linear spin-wave theory. It was shown that only the model, which includes the exchange interactions within eight coordination spheres, describes satisfactorily all observed dispersion curves. The calculation showed that the spin-wave dynamics is governed by the strongest antiferromagnetic intra-chain interaction and three almost the same inter-chain interactions. Other interactions, including ferromagnetic exchange, appeared to be insignificant. The overall energy balance of the antiferromagnetic inter-chain exchange interactions, which couple the moments from the adjacent ferromagnetic layers as well as within a layer, stabilizes ferromagnetic arrangement in the latter. It demonstrates that the pathway geometry plays a crucial role in forming of the magnetic structure.

Chemical Trend of Superconducting Critical Temperatures in Hole-Doped CuBO2, CuAlO2, CuGaO2, and CuInO2

NASA Astrophysics Data System (ADS)

Nakanishi, Akitaka; Katayama-Yoshida, Hiroshi; Ishikawa, Takahiro; Shimizu, Katsuya

2016-09-01

We calculated the superconducting critical temperature (Tc) for hole-doped CuXO2 (X = B, Al, Ga, and In) compounds using first-principles calculations based on rigid band model. The compounds with X = Al, Ga, and In have delafosite-type structures and take maximum Tc values at 0.2-0.3 with respect to the number of holes (Nh) in the unit-cell: 50 K for CuAlO2, 10 K for CuGaO2, and 1 K for CuInO2. The decrease of Tc for this change in X is involved by covalency reduction and lattice softening associated with the increase of ionic mass and radius. For CuBO2 which is a lighter compound than CuAlO2, the delafosite structure is unstable and a body-centered tetragonal structure emerges as the most stable structure. As the results, the electron-phonon interaction is decreased and Tc is lower by approximately 43 K than that of CuAlO2 at the hole-doping conditions of Nh = 0.2-0.3.

Atoxic derivative of botulinum neurotoxin A as a prototype vehicle for targeted delivery to neuronal cytoplasm

USDA-ARS?s Scientific Manuscript database

We have previously described genetic constructs and expression systems that enable facile production of recombinant derivatives of botulinum neurotoxins (BoNTs) that retain the structural and trafficking properties of wt BoNTs. In this report we describe the properties of one such derivative, BoNT/A...

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B.

DOE Office of Scientific and Technical Information (OSTI.GOV)

SWAMINATHAN,S.; ESWARAMOORTHY,S.

2001-11-19

The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases [1]. Clostvidium botulinum neurotoxinsmore » are extremely poisonous proteins with their LD{sub 50} for humans in the range of 0.1 - 1 ng kg{sup -1} [2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and {gamma}-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization [3].« less

A cross-sectional pilot study of compassion fatigue, burnout, and compassion satisfaction in pediatric palliative care providers in the United States.

PubMed

Kase, Samuel M; Waldman, Elisha D; Weintraub, Andrea S

2018-02-05

Compassion fatigue (CF) is secondary traumatic distress experienced by providers from contact with patients' suffering. Burnout (BO) is job-related distress resulting from uncontrollable workplace factors that manifest in career dissatisfaction. Compassion satisfaction (CS) is emotional fulfillment derived from caring for others. The literature on BO in healthcare providers is extensive, whereas CF and CS have not been comprehensively studied. Because of ongoing exposure to patient and family distress, pediatric palliative care (PPC) providers may be at particular risk for CF. We conducted a cross-sectional pilot study of CF, BO, and CS among PPC providers across the United States. The Compassion Fatigue and Satisfaction Self-Test for Helpers and a questionnaire of professional and personal characteristics were distributed electronically and anonymously to PPC physicians and nurses. Logistic and linear regression models for CF, BO, and CS as a function of potential risk factors were constructed. The survey response rate was 39%, primarily consisting of female, Caucasian providers. The prevalence of CF, BO, and CS was 18%, 12%, and 25%, respectively. Distress about a "clinical situation," physical exhaustion, and personal loss were identified as significant determinants of CF. Distress about "coworkers," emotional depletion, social isolation, and "recent involvement in a clinical situation in which life-prolonging activities were not introduced" were significant determinants of BO. Physical exhaustion, personal history of trauma, "recent involvement in a clinical situation in which life-prolonging activities were not introduced," and not discussing distressing issues were significant predictors of lower CS scores. Significance of results CF and BO directly influence the well-being and professional performance of PPC providers. To provide effective compassionate care to patients, PPC providers must be attentive to predictors of these phenomena. Further work is needed to explore additional causes of CF, BO, and CS in PPC providers as well as potential interventions.

78 FR 31975 - Notice of Lodging Proposed Consent Decree

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-28

... Thomas Byrd, Civil Action No. 4:12-cv-53-BO, was lodged with the United States District Court for the... Clean Water Act, 33 U.S.C. 1311(a), to obtain injunctive relief from and impose civil penalties against... impacted areas and to pay a civil penalty. The Department of Justice will accept written comments relating...

Assessment of bovine herpesvirus 4 based vector in chicken.

PubMed

Donofrio, Gaetano; Manarolla, Giovanni; Ravanetti, Lara; Sironi, Giuseppe; Cavirani, Sandro; Cabassi, Clotilde Silvia; Flammini, Cesidio Filippo; Rampin, Tiziana

2008-03-01

The biological characteristics of BoHV-4 make it a good candidate as a gene delivery vector for vaccination purposes. These characteristics include little or no pathogenicity, unlikely oncogenicity, the ability to accommodate large amounts of foreign genetic material, the ability to infect several cell types from different animal species, such as sheep, goats, swine, cats, dogs, rabbits, mink, horses, turkeys, ferrets, monkeys, hamsters, rats, mice, and chickens. In this report, the feasibility to use BoHV-4 based vector in chicken was investigated. Although BoHV-4 was able to replicate, leading to a cytopathic effect in a chicken cell line and infect the chorion allantoic membrane of embryonated eggs, however it was not pathogenic even when a large dose of virus was injected into the chicken. An immune response could be produced against heterologous antigen delivered by a recombinant BoHV-4. These data suggest the feasibility of using BoHV-4 based vector for vaccination purposes in chickens.

Exploiting persistent infection for selection of bovine herpesvirus 4 recombinants.

PubMed

Donofrio, G; Martignani, E; Cavirani, S; Flammini, C F

2005-09-01

Bovine herpesvirus 4 (BoHV-4) is a gamma-herpesvirus with no clear disease association, and due to its biological characteristics, has been suggested as a gene delivery vector. It was demonstrated previously that recombinant BoHV-4 carrying a neomycin-resistance gene was able to infect a human rhabdomyosarcoma cell line (RD-4), resulting in no detectable cytopathic effect (CPE) and allowing selection of G418-resistant persistently-infected cells containing circular episomal viral DNA [Donofrio, G., Cavirani, S., van Santen, V.L., 2000a. Establishment of a cell line persistently infected with recombinant BoHV-4. J. Gen. Virol. 81, 1807-1814.]. Those cells produce infectious virus and infection is predominantly non-permissive and non-cytopathic. Starting from these results, the ability of RD-4 cells to sustain persistent infection was combined with positive selection activity conferred by the neomycin-expression cassette insert, as an easier way to select recombinants of BoHV-4 following homologous recombination in permissive cells. A tool for selecting BoHV-4 recombinants was developed by drug positive selection.

Evidence of natural interspecific recombinant viruses between bovine alphaherpesviruses 1 and 5.

PubMed

Maidana, Silvina Soledad; Craig, Patricio Oliver; Craig, María Isabel; Ludwig, Louisa; Mauroy, Axel; Thiry, Etienne; Romera, Sonia Alejandra

2017-10-15

Closely related bovine alphaherpesviruses 1 (BoHV-1) and 5 (BoHV-5) co-circulate in certain countries, rendering cattle co-infection possible. This is a prerequisite for BoHV recombination. Here, we report the first identification of homologous recombination between field isolates of BoHV-1 and BoHV-5, two alphaherpesviruses belonging to two distinct species with an average genomic similarity of 82.3%. Three isolates of BoHV-5, previously classified as subtype "BoHV-5b", were phylogenetically studied and analyzed via eight PCR sequencing assays dispersed at regular intervals throughout the genome to discriminate between BoHV-1 and BoHV-5. In the phylogenetic analysis, differences of clustering were found in the UL27 gene which encodes the glycoprotein B (gB). We detected two recombination breakpoints in the open reading frame of the UL27 gene. We compared the amino acid sequences of the gB of BoHV-1.1 and 1.2, BoHV-5a and recombinant formerly named BoHV-5b (chimeric gB) and subsequently performed molecular modeling. All structures were alike and, simultaneously, similar to the chimeric gB. Neutralizing antibodies against BoHV-1, BoHV-5 and recombinant viruses were analyzed via serum virus neutralization test using polyclonal sera and a monoclonal antibody against gB to demonstrate an absence of viral escape for both assays. Our results show that homologous recombination between two related species of ruminant alphaherpesviruses can occur in natural field conditions. We found three recombinant field isolates, previously classified as BoHV-5b subtypes, between BoHV-1 and BoHV-5. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensitive and quantitative detection of botulinum neurotoxin in neurons derived from mouse embryonic stem cells.

PubMed

Pellett, Sabine; Du, Zhong-wei; Pier, Christina L; Tepp, William H; Zhang, Su-chun; Johnson, Eric A

2011-01-07

Botulinum neurotoxins (BoNTs), the most poisonous protein toxins known, represent a serious bioterrorism threat but are also used as a unique and important bio-pharmaceutical to treat an increasing myriad of neurological disorders. The only currently accepted detection method by the United States Food and Drug Administration for biological activity of BoNTs and for potency determination of pharmaceutical preparations is the mouse bioassay (MBA). Recent advances have indicated that cell-based assays using primary neuronal cells can provide an equally sensitive and robust detection platform as the MBA to reliably and quantitatively detect biologically active BoNTs. This study reports for the first time a BoNT detection assay using mouse embryonic stem cells to produce a neuronal cell culture. The data presented indicate that this assay can reliably detect BoNT/A with a similar sensitivity as the MBA. Published by Elsevier Inc.

Botulinum neurotoxin G binds synaptotagmin-II in a mode similar to that of serotype B: tyrosine 1186 and lysine 1191 cause its lower affinity.

PubMed

Willjes, Gesche; Mahrhold, Stefan; Strotmeier, Jasmin; Eichner, Timo; Rummel, Andreas; Binz, Thomas

2013-06-04

Botulinum neurotoxins (BoNTs) block neurotransmitter release by proteolyzing SNARE proteins in peripheral nerve terminals. Entry into neurons occurs subsequent to interaction with gangliosides and a synaptic vesicle protein. Isoforms I and II of synaptotagmin were shown to act as protein receptors for two of the seven BoNT serotypes, BoNT/B and BoNT/G, and for mosaic-type BoNT/DC. BoNT/B and BoNT/G exhibit a homologous binding site for synaptotagmin whose interacting part adopts helical structure upon binding to BoNT/B. Whereas the BoNT/B-synaptotagmin-II interaction has been elucidated in molecular detail, corresponding information about BoNT/G is lacking. Here we systematically mutated the synaptotagmin binding site in BoNT/G and performed a comparative binding analysis with mutants of the cell binding subunit of BoNT/B. The results suggest that synaptotagmin takes the same overall orientation in BoNT/B and BoNT/G governed by the strictly conserved central parts of the toxins' binding site. The surrounding nonconserved areas differently contribute to receptor binding. Reciprocal mutations Y1186W and L1191Y increased the level of binding of BoNT/G approximately to the level of BoNT/B affinity, suggesting a similar synaptotagmin-bound state. The effects of the mutations were confirmed by studying the activity of correspondingly mutated full-length BoNTs. On the basis of these data, molecular modeling experiments were employed to reveal an atomistic model of BoNT/G-synaptotagmin recognition. These data suggest a reduced length and/or a bend in the C-terminal part of the synaptotagmin helix that forms upon contact with BoNT/G as compared with BoNT/B and are in agreement with the data of the mutational analyses.

High-level expression, purification, crystallization and preliminary X-ray crystallographic studies of the receptor binding domain of botulinum neurotoxin serotype D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yanfeng; Gao, Xiaoli; Qin, Lin

2010-12-01

Botulinum neurotoxins (BoNTs) are highly toxic proteins for humans and can cause neuroparalytic disease botulism. Due to the limitations of production and manipulation of holoenzymes, expressing non-toxic heavy chain receptor binding domains (HCR) has become a common strategy for vaccine and antibody development. Meanwhile, large quantities and highly purified soluble proteins are required for research areas such as antibody maturation and structural biology. We present high level expression and purification of the BoNT serotype D HCR in E. coli using a codon-optimized cDNA. By varying expression conditions, especially at low temperature, the protein was expressed at a high level withmore » high solubility. About 150-200 mg protein was purified to >90% purity from 1 L cell culture. The recombinant D_HCR was crystallized and the crystals diffracted to 1.65 Å resolution. The crystals belong to space group P212121 with unit cell dimensions a = 60.8 Å, b = 89.7 Å, c = 93.9 Å. Preliminary crystallographic data analysis revealed one molecule in asymmetric unit.« less

Influence of CuO content on the structure of lithium fluoroborate glasses: Spectral and gamma irradiation studies.

PubMed

Abdelghany, A M; ElBatal, H A; EzzElDin, F M

2015-10-05

Glasses of lithium fluoroborate of the composition LiF 15%-B2O3 85% with increasing CuO as added dopant were prepared and characterized by combined optical and FTIR spectroscopy before and after gamma irradiation. The optical spectrum of the undoped glass reveals strong UV absorption with two distinct peaks at about 235 and 310 nm and with no visible bands. This strong UV absorption is related to the presence of unavoidable trace iron impurity (Fe(3+)) within the materials used for the preparation of this glass. After irradiation, the spectrum of the undoped glass shows a decrease of the intensity of the UV bands together with the resolution of an induced visible broad band centered at about 520 nm. The CuO doped glasses reveal the same UV absorption beside a very broad visible band centered at 780 nm and this band shows extension and splitting to several component peaks with higher CuO contents. Upon gamma irradiation, the spectra of all CuO-doped glasses reveal pronounced decrease of their intensities. The response of irradiation on the studied glasses is correlated with suggested photochemical reactions together with some shielding effect of the copper ions. The observed visible band is related to the presence of copper as distorted octahedral Cu(2+) ions. Infrared absorption spectra of the prepared glasses show repetitive characteristic triangular and tetrahedral borate units similar to that published from alkali or alkaline earth oxides B2O3 glasses. A suggested formation of (BO3/2F) tetrahedral units is advanced through action of LiF on B2O3 and these suggested units showing the same position and number as BO4 tetrahedra. Copyright © 2015 Elsevier B.V. All rights reserved.

Materials Data on Ba4Na(BO3)3 (SG:230) by Materials Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristin Persson

2016-04-06

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on EuAl3(BO3)4 (SG:155) by Materials Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristin Persson

2017-04-10

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity.

PubMed

Jin, Rongsheng; Rummel, Andreas; Binz, Thomas; Brunger, Axel T

2006-12-21

Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the neuroparalytic syndrome of botulism. With a lethal dose of 1 ng kg(-1), they pose a biological hazard to humans and a serious potential bioweapon threat. BoNTs bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors), which constitute part of the synaptic vesicle fusion machinery. The molecular details of the toxin-cell recognition have been elusive. Here we report the structure of a BoNT in complex with its protein receptor: the receptor-binding domain of botulinum neurotoxin serotype B (BoNT/B) bound to the luminal domain of synaptotagmin II, determined at 2.15 A resolution. On binding, a helix is induced in the luminal domain which binds to a saddle-shaped crevice on a distal tip of BoNT/B. This crevice is adjacent to the non-overlapping ganglioside-binding site of BoNT/B. Synaptotagmin II interacts with BoNT/B with nanomolar affinity, at both neutral and acidic endosomal pH. Biochemical and neuronal ex vivo studies of structure-based mutations indicate high specificity and affinity of the interaction, and high selectivity of BoNT/B among synaptotagmin I and II isoforms. Synergistic binding of both synaptotagmin and ganglioside imposes geometric restrictions on the initiation of BoNT/B translocation after endocytosis. Our results provide the basis for the rational development of preventive vaccines or inhibitors against these neurotoxins.

Spectroscopic and ultrasonic investigations on structural characterization of borate glass specimen doped with transition metal ions

NASA Astrophysics Data System (ADS)

Sathish, K.; Thirumaran, S.

2015-08-01

The present work describes the glass samples of composition (x% V2O5-(80-x)% B2O3-20% Na2CO3) VBS glass system and (x% MnO2-(80-x)% B2O3-20% Na2CO3) in MBS glass system with mol% ranging from x = 3, 6, 9, 12, 15 and 18 in steps of 3 mol% are prepared by melt quenching technique. For these prepared glass systems, sound velocity (longitudinal and shear velocities) and density have been measured. The sound velocity (longitudinal and shear) was measured by using pulse-echo technique at 5 MHz. The XRD study was carried to out to ascertain the amorphous nature of the glass specimen. Using these measured values, the elastic moduli, Poisson's ratio, Debye temperature, acoustic impedance and thermal expansion coefficient of the two glass systems were evaluated. The elastic and mechanical properties of the prepared glass systems are analyzed from ultrasonic study and the structural characterization from spectroscopic study. The effects due to the doping of transition metal ions with borate have been discussed. In the V2O5 doped glass system, (VBS glass system) the sound velocity, density and elastic moduli, steeply increases after 12 mol% comparatively with MnO2 doped glass system (VBS glass system). The present study critically observes the doping of V2O5 with borate enhances the strengthening of network linkage and hardening of the glassy network structure than MnO2. The IR spectral analysis reveals depolymerization of the borate network and conversion of BO3 or BO4 units with the formation of non-bridging oxygen. The FTIR spectral studies confirm the presence of various functional groups of the sample. FTIR spectrum of sample exhibits broad absorption bands indicating the wide distribution of borate structural units. The effect of Na2CO3, V2O5 and MnO2 contents on the structures of borate glass is evaluated from the FTIR spectra. The topological aspects of the prepared glass samples are exhaustively reported from SEM micrographs.

Effects of penicillin on procaine-elicited bursts of potential in central neuron of snail, Achatina fulica.

PubMed

Chen, Yi-Hung; Lu, Kuan-Ling; Hsiao, Ru-Wan; Lee, Ya-Ling; Tsai, Hong-Chieh; Lin, Chia Hsien; Tsai, Ming-Cheng

2008-08-01

Effects of penicillin on changes in procaine-elicited bursts of potential (BoP) were studied in a central neuron (RP4) of snail, Achatina fulica Ferussac. Procaine elicited BoP in the RP4 neuron while penicillin elicited depolarization of the neuron. Penicillin decreased the BoP elicited by procaine in a concentration-dependent manner. The effect of penicillin on the procaine-elicited BoP was not altered in the preparations treated with ascorbate or L-NAME (N-nitro-L-arginine methyl ester). However, the inhibitory effect of penicillin on the procaine-elicited BoP was enhanced with a decrease in extracellular sodium ion. Sodium ion was one of the important ions contributing to the action potential of the neuron. Two-electrode voltage-clamp studies revealed that penicillin decreased the fast sodium inward current of the neuron. It is concluded that penicillin inhibited the BoP elicited by procaine and sodium ion altered the effect of penicillin on procaine-elicited BoP.

Understanding Complex Tribofilms by Means of H3BO3-B2O3 Model Glasses.

PubMed

Spadaro, F; Rossi, A; Ramakrishna, Shivaprakash N; Lainé, E; Woodward, P; Spencer, N D

2018-02-13

The discovery of the spontaneous reaction of boric oxides with moisture in the air to form lubricious H 3 BO 3 films has led to great interest in the tribology of boron compounds in general. Despite this, a study of the growth kinetics of H 3 BO 3 on a B 2 O 3 substrate under controlled relative humidity (RH) has not yet been reported in the literature. Here, we describe the tribological properties of H 3 BO 3 -B 2 O 3 glass systems after aging under controlled RH over different lengths of time. A series of tribological tests has been performed applying a normal load of 15 N, at both room temperature and 100 °C in YUBASE 4 oil. In addition, the cause of H 3 BO 3 film failure under high-pressure and high-temperature conditions has been studied to find out whether the temperature, the tribostress, or both influence the removal of the lubricious film from the contact points. The following techniques were exploited: confocal Raman spectroscopy to characterize the structure and chemical nature of the glass systems, environmental scanning electron microscopy to examine the morphology of the H 3 BO 3 films developed, atomic force microscopy to monitor changes in roughness as a consequence of the air exposure, focused-ion-beam scanning electron microscopy to measure the average thickness of the H 3 BO 3 films grown over various times on B 2 O 3 glass substrates and to reveal the morphology of the sample in the vertical section, tribological tests to shed light on the system's lubricating properties, and finally small-area X-ray photoelectron spectroscopy to investigate the composition of the transfer film formed on the steel ball while tribotesting.

Four Months of Wearing a Balance Orthotic Improves Measures of Balance and Mobility Among a Cohort of Community-Living Older Adults.

PubMed

Noah, Sean; Gibson-Horn, Cynthia; Vincenzo, Jennifer L

2018-01-18

The Centers for Disease Control and Prevention estimated that there were 29 million falls and 7 million injuries in 2014 in the United States. Falls, decreased balance, and mobility disability are common in older adults and often result in loss of independence. Finding interventions to address these issues is important, as this age group is growing exponentially. Prior studies indicate balance and mobility can be improved by the balance-based torso-weighting (BBTW) assessment implemented through wear of a balance orthotic (BO). This study sought to determine the impact of wearing a BO on balance, mobility, and fall risk over time. This quasiexperimental, 1-group pre-/posttest study investigated the effect of 4 months of daily wear (4 hours per day) of a BO on mobility, balance, and falls efficacy in 30 older adults living in a retirement community with limited mobility defined by a Short Physical Performance Battery (SPPB) score range between 4 and 9 out of a maximum of 12 points. Pre- and posttreatment tests included the Timed Up and Go (TUG), Functional Gait Assessment (FGA), Falls Efficacy Scale (FES), and SPPB. Participants received the BBTW assessment, consisting of individualized assessment of 3-dimensional balance loss, and treatment with a strategically weighted and fitted BO to control balance loss. The BO was worn twice a day for 2 hours (4 hours per day) for 4 months. Participants continued regular activity and no other interventions were provided. All posttests were conducted after 4 months and at least 8 hours after removal of the BO. Subitems from the SPPB (gait speed [GS], 5-time sit-to-stand [FTSST], and tandem stance time [TST]) were analyzed as separate outcome measures. Data were analyzed with paired t tests with a Bonferroni correction (SPPB, GS, FGA, and FES) when statistical assumptions were met. Data that did not meet the statistical assumptions of the paired t test (FTSST, TST, and TUG) were analyzed with Wilcoxon signed rank tests with a Bonferroni correction. Twenty-four subjects, average age 87 (5.7) years, completed the study. Paired t tests indicated that mean group scores on the SPPB, GS, and FGA significantly improved from pre- to posttests. The SPPB improved by 1.3 points (P = .001). GS improved by 0.09 m/s (P = .004) and both mean values improved beyond fall risk cutoffs. The FGA also improved by 2.6 points (P = .001). There were no significant changes in FES scores (P = .110). Wilcoxon signed rank tests indicated median group scores of the FTSST significantly improved from pre- to posttests by 7.4 seconds (P = .002) and median TUG times improved by 3.5 seconds (P = .004). There were no changes in TST (P = .117). This study suggests that wearing a BO for 4 hours per day for 4 months results in improvements in functional assessments related to fall risk (SPPB, GS, FGA, TUG, and FTSST) in a group of older adult participants with limited mobility.

The structure, stability, and infrared spectrum of B 2N, B 2N +, B 2N -, BO, B 2O and B 2N 2.

NASA Astrophysics Data System (ADS)

Martin, J. M. L.; François, J. P.; Gijbels, R.

1992-05-01

The structure, infrared spectrum, and heat of formation of B 2N, B 2N -, BO, and B 2O have been studied ab initio. B 2N is very stable; B 2O even more so. B 2N, B 2N -, B 2O, and probably B 2N + have symmetric linear ground-state structures; for B 2O, an asymmetric linear structure lies about 12 kcal/mol above the ground state. B 2N +, B 2N - and B 2O have intense asymmetric stretching frequencies, predicted near 870, 1590 and 1400 cm -1, respectively. Our predicted harmonic frequencies and isotopic shifts for B 2O confirm the recent experimental identification by Andrews and Burkholder. Absorptions at 1889.5 and 1998.5 cm -1 in noble-gas trapped boron nitride vapor belong the BNB and BNBN ( 3Π), respectively; a tentative assignment of 882.5 cm -1 to BNB + is proposed. Total atomization energies Σ De (Σ D0) are computed (accuracy ±2 kcal/mol) as: BO 193.1 (190.4), B 2O 292.5 (288.7), B 2N 225.0 (250.3) kcal/mol. The ionization potential and electron affinity of B 2N are predicted to be 8.62±0.1 and 3.34±0.1 eV. The MP4-level additivity approximations involved in G1 theory results in errors on the order of 1 kcal/mol in the Σ De values.

Luminescence study of Dy or Ce activated LiCaBO3 phosphor for γ-ray and C5+ ion beam irradiation.

PubMed

Oza, Abha H; Dhoble, N S; Lochab, S P; Dhoble, S J

2015-11-01

The photoluminescence and thermoluminescence characteristics of rare earths (Dy or Ce) activated LiCaBO3 phosphors have been studied. Phosphors were synthesized by modified solid state synthesis. The phosphors were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence (PL) and thermoluminescence (TL) for structural, morphological and luminescence studies. Dy(3+) activated LiCaBO3 shows emission at 486 and 577 nm due to (4) F9/2 →(6) H15/2 and (4) F9/2 → (6) H13/2 transition, respectively, whereas the PL emission spectra of Ce(3+) activated LiCaBO3 phosphor shows a broad band peaking at 432 nm, which is due to the transition from 5d level to the ground state of the Ce(3+) ion. The thermoluminescence study was also carried out for both these phosphors for γ-ray irradiation and carbon beam irradiation. Linearity was studied for a 0.4-3.1 Rad dose γ-rays. Linear behaviour over this dose range was observed. Gamma ray-irradiated phosphors were shown to be negligible fading upon storage. All the samples were also studied for 75 MeV C(5+) ion beam exposure in the range of 3.75 × 10(12) - 7.5 × 10(13) ion cm(-2) fluence. In addition to this, trapping parameters of all the samples were also calculated using Chen's peak shape method. Copyright © 2015 John Wiley & Sons, Ltd.

Quantum dot immunoassays in renewable surface column and 96-well plate formats for the fluorescence detection of Botulinum neurotoxin using high-affinity antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warner, Marvin G.; Grate, Jay W.; Tyler, Abby J.

2009-09-01

A fluorescence sandwich immunoassay using high affinity antibodies and quantum dot (QD) reporters has been developed for detection of botulinum toxin serotype A (BoNT/A). For the development of the assay, a nontoxic recombinant fragment of the holotoxin (BoNT/A-HC-fragment) has been used as a structurally valid simulant for the full toxin molecule. The antibodies used, AR4 and RAZ1, bind to nonoverlapping epitopes present on both the full toxin and on the recombinant fragment. In one format, the immunoassay is carried out in a 96-well plate with detection in a standard plate reader. Detection down to 31 pM of the BoNT/Hc-fragment wasmore » demonstrated with a total incubation time of 3 hours, using AR4 as the capture antibody and QD-coupled RAZ1 as the reporter. In a second format, the AR4 capture antibody was coupled to Sepharose beads, and the immunochemical reactions were carried out in microcentrifuge tubes with an incubation time of 1 hour. These beads were subsequently captured and concentrated in a rotating rod “renewable surface” flow cell as part of a sequential injection fluidic system. This flow cell was equipped with a fiber optic system for fluorescence measurements. In PBS buffer solution matrix, the BoNT/A-HC-fragment was detected to concentrations as low as 5 pM using the fluidic measurement approach.« less

Cytochrome bo(3) from Escherichia coli: the binding and turnover of nitric oxide.

PubMed

Butler, Clive; Forte, Elena; Maria Scandurra, Francesca; Arese, Marzia; Giuffré, Alessandro; Greenwood, Colin; Sarti, Paolo

2002-09-06

The reaction of nitric oxide (NO) with fast and reduced cytochrome bo(3)(cyt bo(3)) from Escherichia coli has been investigated. The stoichiometry of NO binding to cyt bo(3) was determined using an NO electrode in the [NO] range 1-14 microM. Under reducing conditions, the initial decrease in [NO] following the addition of cyt bo(3) corresponded to binding of 1 NO molecule per cyt bo(3) functional unit. After this "rapid" NO binding phase, there was a slow, but significant rate of NO consumption ( approximately 0.3molNOmol bo(3)(-1)min(-1)), indicating that cyt bo(3) possesses a low level of NO reductase activity. The binding of NO to fast pulsed enzyme was also investigated. The results show that in the [NO] range used (1-14 microM) both fast and pulsed oxidised cyt bo(3) bind NO with a stoichiometry of 1:1 with an observed dissociation constant of K(d)=5.6+/-0.6 microM and that NO binding was inhibited by the presence of Cl(-). The binding of nitrite to the binuclear centre causes spectral changes similar to those observed upon NO binding to fast cyt bo(3). These results are discussed in relation to the model proposed by Wilson and co-workers [FEBS Lett. 414 (1997) 281] where the binding of NO to Cu(B)(II) results in the formation of the nitrosonium (Cu(B)(I)-NO(+)) complex. NO(+) then reacts with OH(-), a Cu(B) ligand, to form nitrite, which can bind at the binuclear centre. This work suggests for the first time that the binding of NO to oxidised cyt bo(3) does result in the reduction of Cu(B).

Genetic Characterization of Clostridium botulinum Associated with Type B Infant Botulism in Japan▿

PubMed Central

Umeda, Kaoru; Seto, Yoshiyuki; Kohda, Tomoko; Mukamoto, Masafumi; Kozaki, Shunji

2009-01-01

The 15 proteolytic Clostridium botulinum type B strains, including 3 isolates associated with infant botulism in Japan, were genetically characterized by phylogenetic analysis of boNT/B gene sequences, genotyping, and determination of the boNT/B gene location by using pulsed-field gel electrophoresis (PFGE) for molecular epidemiological analysis of infant botulism in Japan. Strain Osaka05, isolated from a case in 2005, showed a unique boNT/B gene sequence and was considered to be a new BoNT/B subtype by phylogenetic analysis. Strain Osaka06, isolated from a case in 2006, was classified as the B2 subtype, the same as strain 111, isolated from a case in 1995. The five isolates associated with infant botulism in the United States were classified into the B1 subtype. Isolates from food samples in Japan were divided into the B1 and the B2 subtypes, although no relation with infant botulism was shown by PFGE genotyping. The results of PFGE and Southern blot hybridization with undigested DNA suggested that the boNT/B gene is located on large plasmids (approximately 150 kbp, 260 kbp, 275 kbp, or 280 kbp) in five strains belonging to three BoNT/B subtypes from various sources. The botulinum neurotoxin (BoNT) of Osaka05 was suggested to have an antigenicity different from the antigenicities of BoNT/B1 and BoNT/B2 by a sandwich enzyme-linked immunosorbent assay with the recombinant BoNT/B-C-terminal domain. We established a multiplex PCR assay for BoNT/B subtyping which will be useful for epidemiological studies of type B strains and the infectious diseases that they cause. PMID:19571018

Polysaccharides induce radioprotection of murine hemopoietic stem cells and increase the LD50/30 days

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maisin, J.R.; Kondi-Tamba, A.; Mattelin, G.

1986-02-01

Intravenous administration of 60 mg/kg of a polysaccharide (MNR, MNZ, GLP/BO4, GLP/BO5) significantly decreases the mortality of mice exposed to a single dose of X rays. The dose reduction factors (DRF) obtained for MNZ, MNR, GLP/BO4, and GLP/BO5 given intraperitoneally 15 min before exposure were 2.16, 1.93, 1.80, and 1.94, respectively. The DRF was not increased when MNZ or GLP/BO4 were combined with injection of AET before X-ray exposure. The LD50 for the CFUs exposed in vivo in mice was 1.13 Gy for the treated mice and 0.75 Gy for the nontreated mice. This corresponds to a DRF of 1.6.more » The DRF calculated from the slope is 1.27.« less

Immunization of knock-out α/β interferon receptor mice against lethal bluetongue infection with a BoHV-4-based vector expressing BTV-8 VP2 antigen.

PubMed

Franceschi, Valentina; Capocefalo, Antonio; Calvo-Pinilla, Eva; Redaelli, Marco; Mucignat-Caretta, Carla; Mertens, Peter; Ortego, Javier; Donofrio, Gaetano

2011-04-05

New effective tools for vaccine strategies are necessary to limit the spread of bluetongue, an insect-transmitted viral disease of domestic and wild ruminants. In the present study, BoHV-4-based vector cloned as a bacterial artificial chromosome (BAC) was engineered to express the bluetongue virus (BTV) immune-dominant glycoprotein VP2 provided of a heterologous signal peptide to its amino terminal and a trans-membrane domain to its carboxyl terminal (IgK-VP2gDtm), to allow the VP2 expression targeting to the cell membrane fraction. Based on adult α/β interferon receptor knockout (IFNAR(-/-)) mice, a newly generated bluetongue laboratory animal model, a pre-challenge experiment was performed to test BoHV-4 safety on such immune-compromised animal. BoHV-4 infected IFNAR(-/-) mice did not show clinical signs even following the inoculation of BoHV-4 intra-cerebrally, although many areas of the brain got transduced. IFNAR(-/-) mice intraperitoneally inoculated twice with BoHV-4-A-IgK-VP2gDtm at different time points developed serum neutralizing antibodies against BTV and showed a strongly reduced viremia and a longer survival time when challenged with a lethal dose of BTV-8. The data acquired in this pilot study validate BoHV-4-based vector as a safe and effective heterologous antigen carrier/producer for the formulation of enhanced recombinant immunogens for the vaccination against lethal bluetongue. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening

NASA Astrophysics Data System (ADS)

Hu, Xin; Legler, Patricia M.; Southall, Noel; Maloney, David J.; Simeonov, Anton; Jadhav, Ajit

2014-07-01

Botulinum neurotoxin serotype A (BoNT/A) is the most lethal toxin among the Tier 1 Select Agents. Development of potent and selective small molecule inhibitors against BoNT/A zinc metalloprotease remains a challenging problem due to its exceptionally large substrate binding surface and conformational plasticity. The exosites of the catalytic domain of BoNT/A are intriguing alternative sites for small molecule intervention, but their suitability for inhibitor design remains largely unexplored. In this study, we employed two recently identified exosite inhibitors, D-chicoric acid and lomofungin, to probe the structural features of the exosites and molecular mechanisms of synergistic inhibition. The results showed that D-chicoric acid favors binding at the α-exosite, whereas lomofungin preferentially binds at the β-exosite by mimicking the substrate β-sheet binding interaction. Molecular dynamics simulations and binding interaction analysis of the exosite inhibitors with BoNT/A revealed key elements and hotspots that likely contribute to the inhibitor binding and synergistic inhibition. Finally, we performed database virtual screening for novel inhibitors of BoNT/A targeting the exosites. Hits C1 and C2 showed non-competitive inhibition and likely target the α- and β-exosites, respectively. The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication.

Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening.

PubMed

Hu, Xin; Legler, Patricia M; Southall, Noel; Maloney, David J; Simeonov, Anton; Jadhav, Ajit

2014-07-01

Botulinum neurotoxin serotype A (BoNT/A) is the most lethal toxin among the Tier 1 Select Agents. Development of potent and selective small molecule inhibitors against BoNT/A zinc metalloprotease remains a challenging problem due to its exceptionally large substrate binding surface and conformational plasticity. The exosites of the catalytic domain of BoNT/A are intriguing alternative sites for small molecule intervention, but their suitability for inhibitor design remains largely unexplored. In this study, we employed two recently identified exosite inhibitors, D-chicoric acid and lomofungin, to probe the structural features of the exosites and molecular mechanisms of synergistic inhibition. The results showed that D-chicoric acid favors binding at the α-exosite, whereas lomofungin preferentially binds at the β-exosite by mimicking the substrate β-sheet binding interaction. Molecular dynamics simulations and binding interaction analysis of the exosite inhibitors with BoNT/A revealed key elements and hotspots that likely contribute to the inhibitor binding and synergistic inhibition. Finally, we performed database virtual screening for novel inhibitors of BoNT/A targeting the exosites. Hits C1 and C2 showed non-competitive inhibition and likely target the α- and β-exosites, respectively. The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication.

Molecular dynamics simulations of wild type and mutants of botulinum neurotoxin A complexed with synaptic vesicle protein 2C.

PubMed

Wang, Feng; Wan, Hua; Hu, Jian-Ping; Chang, Shan

2015-01-01

Botulinum neurotoxins (BoNTs) are known as the most poisonous biological substances, and they are also used to treat a wide range of medical conditions as well as in the cosmetic applications. Recently, the complex structures of the BoNT/A receptor-binding domain (BoNT/A-RBD) and the synaptic vesicle protein 2C luminal domain (SV2C-LD) were determined by X-ray crystallography. In this article, the wild type (WT) and four mutants of the new structure are studied by molecular dynamics (MD) simulations. The differently decreased structural stabilities of the mutants relative to WT are shown to be consistent with the experimental data of binding affinities. The conformational changes of the five systems are explored by using principal component analysis (PCA) and free energy landscape (FEL) methods. Based on the calculation of interactions at the binding interface, we divide the interface between BoNT/A-RBD and SV2C-LD into two crucial binding regions. Through the comparison of WT and four mutants, we further propose the relationship between the conformational changes of BoNT/A-RBD:SV2C-LD and the interfacial interactions. This study would provide some new insights into the understanding of the dynamics and the interaction mechanism of BoNT/A-RBD:SV2C-LD.

[Role of BoBs technology in early missed abortion chorionic villi].

PubMed

Li, Z Y; Liu, X Y; Peng, P; Chen, N; Ou, J; Hao, N; Zhou, J; Bian, X M

2018-05-25

Objective: To investigate the value of bacterial artificial chromosome-on-beads (BoBs) technology in the genetic analysis of early missed abortion chorionic villi. Methods: Early missed abortion chorionic villi were detected with both conventional karyotyping method and BoBs technology in Peking Union Medical Hospital from July 2014 to March 2015. Compared the results of BoBs with conventional karyotyping analysis to evaluate the sensitivity, specificity and accuracy of this new method. Results: (1) A total of 161 samples were tested successfully in the technology of BoBs, 131 samples were tested successfully in the method of conventional karyotyping. (2) All of the cases obtained from BoBs results in (2.7±0.6) days and obtained from conventional karyotyping results in (22.5±1.9) days. There was significant statistical difference between the two groups ( t= 123.315, P< 0.01) . (3) Out of 161 cases tested in BoBs, 85 (52.8%, 85/161) cases had the abnormal chromosomes, including 79 cases chromosome number abnormality, 4 cases were chromosome segment deletion, 2 cases mosaic. Out of 131 cases tested successfully in conventional karyotyping, 79 (60.3%, 79/131) cases had the abnormal chromosomes including 62 cases chromosome number abnormality, 17 cases other chromosome number abnormality, and the rate of chromosome abnormality between two methods was no significant differences ( P =0.198) . (4) Conventional karyotyping results were served as the gold standard, the accuracy of BoBs for abnormal chromosomes was 82.4% (108/131) , analysed the normal chromosomes (52 cases) and chromosome number abnormality (62 cases) tested in conventional karyotyping, the accuracy of BoBs for chromosome number abnormality was 94.7% (108/114) . Conclusion: BoBs is a rapid reliable and easily operated method to test early missed abortion chorionic villi chromosomal abnormalities.

Anisotropic lattice thermal expansion of PbFeBO 4: A study by X-ray and neutron diffraction, Raman spectroscopy and DFT calculations

DOE PAGES

Murshed, M. Mangir; Mendive, Cecilia B.; Curti, Mariano; ...

2014-11-01

We present the lattice thermal expansion of mullite-type PbFeBO 4 in this study. The thermal expansion coefficients of the metric parameters were obtained from composite data collected from temperature-dependent neutron and X-ray powder diffraction between 10 K and 700 K. The volume thermal expansion was modeled using extended Grüneisen first-order approximation to the zero-pressure equation of state. The additive frame of the model includes harmonic, quasi-harmonic and intrinsic anharmonic potentials to describe the change of the internal energy as a function of temperature. Moreover, the unit-cell volume at zero-pressure and 0 K was optimized during the DFT simulations. Harmonic frequenciesmore » of the optical Raman modes at the Γ-point of the Brillouin zone at 0 K were also calculated by DFT, which help to assign and crosscheck the experimental frequencies. The low-temperature Raman spectra showed significant anomaly in the antiferromagnetic regions, leading to softening or hardening of some phonons. Selected modes were analyzed using a modified Klemens model. The shift of the frequencies and the broadening of the line-widths helped to understand the anharmonic vibrational behaviors of the PbO4, FeO6 and BO3 polyhedra as a function of temperature.« less

Unique Ganglioside Recognition Strategies for Clostridial Neurotoxins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, Marc A.; Fu, Zhuji; Kim, Jung-Ja P.

2012-03-15

Botulinum neurotoxins (BoNTs) and tetanus neurotoxin are the causative agents of the paralytic diseases botulism and tetanus, respectively. The potency of the clostridial neurotoxins (CNTs) relies primarily on their highly specific binding to nerve terminals and cleavage of SNARE proteins. Although individual CNTs utilize distinct proteins for entry, they share common ganglioside co-receptors. Here, we report the crystal structure of the BoNT/F receptor-binding domain in complex with the sugar moiety of ganglioside GD1a. GD1a binds in a shallow groove formed by the conserved peptide motif E ... H ... SXWY ... G, with additional stabilizing interactions provided by two argininemore » residues. Comparative analysis of BoNT/F with other CNTs revealed several differences in the interactions of each toxin with ganglioside. Notably, exchange of BoNT/F His-1241 with the corresponding lysine residue of BoNT/E resulted in increased affinity for GD1a and conferred the ability to bind ganglioside GM1a. Conversely, BoNT/E was not able to bind GM1a, demonstrating a discrete mechanism of ganglioside recognition. These findings provide a structural basis for ganglioside binding among the CNTs and show that individual toxins utilize unique ganglioside recognition strategies.« less

Conformational analysis of GT1B ganglioside and its interaction with botulinum neurotoxin type B: a study by molecular modeling and molecular dynamics.

PubMed

Venkateshwari, Sureshkumar; Veluraja, Kasinadar

2012-01-01

The conformational property of oligosaccharide GT1B in aqueous environment was studied by molecular dynamics (MD) simulation using all-atom model. Based on the trajectory analysis, three prominent conformational models were proposed for GT1B. Direct and water-mediated hydrogen bonding interactions stabilize these structures. The molecular modeling and 15 ns MD simulation of the Botulinum Neuro Toxin/B (BoNT/B) - GT1B complex revealed that BoNT/B can accommodate the GT1B in the single binding mode. Least mobility was seen for oligo-GT1B in the binding pocket. The bound conformation of GT1B obtained from the MD simulation of the BoNT/B-GT1B complex bear a close conformational similarity with the crystal structure of BoNT/A-GT1B complex. The mobility noticed for Arg 1268 in the dynamics was accounted for its favorable interaction with terminal NeuNAc. The internal NeuNAc1 tends to form 10 hydrogen bonds with BoNT/B, hence specifying this particular site as a crucial space for the therapeutic design that can restrict the pathogenic activity of BoNT/B.

Granting Teachers the "Benefit of the Doubt" in Performance Evaluations

ERIC Educational Resources Information Center

Rogge, Nicky

2011-01-01

Purpose: This paper proposes a benefit of the doubt (BoD) approach to construct and analyse teacher effectiveness scores (i.e. SET scores). Design/methodology/approach: The BoD approach is related to data envelopment analysis (DEA), a linear programming tool for evaluating the relative efficiency performance of a set of similar units (e.g. firms,…

Effect of stimulation intensity and botulinum toxin isoform on rat bladder strip contractions.

PubMed

Smith, Christopher P; Boone, Timothy B; de Groat, William C; Chancellor, Michael B; Somogyi, George T

2003-07-15

The present experiments compared the inhibitory effects of botulinum toxin A (BoNT-A) and botulinum toxin D (BoNT-D) on neurally evoked contractions of rat bladder strips. We examined the effect of fatigue (trains of 100 shocks at 20Hz every 20s for 10min) followed by non-fatigue stimulation (trains of 100 shocks at 20Hz every 100s for 20min) on the onset of effect and potency of the two toxins. For non-fatigue experiments, strips were untreated (n=4); or incubated with 1.36nM BoNT-A (n=4). During fatigue experiments, strips were untreated (n=5); or treated with either 1.36nM BoNT-A (n=6) or 0.8nM BoNT-D (n=6). In non-fatigue experiments, BoNT-A produced significant decreases in contractile area after 1h of stimulation compared to untreated strips (P<0.05). After three series of fatigue stimulation, differences in recovery amplitude and area between untreated versus BoNT-A, and untreated versus BoNT-D bladder strips, were statistically significant (P<0.05). The onset of inhibitory effect was quicker in BoNT-D-treated strips, as a significant reduction (P<0.05) in recovery of contractile area was observed after 1h of stimulation compared to both untreated and BoNT-A-treated preparations. In addition, treated (BoNT-A and BoNT-D) and untreated bladder strips responded similarly to atropine, suggesting that the effects of BoNT result from inhibition of both acetylcholine and ATP release. Our results demonstrate that BoNT-D may be a more effective agent to inhibit transmitter release from autonomic nerves of the rat lower urinary tract. Moreover, in our hands, non-fatigue stimulation is as effective as fatigue stimulation in inhibiting bladder strip contractions.

Botulinum toxin A in the treatment of glabellar lines: scheduling the next injection.

PubMed

Ascher, Benjamin; Zakine, Benjamin; Kestemont, Philippe; Baspeyras, Martine; Bougara, Ali; Niforos, François; Malet, Thierry; Santini, José

2005-01-01

A single intramuscular treatment with botulinum toxin A (BoNT-A) into the facial muscles underlying glabellar rhytids has been shown to effectively attenuate or totally erase these lines for at least 3 months. We sought to evaluate the optimal time for a second injection of BoNT-A (Dysport, Ipsen). One hundred patients with moderate to severe glabellar rhytids at rest were randomized to a first, double-blind injection of 50 U of BoNT-A (n = 50) divided into 5 intramuscular sites, or placebo (n = 50). At monthly intervals between Month 3 and Month 6, the patient and the investigator consensually decided to repeat the injection with open-label BoNT-A in both groups. The main outcome was the time between the first and second injections. Responder ratings (mild or no glabellar lines) after the first and second injections, patient satisfaction, and safety were also assessed. At Months 3 and 4 after the first injection, the cumulative percentage of patients having a second injection was lower in the BoNT-A group compared to the placebo group, with a significant difference at Month 4. Following the first double-blind injection, responder rates were significantly higher in BoNT-A group (up to 75%) compared to placebo up to Month 4, and a large majority of patients were significantly satisfied with the BoNT-A treatment at Month 4 (75% satisfied and completely satisfied versus 9.1% with placebo) and Month 5 (86.7% versus 0%, respectively). Headache was the most frequent adverse event in the BoNT-A group (10% versus 6% in the placebo group). No blepharoptosis was reported. The effectiveness of 50 U of BoNT-A was confirmed for the treatment of glabellar lines. A second injection was sought within 3 to 4 months by most patients and investigators. Both injections were safe.

High-pressure synthesis, crystal chemistry and physics of perovskites with small cations at the A site.

PubMed

Belik, Alexei A; Yi, Wei

2014-04-23

ABO3 perovskites with small cations at the A site (A = Sc(3+), In(3+) and Mn(2+) and B = Al(3+) and transition metals) are reviewed. They extend the corresponding families of perovskites with A(3+) = Y, La-Lu, and Bi and A(2+) = Cd, Ca, Sr and Ba and exhibit the largest structural distortions. As a result of these large distortions, they show, in many cases, distinct structural and magnetic properties. These are manifested in: B-site-ordered monoclinic structures of ScMnO3 and 'InMnO3'; an unusual superstructure of ScRhO3 and InRhO3; antiferromagnetic ground states and multiferroic properties of Sc2NiMnO6 and In2NiMnO6; two magnetic transitions in ScCrO3 and InCrO3 with very close transition temperatures; a Pnma-to-P-1 structural transition and k = (½, 0, ½) magnetic ordering in ScVO3; and incommensurate magnetic ordering of Mn(2+) spins in metallic MnVO3. A large number of simple ScBO3, InBO3 and MnBO3 perovskites has not been synthesized yet, and the number of experimental and theoretical works on each known ScBO3, InBO3 and MnBO3 perovskites counts to only one or two (except for ScAlO3). The synthesis, crystal chemistry and physics of perovskites with small cations at the A site is an emerging field in perovskite science.

Improved Electrochemical Performance of Carbon-Coated LiFeBO 3 Nanoparticles for Lithium-Ion Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhaoping; Wang, Yiping; Hu, Querui

2015-09-01

Carbon-coated LiFeBO 3 nanoparticles have been successfully prepared by surfactant-assisted ball milling and a size selection process based on centrifugal separation. We observed monodispersed LiFeBO 3 nanoparticles with dimensions of 10–20 nm by transmission electron microscope. The introduced surfactant acts as the dispersant as well as the carbon source for LiFeBO 3 nanoparticles. Greatly improved discharge capacities of 190.4 mA h g –1 at 0.1 C and 106.6 mA h g –1 at 1 C rate have been achieved in the LiFeBO 3 nanoparticles when cycling the cells between 1.0 V and 4.8 V. Meanwhile, the as-prepared micro-size LiFeBO 3more » electrodes show lower discharge capacities of 142 mA h g –1 and 93.3 mA h g –1 at 0.1 C and 1 C rates. Moreover, the post-treated LiFeBO 3 nanostructure has drastically enhanced the electrochemical performance due to the short diffusion length and ameliorated electrical contract between LiFeBO 3 nano particles.« less

Identification of small molecule inhibitors of botulinum neurotoxin serotype E via footprint similarity

DOE PAGES

Zhou, Yuchen; McGillick, Brian E.; Teng, Yu-Han Gary; ...

2016-07-18

Botulinum neurotoxins (BoNT) are among the most poisonous substances known, and of the 7 serotypes (A–G) identified thus far at least 4 can cause death in humans. Here, the goal of this work was identification of inhibitors that specifically target the light chain catalytic site of the highly pathogenic but lesser-studied E serotype (BoNT/E). Large-scale computational screening, employing the program DOCK, was used to perform atomic-level docking of 1.4 million small molecules to prioritize those making favorable interactions with the BoNT/E site. In particular, ‘footprint similarity’ (FPS) scoring was used to identify compounds that could potentially mimic features on themore » known substrate tetrapeptide RIME. Among 92 compounds purchased and experimentally tested, compound C562-1101 emerged as the most promising hit with an apparent IC 50 value three-fold more potent than that of the first reported BoNT/E small molecule inhibitor NSC-77053. Additional analysis showed the predicted binding pose of C562-1101 was geometrically and energetically stable over an ensemble of structures generated by molecular dynamic simulations and that many of the intended interactions seen with RIME were maintained. Finally, several analogs were also computationally designed and predicted to have further molecular mimicry thereby demonstrating the potential utility of footprint-based scoring protocols to help guide hit refinement.« less

Identification of small molecule inhibitors of botulinum neurotoxin serotype E via footprint similarity.

PubMed

Zhou, Yuchen; McGillick, Brian E; Teng, Yu-Han Gary; Haranahalli, Krupanandan; Ojima, Iwao; Swaminathan, Subramanyam; Rizzo, Robert C

2016-10-15

Botulinum neurotoxins (BoNT) are among the most poisonous substances known, and of the 7 serotypes (A-G) identified thus far at least 4 can cause death in humans. The goal of this work was identification of inhibitors that specifically target the light chain catalytic site of the highly pathogenic but lesser-studied E serotype (BoNT/E). Large-scale computational screening, employing the program DOCK, was used to perform atomic-level docking of 1.4 million small molecules to prioritize those making favorable interactions with the BoNT/E site. In particular, 'footprint similarity' (FPS) scoring was used to identify compounds that could potentially mimic features on the known substrate tetrapeptide RIME. Among 92 compounds purchased and experimentally tested, compound C562-1101 emerged as the most promising hit with an apparent IC 50 value three-fold more potent than that of the first reported BoNT/E small molecule inhibitor NSC-77053. Additional analysis showed the predicted binding pose of C562-1101 was geometrically and energetically stable over an ensemble of structures generated by molecular dynamic simulations and that many of the intended interactions seen with RIME were maintained. Several analogs were also computationally designed and predicted to have further molecular mimicry thereby demonstrating the potential utility of footprint-based scoring protocols to help guide hit refinement. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of small molecule inhibitors of botulinum neurotoxin serotype E via footprint similarity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Yuchen; McGillick, Brian E.; Teng, Yu-Han Gary

Botulinum neurotoxins (BoNT) are among the most poisonous substances known, and of the 7 serotypes (A–G) identified thus far at least 4 can cause death in humans. Here, the goal of this work was identification of inhibitors that specifically target the light chain catalytic site of the highly pathogenic but lesser-studied E serotype (BoNT/E). Large-scale computational screening, employing the program DOCK, was used to perform atomic-level docking of 1.4 million small molecules to prioritize those making favorable interactions with the BoNT/E site. In particular, ‘footprint similarity’ (FPS) scoring was used to identify compounds that could potentially mimic features on themore » known substrate tetrapeptide RIME. Among 92 compounds purchased and experimentally tested, compound C562-1101 emerged as the most promising hit with an apparent IC 50 value three-fold more potent than that of the first reported BoNT/E small molecule inhibitor NSC-77053. Additional analysis showed the predicted binding pose of C562-1101 was geometrically and energetically stable over an ensemble of structures generated by molecular dynamic simulations and that many of the intended interactions seen with RIME were maintained. Finally, several analogs were also computationally designed and predicted to have further molecular mimicry thereby demonstrating the potential utility of footprint-based scoring protocols to help guide hit refinement.« less

Polarized spectral properties and potential application of large-size Nd3+:Ba3Gd2(BO3)4 crystal

NASA Astrophysics Data System (ADS)

Gao, S. F.; Lv, S. Z.; Zhu, Z. J.; Wang, Y.; You, Z. Y.; Li, J. F.; Xu, J. L.; Wang, H. Y.; Tu, C. Y.

2014-06-01

The Nd3+-doped Ba3Gd2(BO3)4 crystal with high optical quality and large size is reported in this paper. The growing processes and characteristics of Nd3+:Ba3Gd2(BO3)4 crystal are discussed. The absorption and luminescence spectra of Nd3+ in Ba3Gd2(BO3)4 crystal were measured at room temperature. The luminescence decay curve in correspondence with the 4F3/2 →4I11/2 transition centered at 1062 nm was also measured. The JO intensity parameters Ωt (t = 2,4,6) were calculated to be Ω2 = 1.263, Ω4 = 2.496, Ω6 = 3.606. The radiative lifetime τr and fluorescence lifetime τf are 317.771 and 115 μs respectively, and the fluorescence quantum efficiency is 37.1%.

Preclinical assessment of potential interactions between botulinum toxin and neuromodulation for bladder micturition reflex.

PubMed

Su, Xin; Nickles, Angela; Nelson, Dwight E

2015-06-09

While botulinum toxin A (BoNT-A) has become a more commonly used second-line treatment for patients with detrusor overactivity, it remains unknown whether the impacts of this therapy may persist to influence other therapies such as sacral neuromodulation. In this preclinical study we have evaluated urodynamic functions to intradetrusor injection of BoNT-A and the bladder inhibitory effects of spinal nerve stimulation (SNS) following BoNT-A treatment. Female rats were anesthetized with 3 % isoflurane. BoNT-A (2 units, 0.2 ml) or saline were injected into the detrusor. Rats then were housed for 2 days to 1 month before neuromodulation study. Monopolar electrodes were placed under each of the L6 spinal nerve bilaterally under urethane anesthesia. A bladder cannula was inserted via the urethra for saline infusion and intravesical pressure recording. Intradetrusor injection of BoNT-A for 1-2 weeks or 1 month significantly increased bladder capacity compared with saline injection (p < 0.05, two-way ANOVA). Following BoNT-A, SNS attenuated the frequency of bladder contractions, either eliminating bladder contractions or reducing the contraction frequency during electrical stimulation. Inhibition of the contraction frequency by SNS following BoNT-A treated rats was not different from that measured following saline injection. BoNT-A increased the bladder capacity, but compensating for additional saline infusion to the enlarged urinary bladder in BoNT-A pretreated rats, the bladder contractions induced by bladder filling were attenuated by SNS. BoNT-A did not alter the ability of SNS to inhibit bladder contraction following intradetrusor injection of BoNT-A for 2 days, 1-2 weeks or 1 month. These results support further pre-clinical and clinical studies to evaluate potential interactions or combination therapy with neuromodulation and intradetrusor BoNT-A therapeutic approaches.

Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity

USDA-ARS?s Scientific Manuscript database

Botulinum neurotoxins (BoNTs) are highly potent oral poisons produced by Clostridium botulinum. BoNTs are secreted along with several auxiliary proteins forming progenitor toxin complexes (PTC). Here, we report the structure of a ~760 kDa 14-subunit PTC using a combination of X-ray crystallography a...

Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway

PubMed Central

Wattam, Alice R.; Inzana, Thomas J.; Williams, Kelly P.; Mane, Shrinivasrao P.; Shukla, Maulik; Almeida, Nalvo F.; Dickerman, Allan W.; Mason, Steven; Moriyón, Ignacio; O’Callaghan, David; Whatmore, Adrian M.; Sobral, Bruno W.; Tiller, Rebekah V.; Hoffmaster, Alex R.; Frace, Michael A.; De Castro, Cristina; Molinaro, Antonio; Boyle, Stephen M.; De, Barun K.; Setubal, João C.

2012-01-01

ABSTRACT Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted. Here we present a phylogenomic analysis of the draft genome sequences of BO1T and BO2 and of the Australian rodent strains 83-13 and NF2653 that shows that they form two groups well separated from the other sequenced Brucella spp. Several important differences were noted. Both BO1T and BO2 did not agglutinate significantly when live or inactivated cells were exposed to monospecific A and M antisera against O-side chain sugars composed of N-formyl-perosamine. While BO1T maintained the genes required to synthesize a typical Brucella O-antigen, BO2 lacked many of these genes but still produced a smooth LPS (lipopolysaccharide). Most missing genes were found in the wbk region involved in O-antigen synthesis in classic smooth Brucella spp. In their place, BO2 carries four genes that other bacteria use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and chemical analyses showed that BO2 carries an antigenically different O-antigen made of repeating hexose-rich oligosaccharide units that made the LPS water-soluble, which contrasts with the homopolymeric O-antigen of other smooth brucellae that have a phenol-soluble LPS. The results demonstrate the existence of a group of early-diverging brucellae with traits that depart significantly from those of the Brucella species described thus far. PMID:22930339

Temperature dependence of local structural changes around transition metal centers Cr3+ and Mn2+ in RAl3(BO3)4 crystals studied by EMR

NASA Astrophysics Data System (ADS)

Açıkgöz, Muhammed; Rudowicz, Czesław; Gnutek, Paweł

2017-11-01

Theoretical investigations are carried out to determine the temperature dependence of the local structural parameters of Cr3+ and Mn2+ ions doped into RAl3(BO3)4 (RAB, R = Y, Eu, Tm) crystals. The zero-field splitting (ZFS) parameters (ZFSPs) obtained from the spin Hamiltonian (SH) analysis of EMR (EPR) spectra serve for fine-tuning the theoretically predicted ZFSPs obtained using the semi-empirical superposition model (SPM). The SPM analysis enables to determine the local structure changes around Cr3+ and Mn2+ centers in RAB crystals and explain the observed temperature dependence of the ZFSPs. The local monoclinic C2 site symmetry of all Al sites in YAB necessitates consideration of one non-zero monoclinic ZFSP (in the Stevens notation, b21) for Cr3+ ions. However, the experimental second-rank ZFSPs (D =b20 , E = 1 / 3b22) were expressed in a nominal principal axis system. To provide additional insight into low symmetry aspects, the distortions (ligand's distances ΔRi and angular distortions Δθi) have been varied while preserving monoclinic site symmetry, in such way as to obtain the calculated values (D, E) close to the experimental ones, while keeping b21 close to zero. This procedure yields good matching of the calculated ZFSPs and the experimental ones, and enables determination of the corresponding local distortions. The present results may be useful in future studies aimed at technological applications of the Huntite-type borates with the formula RM3(BO3)4. The model parameters determined here may be utilized for ZFSP calculations for Cr3+ and Mn2+ ions at octahedral sites in single-molecule magnets and single-chain magnets.

Effects of scandium substitution on the crystal structure and luminescence properties of LuBO{sub 3}: Ce{sup 3+}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Yuntao, E-mail: caswyt@hotmail.com; Ren, Guohao, E-mail: rgh@mail.sic.ac.cn; Ding, Dongzhou

2012-10-15

The calcite phase of LuBO{sub 3} and ScBO{sub 3} polycrystalline powders were synthesized by solid state reaction method, and the Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce (x=0.2, 0.5, 0.7) single crystals were grown by the Czochralski method. A large composition deviation between the initial polycrystalline powders and final single crystal was confirmed by electron probe micro-analysis. Raman spectroscopy revealed that moderate lattice disorder was induced by scandium substitution. However, based on the single crystal X-ray study, we finally concluded that the crystal structure of lutetium scandium orthoborate still crystallized in the rhombohedral system belonging to R3{sup -}c. Furthermore, the relationship between themore » energies of the five 5d levels of Ce{sup 3+} and the crystalline environment was revealed. The total redshift, total crystal field splitting, and centroid shift of Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce{sup 3+} were calculated based on their VUV excitation spectra. The variations trend of these observed spectroscopic parameters was in accordance with the predicted ones. - Graphical abstract: The crystal structure of Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce is rhombohedral system with R3{sup -}c space group. The relationship between the energies of the five Ce{sup 3+} 5d levels and the crystalline environment is established. Highlights: Black-Right-Pointing-Pointer Moderate lattice disorder is induced by scandium doping. Black-Right-Pointing-Pointer The crystal structure of Lu{sub 1-x}Sc{sub x}BO{sub 3}:Ce is rhombohedral system with R3{sup -}c space group. Black-Right-Pointing-Pointer Relationship between energies of Ce{sup 3+} 5d levels and crystalline environment is established. Black-Right-Pointing-Pointer The spectroscopic parameters are experimentally and theoretically calculated.« less

Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections.

PubMed

Minamoto, Viviane B; Suzuki, Kentaro P; Bremner, Shannon N; Lieber, Richard L; Ward, Samuel R

2015-10-01

Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8). The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber-type grouping. These experiments demonstrate a disproportionately greater effect of repeated BoNT injections. © 2015 Wiley Periodicals, Inc.

Clinical Uses of Botulinum Neurotoxins: Current Indications, Limitations and Future Developments

PubMed Central

Chen, Sheng

2012-01-01

Botulinum neurotoxins (BoNTs) cause flaccid paralysis by interfering with vesicle fusion and neurotransmitter release in the neuronal cells. BoNTs are the most widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat strabismus, blepharospam, and hemificial spasm as early as 1989 and then for treatment of cervical dystonia, glabellar facial lines, axillary hyperhidrosis, chronic migraine and for cosmetic use. Due to its high efficacy, longevity of action and satisfactory safety profile, it has been used empirically in a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, and painful disorders. Currently available BoNT therapies are limited to neuronal indications with the requirement of periodic injections resulting in immune-resistance for some indications. Recent understanding of the structure-function relationship of BoNTs prompted the engineering of novel BoNTs to extend therapeutic interventions in non-neuronal systems and to overcome the immune-resistance issue. Much research still needs to be done to improve and extend the medical uses of BoNTs. PMID:23162705

Na{sub 6}B{sub 13}O{sub 22.5}, a new noncentrosymmetric sodium borate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penin, N.; Touboul, M.; Nowogrocki, G.

2005-03-15

Na{sub 6}B{sub 13}O{sub 22.5} (B/Na=2.17) single crystals were obtained by heating, melting and appropriately cooling borax, Na{sub 2}[B{sub 4}O{sub 5}(OH){sub 4}].8H{sub 2}O. Its formula has been determined by the resolution of the structure from single-crystal X-ray diffraction data. The compound crystallizes in the noncentrosymmetric orthorhombic Iba2 space group, with the following unit cell parameters: a=33.359(11)A, b=9.554(3)A, c=10.644(4)A; V=3392.4(19)A{sup 3}; Z=8. The crystal structure was solved from 3226 reflections until R{sub 1}=0.0385. It exhibits a three-dimensional framework built up from BO{sub 3} triangles ({delta}) and BO{sub 4} tetrahedra (T). Two kinds of borate groups can be considered forming two different doublemore » B{sub 3}O{sub 3} rings: two B{sub 4}O{sub 9} (linkage by two boron atoms) and one B{sub 5}O{sub 11} (linkage by one boron atom); the shorthand notation of the new fundamental building block (FBB) existing in this compound is: 13: {infinity}{sup 3} [(5: 3{delta}+2T)+2(4: 2{delta}+2T)]. The discovery of this new borate questions the real number of Na{sub 2}B{sub 4}O{sub 7} varieties. The existence of Na{sub 6}B{sub 13}O{sub 22.5} (B/Na=2.17) and of another recently discovered borate, Na{sub 3}B{sub 7}O{sub 12} (B/Na=2.33; FBB 7: {infinity}{sup 3} [(3: 2{delta}+T)+(3: {delta}+2T)+(1: {delta})], with a composition close to the long-known borate {alpha}-Na{sub 2}B{sub 4}O{sub 7} (B/Na=2; FBB 8: {infinity}{sup 3} [(5: 3{delta}+2T)+(3: 2{delta}+T)], may explain the very complex equilibria reported in the Na{sub 2}O-B{sub 2}O{sub 3} phase diagram, especially in this range of composition.« less

Structure Based Discovery of Pan Active Botulinum Neurotoxin Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vieni, Casey; McGillick, Brian; Kumaran, Desigan

Clostridium botulinum neurotoxins (BoNTs) released by the bacterium Clostridium botulinum are the most potent toxins causing the fatal disease called botulism. There are seven distinct serotypes of BoNTs (A to G) released by various strains of botulinum. They all have high sequence homology and similar three-dimensional structure. The toxicity of BoNT follows a four-step process – binding, internalization, translocation, and cleavage of its target protein, one of the three components of the SNARE complex (Soluble N-ethylmaleimde-sensitive factor attachment protein receptor) required for membrane docking and neurotransmitter release. Cleavage of one of the three proteins causes blockage of neurotransmitter release leadingmore » to flaccid paralysis. Though anyone of the above four steps could be a target for developing antidotes for botulism, the catalytic domain is the most suitable target for post exposure treatment. Of the seven serotypes BoNT/A, B, E and probably F affect humans, with BoNT/A considered to be the most potent. Development of drugs for botulism is focused on serotype specific inhibitors, but a pan-active inhibitor acting on several serotypes is preferable since it is difficult to identify the serotype before the treatment, especially since there is at least a 36-hour window before botulism can be diagnosed. Using structure-based drug discovery, we have developed three heptapeptides based on the SNARE proteins which inhibit BoNT/A, B and E equally well. Probable reasons for pan-activity of these peptides are discussed.« less

Structure Based Discovery of Pan Active Botulinum Neurotoxin Inhibitors

DOE PAGES

Vieni, Casey; McGillick, Brian; Kumaran, Desigan; ...

2018-02-14

Clostridium botulinum neurotoxins (BoNTs) released by the bacterium Clostridium botulinum are the most potent toxins causing the fatal disease called botulism. There are seven distinct serotypes of BoNTs (A to G) released by various strains of botulinum. They all have high sequence homology and similar three-dimensional structure. The toxicity of BoNT follows a four-step process – binding, internalization, translocation, and cleavage of its target protein, one of the three components of the SNARE complex (Soluble N-ethylmaleimde-sensitive factor attachment protein receptor) required for membrane docking and neurotransmitter release. Cleavage of one of the three proteins causes blockage of neurotransmitter release leadingmore » to flaccid paralysis. Though anyone of the above four steps could be a target for developing antidotes for botulism, the catalytic domain is the most suitable target for post exposure treatment. Of the seven serotypes BoNT/A, B, E and probably F affect humans, with BoNT/A considered to be the most potent. Development of drugs for botulism is focused on serotype specific inhibitors, but a pan-active inhibitor acting on several serotypes is preferable since it is difficult to identify the serotype before the treatment, especially since there is at least a 36-hour window before botulism can be diagnosed. Using structure-based drug discovery, we have developed three heptapeptides based on the SNARE proteins which inhibit BoNT/A, B and E equally well. Probable reasons for pan-activity of these peptides are discussed.« less

Structures and chemical bonding of B{sub 3}O{sub 3}{sup −/0} and B{sub 3}O{sub 3}H{sup −/0}: A combined photoelectron spectroscopy and first-principles theory study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Li-Juan; Xu, Hong-Guang; Feng, Gang

We present a combined photoelectron spectroscopy and first-principles theory study on the structural and electronic properties and chemical bonding of B{sub 3}O{sub 3}{sup −/0} and B{sub 3}O{sub 3}H{sup −/0} clusters. The concerted experimental and theoretical data show that the global-minimum structures of B{sub 3}O{sub 3} and B{sub 3}O{sub 3}H neutrals are very different from those of their anionic counterparts. The B{sub 3}O{sub 3}{sup −} anion is characterized to possess a V-shaped OB–B–BO chain with overall C{sub 2v} symmetry (1A), in which the central B atom interacts with two equivalent boronyl (B≡O) terminals via B–B single bonds as well as withmore » one O atom via a B=O double bond. The B{sub 3}O{sub 3}H{sup −} anion has a C{sub s} (2A) structure, containing an asymmetric OB–B–OBO zig-zag chain and a terminal H atom interacting with the central B atom. In contrast, the C{sub 2v} (1a) global minimum of B{sub 3}O{sub 3} neutral contains a rhombic B{sub 2}O{sub 2} ring with one B atom bonded to a BO terminal and that of neutral B{sub 3}O{sub 3}H (2a) is also of C{sub 2v} symmetry, which is readily constructed from C{sub 2v} (1a) by attaching a H atom to the opposite side of the BO group. The H atom in B{sub 3}O{sub 3}H{sup −/0} (2A and 2a) prefers to interact terminally with a B atom, rather than with O. Chemical bonding analyses reveal a three-center four-electron (3c-4e) π hyperbond in the B{sub 3}O{sub 3}H{sup −} (2A) cluster and a four-center four-electron (4c-4e) π bond (that is, the so-called o-bond) in B{sub 3}O{sub 3} (1a) and B{sub 3}O{sub 3}H (2a) neutral clusters.« less

Kennedy, the early sixties, and visitation by the angel of death.

PubMed

O'Toole, D; Chase, C C L; Miller, M M; Campen, H Van

2014-11-01

The inaugural issue of Pathologia Veterinaria in 1964 contained the first detailed account of lesions in aborted fetuses following natural, experimental, and postvaccinal infection with bovine herpesvirus 1 (BoHV-1). The article, written by pathologists Kennedy and Richards, described diagnostic gross and histologic features in 13 bovine fetuses. The authors provided clinical and epidemiologic features of 1 postvaccination outbreak, including the absence of clinical signs in infected dams and the propensity for abortions to occur after 6 months' gestation. Subsequent field and experimental studies corroborated and expanded these observations. As a result of this and later reports, veterinarians became alert to the association between infectious bovine rhinotracheitis and abortion, including the risks of exposing pregnant cattle to live vaccinal BoHV-1. Methods were developed to corroborate a morphologic diagnosis of herpetic abortion in cattle, including immunofluorescence, immunohistochemistry, and polymerase chain reaction methods. Outbreaks of postvaccinal BoHV-1 abortion in the United States began to be reported with apparently increased frequency in the early 2000s. This coincided with licensure in 2003 of modified live BoHV-1 vaccines intended for use in pregnant cattle, which are now sold by 3 manufacturers. Ten recent herd episodes of postvaccinal BoHV-1 abortion are reported. All 10 BoHV-1 isolates had single-nucleotide polymorphism (SNPs) profiles previously identified in a group of BoHV-1 isolates that contains vaccine strains, based on a BoHV-1 SNP classification system. They lacked SNP features typical of those in characterized field-type strains of BoHV-1. © The Author(s) 2014.

Synthesis, electrical and magnetic properties of sodium borosilicate glasses containing Co-ferrites nanoparticles

NASA Astrophysics Data System (ADS)

Othman, H. A.; Eltabey, M. M.; Ibrahim, Samia. E.; El-Deen, L. M. Sharaf; Elkholy, M. M.

2017-02-01

Co-ferrites nanoparticles that have been prepared by the co-precipitation method were added to sodium borosilicate (Na2O-B2O3-SiO2) glass matrix by the solid solution method and they were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and magnetization measurements. (XRD) revealed the formation of the Co-ferrite magnetic crystalline phase embedded in an amorphous matrix in all the samples. The investigated samples by (TEM) showed the formation of the cobalt ferrite nanoparticles with a spherical shape and highly monodispersed with an average size about 13 nm. IR data revealed that the BO3 and BO4 are the main structural units of these samples network. IR spectra of the investigated samples showed the characteristic vibration bands of Co-ferrite. Composition and frequency dependent dielectric properties of the prepared samples were measured at room temperature in the frequency range 100-100 kHz. The conductivity was found to increase with increasing cobalt ferrite content. The variations of conductivity and dielectric properties with frequency and composition were discussed. Magnetic hysteresis loops were traced at room temperature using VSM and values of saturation magnetization MS and coercive field HC were determined. The obtained results revealed that a ferrimagnetic behavior were observed and as Co-ferrite concentration increases the values of MS and HC increase from 2.84 to 8.79 (emu/g) and from 88.4 to 736.3 Oe, respectively.

Formation, stability and crystal structure of mullite-type Al{sub 6−x}B{sub x}O{sub 9}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoffmann, K., E-mail: Kristin.Hoffmann@uni-bremen.de; Institut für Anorganische Chemie und Kristallographie, FB02, Leobener Straße/NW2, Universität Bremen, D-28359 Bremen; Hooper, T.J.N.

2016-11-15

Mullite-type Al{sub 6−x}B{sub x}O{sub 9} compounds were studied by means of powder diffraction and spectroscopic methods. The backbones of this structure are chains of edge-connected AlO{sub 6} octahedra crosslinked by AlO- and BO-polyhedra. Rietveld refinements show that the a and b lattice parameters can be well resolved, thus representing an orthorhombic metric. A continuous decrease of the lattice parameters most pronounced in c-direction indicates a solid solution for Al{sub 6−x}B{sub x}O{sub 9} with 1.09≤x≤2. A preference of boron in 3-fold coordination is confirmed by {sup 11}B MAS NMR spectroscopy and Fourier calculations based on neutron diffraction data collected at 4more » K. Distance Least Squares modeling was performed to simulate a local geometry avoiding long B-O distances linking two octahedral chains by planar BO{sub 3} groups yielding split positions for the oxygen atoms and a strong distortion in the octahedral chains. The lattice thermal expansion was calculated using the Grüneisen first-order equation of state Debye-Einstein-Anharmonicity model. - Graphical abstract: Local distortion induced by boron linking the octahedral chains. - Highlights: • Decreasing lattice parameters indicate a solid solution for Al{sub 6−x}B{sub x}O{sub 9} (1.09≤x≤2). • B-atoms induce a local distortion of neighboring AlO{sub 6} octahedra. • A preference of boron in BO{sub 3} coordination is confirmed by {sup 11}B MAS NMR spectroscopy. • An optimized structural model for Al{sub 6−x}B{sub x}O{sub 9} is presented.« less

Effect of Osmotic Shock and Low Salt Concentration on Survival and Density of Bacteriophages T4B and T4Bo1

PubMed Central

Leibo, Stanley P.; Mazur, Peter

1966-01-01

Measurements of survival and buoyant densities of bacteriophages T4B, T4Bo1, and T4D have demonstrated the following: (a) After suspension in a concentrated salt solution, T4B and T4D are sensitive both to osmotic shock and to subsequent exposure to low monovalent salt concentrations. (b) Sensitivity of T4B to dilution from a concentrated salt solution is dependent on dilution rate, that of T4D is less dependent, and that of T4Bo1 is independent. (c) Sensitivity of all three phages to low salt concentrations depends on initial salt concentrations to a variable extent. (d) Density gradient profiles indicate that nearly half of osmotically shocked T4B retain their DNA. Similar analysis demonstrates that few, if any, T4Bo1 lose DNA when subjected to a treatment causing 90% loss of infectivity. (e) The effective buoyant densities of T4B and T4Bo1 depend significantly on the dilution treatments to which the phages are subjected prior to centrifugation in CsCl gradients. These data are explicable in terms of the different relative permeabilities of the phages to water and solutes, and of alterations in the counterion distribution surrounding the DNA within the phage heads. PMID:5972376

Substrate-based inhibitors exhibiting excellent protective and therapeutic effects against Botulinum Neurotoxin A intoxication.

PubMed

Guo, Jiubiao; Wang, Jinglin; Gao, Shan; Ji, Bin; Waichi Chan, Edward; Chen, Sheng

2015-11-20

Potent inhibitors to reverse Botulinum neurotoxins (BoNTs) activity in neuronal cells are currently not available. A better understanding of the substrate recognition mechanism of BoNTs enabled us to design a novel class of peptide inhibitors which were derivatives of the BoNT/A substrate, SNAP25. Through a combination of in vitro, cellular based, and in vivo mouse assays, several potent inhibitors of approximately one nanomolar inhibitory strength both in vitro and in vivo have been identified. These compounds represent the first set of inhibitors that exhibited full protection against BoNT/A intoxication in mice model with undetectable toxicity. Our findings validated the hypothesis that a peptide inhibitor targeting the two BoNT structural regions which were responsible for substrate recognition and cleavage respectively could exhibit excellent inhibitory effect, thereby providing insight on future development of more potent inhibitors against BoNTs.

Optical stability of 3d transition metal ions doped-cadmium borate glasses towards γ-rays interaction

NASA Astrophysics Data System (ADS)

Marzouk, M.; ElBatal, H.; Eisa, W.

2016-07-01

This work reports the preparation of glasses of binary cadmium borate with the basic composition (mol% 45 CdO 55 B2O3) and samples of the same composition containing 0.2 wt% dopants of 3d transition metal (TM) oxides (TiO2 → CuO). The glasses have been investigated by combined optical and Fourier Transform infrared spectroscopic measurements before and after being subjected to gamma irradiation with a dose of 8 Mrad (8 × 104 Gy). Optical absorption of the undoped glass before irradiation reveals strong charge transfer UV absorption which is related to the presence of unavoidable contaminated trace iron impurities (mainly Fe3+) within the raw materials used for the preparation of the base cadmium borate glass. The optical spectra of the 3d TM ions exhibit characteristic bands which are related the stable oxidation state of the 3d TM ions within the host glass. Gamma irradiation produces some limited variations in the optical spectra due to the stability of the host glass containing high percent 45 mol% of heavy metal oxide (CdO) which causes some shielding effects towards irradiation. From the absorption edge data, the values of the optical band gap Eopt and Urbach energy (ΔE) have been calculated. The values of the optical energy gap are found to be dependent on the glass composition. Infrared absorption spectral measurements reveal characteristic absorption bands due to both triangular and tetrahedral borate groups with the BO3 units vibrations more intense than BO4 units due to the known limit value for the change of BO3 to BO4 groups. The introduction of 3d TM ions with the doping level (0.2 wt%) causes no changes in the number or position of the IR bands because of the presence of TM ions in modifying sites in the glass network. It is observed that gamma irradiation causes some limited changes in the FT-IR spectral bands due to the stability of the host heavy cadmium borate glass.

Effect of Gd2O3 doping on structure and boron volatility of borosilicate glass sealants in solid oxide fuel cells-A study on the La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) cathode

NASA Astrophysics Data System (ADS)

Zhang, Qi; Tan, Shengwei; Ren, Mengyuan; Yang, Hsiwen; Tang, Dian; Chen, Kongfa; Zhang, Teng; Jiang, San Ping

2018-04-01

Boron volatility is one of the most important properties of borosilicate-based glass sealants in solid oxide fuel cells (SOFCs), as boron contaminants react with lanthanum-containing cathodes, forming LaBO3 and degrading the activity of SOFCs. Here, we report that the reaction between the volatile boron and a La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) cathode during polarization can be significantly reduced by doping aluminoborosilicate glass with Gd2O3. Specifically, the Gd cations in glass with 2 mol.% Gd2O3 dissolve preferentially in the borate-rich environment to form more Gd-metaborate structures and promote the formation of calcium metaborate (CaB2O4); they also condense the B-O network after heat treatment, which suppresses poisoning by boron contaminants on the LSCF cathode. The results provide insights into design and development of a reliable sealing glass for SOFC applications.

Evolution of the mössbauer spectra of ludwigite Co3 - x Fe x O2BO3 with substitution of iron for cobalt

NASA Astrophysics Data System (ADS)

Knyazev, Yu. V.; Ivanova, N. B.; Bayukov, O. A.; Kazak, N. V.; Bezmaternykh, L. N.; Vasiliev, A. D.

2013-06-01

A concentration series of single crystals of iron-cobalt ludwigites Co3 - x Fe x O2BO3 ( x = 0.0125, 0.025, 0.050, 0.10, 1.0) has been synthesized. The structure has been studied using X-ray diffraction and Mössbauer effect. A preferred occupation of nonequivalent crystallographic positions by iron in the ludwigite structure has been revealed. It has been found that the valence of substituting iron ions is three. It has been revealed that the structure of the γ-resonance spectrum of Co2FeO2BO3 is complicated due to a composition disorder in the system.

Influence of Temperature on Transdermal Penetration Enhancing Mechanism of Borneol: A Multi-Scale Study

PubMed Central

Yin, Qianqian; Wang, Ran; Yang, Shufang; Wu, Zhimin; Guo, Shujuan; Dai, Xingxing; Qiao, Yanjiang; Shi, Xinyuan

2017-01-01

The influence of temperature on the transdermal permeation enhancing mechanism of borneol (BO) was investigated using a multi-scale method, containing a coarse-grained molecular dynamic (CG-MD) simulation, an in vitro permeation experiment, and a transmission electron microscope (TEM) study. The results showed that BO has the potential to be used as a transdermal penetration enhancer to help osthole (OST) penetrate into the bilayer. With the increasing temperature, the stratum corneum (SC) becomes more flexible, proving to be synergistic with the permeation enhancement of BO, and the lag time (TLag) of BO and OST are shortened. However, when the temperature increased too much, with the effect of BO, the structure of SC was destroyed; for example, a water pore was formed and the micelle reversed. Though there were a number of drugs coming into the SC, the normal bilayer structure was absent. In addition, through comparing the simulation, in vitro experiment, and TEM study, we concluded that the computer simulation provided some visually detailed information, and the method plays an important role in related studies of permeation. PMID:28106833

Structural basis of the pH-dependent assembly of a botulinum neurotoxin complex.

PubMed

Matsui, Tsutomu; Gu, Shenyan; Lam, Kwok-Ho; Carter, Lester G; Rummel, Andreas; Mathews, Irimpan I; Jin, Rongsheng

2014-11-11

Botulinum neurotoxins (BoNTs) are among the most poisonous biological substances known. They assemble with non-toxic non-hemagglutinin (NTNHA) protein to form the minimally functional progenitor toxin complexes (M-PTC), which protects BoNT in the gastrointestinal tract and releases it upon entry into the circulation. Here we provide molecular insight into the assembly between BoNT/A and NTNHA-A using small-angle X-ray scattering. We found that the free form BoNT/A maintains a pH-independent conformation with limited domain flexibility. Intriguingly, the free form NTNHA-A adopts pH-dependent conformational changes due to a torsional motion of its C-terminal domain. Once forming a complex at acidic pH, they each adopt a stable conformation that is similar to that observed in the crystal structure of the M-PTC. Our results suggest that assembly of the M-PTC depends on the environmental pH and that the complex form of BoNT/A is induced by interacting with NTNHA-A at acidic pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

8-Hydroxyquinoline and hydroxamic acid inhibitors of botulinum neurotoxin BoNT/A.

PubMed

Dickerson, Tobin J; Smith, Garry R; Pelletier, Jeffrey C; Reitz, Allen B

2014-01-01

We describe here the state of the art of certain aspects concerning potential small molecule therapy directed toward botulism, by inhibition of the zinc-protease containing light chain (LC) of botulinum neurotoxin BoNT/A from the anaerobic bacillus Clostridium botulinum. Botulinum neurotoxins (BoNTs) are comprised of eight serologically-distinct proteins (A - H), several of which are further divided, such as BoNT/A which has five subtypes. The BoNTs are the most toxic substances known to mankind, causing a form of flaccid paralysis that can be rapid and is often lethal. BoNT/A is comprised of a ~100 kDa heavy chain (HC) attached via a single disulfide Cys-Cys bond to a ~50 kDa LC. The HC mediates transport to and uptake by presynaptic glutamatergic neurons, where the LC cleaves the protein SNAP-25 and thus prevents vesicular trafficking and release of acetylcholine. The Zn-endoprotease activity of the LC of BoNT/A is a target for the development of small molecule inhibitors of BoNT/A-mediated toxicity. A variety of BoNT/A LC inhibitors have been described to date and we focus here primarily on the Zn-binding 8-hydroxyquinoline structural type as well as some of the previously-described hydroxamic acids.

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

PubMed

Jhang, Jia-Fong; Kuo, Hann-Chorng

2015-06-18

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

Comparative Study of the Magnetoelectric Effect in HoAl3(BO3)4 and HoGa3(BO3)4 Single Crystals

NASA Astrophysics Data System (ADS)

Freidman, A. L.; Dubrovskii, A. A.; Temerov, V. L.; Gudim, I. A.

2018-03-01

The comparative study of the magnetoelectric properties and magnetostriction of HoGa3(BO3)4 and HoAl3(BO3)4 single crystals has been carried out. The investigated compounds exhibit qualitatively similar magnetodielectric and inverse magnetoelectric ME E effects with the close absolute values, which is indicative of the weak effect of a nonmagnetic metal ion. On the contrary, the magnetostriction of the galloborate has been found to be threefold higher than that of the alumoborate. In addition, the difference between the qualitative behaviors of magnetostriction has been established: the magnetic-field dependence of magnetostriction for the alumoborate has the maximum near 70 kOe at T = 4.2 K, while the galloborate magnetostriction has no maximum and does not saturate in a field of 140 kOe.

Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study.

PubMed

Lee, Franklin C; Holt, Sarah K; Hsi, Ryan S; Haynes, Brandon M; Harper, Jonathan D

2017-02-01

To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intraoperatively, in the recovery unit, and at home was recorded. Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and "high-pain" measure (P = .02) CONCLUSION: B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits. Copyright © 2016 Elsevier Inc. All rights reserved.

Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study

PubMed Central

Lee, Franklin C.; Holt, Sarah K.; Hsi, Ryan S.; Haynes, Brandon M.; Harper, Jonathan D.

2017-01-01

OBJECTIVE To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. METHODS A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intra-operatively, in the recovery unit, and at home was recorded. RESULTS Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and “high-pain” measure (P = .02) CONCLUSION B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits. PMID:27658661

Piano-stool lutetium amido and imido compounds supported by a constrained bis(oxazoline)cyclopentadienyl ligand

DOE PAGES

Lampland, Nicole L.; Zhu, Jing; Hovey, Megan; ...

2015-06-25

{Bo MCp tet}Lu(CH 2Ph) 2 ( 1; Bo MCp tet = MeC(Ox Me2 2C 5Me 4; Ox Me2 = 4,4-dimethyl-2-oxazoline) was prepared in 95% yield from the reaction of Bo MCp tetH and Lu(CH 2Ph) 3THF 3. Compound 1 reacts with 1 or 2 equiv of H 2NCH 2R (R = C 6H 5, 1-C 10H 7) to give the corresponding imido complexes [{Bo MCp tet}LuNCH 2R] 2 (R = C 6H 5 ( 2a), 1-C 10H 7 ( 2b)) or amido complexes {Bo MCp tet}Lu(NHCH 2R) 2 (R = C 6H 5 ( 3a), 1-C 10H 7 ( 3b)).more » When isolated, the imido species are insoluble in nonprotic organic solvents. Crystallographic characterization reveals dimeric [{Bo MCp tet}LuNCH 2(1-C 10H 7)] 2 in the solid state. The reaction of 1 and NH3B(C6F5)3 affords crystallographically characterized {Bo MCp tet}Lu{NHB(C 6F 5) 2}C 6F 5. This species is proposed to form via a transient lutetium imido, which undergoes C6F5 migration to the lutetium center.« less

Magneto-optical spectra and electron structure of Nd0.5Gd0.5Fe3(BO3)4 single crystal

NASA Astrophysics Data System (ADS)

Malakhovskii, A. V.; Gnatchenko, S. L.; Kachur, I. S.; Piryatinskaya, V. G.; Sukhachev, A. L.; Temerov, V. L.

2016-03-01

Polarized absorption spectra and magnetic circular dichroism (MCD) spectra of Nd0.5Gd0.5Fe3(BO3)4 single crystal were measured in the range of 10000-21000 cm-1 and at temperatures 2-300 K. On the basis of these data, in the paramagnetic state of the crystal, the 4f states of the Nd3+ ion were identified in terms of the irreducible representations and in terms of | J , ±MJ 〉 wave functions of the free atom. The changes of the Landé factor during f-f transitions were found theoretically in the | J , ±MJ 〉 wave functions approximation and were determined experimentally with the help of the measured MCD spectra. In the majority of cases the experimentally found values are close to the theoretically predicted ones.

Growth, spectroscopic properties and laser output of Er : Ca 4YO(BO 3) 3 and Er : Yb : Ca 4YO(BO 3) 3 crystals

NASA Astrophysics Data System (ADS)

Zhang, Huaijin; Meng, Xianlin; Wang, Changqing; Wang, Pu; Zhu, Li; Liu, Xuesong; Dong, Chunming; Yang, Yuyong; Cheng, Ruiping; Dawes, Judith; Piper, Jim; Zhang, Shaojun; Sun, Lianke

2000-09-01

In this paper, Er : Ca 4YO(BO 3) 3 (Er : YCOB) and Er : Yb : Ca 4YO(BO 3) 3 (Er : Yb : YCOB) crystals with large size and excellent quality have been grown by the Czochralski method. The absorption and emission spectra of Er : YCOB and Er : Yb : YCOB crystals have been measured; the emission spectrum of Er : Yb : YCOB crystal shows that the strongest emission peak is located at 1537 nm. An output power of about 2 mW at the wavelength of 1553 nm has been obtained under the pumping power of a fiber-coupled laser diode (LD) of 1600 mW at 976 nm, using a Y direction cut 2.5 mm thick Er : Yb : YCOB crystal sample.

Potent neutralization of botulinum neurotoxin/B by synergistic action of antibodies recognizing protein and ganglioside receptor binding domain.

PubMed

Chen, Changchun; Wang, Shuhui; Wang, Huajing; Mao, Xiaoyan; Zhang, Tiancheng; Ji, Guanghui; Shi, Xin; Xia, Tian; Lu, Weijia; Zhang, Dapeng; Dai, Jianxin; Guo, Yajun

2012-01-01

Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed. We selected 3 neutralizing mAbs which recognize different non-overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against BoNT/B. By comparing the neutralizing effects among different combination groups, we found that 8E10, response to ganglioside receptor binding site, could synergy with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding sites. However, the combination of 5G10 with 2F4 blocking protein receptor binding sites did not achieve synergistical effects. Moreover, we found that the binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might cross-protect the challenge of different serotypes of BoNTs in vivo. The combination of two mAbs recognizing different receptors' binding domain in BoNTs has a synergistic effect. 8E10 is a potential universal partner for the synergistical combination with other mAb against protein receptor binding domain in BoNTs of other serotypes.

A camelid single-domain antibody neutralizes botulinum neurotoxin A by blocking host receptor binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Guorui; Lam, Kwok-ho; Weisemann, Jasmin

Antibody treatment is currently the only available countermeasure for botulism, a fatal illness caused by flaccid paralysis of muscles due to botulinum neurotoxin (BoNT) intoxication. Among the seven major serotypes of BoNT/A-G, BoNT/A poses the most serious threat to humans because of its high potency and long duration of action. Prior to entering neurons and blocking neurotransmitter release, BoNT/A recognizes motoneurons via a dual-receptor binding process in which it engages both the neuron surface polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Previously, we identified a potent neutralizing antitoxin against BoNT/A1 termed ciA-C2, derived from a camelid heavy-chain-only antibody (VHH).more » In this study, we demonstrate that ciA-C2 prevents BoNT/A1 intoxication by inhibiting its binding to neuronal receptor SV2. Furthermore, we determined the crystal structure of ciA-C2 in complex with the receptor-binding domain of BoNT/A1 (HCA1) at 1.68 Å resolution. The structure revealed that ciA-C2 partially occupies the SV2-binding site on H CA1, causing direct interference of HCA1 interaction with both the N-glycan and peptide-moiety of SV2. Interestingly, this neutralization mechanism is similar to that of a monoclonal antibody in clinical trials, despite that ciA-C2 is more than 10-times smaller. Taken together, these results enlighten our understanding of BoNT/A1 interactions with its neuronal receptor, and further demonstrate that inhibiting toxin binding to the host receptor is an efficient countermeasure strategy.« less

The mechanism of long phosphorescence of SrAl{sub 2-x}B{sub x}O{sub 4} (0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nag, Abanti; Kutty, T.R.N

2004-03-01

The role of B{sub 2}O{sub 3} in realizing the long phosphorescence of Eu(II)+Dy(III) doped strontium aluminates has been investigated. IR and solid state {sup 27}Al MAS NMR spectra show the incorporation of boron as BO{sub 4} in the AlO{sub 4} framework of SrAl{sub 2}O{sub 4} and Sr{sub 4}Al{sub 14}O{sub 25}. Phosphor, made free of glassy phases by washing with hot acetic acid+glycerol, did not show any photoconductivity under UV irradiation, indicating that the mechanism involving hole conduction in valence band is untenable for long phosphorescence. EPR studies confirm the presence of both electron and hole trap centers. Dy{sup 3+} formsmore » substitutional defect complex with borate; [Dy-BO{sub 4}-V{sub Sr}]{sup 2-}, and acts as a hole trap center. The electron centers are formed by the oxygen vacancies associated with BO{sub 3}{sup 3-}, i.e. [BO{sub 3}-V{sub O}]{sup 3-}. Under indigo light or near UV irradiation, the photoinduced electron centers are formed as [BO{sub 3}-V{sub O}(e')]{sup 4-}. The holes are released from [Dy-BO{sub 4}-V{sub Sr}(h{center_dot})]{sup 1-} under thermal excitation at room temperature. The recombination of electrons with holes releases energy which is expended to excite Eu{sup 2+} to induce long phosphorescence.« less

OPTICAL AND SPECTROSCOPIC STUDIES OF Fe2O3-Bi2O3-B2O3:V2O5 GLASSES

NASA Astrophysics Data System (ADS)

Sanjay; Kishore, N.; Agarwal, A.; Dahiya, S.; Pal, Inder; Kumar, Navin

2013-11-01

The glasses of compositions xFe2O3ṡ (40 - x)Bi2O3ṡ60B2O3ṡ2V2O5 have been prepared by the standard melt-quenching technique. Amorphous nature of these samples is ascertained by XRD patterns. The presence of BO3 and BO4 units is identified by IR spectra of glass samples. The absorption edge (λcut-off) shifts toward longer wavelengths with an increase in Fe2O3 content in the glass matrix. The values of optical band gap energy for indirect allowed and forbidden transitions have been determined and it is found to decrease with increase in transition metal ions. The Urbach's energy is used to characterize the degree of disorder in amorphous solids.

Elastic properties and short-range structural order in mixed network former glasses.

PubMed

Wang, Weimin; Christensen, Randilynn; Curtis, Brittany; Hynek, David; Keizer, Sydney; Wang, James; Feller, Steve; Martin, Steve W; Kieffer, John

2017-06-21

Elastic properties of alkali containing glasses are of great interest not only because they provide information about overall structural integrity but also they are related to other properties such as thermal conductivity and ion mobility. In this study, we investigate two mixed-network former glass systems, sodium borosilicate 0.2Na 2 O + 0.8[xBO 1.5 + (1 - x)SiO 2 ] and sodium borogermanate 0.2Na 2 O + 0.8[xBO 1.5 + (1 - x)GeO 2 ] glasses. By mixing network formers, the network topology can be changed while keeping the network modifier concentration constant, which allows for the effect of network structure on elastic properties to be analyzed over a wide parametric range. In addition to non-linear, non-additive mixed-glass former effects, maxima are observed in longitudinal, shear and Young's moduli with increasing atomic number density. By combining results from NMR spectroscopy and Brillouin light scattering with a newly developed statistical thermodynamic reaction equilibrium model, it is possible to determine the relative proportions of all network structural units. This new analysis reveals that the structural characteristic predominantly responsible for effective mechanical load transmission in these glasses is a high density of network cations coordinated by four or more bridging oxygens, as it provides for establishing a network of covalent bonds among these cations with connectivity in three dimensions.

Genetic variation of temperature-regulated curd induction in cauliflower: elucidation of floral transition by genome-wide association mapping and gene expression analysis

PubMed Central

Matschegewski, Claudia; Zetzsche, Holger; Hasan, Yaser; Leibeguth, Lena; Briggs, William; Ordon, Frank; Uptmoor, Ralf

2015-01-01

Cauliflower (Brassica oleracea var. botrytis) is a vernalization-responsive crop. High ambient temperatures delay harvest time. The elucidation of the genetic regulation of floral transition is highly interesting for a precise harvest scheduling and to ensure stable market supply. This study aims at genetic dissection of temperature-dependent curd induction in cauliflower by genome-wide association studies and gene expression analysis. To assess temperature-dependent curd induction, two greenhouse trials under distinct temperature regimes were conducted on a diversity panel consisting of 111 cauliflower commercial parent lines, genotyped with 14,385 SNPs. Broad phenotypic variation and high heritability (0.93) were observed for temperature-related curd induction within the cauliflower population. GWA mapping identified a total of 18 QTL localized on chromosomes O1, O2, O3, O4, O6, O8, and O9 for curding time under two distinct temperature regimes. Among those, several QTL are localized within regions of promising candidate flowering genes. Inferring population structure and genetic relatedness among the diversity set assigned three main genetic clusters. Linkage disequilibrium (LD) patterns estimated global LD extent of r2 = 0.06 and a maximum physical distance of 400 kb for genetic linkage. Transcriptional profiling of flowering genes FLOWERING LOCUS C (BoFLC) and VERNALIZATION 2 (BoVRN2) was performed, showing increased expression levels of BoVRN2 in genotypes with faster curding. However, functional relevance of BoVRN2 and BoFLC2 could not consistently be supported, which probably suggests to act facultative and/or might evidence for BoVRN2/BoFLC-independent mechanisms in temperature-regulated floral transition in cauliflower. Genetic insights in temperature-regulated curd induction can underpin genetically informed phenology models and benefit molecular breeding strategies toward the development of thermo-tolerant cultivars. PMID:26442034

Structure and crystallization of SiO2 and B2O3 doped lithium disilicate glasses from theory and experiment.

PubMed

Erlebach, Andreas; Thieme, Katrin; Sierka, Marek; Rüssel, Christian

2017-09-27

Solid solutions of SiO 2 and B 2 O 3 in Li 2 O·2SiO 2 are synthesized and characterized for the first time. Their structure and crystallization mechanisms are investigated employing a combination of simulations at the density functional theory level and experiments on the crystallization of SiO 2 and B 2 O 3 doped lithium disilicate glasses. The remarkable agreement of calculated and experimentally determined cell parameters reveals the preferential, kinetically controlled incorporation of [SiO 4 ] and [BO 4 ] at the Li + lattice sites of the Li 2 O·2SiO 2 crystal structure. While the addition of SiO 2 increases the glass viscosity resulting in lower crystal growth velocities, glasses containing B 2 O 3 show a reduction of both viscosities and crystal growth velocities. These observations could be rationalized by a change of the chemical composition of the glass matrix surrounding the precipitated crystal phase during the course of crystallization, which leads to a deceleration of the attachment of building units required for further crystal growth at the liquid-crystal interface.

Genomic insights into the evolution and ecology of botulinum neurotoxins.

PubMed

Mansfield, Michael J; Doxey, Andrew C

2018-06-01

Clostridial neurotoxins, which include botulinum neurotoxins (BoNTs) and tetanus neurotoxins, have evolved a remarkably sophisticated structure and molecular mechanism fine-tuned for the targeting and cleavage of vertebrate neuron substrates leading to muscular paralysis. How and why did this toxin evolve? From which ancestral proteins are BoNTs derived? And what is, or was, the primary ecological role of BoNTs in the environment? In this article, we examine these questions in light of recent studies identifying homologs of BoNTs in the genomes of non-clostridial bacteria, including Weissella, Enterococcus and Chryseobacterium. Genomic and phylogenetic analysis of these more distantly related toxins suggests that they are derived from ancient toxin lineages that predate the evolution of BoNTs and are not limited to the Clostridium genus. We propose that BoNTs have therefore evolved from a precursor family of BoNT-like toxins, and ultimately from non-neurospecific toxins that cleaved different substrates (possibly non-neuronal SNAREs). Comparison of BoNTs with these related toxins reveals several unique molecular features that underlie the evolution of BoNT's unique function, including functional shifts involving all four domains, and gain of the BoNT gene cluster associated proteins. BoNTs then diversified to produce the existing serotypes, including TeNT, and underwent repeated substrate shifts from ancestral VAMP2 specificity to SNAP25 specificity at least three times in their history. Finally, similar to previous proposals, we suggest that one ecological role of BoNTs could be to create a paralytic phase in vertebrate decomposition, which provides a competitive advantage for necrophagous scavengers that in turn facilitate the spread of Clostridium botulinum and its toxin.

Botulinum Toxin in Secondarily Nonresponsive Patients with Spasmodic Dysphonia.

PubMed

Mor, Niv; Tang, Christopher; Blitzer, Andrew

2016-09-01

Chemodenervation with botulinum toxin (BoNT) has been effective and well tolerated for all types of dystonia for >30 years. We reviewed outcomes of our patients treated with BoNT serotype A (BoNT-A) for spasmodic dysphonia (SD) who became secondarily nonresponsive. We found that 8 of 1400 patients became nonresponsive to BoNT-A (0.57%), which is lower than the secondary nonresponse rate in other dystonias. After a cessation period, 4 of our patients resumed BoNT-A injections, and recurrence of immunoresistance was not seen in any of them. When compared with patients with other dystonias, patients with SD receive extremely low doses of BoNT. Small antigen challenge may explain the lower rate of immunoresistance and long-lasting efficacy after BoNT-A is restarted among secondary nonresponsive patients with SD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Hydrolysis and regeneration of sodium borohydride (NaBH4) - A combination of hydrogen production and storage

NASA Astrophysics Data System (ADS)

Chen, W.; Ouyang, L. Z.; Liu, J. W.; Yao, X. D.; Wang, H.; Liu, Z. W.; Zhu, M.

2017-08-01

Sodium borohydride (NaBH4) hydrolysis is a promising approach for hydrogen generation, but it is limited by high costs, low efficiency of recycling the by-product, and a lack of effective gravimetric storage methods. Here we demonstrate the regeneration of NaBH4 by ball milling the by-product, NaBO2·2H2O or NaBO2·4H2O, with MgH2 at room temperature and atmospheric pressure without any further post-treatment. Record yields of NaBH4 at 90.0% for NaBO2·2H2O and 88.3% for NaBO2·4H2O are achieved. This process also produces hydrogen from the splitting of coordinate water in hydrated sodium metaborate. This compensates the need for extra hydrogen for generating MgH2. Accordingly, we conclude that our unique approach realizes an efficient and cost-effective closed loop system for hydrogen production and storage.

Two-Dimensional Stoichiometric Boron Oxides as a Versatile Platform for Electronic Structure Engineering.

PubMed

Zhang, Ruiqi; Li, Zhenyu; Yang, Jinlong

2017-09-21

Oxides of two-dimensional (2D) atomic crystals have been widely studied due to their unique properties. In most 2D oxides, oxygen acts as a functional group, which makes it difficult to control the degree of oxidation. Because borophene is an electron-deficient system, it is expected that oxygen will be intrinsically incorporated into the basal plane of borophene, forming stoichiometric 2D boron oxide (BO) structures. By using first-principles global optimization, we systematically explore structures and properties of 2D BO systems with well-defined degrees of oxidation. Stable B-O-B and OB 3 tetrahedron structure motifs are identified in these structures. Interesting properties, such as strong linear dichroism, Dirac node-line (DNL) semimetallicity, and negative differential resistance, have been predicted for these systems. Our results demonstrate that 2D BO represents a versatile platform for electronic structure engineering via tuning the stoichiometric degree of oxidation, which leads to various technological applications.

Efficient continuous-wave and passively Q-switched pulse laser operations in a diffusion-bonded sapphire/Er:Yb:YAl3(BO3)4/sapphire composite crystal around 1.55 μm.

PubMed

Chen, Yujin; Lin, Yanfu; Huang, Jianhua; Gong, Xinghong; Luo, Zundu; Huang, Yidong

2018-01-08

A composite crystal consisting of a 1.5-mm-thick Er:Yb:YAl 3 (BO 3 ) 4 crystal between two 1.2-mm-thick sapphire crystals was fabricated by the thermal diffusion bonding technique. Compared with a lone Er:Yb:YAl 3 (BO 3 ) 4 crystal measured under the identical experimental conditions, higher laser performances were demonstrated in the sapphire/Er:Yb:YAl 3 (BO 3 ) 4 /sapphire composite crystal due to the reduction of the thermal effects. End-pumped by a 976 nm laser diode in a hemispherical cavity, a 1.55 μm continuous-wave laser with a maximum output power of 1.75 W and a slope efficiency of 36% was obtained in the composite crystal when the incident pump power was 6.54 W. Passively Q-switched by a Co 2+ :MgAl 2 O 4 crystal, a 1.52 μm pulse laser with energy of 10 μJ and repetition frequency of 105 kHz was also realized in the composite crystal. Pulse width was 315 ns. The results show that the sapphire/Er:Yb:YAl 3 (BO 3 ) 4 /sapphire composite crystal is an excellent active element for 1.55 μm laser.

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

PubMed Central

Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto

2017-01-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. PMID:28356439

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

PubMed

Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

2017-04-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

A robust bi-orthogonal/dynamically-orthogonal method using the covariance pseudo-inverse with application to stochastic flow problems

NASA Astrophysics Data System (ADS)

Babaee, Hessam; Choi, Minseok; Sapsis, Themistoklis P.; Karniadakis, George Em

2017-09-01

We develop a new robust methodology for the stochastic Navier-Stokes equations based on the dynamically-orthogonal (DO) and bi-orthogonal (BO) methods [1-3]. Both approaches are variants of a generalized Karhunen-Loève (KL) expansion in which both the stochastic coefficients and the spatial basis evolve according to system dynamics, hence, capturing the low-dimensional structure of the solution. The DO and BO formulations are mathematically equivalent [3], but they exhibit computationally complimentary properties. Specifically, the BO formulation may fail due to crossing of the eigenvalues of the covariance matrix, while both BO and DO become unstable when there is a high condition number of the covariance matrix or zero eigenvalues. To this end, we combine the two methods into a robust hybrid framework and in addition we employ a pseudo-inverse technique to invert the covariance matrix. The robustness of the proposed method stems from addressing the following issues in the DO/BO formulation: (i) eigenvalue crossing: we resolve the issue of eigenvalue crossing in the BO formulation by switching to the DO near eigenvalue crossing using the equivalence theorem and switching back to BO when the distance between eigenvalues is larger than a threshold value; (ii) ill-conditioned covariance matrix: we utilize a pseudo-inverse strategy to invert the covariance matrix; (iii) adaptivity: we utilize an adaptive strategy to add/remove modes to resolve the covariance matrix up to a threshold value. In particular, we introduce a soft-threshold criterion to allow the system to adapt to the newly added/removed mode and therefore avoid repetitive and unnecessary mode addition/removal. When the total variance approaches zero, we show that the DO/BO formulation becomes equivalent to the evolution equation of the Optimally Time-Dependent modes [4]. We demonstrate the capability of the proposed methodology with several numerical examples, namely (i) stochastic Burgers equation: we analyze the performance of the method in the presence of eigenvalue crossing and zero eigenvalues; (ii) stochastic Kovasznay flow: we examine the method in the presence of a singular covariance matrix; and (iii) we examine the adaptivity of the method for an incompressible flow over a cylinder where for large stochastic forcing thirteen DO/BO modes are active.

Rare earth-doped lead borate glasses and transparent glass-ceramics: structure-property relationship.

PubMed

Pisarski, W A; Pisarska, J; Mączka, M; Lisiecki, R; Grobelny, Ł; Goryczka, T; Dominiak-Dzik, G; Ryba-Romanowski, W

2011-08-15

Correlation between structure and optical properties of rare earth ions in lead borate glasses and glass-ceramics was evidenced by X-ray-diffraction, Raman, FT-IR and luminescence spectroscopy. The rare earths were limited to Eu(3+) and Er(3+) ions. The observed BO(3)↔BO(4) conversion strongly depends on the relative PbO/B(2)O(3) ratios in glass composition, giving important contribution to the luminescence intensities associated to (5)D(0)-(7)F(2) and (5)D(0)-(7)F(1) transitions of Eu(3+). The near-infrared luminescence and up-conversion spectra for Er(3+) ions in lead borate glasses before and after heat treatment were measured. The more intense and narrowing luminescence lines suggest partial incorporation of Er(3+) ions into the orthorhombic PbF(2) crystalline phase, which was identified using X-ray diffraction analysis. Copyright © 2010 Elsevier B.V. All rights reserved.

Gamma-ray shielding effect of Gd3+ doped lead barium borate glasses

NASA Astrophysics Data System (ADS)

Kummathi, Harshitha; Naveen Kumar, P.; Vedavathi T., C.; Abhiram, J.; Rajaramakrishna, R.

2018-05-01

The glasses of the batch xPbO: 10BaO: (90-x)B2O3: 0.2Gd2O3 (x = 40,45,50 mol %) were prepared by melt-quench technique. The work emphasizes on gamma ray shielding effect on doped lead glasses. The role of Boron is significant as it acts as better neutron attenuator as compared with any other materials, as the thermal neutron cross-sections are high for Gadolinium, 0.2 mol% is chosen as the optimum concentration for this matrix, as higher the concentration may lead to further increase as it produces secondary γ rays due to inelastic neutron scattering. Shielding effects were studied using Sodium Iodide (NaI) - Scintillation Gamma ray spectrometer. It was found that at higher concentration of lead oxide (PbO) in the matrix, higher the attenuation which can be co-related with density. Infra-red (I.R.) spectra reveals that the conversion of Lose triangles to tight tetrahedral structure results in enhancement of shielding properties. The Differential Scanning Calorimeter (D.S.C.) study also reveals that the increase in glass forming range increases the stability which in-turn results in inter-conversion of BO3 to BO4 units such that the density of glass increases with increase in PbO content, resulting in much stable and efficient gamma ray shielding glasses.

A Preliminary Analysis of Compassion Satisfaction and Compassion Fatigue With Considerations for Nursing Unit Specialization and Demographic Factors.

PubMed

Mooney, Claire; Fetter, Katrina; Gross, Brian W; Rinehart, Cole; Lynch, Caitlin; Rogers, Frederick B

Compassion fatigue (CF), or vicarious traumatization, is a state of physical/emotional distress that results from caring for those experiencing pain. We sought to characterize levels of CF in intensive care unit (ICU) and oncology nursing populations with subanalyses comparing specific personal/professional demographic factors. The Professional Quality of Life (ProQOL) scale, a validated tool for assessing CF, burnout (BO), and compassion satisfaction (CS), was distributed to the ICU and oncology divisions of a community hospital. Demographic data and ProQOL scale scores were collected and compared within specialty and gender subgroups. Two-sample t tests and regression analyses were used to compare groups. Statistical significance was defined as p < .05. A total of 86 nurses submitted completed surveys able to be analyzed. Levels of CS were significantly lower (p = .023) and levels of BO were significantly higher (p = .029) in ICU nurses than in oncology nurses. Male nurses exhibited significantly higher CS (p = .001) and significantly lower BO (p = .021) and CF (p = .014) than female nurses. Intensive care unit nurses and female nurses from both ICU and oncology specialties may be at increased risk for developing a poorer overall ProQOL and CF.

Antiviral Immunotoxin Against Bovine herpesvirus-1: Targeted Inhibition of Viral Replication and Apoptosis of Infected Cell

PubMed Central

Xu, Jian; Li, Xiaoyang; Jiang, Bo; Feng, Xiaoyu; Wu, Jing; Cai, Yunhong; Zhang, Xixi; Huang, Xiufen; Sealy, Joshua E.; Iqbal, Munir; Li, Yongqing

2018-01-01

Bovine herpesvirus 1 (BoHV-1) is a highly contagious viral pathogen which causes infectious bovine rhinotracheitis in cattle worldwide. Currently, there is no antiviral prophylactic treatment available capable of mitigating the disease impact and facilitating recovery from latent infection. In this study, we have engineered a novel recombinant anti-BoHV-1 immunotoxin construct termed “BoScFv-PE38” that consists of a single-chain monoclonal antibody fragment (scFv) fused with an active domain of Pseudomonas exotoxin A as a toxic effector (PE38). The recombinant BoScFv-PE38 immunotoxin expressed in a prokaryotic expression system has specific binding affinity for BoHV-1 glycoprotein D (gD) with a dissociation constant (Kd) of 12.81 nM and for BoHV-1 virus particles with a Kd value of 97.63 nM. We demonstrate that the recombinant BoScFv-PE38 is internalized into MDBK cell compartments that inhibit BoHV-1 replication with a half-maximal inhibitory concentration (IC50) of 4.95 ± 0.33 nM and a selective index (SI) of 456 ± 31. Furthermore, the BoScFv-PE38 exerted a cytotoxic effect through the induction of ATP and ammonia, leading to apoptosis of BoHV-1-infected cells and the inhibition of BoHV-1 replication in MDBK cells. Collectively, we show that BoScFv-PE38 can potentially be employed as a therapeutic agent for the treatment of BoHV-1 infection. PMID:29670605

Isolation and quantification of botulinum neurotoxin from complex matrices using the BoTest matrix assays.

PubMed

Dunning, F Mark; Piazza, Timothy M; Zeytin, Füsûn N; Tucker, Ward C

2014-03-03

Accurate detection and quantification of botulinum neurotoxin (BoNT) in complex matrices is required for pharmaceutical, environmental, and food sample testing. Rapid BoNT testing of foodstuffs is needed during outbreak forensics, patient diagnosis, and food safety testing while accurate potency testing is required for BoNT-based drug product manufacturing and patient safety. The widely used mouse bioassay for BoNT testing is highly sensitive but lacks the precision and throughput needed for rapid and routine BoNT testing. Furthermore, the bioassay's use of animals has resulted in calls by drug product regulatory authorities and animal-rights proponents in the US and abroad to replace the mouse bioassay for BoNT testing. Several in vitro replacement assays have been developed that work well with purified BoNT in simple buffers, but most have not been shown to be applicable to testing in highly complex matrices. Here, a protocol for the detection of BoNT in complex matrices using the BoTest Matrix assays is presented. The assay consists of three parts: The first part involves preparation of the samples for testing, the second part is an immunoprecipitation step using anti-BoNT antibody-coated paramagnetic beads to purify BoNT from the matrix, and the third part quantifies the isolated BoNT's proteolytic activity using a fluorogenic reporter. The protocol is written for high throughput testing in 96-well plates using both liquid and solid matrices and requires about 2 hr of manual preparation with total assay times of 4-26 hr depending on the sample type, toxin load, and desired sensitivity. Data are presented for BoNT/A testing with phosphate-buffered saline, a drug product, culture supernatant, 2% milk, and fresh tomatoes and includes discussion of critical parameters for assay success.

FTIR spectra and properties of iron borophosphate glasses containing simulated nuclear wastes

NASA Astrophysics Data System (ADS)

Liao, Qilong; Wang, Fu; Chen, Kuiru; Pan, Sheqi; Zhu, Hanzhen; Lu, Mingwei; Qin, Jianfa

2015-07-01

30 wt.% simulated nuclear wastes were successfully immobilized by B2O3-doped iron phosphate base glasses. The structure and thermal stability of the prepared wasteforms were characterized by Fourier transform infrared spectroscopy and differential thermal analysis, respectively. The subtle structural variations attributed to different B2O3 doping modes have been discussed in detail. The results show that the thermal stability and glass forming tendency of the iron borophosphate glass wasteforms are faintly affected by different B2O3 doping modes. The main structural networks of iron borophosphate glass wasteforms are PO43-, P2O74-, [BO4] groups. Furthermore, for the wasteform prepared by using 10B2O3-36Fe2O3-54P2O5 as base glass, the distributions of Fe-O-P bonds, [BO4], PO43- and P2O74- groups are optimal. In general, the dissolution rate (DR) values of the studied iron borophosphate wasteforms are about 10-8 g cm-2 min-1. The obtained conclusions can offer some useful information for the disposal of high-level radioactive wastes using boron contained phosphate glasses.

Evaluation of botulinum toxin type A effectiveness in preventing postoperative intraperitoneal adhesions

PubMed Central

Uysal, Erdal

2017-01-01

Purpose Postoperative intraperitoneal adhesions (PIAs) are one of the most important problems surgeons have to face after laparotomies. In this study, we aimed to evaluate the effectiveness of local application of botulinum toxin type A (BoNT-A) in various dosages on the prevention of intra-abdominal adhesions in rats with experimental intra-abdominal adhesions. Methods Forty Wistar Albino female rats were randomly separated into 4 groups. The 4 groups were determined as follows: Control (group 1, n = 10); Sham (group 2, n = 10); 10-µg/kg low-dose BoNT-A (group 3, n = 10) and 30-µg/kg high-dose BoNT-A (group 4, n = 10). Subserosal injuries were created on the caecum of all rats. Laparotomy was performed on the fifth day. Adhesion scores, histopathological examination, and E-cadherin expression levels were evaluated. Results General adhesion scores for groups 1 and 2 were determined to be significantly high when compared to group 4 (P < 0.001). A significant difference was also determined between groups 3 and 4 in terms of general adhesion scores (P < 0.05). In pair comparisons, a significant decrease in high-dose BoNT-A group (group 4) when compared to groups 1 and 2 in terms of neovascularization, fibroblast density, collagen deposition and inflammatory cell count was determined (P < 0.05). Conclusion A significant decrease was observed only in postoperative PIAs in the high-dose BoNT-A group between all 4 rat-groups with experimentally created postoperative PIAs. In this study, high-dose BoNT-A is determined to be an effective agent in preventing postoperative PIAs. PMID:28706891

Botulinum Toxin in Aesthetic Medicine: Myths and Realities

PubMed Central

Monheit, Gary; Greener, Mark; Pickett, Andy

2018-01-01

BACKGROUND Several formulations of Botulinum toxin serotype A (BoNT-A) for aesthetic indications are available, with numbers likely to increase. Preparations are not interchangeable, based on dose unit comparisons. OBJECTIVE Numerous myths and misconceptions regarding the use of BoNT-A for aesthetic indications have arisen, which this review aims to lay to rest. MATERIALS AND METHODS This review assesses evidence for and against each of the most common myths regarding BoNT use in aesthetics. RESULTS BoNT-A neurotoxin/protein complexes are irrelevant to the toxin's therapeutic/aesthetic indications. BoNT-A neurotoxin/protein complexes do not influence movement from injection site or immunogenicity. Any relationship between neutralizing antibody formation and clinical response is complex and clinicians should consider other factors that may induce an apparent loss of clinical response. Diffusion appears predominately, perhaps exclusively, dose dependent. Careful placement and correct dosing optimizes likelihood of good outcomes. Manufacturers recommend reconstitution of products with sterile nonpreserved saline. However, compelling evidence suggests that reconstitution using preserved saline dramatically improves patient comfort without compromising efficacy. Several post-treatment instructions/restrictions are widely used despite the lack of evidence, but muscle activity after injection may be beneficial. Cooling the treatment area might hinder BoNT-A translocation and should probably be abandoned. CONCLUSION The existing evidence suggests that experienced users should achieve equivalent results regardless of BoNT-A formulation, but additional, well-designed, adequately powered, controlled randomized studies should be performed. PMID:29016535

Inner Harbor Navigation Canal Basin Velocity Analysis

DTIC Science & Technology

2014-10-01

ER D C/ CH L TR -1 4- 12 Inner Harbor Navigation Canal Basin Velocity Analysis Co as ta l a nd H yd ra ul ic s La bo ra to ry...Mississippi River Gulf Outlet (MRGO). The structures allow for continued navigation, and the gate structures are designed to remain open during...Water Way (GIWW) just east of the Mississippi River Gulf Outlet (MRGO). The planned structures allow for continued navigation in the IHNC, Bayou

Photoelectron spectroscopy of B4O4-: Dual 3c-4e π hyperbonds and rhombic 4c-4e o-bond in boron oxide clusters

NASA Astrophysics Data System (ADS)

Tian, Wen-Juan; Zhao, Li-Juan; Chen, Qiang; Ou, Ting; Xu, Hong-Guang; Zheng, Wei-Jun; Zhai, Hua-Jin; Li, Si-Dian

2015-04-01

Gas-phase anion photoelectron spectroscopy (PES) is combined with global structural searches and electronic structure calculations at the hybrid Becke 3-parameter exchange functional and Lee-Yang-Parr correlation functional (B3LYP) and single-point coupled-cluster with single, double, and perturbative triple excitations (CCSD(T)) levels to probe the structural and electronic properties and chemical bonding of the B4O40/- clusters. The measured PES spectra of B4O4- exhibit a major band with the adiabatic and vertical detachment energies (ADE and VDE) of 2.64 ± 0.10 and 2.81 ± 0.10 eV, respectively, as well as a weak peak with the ADE and VDE of 1.42 ± 0.08 and 1.48 ± 0.08 eV. The former band proves to correspond to the Y-shaped global minimum of Cs B4O4- (2A″), with the calculated ADE/VDE of 2.57/2.84 eV at the CCSD(T) level, whereas the weak band is associated with the second lowest-energy, rhombic isomer of D2h B4O4- (2B2g) with the predicted ADE/VDE of 1.43/1.49 eV. Both anion structures are planar, featuring a B atom or a B2O2 core bonded with terminal BO and/or BO2 groups. The same Y-shaped and rhombic structures are also located for the B4O4 neutral cluster, albeit with a reversed energy order. Bonding analyses reveal dual three-center four-electron (3c-4e) π hyperbonds in the Y-shaped B4O40/- clusters and a four-center four-electron (4c-4e) π bond, that is, the so-called o-bond in the rhombic B4O40/- clusters. This work is the first experimental study on a molecular system with an o-bond.

In Vivo Toxicity and Immunological Characterization of Detoxified Recombinant Botulinum Neurotoxin Type A.

PubMed

Ravichandran, Easwaran; Janardhanan, Pavithra; Patel, Kruti; Riding, Stephen; Cai, Shuowei; Singh, Bal Ram

2016-03-01

A double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT. We determined lethality (LD50) of deactivated recombinant botulinum neurotoxin (drBoNT/A) to be 24.0 μg by intraperitoneal route (i.p). The polypeptide drBoNT/A labeled with near infra-red dye 800 (NIR 800) was used to examine its distribution to different organs using whole body imaging when administered to mice via intravenous (i.v) or i.p route. Also, drBoNT/A was used to evaluate its immunogenicity in Balb/C mice model. drBoNT/A was found to be highly immunogenic when tested under various in vivo conditions in Balb/C mice model. For the first time we have demonstrated that a full length 150 kDa drBoNT/A, by administering via inhalation route in mice model, has evoked both circulating immunoglobulin levels of IgG and secretory IgA at the mucosal surface. The immunoglobulin levels were sufficient enough to protect against the challenge dose of native BoNT toxin in mice model. Tissue distribution of drBoNT/A seems to be similar to that of native toxin. Based on the characteristics described in this report this nontoxic holotoxin protein will assist us to explore the window of opportunity available for therapeutic treatment in case of unnatural poisoning, and also it can be an effective vaccine candidate.

Structural, thermal, optical and dielectric studies of Dy3+: B2O3-ZnO-PbO-Na2O-CaO glasses for white LEDs application

NASA Astrophysics Data System (ADS)

Mohammed, Al-B. F. A.; Lakshminarayana, G.; Baki, S. O.; Halimah, M. K.; Kityk, I. V.; Mahdi, M. A.

2017-11-01

Dy3+-doped borate glasses with nominal composition (60-x) B2O3-10 ZnO-10 PbO-10 Na2O-10 CaO-(x) Dy2O3 (x = 0, 0.1, 0.2, 0.5, 0.75, 1.0, 1.5 and 2.0 mol%) were prepared by the melt quenching technique. The XRD and SEM confirm the amorphous nature of the glasses and through EDAX, all the related elements were found in the synthesized glasses. The vibrations of metal cations such as Pb2+ and Zn2+, B-O-B bond bending vibrations from pentaborate groups, bending vibrations of BO3 triangles, and stretching vibrations of tetrahedral BO4- units etc. are identified from the respective FTIR and Raman spectra including the non-hygroscopic nature of the synthesized glasses. The TGA and DSC measurements were performed to study thermal properties, where ΔT >100 °C (ΔT = Tx - Tg) for all the glasses. Among all the Dy3+-doped glasses, the 0.75 mol% Dy3+-doped glass shows the highest PL intensity with four emissions, where the two transitions corresponding to 4F9/2 → 6H15/2 (blue) and 4F9/2 → 6H13/2 (yellow) are observed more intense than the others. The CIE chromaticity (x,y) coordinates for BZPNCDy 0.1 mol% glass are (0.398, 0.430), close to the white light region in the CIE 1931 chromaticity diagram. The dielectric properties of the 0.75 mol% Dy3+-doped glass such as dielectric constant, dielectric loss and AC conductivity were studied in the various frequencies and temperature.

Examining a knowledge domain: Interactive visualization of the Geographic Information Science and Technology Body of Knowledge 1

NASA Astrophysics Data System (ADS)

Stowell, Marilyn Ruth

This research compared the effectiveness and performance of interactive visualizations of the GIS&T Body of Knowledge 1. The visualizations were created using Processing, and display the structure and content of the Body of Knowledge using various spatial layout methods: the Indented List, Tree Graph, treemap and Similarity Graph. The first three methods utilize the existing hierarchical structure of the BoK text, while the fourth method (Similarity Graph) serves as a jumping off point for exploring content-based visualizations of the BoK. The following questions have guided the framework of this research: (1) Which of the spatial layouts is most effective for completing tasks related to the GIS&T; BoK overall? How do they compare to each other in terms of performance? (2) Is one spatial layout significantly more or less effective than others for completing a particular cognitive task? (3) Is the user able to utilize the BoK as a basemap or reference system and make inferences based on BoK scorecard overlays? (4) Which design aspects of the interface assist in carrying out the survey objectives? Which design aspects of the application detract from fulfilling the objectives? To answer these questions, human subjects were recruited to participate in a survey, during which they were assigned a random spatial layout and were asked questions about the BoK based on their interaction with the visualization tool. 75 users were tested, 25 for each spatial layout. Statistical analysis revealed that there were no statistically significant differences between means for overall accuracy when comparing the three visualizations. In looking at individual questions, Tree Graph and Indented List yielded statistically significant higher scores for questions regarding the structure of the Body of Knowledge, as compared to the treemap. There was a significant strong positive correlation between the time taken to complete the survey and the final survey score. This correlation was particularly strong with treemap, possibly confirming the steeper learning curve with the more complex layout. Users were asked for feedback on the perceived "ease" of using the interface, and though few users said the interface was easy to use, there was a positive correlation between perceived "ease" and overall score. Qualitative feedback revealed that the external controls on the interface were not inviting to use, and the interface overall was not intuitive. Additional human subjects were recruited from the professional GIS community to participate in testing remotely. These results weren't significant due to small sample size, but helped to verify the feedback and results from the controlled testing.

The biological activity of botulinum neurotoxin type C is dependent upon novel types of ganglioside binding sites.

PubMed

Strotmeier, Jasmin; Gu, Shenyan; Jutzi, Stephan; Mahrhold, Stefan; Zhou, Jie; Pich, Andreas; Eichner, Timo; Bigalke, Hans; Rummel, Andreas; Jin, Rongsheng; Binz, Thomas

2011-07-01

The seven botulinum neurotoxins (BoNT) cause muscle paralysis by selectively cleaving core components of the vesicular fusion machinery. Their extraordinary activity primarily relies on highly specific entry into neurons. Data on BoNT/A, B, E, F and G suggest that entry follows a dual receptor interaction with complex gangliosides via an established ganglioside binding region and a synaptic vesicle protein. Here, we report high resolution crystal structures of the BoNT/C cell binding fragment alone and in complex with sialic acid. The WY-motif characteristic of the established ganglioside binding region was located on an exposed loop. Sialic acid was co-ordinated at a novel position neighbouring the binding pocket for synaptotagmin in BoNT/B and G and the sialic acid binding site in BoNT/D and TeNT respectively. Employing synaptosomes and immobilized gangliosides binding studies with BoNT/C mutants showed that the ganglioside binding WY-loop, the newly identified sialic acid-co-ordinating pocket and the area corresponding to the established ganglioside binding region of other BoNTs are involved in ganglioside interaction. Phrenic nerve hemidiaphragm activity tests employing ganglioside deficient mice furthermore evidenced that the biological activity of BoNT/C depends on ganglioside interaction with at least two binding sites. These data suggest a unique cell binding and entry mechanism for BoNT/C among clostridial neurotoxins. © 2011 Blackwell Publishing Ltd.

Linking 1D Transition-Metal Coordination Polymers and Different Inorganic Boron Oxides To Construct a Series of 3D Inorganic-Organic Hybrid Borates.

PubMed

Zhi, Shao-Chen; Wang, Yue-Lin; Sun, Li; Cheng, Jian-Wen; Yang, Guo-Yu

2018-02-05

Three inorganic-organic hybrid borates, M(1,4-dab)[B 5 O 7 (OH) 3 ] [M = Zn (1), Cd (2), 1,4-dab = 1,4-diaminobutane)] and Co(1,3-dap)[B 4 O 7 ] (3, 1,3-dap = 1,3-diaminopropane), which integrated characteristics of 1D coordination polymers and 1D/3D inorganic boron oxides have been obtained under solvothermal conditions. Compounds 1 and 2 are isostructural and crystallize in a centrosymmetric space group P2 1 /c; the 3D achiral structures of 1 and 2 consist of the nonhelical Zn/Cd-1,4-dap coordination polymers and 1D B-O chains. Compound 3 crystallizes in a chiral space group P4 3 2 1 2; the helical Co-1,3-dap coordination polymer chains are entrained within a 3D B-O network and finally form the chiral framework. Compounds 1-3 represent good examples of using coordination polymers to construct mixed-motif inorganic-organic hybrid borates. Compounds 1 and 2 display blue luminescence when excited with UV light.

Simple, Affordable and Sustainable Borehole Observatories for Complex Monitoring Objectives

NASA Astrophysics Data System (ADS)

Kopf, A.; Freudenthal, T.; Ratmeyer, V.; Wefer, G.

2014-12-01

Seafloor drill rigs are remotely operated systems that provide a cost effective means to recover sedimentary records of the upper sub-seafloor deposits. Recent increases in their payload included downhole logging tools or autoclave coring systems. We here report on another milestone in using seafloor rigs: The development and installation of shallow borehole observatories. Three different systems have been developed for the MeBo seafloor drill, which is operated by MARUM, Univ. Bremen, Germany. A simple design, the MeBoPLUG, separates the inner borehole from the overlying ocean by using o-ring seals at the conical threads of the drill pipe. The systems are self-contained and include data loggers, batteries, thermistors and a differential pressure sensor. A second design, the so-called MeBoCORK, is more sophisticated and also hosts an acoustic modem for data transfer and, if desired, fluid sampling capability using osmotic pumps. Of these MeBoCORKs, two systems have to be distinguished: The CORK-A (A = autonomous) can be installed by the MeBo alone and monitors pressure and temperature inside and above the borehole (the latter for reference). The CORK-B (B = bottom) has a higher payload and can additionally be equipped with geochemical, biological or other physical components. Owing to its larger size, it is installed by ROV and utilises a hotstab connection in the upper portion of the drill string. Either design relies on a hostab connection from beneath which coiled tubing with a conical drop weight is lowered to couple to the formation. These tubes are fluid-saturated and either serve to transmit pore pressure signals or collect pore water in the osmo-sampler. The third design, the MeBoPUPPI (Pop-Up Pore Pressure Instrument), is similar to the MeBoCORK-A and monitors pore pressure and temperature in a self-contained manner. Instead of transferring data upon command using an acoustic modem, the MeBoPUPPI contains a pop-up telemetry with Iridium link. After a predefined period, the data unit with satellite link is released, ascends to the sea surface, and remains there for up to two weeks while sending the long-term data sets to shore. In 2012, 2 MeBoPLUGs, 1 MeBoCORK-A and 1 MeBoCORK-B were installed with MeBo in the Nankai Trough, Japan, and data were successfully downloaded from the CORKs.

Synthesis and characterization of polycrystalline brownmillerite cobalt doped Ca2Fe2O5

NASA Astrophysics Data System (ADS)

Dhankhar, Suchita; Bhalerao, Gopal; Baskar, K.; Singh, Shubra

2016-05-01

Brownmillerite compounds with general formula A2BB'O5 (BB' = Mn, Al, Fe, Co) have attracted attention in wide range of applications such as in solid oxide fuel cell, oxygen separation membrane and photocatalysis. Brownmillerite compounds have unique structure with alternate layers of BO6 octahedral layers and BO4 tetrahedral layers. Presence of dopants like Co in place of Fe increases oxygen vacancies. In the present work we have synthesized polycrystalline Ca2Fe2O5 and Ca2Fe1-xCoxO5 (x = 0.01, 0.03) by citrate combustion route. The as prepared samples were characterized by XRD using PANalytical X'Pert System, DRS (Diffuse reflectance spectroscopy) and SEM (Scanning electron microscopy).

Growth and laser properties of Yb : Ca 4YO(BO 3) 3 crystal

NASA Astrophysics Data System (ADS)

Zhang, Huaijin; Meng, Xianlin; Zhu, Li; Wang, Pu; Liu, Xuesong; Cheng, Ruiping; Dawes, Judith; Dekker, Peter; Zhang, Shaojun; Sun, Lianke

1999-04-01

Yb : Ca 4YO(BO 3) 3 (Yb : YCOB) crystal has been grown by the Czochralski method. The absorption and fluorescence spectra have been measured. The green luminescence is also observed. The output laser at 1032 nm has been demonstrated pumped by laser diode (LD) at 976.4 nm.

A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

PubMed

Harrell, William A; Vieira, Rebecca C; Ensel, Susan M; Montgomery, Vicki; Guernieri, Rebecca; Eccard, Vanessa S; Campbell, Yvette; Roxas-Duncan, Virginia; Cardellina, John H; Webb, Robert P; Smith, Leonard A

2017-02-01

Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC 50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay. Published by Elsevier Ltd.

NH4 Be2 BO3 F2 and γ-Be2 BO3 F: Overcoming the Layering Habit in KBe2 BO3 F2 for the Next-Generation Deep-Ultraviolet Nonlinear Optical Materials.

PubMed

Peng, Guang; Ye, Ning; Lin, Zheshuai; Kang, Lei; Pan, Shilie; Zhang, Min; Lin, Chensheng; Long, Xifa; Luo, Min; Chen, Yu; Tang, Yu-Huan; Xu, Feng; Yan, Tao

2018-05-12

KBe 2 BO 3 F 2 (KBBF) is still the only practically usable crystal that can generate deep-ultraviolet (DUV) coherent light by direct second harmonic generation (SHG). However, applications are hindered by layering, leading to difficulty in the growth of thick crystals and compromised mechanical integrity. Despite efforts, it is still a great challenge to discover new nonlinear optical (NLO) materials that overcome the layering while keeping the DUV SHG available. Now, two new DUV NLO beryllium borates have been successfully designed and synthesized, NH 4 Be 2 BO 3 F 2 (ABBF) and γ-Be 2 BO 3 F (γ-BBF), which not only overcome the layering but also can be used as next-generation DUV NLO materials with the shortest type I phase-matching second-harmonic wavelength down to 173.9 nm and 146 nm, respectively. Significantly, γ-BBF is superior to KBBF in all metrics and would be the most outstanding DUV NLO crystal. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthetic lipophilic antioxidant BO-653 suppresses HCV replication.

PubMed

Yasui, Fumihiko; Sudoh, Masayuki; Arai, Masaaki; Kohara, Michinori

2013-02-01

The influence of the intracellular redox state on the hepatitis C virus (HCV) life cycle is poorly understood. This study demonstrated the anti-HCV activity of 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653), a synthetic lipophilic antioxidant, and examined whether BO-653's antioxidant activity is integral to its anti-HCV activity. The anti-HCV activity of BO-653 was investigated in HuH-7 cells bearing an HCV subgenomic replicon (FLR3-1 cells) and in HuH-7 cells infected persistently with HCV (RMT-tri cells). BO-653 inhibition of HCV replication was also compared with that of several hydrophilic and lipophilic antioxidants. BO-653 suppressed HCV replication in FLR3-1 and RMT-tri cells in a concentration-dependent manner. The lipophilic antioxidants had stronger anti-HCV activities than the hydrophilic antioxidants, and BO-653 displayed the strongest anti-HCV activity of all the antioxidants examined. Therefore, the anti-HCV activity of BO-653 was examined in chimeric mice harboring human hepatocytes infected with HCV. The combination treatment of BO-653 and polyethylene glycol-conjugated interferon-α (PEG-IFN) decreased serum HCV RNA titer more than that seen with PEG-IFN alone. These findings suggest that both the lipophilic property and the antioxidant activity of BO-653 play an important role in the inhibition of HCV replication. Copyright © 2012 Wiley Periodicals, Inc.

Spectroscopic and crystal-field analysis of new Yb-doped laser materials

NASA Astrophysics Data System (ADS)

Haumesser, Paul-Henri; Gaumé, Romain; Viana, Bruno; Antic-Fidancev, Elisabeth; Vivien, Daniel

2001-06-01

Crystal-field effects are very important as far as laser performances of Yb-doped materials are concerned. In order to simplify the interpretation of low-temperature spectra, two tools derived from a careful examination of crystal-field interaction are presented. Both approaches are successfully applied in the case of new Yb-doped materials, namely Ca3Y2(BO3)4 (CYB), Ca3Gd2(BO3)4 (CaGB), Sr3Y(BO3)3 (SrYBO), Ba3Lu(BO3)3 (BLuB), Y2SiO5 (YSO), Ca2Al2SiO7 (CAS) and SrY4(SiO4)3O (SYS). The 2F7/2 splitting is particularly large in these materials and favourable to a quasi-three-level laser operating scheme. Calculations performed using the point charge electrostatic model for these compounds and using a consistent set of effective atomic charges confirm the experimental results. This should permit to use this model in a predictive approach.

A Multimodal Adaptive Wireless Control Interface for People With Upper-Body Disabilities.

PubMed

Fall, Cheikh Latyr; Quevillon, Francis; Blouin, Martine; Latour, Simon; Campeau-Lecours, Alexandre; Gosselin, Clement; Gosselin, Benoit

2018-06-01

This paper describes a multimodal body-machine interface (BoMI) to help individuals with upper-limb disabilities using advanced assistive technologies, such as robotic arms. The proposed system uses a wearable and wireless body sensor network (WBSN) supporting up to six sensor nodes to measure the natural upper-body gesture of the users and translate it into control commands. Natural gesture of the head and upper-body parts, as well as muscular activity, are measured using inertial measurement units (IMUs) and surface electromyography (sEMG) using custom-designed multimodal wireless sensor nodes. An IMU sensing node is attached to a headset worn by the user. It has a size of 2.9 cm 2.9 cm, a maximum power consumption of 31 mW, and provides angular precision of 1. Multimodal patch sensor nodes, including both IMU and sEMG sensing modalities are placed over the user able-body parts to measure the motion and muscular activity. These nodes have a size of 2.5 cm 4.0 cm and a maximum power consumption of 11 mW. The proposed BoMI runs on a Raspberry Pi. It can adapt to several types of users through different control scenarios using the head and shoulder motion, as well as muscular activity, and provides a power autonomy of up to 24 h. JACO, a 6-DoF assistive robotic arm, is used as a testbed to evaluate the performance of the proposed BoMI. Ten able-bodied subjects performed ADLs while operating the AT device, using the Test d'Évaluation des Membres Supérieurs de Personnes Âgées to evaluate and compare the proposed BoMI with the conventional joystick controller. It is shown that the users can perform all tasks with the proposed BoMI, almost as fast as with the joystick controller, with only 30% time overhead on average, while being potentially more accessible to the upper-body disabled who cannot use the conventional joystick controller. Tests show that control performance with the proposed BoMI improved by up to 17% on average, after three trials.

Mode of VAMP Substrate Recognition and Inhibition of Clostridium botulinum Neurotoxin F

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, R.; Schmidt, J; Stafford, R

2009-01-01

Clostridium botulinum neurotoxins (BoNTs) cleave neuronal proteins responsible for neurotransmitter release, causing the neuroparalytic disease botulism. BoNT serotypes B, D, F and G cleave and inactivate vesicle-associated membrane protein (VAMP), each at a unique peptide bond. The specificity of BoNTs depends on the mode of substrate recognition. We have investigated the mechanism of substrate recognition of BoNT F by determining the crystal structures of its complex with two substrate-based inhibitors, VAMP 22-58/Gln58D-cysteine and 27-58/Gln58D-cysteine. The inhibitors bind to BoNT F in the canonical direction (as seen for BoNTs A and E substrates) but are positioned specifically via three major exositesmore » away from the active site. The cysteine sulfur of the inhibitors interacts with the zinc and exists as sulfinic acid in the inhibitor VAMP 27-58/Gln58D-cysteine. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis.« less

A putative functional MYB transcription factor induced by low temperature regulates anthocyanin biosynthesis in purple kale (Brassica Oleracea var. acephala f. tricolor).

PubMed

Zhang, Bin; Hu, Zongli; Zhang, Yanjie; Li, Yali; Zhou, Shuang; Chen, Guoping

2012-02-01

The purple kale (Brassica Oleracea var. acephala f. tricolor) is a mutation in kales, giving the mutant phenotype of brilliant purple color in the interior. Total anthocyanin analysis showed that the amount of anthocyanins in the purple kale was up to 1.73 mg g(-1) while no anthocyanin was detected in the white kale. To elucidate the molecular mechanism of the anthocyanin biosynthesis in the purple kale, we analyzed the expression of structural genes and some transcription factors associated with anthocyanin biosynthesis in the purple cultivar "Red Dove" and the white cultivar "White Dove". The result showed that nearly all the anthocyanin biosynthetic genes showed higher expression levels in the purple cultivar than in the white cultivar, especially for DFR and ANS, they were barely detected in the white cultivar. Interestingly, the fact that a R2R3 MYB transcription factor named BoPAP1 was extremely up-regulated in the purple kale and induced by low temperature attracted our attention. Further sequence analysis showed that BoPAP1 shared high similarity with AtPAP1 and BoMYB1. In addition, the anthocyanin accumulation in the purple kale is strongly induced by the low temperature stress. The total anthocyanin contents in the purple kale under low temperature were about 50-fold higher than the plants grown in the greenhouse. The expression of anthocyanin biosynthetic genes C4H, F3H, DFR, ANS and UFGT were all enhanced under the low temperature. These evidences strongly suggest that BoPAP1 may play an important role in activating the anthocyanin structural genes for the abundant anthocyanin accumulation in the purple kale.

Molecular Assembly of Clostridium botulinum progenitor M complex of type E.

PubMed

Eswaramoorthy, Subramaniam; Sun, Jingchuan; Li, Huilin; Singh, Bal Ram; Swaminathan, Subramanyam

2015-12-07

Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. The similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.

Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inui, Ken; Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472; Sagane, Yoshimasa

2012-03-16

Highlights: Black-Right-Pointing-Pointer BoNT and NTNHA proteins share a similar protein architecture. Black-Right-Pointing-Pointer NTNHA and BoNT were both identified as zinc-binding proteins. Black-Right-Pointing-Pointer NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. Black-Right-Pointing-Pointer Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structuremore » classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X{sub 35}-D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.« less

Effect of alkali earth oxides on hydroxy-carbonated apatite nano layer formation for SiO2-BaO-CaO-Na2O-P2O5 glass system

NASA Astrophysics Data System (ADS)

Kiran, P.; Ramakrishna, V.; Shashikala, H. D.; Udayashankar, N. K.

2017-11-01

Barium soda lime phosphosilicate [(58SiO2-(32 - x)BaO- xCao-6Na2O-4P2O5 (where x = 15, 20, 25 and 30 mol%)] samples were synthesised using conventional sol-gel method at 700 °C sintering temperature. Thermal, structural properties were studied using thermo gravimetric analysis and differential thermal analysis, X-ray diffraction, scanning electron microscopy, fourier transform infrared and Raman spectroscopy. Using Raman spectra non-bridging oxygen concentrations were estimated. The hydroxy-carbonated apatite (HCA) layer formation on samples was analysed for 7 days using simulated body fluid (SBF) soaked samples. The growth of HCA layers self-assembled on the sample surface was discussed as a function of NBO/BO ratio. Results indicated that the number of Ca2+ ions released into SBF solution in dissolution process and weight loss of SB-treated samples vary with NBO/BO ratio. The changes in NBO/BO ratios were observed to be proportional to HCA forming ability of barium soda lime phosphosilicate glasses.

Silylene-Nickel Promoted Cleavage of B-O Bonds: From Catechol Borane to the Hydroborylene Ligand.

PubMed

Hadlington, Terrance J; Szilvási, Tibor; Driess, Matthias

2017-06-19

The first 16 valence electron [bis(NHC)](silylene)Ni 0 complex 1, [( TMS L)ClSi:→Ni(NHC) 2 ], bearing the acyclic amido-chlorosilylene ( TMS L)ClSi: ( TMS L=N(SiMe 3 )Dipp; Dipp=2,6-Pr i 2 C 6 H 4 ) and two NHC ligands (N-heterocyclic carbene=:C[(Pr i )NC(Me)] 2 ) was synthesized in high yield and structurally characterized. Compound 1 is capable of facile dihydrogen activation under ambient conditions to give the corresponding HSi-NiH complex 2. Most notably, 1 reacts with catechol borane to afford the unprecedented hydroborylene-coordinated (chloro)(silyl)nickel(II) complex 3, {[cat( TMS L)Si](Cl)Ni←:BH(NHC) 2 }, via the cleavage of two B-O bonds and simultaneous formation of two Si-O bonds. The mechanism for the formation of 3 was rationalized by means of DFT calculations, which highlight the powerful synergistic effects of the Si:→Ni moiety in the breaking of incredibly strong B-O bonds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comprehensive studies of the Ag+ effect on borosilicate glass ceramics containing Ag nanoparticles and Er-doped hexagonal NaYF4 nanocrystals: morphology, structure, and 2.7 μm emission

NASA Astrophysics Data System (ADS)

Liu, Qunhuo; Tian, Ying; Tang, Wenhua; Jing, Xufeng; Zhang, Junjie; Xu, Shiqing

2018-05-01

In this work, we have performed a comprehensive investigation of the Ag+ concentration effect on the morphological, thermal, structural, and mid-infrared emission properties of novel oxyfluoride borosilicate glasses and glass ceramics containing both Ag nanoparticles and erbium-doped hexagonal NaYF4 nanocrystals. The effect of Ag+ ions on the glass forming and crystallization processes was discussed in detail by glass structural analysis. It was found that the Ag+ concentration can affect the distribution of Na+ ion and bridge oxygen in boron-rich and silicon-rich phases, which induced the transformation between BO3 triangles and BO4 tetrahedra during crystallization process. In addition, there was a turning point when the doped Ag+ ion concentration reached its solubility in the borosilicate glass. Furthermore, the enhancement of the 2.7 μm emission and the reduction of the lifetime of the 4I13/2 level were observed both in glasses and in glass ceramics, and its origin was revealed by qualitative and quantitative analyses of the Er3+-Ag nanoparticles (localized electric field enhancement) and Er3+-Er3+ (nonradiative resonance energy transfer) interactions within glasses and glass ceramics. Moreover, the high lifetime of the 4I11/2 level (2.12 ms) and the peak emission cross section in 2.7 μm (6.8×10-21 cm2) suggested that the prepared glass ceramics have promising mid-infrared laser applications.

Expression of bovine non-classical major histocompatibility complex class I proteins in mouse P815 and human K562 cells.

PubMed

Parasar, Parveen; Wilhelm, Amanda; Rutigliano, Heloisa M; Thomas, Aaron J; Teng, Lihong; Shi, Bi; Davis, William C; Suarez, Carlos E; New, Daniel D; White, Kenneth L; Davies, Christopher J

2016-08-01

Major histocompatibility complex class I (MHC-I) proteins can be expressed as cell surface or secreted proteins. To investigate whether bovine non-classical MHC-I proteins are expressed as cell surface or secreted proteins, and to assess the reactivity pattern of monoclonal antibodies with non-classical MHC-I isoforms, we expressed the MHC proteins in murine P815 and human K562 (MHC-I deficient) cells. Following antibiotic selection, stably transfected cell lines were stained with H1A or W6/32 antibodies to detect expression of the MHC-I proteins by flow cytometry. Two non-classical proteins (BoLA-NC1*00501 and BoLA-NC3*00101) were expressed on the cell surface in both cell lines. Surprisingly, the BoLA-NC4*00201 protein was expressed on the cell membrane of human K562 but not mouse P815 cells. Two non-classical proteins (BoLA-NC1*00401, which lacks a transmembrane domain, and BoLA-NC2*00102) did not exhibit cell surface expression. Nevertheless, Western blot analyses demonstrated expression of the MHC-I heavy chain in all transfected cell lines. Ammonium-sulfate precipitation of proteins from culture supernatants showed that BoLA-NC1*00401 was secreted and that all surface expressed proteins where shed from the cell membrane by the transfected cells. Interestingly, the surface expressed MHC-I proteins were present in culture supernatants at a much higher concentration than BoLA-NC1*00401. This comprehensive study shows that bovine non-classical MHC-I proteins BoLA-NC1*00501, BoLA-NC3*00101, and BoLA-NC4*00201 are expressed as surface isoforms with the latter reaching the cell membrane only in K562 cells. Furthermore, it demonstrated that BoLA-NC1*00401 is a secreted isoform and that significant quantities of membrane associated MHC-I proteins can be shed from the cell membrane. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Oral vaccination with an adenovirus-vectored vaccine protects against botulism

PubMed Central

Chen, Shan; Xu, Qingfu; Zeng, Mingtao

2013-01-01

We have previously shown that an adenovirus vectored vaccine delivered intramuscularly or intranasally was effective in protection against botulism in a mouse model. The adenoviral vector encodes a human codon-optimized heavy chain C-fragment (HC50) of botulinum neurotoxin type C (BoNT/C). Here, we evaluate the same vaccine candidate as an oral vaccine against BoNT/C in a mouse model. To elicit protective immunity, the mice were orally vaccinated with a single dose of 1×104 to 1×107 plaque forming units (pfu) of the adenoviral vector. The immune sera, collected six weeks after oral vaccination with 2×107 pfu adenovirus, has shown an ability to neutralize the biological activity of BoNT/C in vitro. Additionally, animals receiving a single dose of 2×106 pfu adenovirus or greater were completely protected against challenge with 100×MLD50 of BoNT/C. The data demonstrated the feasibility to develop an adenovirus-based oral vaccine against botulism. PMID:23295065

The evolution and outcome of surveillance of Barrett's oesophagus over four decades in a UK District General Hospital.

PubMed

Royston, Christine; Caygill, Christine; Charlett, Andre; Bardhan, Karna Dev

2016-12-01

We present the long-term outcome of Barrett's oesophagus (BO) at a District General Hospital set against the increasing numbers of patients with gastro-oesophageal reflux disease (GORD). Data were collected prospectively over 37 years. Comparison of GORD without Barrett's (NoBO) versus BO was performed from 1/1/1977 to 31/12/2001 when the NoBO database closed and outcomes of all cases of BO diagnosed until 31/12/2011 and followed up until 31/12/2013 have been reported. During the period 1977-2001 the number of GORD NoBO cases was 11 610, and that of BO cases was 764 (6.2% of all GORD); total number of BO cases in 1977-2011 was 1468. NoBO patients were younger than BO patients: 52.2 versus 61.6 years. There was a male predominance in both groups: NoBO 55% and BO 62% (P<0.0001). The prevalence of oesophageal adenocarcinoma (OAC) was 87/1468 (5.9%) BO cases. Its incidence was 54/1381 (3.9%); the mean interval between the diagnosis of BO and incident OAC was 9 years (range 13 months-25.4 years); there was one OAC per 192 patient-years of follow-up (0.52% per year). Mortality was significantly lower in 37 patients under endoscopic surveillance at the time OAC was diagnosed (51 vs. 88% P=0.0141) partly because of older age and comorbidity of the other 17, in whom serial endoscopy was contraindicated. A proportional hazards model to allow for age estimated that the hazard rate ratio was lower in the surveillance group; however, this difference did not reach statistical significance (0.64, 95% confidence interval 0.30-1.48, P=0.08). Excluding prevalent cancers from both groups, mortality in BO was double that in NoBO (47 vs. 24%). These 37 years of observation suggest, but do not confirm, that endoscopic surveillance may reduce the risk of death from OAC. Modern technology is likely to yield better results, but larger prospective studies are needed to confirm the benefits.

Structural and mutational analyses of the receptor binding domain of botulinum D/C mosaic neurotoxin: Insight into the ganglioside binding mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuemket, Nipawan; Tanaka, Yoshikazu; Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810

2011-07-29

Highlights: {yields} We determined the crystal structure of the receptor binding domain of BoNT in complex with 3'-sialyllactose. {yields} An electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. {yields} Alanine site-directed mutagenesis showed that GBS and GBL are important for ganglioside binding. {yields} A cell binding mechanism, which involves cooperative contribution of two sites, was proposed. -- Abstract: Clostridium botulinum type D strain OFD05, which produces the D/C mosaic neurotoxin, was isolated from cattle killed by the recent botulism outbreak in Japan. The D/C mosaic neurotoxin is the most toxic of the botulinummore » neurotoxins (BoNT) characterized to date. Here, we determined the crystal structure of the receptor binding domain of BoNT from strain OFD05 in complex with 3'-sialyllactose at a resolution of 3.0 A. In the structure, an electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. Alanine site-directed mutagenesis showed the significant contribution of the residues surrounding the cleft to ganglioside recognition. In addition, a loop adjoining the cleft also plays an important role in ganglioside recognition. In contrast, little effect was observed when the residues located around the surface previously identified as the protein receptor binding site in other BoNTs were substituted. The results of cell binding analysis of the mutants were significantly correlated with the ganglioside binding properties. Based on these observations, a cell binding mechanism of BoNT from strain OFD05 is proposed, which involves cooperative contribution of two ganglioside binding sites.« less

Boron environments in Pyrex® glass--a high resolution, Double-Rotation NMR and thermodynamic modelling study.

PubMed

Howes, A P; Vedishcheva, N M; Samoson, A; Hanna, J V; Smith, M E; Holland, D; Dupree, R

2011-07-07

It is shown, using the important technological glass Pyrex® as an example, that 1D and 2D (11)B Double-Rotation (DOR) NMR experiments, in combination with thermodynamic modelling, are able to provide unique structural information about complex glasses. (11)B DOR NMR has been applied to Pyrex® glass in order to remove both dipolar and quadrupolar broadening of the NMR lines, leading to high resolution spectra that allow unambiguous, accurate peak fitting to be carried out, of particular importance in the case of the 3-coordinated [BO(3)] (B3) trigonal planar environments. The data obtained are of sufficient quality that they can be used to test the distributions of borate and borosilicate superstructural units predicted by the thermodynamics-based Model of Associated Solutions. The model predicts the dominant boron-containing chemical groupings in Pyrex® glass to be those associated with B(2)O(3) and sodium tetraborate (with smaller amounts of sodium triborate, sodium diborate, sodium pentaborate, danburite and reedmergnerite). Excellent agreement is found between model and experiment provided the (11)B peaks with isotropic chemical shifts of -1.4 ppm and 0.5 ppm are assigned to B4 species from borosilicate units ([B(OSi)(4)] and [B(OSi)(3)(OB)]) and borate superstructural units (mainly triborate rings with some pentaborate and diborate) respectively. The peaks with isotropic shifts of 14 ppm and 18.1 ppm are then assigned to B3 in borate superstructural units (mainly triborate and pentaborate along with connecting B3) and boroxol rings respectively. The assignments of the DOR NMR peaks, are supported by the presence of cross-peaks in (11)B spin-diffusion DOR NMR spectra which can be used to develop a structural model in which B(2)O(3)-like regions are linked, via borate and borosilicate superstructural units, to the majority silica network. Pyrex® is thus shown to have a heterogeneous structure, with distinct molecular groupings that are far removed from a random distribution of network polyhedra with only short-range order. This journal is © the Owner Societies 2011

Molecular composition and extinction coefficient of native botulinum neurotoxin complex produced by Clostridium botulinum hall A strain.

PubMed

Bryant, Anne-Marie; Davis, Jenny; Cai, Shuowei; Singh, Bal Ram

2013-02-01

Seven distinct strains of Clostridium botulinum (type A to G) each produce a stable complex of botulinum neurotoxin (BoNT) along with neurotoxin-associated proteins (NAPs). Type A botulinum neurotoxin (BoNT/A) is produced with a group of NAPs and is commercially available for the treatment of numerous neuromuscular disorders and cosmetic purposes. Previous studies have indicated that BoNT/A complex composition is specific to the strain, the method of growth and the method of purification; consequently, any variation in composition of NAPs could have significant implications to the effectiveness of BoNT based therapeutics. In this study, a standard analytical technique using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and densitometry analysis was developed to accurately analyze BoNT/A complex from C. botulinum type A Hall strain. Using 3 batches of BoNT/A complex the molar ratio was determined as neurotoxin binding protein (NBP, 124 kDa), heavy chain (HC, 90 kDa), light chain (LC, 53 kDa), NAP-53 (50 kDa), NAP-33 (36 kDa), NAP-22 (24 kDa), NAP-17 (17 kDa) 1:1:1:2:3:2:2. With Bradford, Lowry, bicinchoninic acid (BCA) and spectroscopic protein estimation methods, the extinction coefficient of BoNT/A complex was determined as 1.54 ± 0.26 (mg/mL)(-1)cm(-1). These findings of a reproducible BoNT/A complex composition will aid in understanding the molecular structure and function of BoNT/A and NAPs.

Louisiana Coastal Area, Louisiana. Freshwater Diversion to Barataria and Breton Sound Basins. Feasibility Study. Volume 4. Public Views and Responses.

DTIC Science & Technology

1984-09-01

Pontchartrain, Lake BoLgne, and Chandeleur Sound were mentioned as possible sites. Mr. Moore proposed that structures for this project be designed with...milasures will be needed, such as a diversion into Lake Pontchartrain ani thence Chandeleur and Mississippi Sounds, being proposed unler the Missis

NWHSS Implement Family Member Assessment Component in the Millennium Cohort Study

DTIC Science & Technology

2012-10-01

before em ail 10/4/2011 after em ail Jum bo W ith Survey (N  = 24320) Jum bo W ithO ut Survey (N  = 24320) Letter Size (N  = 24320) Vanilla M arried...M arried M arried M arried  (N  = 24324) Vanilla N ot M arried (N  = 98938) Jum bo W ith Survey (N  = 24320) Jum bo W ithO ut Survey (N  = 24320

Laboratory Findings Suggesting an Association Between BoHV-4 and Bovine Abortions in Southern Belgium.

PubMed

Delooz, L; Czaplicki, G; Houtain, J Y; Dal Pozzo, F; Saegerman, C

2017-08-01

Abortions cause heavy economic losses for the bovine sector. The use of a standardized panel of analyses covering a large spectrum of pathogens responsible of abortion in cattle allowed demonstrating the direct involvement of at least one pathogen in 57% of analysed abortions in the southern part of Belgium. This result suggests a margin of improvement in the diagnostic efficacy. In order to evaluate the interest to broaden the list of pathogens included in the panel of analyses, the implication of bovine herpesvirus 4 (BoHV-4) in abortion was assessed by two different studies. In the first study, coupled serology was performed after abortion on 714 dams to identify specific seroconversion against BoHV-4. The overall seroconversion in cows was 19.5%, with a higher frequency in primiparous compared to multiparous females. In addition, the type of breed (beef cattle) and the time period from the fourth quarter 2008 until the last quarter 2009 were significantly related to the seroconversion of cows. The second study investigated the virus ability to infect the foetus. In this study, 368 cases of bovine abortions were specifically tested for BoHV-4, using PCR on foetus tissues and ELISA on dam and foetus sera. The results showed a maternal seroprevalence of 64.7%, a foetal seroprevalence of 0.8% and a PCR prevalence in foetuses of 1.1%, demonstrating the ability of BoHV-4 to infect the foetus. © 2016 Blackwell Verlag GmbH.

The effect of B 2O 3 addition on the crystallization of amorphous TiO 2-ZrO 2 mixed oxide

NASA Astrophysics Data System (ADS)

Mao, Dongsen; Lu, Guanzhong

2007-02-01

The effect of B 2O 3 addition on the crystallization of amorphous TiO 2-ZrO 2 mixed oxide was investigated by X-ray diffraction (XRD), thermogravimetric and differential thermal analysis (TG/DTA). TiO 2-ZrO 2 mixed oxide was prepared by co-precipitation method with aqueous ammonia as the precipitation reagent. Boric acid was used as a source of boria, and boria contents varied from 2 to 20 wt%. The results indicate that the addition of small amount of boria (<8 wt%) hinders the crystallization of amorphous TiO 2-ZrO 2 into a crystalline ZrTiO 4 compound, while a larger amount of boria (⩾8 wt%) promotes the crystallization process. FT-IR spectroscopy and 11B MAS NMR results show that tetrahedral borate species predominate at low boria loading, and trigonal borate species increase with increasing boria loading. Thus it is concluded that highly dispersed tetrahedral BO 4 units delay, while a build-up of trigonal BO 3 promote, the crystallization of amorphous TiO 2-ZrO 2 to form ZrTiO 4 crystals.

The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond.

PubMed

Grando, S A; Zachary, C B

2018-05-01

There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. This review aims to provide an update on the non-neuronal and nonmuscular effects of botulinum toxin. We critically analysed recent reports on the structure and function of cellular signalling systems subserving biological effects of BoNTs. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in how BoNT binds to, and acts on, neuronal vs. non-neuronal cells. The non-neuronal cells that express one or more BoNT/A-binding proteins, and/or cleavage target synaptosomal-associated protein 25, include: epidermal keratinocytes; mesenchymal stem cells from subcutaneous adipose; nasal mucosal cells; urothelial cells; intestinal, prostate and alveolar epithelial cells; breast cell lines; neutrophils; and macrophages. Serotype BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. Nontraditional applications of BoNT have been reported for the treatment of the following dermatological conditions: hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland naevi, congenital eccrine naevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies have demonstrated the ability of BoNT/A to protect skin flaps, facilitate wound healing, decrease thickness of hypertrophic scars, produce an anti-ageing effect, improve a mouse model of psoriasiform dermatitis, and have also revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anticancer properties. BoNTs have a much wider range of applications than originally understood, and the individual cellular responses to the cholinergic impacts of BoNTs could provide fertile ground for future studies. © 2017 British Association of Dermatologists.

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

PubMed

Garcia-Rodriguez, Consuelo; Razai, Ali; Geren, Isin N; Lou, Jianlong; Conrad, Fraser; Wen, Wei-Hua; Farr-Jones, Shauna; Smith, Theresa J; Brown, Jennifer L; Skerry, Janet C; Smith, Leonard A; Marks, James D

2018-03-01

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (K D ). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had K D values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.

Identification and expression analysis of BoMF25, a novel polygalacturonase gene involved in pollen development of Brassica oleracea.

PubMed

Lyu, Meiling; Liang, Ying; Yu, Youjian; Ma, Zhiming; Song, Limin; Yue, Xiaoyan; Cao, Jiashu

2015-06-01

BoMF25 acts on pollen wall. Polygalacturonase (PG) is a pectin-digesting enzyme involved in numerous plant developmental processes and is described to be of critical importance for pollen wall development. In the present study, a PG gene, BoMF25, was isolated from Brassica oleracea. BoMF25 is the homologous gene of At4g35670, a PG gene in Arabidopsis thaliana with a high expression level at the tricellular pollen stage. Collinear analysis revealed that the orthologous gene of BoMF25 in Brassica campestris (syn. B. rapa) genome was probably lost because of genome deletion and reshuffling. Sequence analysis indicated that BoMF25 contained four classical conserved domains (I, II, III, and IV) of PG protein. Homology and phylogenetic analyses showed that BoMF25 was clustered in Clade F. The putative promoter sequence, containing classical cis-acting elements and pollen-specific motifs, could drive green fluorescence protein expression in onion epidermal cells. Quantitative RT-PCR analysis suggested that BoMF25 was mainly expressed in the anther at the late stage of pollen development. In situ hybridization analysis also indicated that the strong and specific expression signal of BoMF25 existed in pollen grains at the mature pollen stage. Subcellular localization showed that the fluorescence signal was observed in the cell wall of onion epidermal cells, which suggested that BoMF25 may be a secreted protein localized in the pollen wall.

Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation Procedures.

PubMed

Alter, Katharine E; Karp, Barbara I

2017-12-28

Injections of botulinum neurotoxins (BoNTs) are prescribed by clinicians for a variety of disorders that cause over-activity of muscles; glands; pain and other structures. Accurately targeting the structure for injection is one of the principle goals when performing BoNTs procedures. Traditionally; injections have been guided by anatomic landmarks; palpation; range of motion; electromyography or electrical stimulation. Ultrasound (US) based imaging based guidance overcomes some of the limitations of traditional techniques. US and/or US combined with traditional guidance techniques is utilized and or recommended by many expert clinicians; authors and in practice guidelines by professional academies. This article reviews the advantages and disadvantages of available guidance techniques including US as well as technical aspects of US guidance and a focused literature review related to US guidance for chemodenervation procedures including BoNTs injection.

Long-term facial improvement after repeated BoNT-A injections and mirror biofeedback exercises for chronic facial synkinesis: a case-series study.

PubMed

Mandrini, Silvia; Comelli, Mario; Dall'angelo, Anna; Togni, Rossella; Cecini, Miriam; Pavese, Chiara; Dalla Toffola, Elena

2016-12-01

Only few studies have considered the effects of the combined treatment with onabotulinumtoxinA (BoNT-A) injections and biofeedback (BFB) rehabilitation in the recovery of postparetic facial synkinesis (PPFS). To explore the presence of a persistent improvement in facial function out of the pharmacological effect of BoNT-A in subjects with established PPFS, after repeated sessions of BoNT-A injections combined with an educational facial training program using mirror biofeedback (BFB) exercises. Secondary objective was to investigate the trend of the presumed persistent improvement. Case-series study. Outpatient Clinic of Physical Medicine and Rehabilitation Unit. Twenty-seven patients (22 females; mean age 45±16 years) affected by an established peripheral facial palsy, treated with a minimum of three BoNT-A injections in association with mirror BFB rehabilitation. The interval between consecutive BoNT-A injections was at least five months. At baseline and before every BoNT-A injection+mirror BFB session (when the effect of the previous BoNT-A injection had vanished), patients were assessed with the Italian version of Sunnybrook Facial Grading System (SB). The statistical analysis considered SB composite and partial scores before each treatment session compared to the baseline scores. A significant improvement of the SB composite and partial scores was observed until the fourth session. Considering the "Symmetry of Voluntary Movement" partial score, the main improvement was observed in the muscles of the lower part of the face. In a chronic stage of postparetic facial synkinesis, patients may benefit from a combined therapy with repeated BoNT-A injections and an educational facial training program with mirror BFB exercises, gaining an improvement of the facial function up to the fourth session. This improvement reflects the acquired ability to use facial muscle correctly. It doesn't involve the injected muscles but those trained with mirror biofeedback exercises and it persists also when BoNT-A action has vanished. The combined therapy with repeated BoNT-A injections and an educational facial training program using mirror BFB exercises may be useful in the motor recovery of the muscles of the lower part of the face not injected but trained.

Roymillerite, Pb24Mg9(Si9AlO28)(SiO4)(BO3)(CO3)10(OH)14O4, a new mineral: mineralogical characterization and crystal chemistry

NASA Astrophysics Data System (ADS)

Chukanov, Nikita V.; Jonsson, Erik; Aksenov, Sergey M.; Britvin, Sergey N.; Rastsvetaeva, Ramiza K.; Belakovskiy, Dmitriy I.; Van, Konstantin V.

2017-11-01

The new mineral roymillerite Pb24Mg9(Si9AlO28)(SiO4)(BO3)(CO3)10(OH)14O4, related to britvinite and molybdophyllite, was discovered in a Pb-rich assemblage from the Kombat Mine, Grootfontein district, Otjozondjupa region, Namibia, which includes also jacobsite, cerussite, hausmannite, sahlinite, rhodochrosite, barite, grootfonteinite, Mn-Fe oxides, and melanotekite. Roymillerite forms platy single-crystal grains up to 1.5 mm across and up to 0.3 mm thick. The new mineral is transparent, colorless to light pink, with a strong vitreous lustre. Cleavage is perfect on (001). Density calculated using the empirical formula is equal to 5.973 g/cm3. Roymillerite is optically biaxial, negative, α = 1.86(1), β ≈ γ = 1.94(1), 2 V (meas.) = 5(5)°. The IR spectrum shows the presence of britvinite-type tetrahedral sheets, {CO}3^{2 - }, {BO}3^{3 - }, and OH- groups. The chemical composition is (wt%; electron microprobe, H2O and CO2 determined by gas chromatography, the content of B2O3 derived from structural data): MgO 4.93, MnO 1.24, FeO 0.95, PbO 75.38, B2O3 0.50, Al2O3 0.74, CO2 5.83, SiO2 7.90, H2O 1.8, total 99.27. The empirical formula based on 83 O atoms pfu (i.e. Z = 1) is Pb24.12Mg8.74Mn1.25Fe0.94B1.03Al1.04C9.46Si9.39H14.27O83. The crystal structure was determined using single-crystal X-ray diffraction data. The new mineral is triclinic, space group P \\bar{1}, with a = 9.315(1), b = 9.316(1), c = 26.463(4) Å, α = 83.295(3)°, β = 83.308(3)°, γ = 60.023(2)°, V = 1971.2(6) Å3. The crystal structure of roymillerite is based built by alternating pyrophyllite-type TOT-modules Mg9(OH)8[(Si,Al)10O28] and I-blocks Pb24(OH)6O4(CO3)10(BO3,SiO4). The strongest lines of the powder X-ray diffraction pattern [ d, Å (I, %) ( hkl)] are: 25.9 (100) (001), 13.1 (11) (002), 3.480 (12) (017, 107, -115, 1-15), 3.378 (14) (126, 216), 3.282 (16) (-2-15, -1-25), 3.185 (12) (-116, 1-16), 2.684 (16) (031, 301, 030, 300, 332, -109, 0-19, 1-18), 2.382 (11) (0.0.-11). Roymillerite is named to honor Dr. Roy McG. Miller for his important contributions to the knowledge of the geology of Namibia.

Charge ordering and multiferroicity in Fe{sub 3}BO{sub 5} and Fe{sub 2}MnBO{sub 5} oxyborates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maignan, A., E-mail: antoine.maignan@ensicaen.fr; Lainé, F.; Guesdon, A.

2017-02-15

The comparison of Fe{sub 3}BO{sub 5} and Fe{sub 2}MnBO{sub 5} reveals that the 2Fe{sup 2+}: Fe{sup 3+} charge ordering of the former is suppressed in the latter. Spin dynamics probed by ac susceptibility are strongly affected by the substitution, inducing superparamagnetism at low temperature in Fe{sub 2}MnBO{sub 5}. Interestingly, for both oxyborates, glassiness is observed in the dielectric properties at low temperature, but only Fe{sub 3}BO{sub 5} shows a magnetodielectric effect close to its lower magnetic transition. A change in the electrical polarization, measured by pyroelectric current integration, is observed in Fe{sub 3}BO{sub 5} and is even more pronounced inmore » Fe{sub 2}MnBO{sub 5}. Such results suggest that these oxyborates behave like antiferromagnetic relaxor ferroelectrics. These features are proposed to be related to the distribution of the species (Fe{sup 3+}, Fe{sup 2+} and Mn{sup 2+}) over the four transition metal sites forming the ludwigite structure. - Graphical abstract: 90 K [010] electron diffraction patterns of Fe{sub 3}BO{sub 5}. The yellow arrows in the pattern indicate the extra-spots corresponding to the superstructure induced by the charge ordering. - Highlights: • The TEM (ED) study of the Fe{sub 3}BO{sub 5} oxyborate at 90 K reveals a superstructure related to a Fe{sup 2+}/Fe{sup 3+} ordering. • The Fe{sub 2}MnBO{sub 5}, Mn-substituted counterpart, does not show such ordering. • Our magnetic and electric measurements demonstrate that these magnetic ferrites exhibit glassiness in their charges (relaxor-type) with additional superparamagnetism at low T for Fe{sub 2}MnBO{sub 5} and magnetodielectric coupling near T{sub N2}=72 K in Fe{sub 3}BO{sub 5}. • The pyroelectric measurements confirm the existence of a ferroelectric behavior in these antiferromagnets. Accordingly, our results open the route to the study of other large class of the M{sub 2}{sup 2+}M’{sup 3+}BO{sub 5} ludwigites and to their complex magnetism and its relationship to relaxor ferroelectricity.« less

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar G.; Swaminathan S.; Kumaran, D.

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC{sub 50} of 0.9 {micro}M and a K{sub i} ofmore » 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.« less

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling.

PubMed

Kumar, Gyanendra; Kumaran, Desigan; Ahmed, S Ashraf; Swaminathan, Subramanyam

2012-05-01

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC(50) of 0.9 µM and a K(i) of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features. © 2012 International Union of Crystallography

Mini-CORK observatories using the MeBo seafloor drill rig - a new development for long-term data acquisition and sampling in shallow boreholes

NASA Astrophysics Data System (ADS)

Kopf, A.; Freudenthal, T.; Ratmeyer, V.; Bergenthal, M.; Renken, J.; Zabel, M.; Wefer, G.

2011-12-01

State of the art technology for long-term monitoring of fluid migration within the sea floor is the sealing of a borehole with a Circulation Obviation Retrofit Kit (CORK) after sensor installation and/or fluid sampling devices within the drill string. However, the combined used of a drilling vessels and a remotely operated drilling (ROV) required for a CORK installation in the deep sea is a costly exercise that limits the number of monitoring stations installed. Robotic sea floor drill rigs are a cost effective alternative for shallow drillings down to 50-100 m below sea floor. Here we present a Mini-CORK system that is developed for installation with the sea floor drill rig MeBo. This rig was developed at MARUM Research Centre, University of Bremen in 2005 and can sample the sea floor in water depths up to 2000 m. The MeBo is deployed on the seabed and remotely controlled from the vessel. All required drill tools for wire-line core drilling down to 70 m below sea floor are stored on two rotating magazines and can be loaded below the top drive drill head for assembling the drill string. For one of the upcoming cruises with RV Sonne offshore Japan (Nankai Trough accretionary prism), MeBo will be used for the first time to place observatories. Two different designs have been developed. The first, relatively simple long-term device resembles a MeBo drill rod in its geometry, and contains a pressure and temperature transducer in the borehole plus an identical pair of transducers for seafloor reference. The device also contains a data logger, battery unit, and an acoustic modem so that data can be downloaded at any time from a ship of opportunity. The key element at the base of the observatory rod is a seal at the conical thread to separate the borehole hydraulically from the overlying water body. It is realized by an adapter, which also contains a hotstab hydraulic connection and an electrical connection. The second observatory device is a seafloor unit, which replaces part of the first unit and which is deployed by ROV. In essence, the upper portion of the former observatory is taken away by ROV, and an umbilical containing hydraulic lines and tubing to withdraw formation water from the borehole is plugged into the hotstab female adapter by ROV. At the far end, the umbilical is connected to a seafloor unit with battery power, data logger, P and T transducers, and the same acoustic modem as the former one. In addition, the latter contains osmo samplers and biological chambers (FLOCS) for in situ sampling and experiments. After the envisaged deployment period, the entire unit is replaced while an identical one is prepared on deck and lowered from the vessel. In theory, the MeBo hole infinitely serves as an access to depth since no electronic, but only tubing is lowered into the (open) hole. In summary, long-term borehole installations with MeBo offer an affordable way to measure key physical properties over time and sample the formation fluids for geochemistry and microbiology (in case of the second, ROV-deployed CORK).

Synthesis, crystal structure refinement, and nonlinear-optical properties of CaB{sub 3}O{sub 5}(OH): Comparative crystal chemistry of calcium triborates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamnova, N. A., E-mail: aks.crys@gmail.com; Aksenov, S. M.; Stefanovich, S. Yu.

Calcium triborate CaB{sub 3}O5(OH) obtained by hydrothermal synthesis in the Ca(OH){sub 2}–H{sub 3}BO{sub 3}–Na{sub 2}CO{sub 3}–KCl system is studied by single-crystal X-ray diffraction. The parameters of the orthorhombic unit cell are as follows: a = 13.490(1), b = 6.9576(3), and c = 4.3930(2) Å; V = 412.32(3) Å{sup 3} and space group Pna2{sub 1}. The structure is refined in the anisotropic approximation of the atomic displacement parameters to R = 4.28% using 972 vertical bar F vertical bar > 4σ(F). It is confirmed that the crystal structure of Ca triborate CaB{sub 3}O{sub 5}(OH) is identical to that described earlier. Themore » hydrogen atom is localized. An SHG signal stronger than that of the quartz standard is registered. The phase transition of calcium triborate into calciborite is found on heating. The comparative crystal-chemical analysis of a series of borates with the general chemical formula 2CaO · 3B{sub 2}O{sub 3} · nH{sub 2}O (n = 0–13) with the constant CaO: B{sub 2}O{sub 3}= 2: 3 ratio and variable content of water is performed.« less

Bovine Herpesvirus-4-Based Vector Delivering Peste des Petits Ruminants Virus Hemagglutinin ORF Induces both Neutralizing Antibodies and Cytotoxic T Cell Responses

PubMed Central

Macchi, Francesca; Rojas, José Manuel; Verna, Andrea Elizabeth; Sevilla, Noemí; Franceschi, Valentina; Tebaldi, Giulia; Cavirani, Sandro; Martín, Verónica; Donofrio, Gaetano

2018-01-01

Peste des Petits Ruminants Virus (PPRV) is an extremely infective morbillivirus that primarily affects goats and sheep. In underdeveloped countries where livestock are the main economical resource, PPRV causes considerable economic losses. Protective live attenuated vaccines are currently available but they induce antibody responses similar to those produced in PPRV naturally infected animals. Effective vaccines able to distinguish between vaccinated and naturally infected animals are required to PPRV control and eradication programs. Hemagglutinin (H) is a highly immunogenic PPRV envelope glycoprotein displaying both hemagglutinin and neuraminidase activities, playing a crucial role in virus attachment and penetration. In this study, a recombinant Bovine Herpesvirus-4 (BoHV-4)-based vector delivering an optimized PPRV-Hemagglutinin expression cassette, BoHV-4-A-PPRV-H-ΔTK, was assessed in immunocompetent C57BL/6 mice. BoHV-4-A-PPRV-H-ΔTK-immunization elicited both cellular and humoral immune responses with specific T cell, cytotoxic T lymphocyte, and sero-neutralizing antibody against PPRV. These data suggest recombinant BoHV-4-A-PPRV-H-ΔTK as an effective vaccine candidate to protect against PPRV herd infection and potentially applicable for eradication programs. PMID:29556236

Vibrational spectroscopy of the borate mineral tunellite SrB6O9(OH)2·3(H2O) - Implications for the molecular structure

NASA Astrophysics Data System (ADS)

Frost, Ray L.; López, Andrés; Scholz, Ricardo; Xi, Yunfei

2014-02-01

Tunellite is a strontium borate mineral with formula: SrB6O9(OH)2·3(H2O) and occurs as colorless crystals in the monoclinic pyramidal crystal system. An intense Raman band at 994 cm-1 was assigned to the BO stretching vibration of the B2O3 units. Raman bands at 1043, 1063, 1082 and 1113 cm-1 are attributed to the in-plane bending vibrations of trigonal boron. Sharp Raman bands observed at 464, 480, 523, 568 and 639 cm-1 are simply defined as trigonal and tetrahedral borate bending modes. The Raman spectrum clearly shows intense Raman bands at 3567 and 3614 cm-1, attributed to OH units. The molecular structure of a natural tunellite has been assessed by using vibrational spectroscopy.

Adam, Eve and the reflux enigma: age and sex differences across the gastro-oesophageal reflux spectrum.

PubMed

Royston, Christine; Bardhan, Karna D

2017-06-01

We present demographic differences across the gastro-oesophageal reflux disease (GORD) spectrum in a UK District General Hospital. Data were prospectively collected over 37 years. At endoscopy patients were categorized as: erosive oesophagitis (EO), Barrett's oesophagus (BO) or nonerosive reflux disease (NER). Analysis 1: comparison of EO, BO and NER 1977-2001 when the database for GORD without BO closed. Analysis 2: demographic differences in oesophageal adenocarcinoma (OAC) in total BO population diagnosed 1977-2011. GORD 1977-2001 (n=11 944): sex, male predominance in EO and BO but not NER; male : female ratios, 1.81, 1.65, 0.87, respectively (P<0.0001); mean age at presentation, EO 54 years, BO 62 years, NER 50 years; women were older than men by 10, 7 and 6 years, respectively.BO 1977-2011: prevalent OAC, 87/1468 (6%); male : female ratio, 4.1 (P<0.0001); incident OAC, 54/1381 (3.9%); male : female ratio, 3.5 (P<0.0001). Among all BO, more men developed OAC (3 vs. 0.9%). Within each sex, proportion of OAC higher among men (4.9 vs. 2.3%); at OAC diagnosis women were slightly but not significantly older (69.9 vs. 72.3 years, P=0.322). Two views may explain our findings. First, women have either milder reflux, or reduced mucosal sensitivity hence reflux remains silent for longer. Alternatively, women genuinely develop reflux later, that is, are more protected and for longer from developing GORD and its complications. Early evidence is emerging that female sex hormones may indeed have a protective role in GORD during the reproductive period. We suggest reflux and its consequences may be an example of 'protection' conferred on Eve.

Botulinum toxin type a injections for cervical and shoulder girdle myofascial pain using an enriched protocol design.

PubMed

Nicol, Andrea L; Wu, Irene I; Ferrante, F Michael

2014-06-01

Myofascial pain syndrome is a regional condition of muscle pain and stiffness and is classically characterized by the presence of trigger points in affected musculature. Botulinum toxin type A (BoNT-A) has been shown to have antinociceptive properties and elicit sustained muscle relaxation, thereby possibly affording even greater relief than traditional strategies. Our goal was to determine whether direct injection of BoNT-A into painful muscle groups is effective for cervical and shoulder girdle myofascial pain. An enriched protocol design was used, wherein 114 patients with cervical and shoulder girdle myofascial pain underwent injection of BoNT-A to determine their response to the drug. Fifty-four responders were then enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. Pain scales and quality of life measures were assessed at baseline and at routine follow-up visits until completion of the study after 26 weeks. Injection of BoNT-A into painful muscle groups improved average visual numerical pain scores in subjects who received a second dose of BoNT-A compared to placebo (P = 0.019 [0.26, 2.78]). Subjects who received a second dose of BoNT-A had a reduced number of headaches per week (P = 0.04 [0.07, 4.55]). Brief Pain Inventory interference scores for general activity and sleep were improved (P = 0.046 [0.038, 3.700] and 0.02 [0.37, 4.33], respectively) in those who received a second dose of BoNT-A. BoNT-A injected directly into painful muscle groups improves average pain scores and certain aspects of quality of life in patients experiencing severe cervical and shoulder girdle myofascial pain.

Cation Ordering within the Perovskite Block of a Six-layer Ruddlesden-Popper Oxide from Layer-by-layer Growth

NASA Astrophysics Data System (ADS)

Yan, Lei; Niu, H. J.; Rosseinsky, M. J.

2011-03-01

The (AO)(A BO3)n Ruddlesden-Popper structure is an archetypal complex oxide consisting of two distinct structural units, an (AO) rock salt layer separating an n-octahedra thick perovskite block. Conventional high-temperature oxide synthesis methods cannot access members with n > 3 , butlowtemperaturelayer - by - layerthinfilmmethodsallowthepreparationofmaterialswiththickerperovskiteblocks , exploitinghighsurfacemobilityandlatticematchingwiththesubstrate . Thispresentationdescribesthegrowthofann = 6 memberCaO / (ABO 3)n (ABO 3 : CaMnO 3 , La 0.67 Ca 0.33 MnO 3 orCa 0.85 Sm 0.15 MnO 3) epitaxialsinglecrystalfilmsonthe (001) SrTiO 3 substrates by pulsed laser deposition with the assistance of a reflection high energy electron diffraction (RHEED).

Synthesis and studies on microhardness of alkali zinc borate glasses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Subhashini,, E-mail: subhashini.p.p@gmail.com; Bhattacharya, Soumalya, E-mail: subhashini.p.p@gmail.com; Shashikala, H. D., E-mail: subhashini.p.p@gmail.com

2014-04-24

The mixed alkali effect on zinc borate glasses have been reported. The glass systems of nominal composition 10Zn+xLi{sub 2}O+yNa{sub 2}O+80B{sub 2}O{sub 3} (x = y = 0, 5, 10, 15 mol%) were prepared using standard melt quenching method. The structural, physical and mechanical properties of the samples have been studied using X-ray diffraction(XRD), density measurement and Vickers hardness measurement, respectively. A consistent increase in the density was observed, which explains the role of the modifiers (Li{sub 2}O and Na{sub 2}O) in the network modification of borate structure. The molar volume is decreasing linearly with the alkali concentration, which is attributedmore » to the conversion of tetrahedral boron (BO{sub 4/2}){sup −} into (BO{sub 3/2}){sup −}. The microhardness studies reveals the anisotropy nature of the material. It further confirms that the samples belong to hard glass category.« less

Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

PubMed

Mukund, Kavitha; Mathewson, Margie; Minamoto, Viviane; Ward, Samuel R; Subramaniam, Shankar; Lieber, Richard L

2014-11-01

This study provides global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)-treated muscle over a 1-year period. Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n = 4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks. Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoforms, activation of genes in competing pathways of repair and atrophy, impaired mitochondrial biogenesis, and increased metal ion imbalance. Adaptations of the basal lamina and fibrillar extracellular matrix (ECM) occurred by 4 weeks. The muscle transcriptome returned to its unperturbed state 12 weeks after injection. Acute transcriptional adaptations resemble denervated muscle with some subtle differences, but resolved more quickly compared with denervation. Overall, gene expression across time correlates with the generally accepted BoNT-A time course and suggests that the direct action of BoNT-A in skeletal muscle is relatively rapid. © 2014 Wiley Periodicals, Inc.

Assessment of growth and spectral properties of Cr3+-doped La0.83Y0.29Sc2.88(BO3)4 crystal

NASA Astrophysics Data System (ADS)

Huang, Yisheng; Sun, Shijia; Lin, Zhoubin; Zhang, Lizhen; Wang, Guofu

2017-10-01

This paper reports the spectral characteristic of Cr3+-doped La0.83Y0.29 Sc2.88 (BO3)4 crystal. Cr3+-doped La0.83Y0.29Sc2.88 (BO3)4 crystal was grown from a flux of Li6B4O9 by the top seeded Solution growth method. Cr3+:La0.83Y0.29 Sc2.88 (BO3)4 crystal exhibits broad absorption and emission bands of Cr3+ ions. The absorption cross-section σa is 3.38 × 10-20 cm2 at 467 nm and 4.40 × 10-20 cm2 at 656 nm for E//c, respectively. The emission band with a peak at 906 nm has a full width at half maximum (FWHM) of 188 nm for E//c. The emission cross-section σe at 906 nm is 2.35 × 10-20 cm2 for E//c axis and 2.03 × 10-20 cm2 for E⊥c axis. The fluorescence lifetime of 4T2 → 4A2 transition is 37.7 μs. The investigated result indicates that it may be considered as a potential CW tunable laser crystal material.

The relationship between workplace violence, perceptions of safety, and Professional Quality of Life among emergency department staff members in a Level 1 Trauma Centre.

PubMed

Copeland, Darcy; Henry, Melissa

2018-02-02

Emergency department staff members are frequently exposed to workplace violence which may have physical, psychological, and workforce related consequences. The purpose of this study was to examine the relationships between exposure to workplace violence, tolerance to violence, expectations of violence, perceptions of workplace safety, and Professional Quality of Life (compassion satisfaction - CS, burnout - BO, secondary traumatic stress - STS) among emergency department staff members. A cross-sectional design was used to survey all emergency department staff members from a suburban Level 1 Trauma Centre in the western United States. All three dimensions of Professional Quality of Life were associated with exposure to non-physical patient violence including: general threats (CS p = .012, BO p = .001, STS p = .035), name calling (CS p = .041, BO p = .021, STS p = .018), and threats of lawsuit (CS p = .001, BO p = .001, STS p = .02). Tolerance to violence was associated with BO (p = .004) and CS (p = .001); perception of safety was associated with BO (p = .018). Exposure to non-physical workplace violence can significantly impact staff members' compassion satisfaction, burnout and secondary traumatic stress. Greater attention should be paid to the effect of non-physical workplace violence. Additionally, addressing tolerance to violence and perceptions of safety in the workplace may impact Professional Quality of Life. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantitative analysis of levels of serum immunoglobulin G against botulinum neurotoxin type D and association with protection in natural outbreaks of cattle botulism.

PubMed

Steinman, A; Chaffer, M; Elad, D; Shpigel, N Y

2006-08-01

The recent outbreaks of cattle botulism in vaccinated Israeli dairy cattle prompted us to determine vaccine efficacy and reasons for vaccine failure. Analysis of clinical signs, feeding practice, vaccination history, and epidemic curves enabled us to define a study population in two outbreaks, where high doses of Clostridium botulinum neurotoxin type D (BoNT/D) were evenly consumed by the affected animal groups. Attack rates among unvaccinated 6- to 24-month-old heifers were 96% (55/57) and 85% (53/62). The attack rates in vaccinated parity 1, 2, and >or=3 cows were 40.4% (21/52), 14.3% (4/28), and 5.6% (3/54), respectively. Vaccine efficacies for these cow groups were 52.5%, 83.2%, and 93.4%, respectively. In younger, unvaccinated 2- to 6-month-old calves, presumably protected by maternal antibodies, the attack rate was 24% (17/71). These differences correlated with significant differences in levels of specific anti-BoNT/D antibody in serum by an enzyme-linked immunosorbent assay (ELISA). The ELISA performance for predicting protection was analyzed by receiver operating characteristic analysis and was found to be highly significant, with an area under the curve of 0.941 (standard error, 0.034; 95% confidence interval, 0.875 to 1.008; P < 0.000). No animals with serum ELISA unit levels above 0.33 were affected in these exposed groups. At this cutoff level, the specificity of the ELISA was 100%, sensitivity was 67%, and accuracy was 92%. We concluded that botulinum toxoids can confer adequate protection against natural exposure to lethal doses of BoNT/D; however, the vaccination protocols should be optimized. Our in-house ELISA system will enable us to optimize vaccination protocols in the animal population.

Botulinum toxin type A products are not interchangeable: a review of the evidence

PubMed Central

Brin, Mitchell F; James, Charmaine; Maltman, John

2014-01-01

Botulinum toxin type A (BoNTA) products are injectable biologic medications derived from Clostridium botulinum bacteria. Several different BoNTA products are marketed in various countries, and they are not interchangeable. Differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. These differences result in a specific set of interactions between each BoNTA product and the tissue injected. Consequently, the products show differences in their in vivo profiles, including preclinical dose response curves and clinical dosing, efficacy, duration, and safety/adverse events. Most, but not all, published studies document these differences, suggesting that individual BoNTA products act differently depending on experimental and clinical conditions, and these differences may not always be predictable. Differentiation through regulatory approvals provides a measure of confidence in safety and efficacy at the specified doses for each approved indication. Moreover, the products differ in the amount of study to which they have been subjected, as evidenced by the number of publications in the peer-reviewed literature and the quantity and quality of clinical studies. Given that BoNTAs are potent biological products that meet important clinical needs, it is critical to recognize that their dosing and product performance are not interchangeable and each product should be used according to manufacturer guidelines. PMID:25336912

Photoelectron spectroscopy of B4O4 (-): Dual 3c-4e π hyperbonds and rhombic 4c-4e o-bond in boron oxide clusters.

PubMed

Tian, Wen-Juan; Zhao, Li-Juan; Chen, Qiang; Ou, Ting; Xu, Hong-Guang; Zheng, Wei-Jun; Zhai, Hua-Jin; Li, Si-Dian

2015-04-07

Gas-phase anion photoelectron spectroscopy (PES) is combined with global structural searches and electronic structure calculations at the hybrid Becke 3-parameter exchange functional and Lee-Yang-Parr correlation functional (B3LYP) and single-point coupled-cluster with single, double, and perturbative triple excitations (CCSD(T)) levels to probe the structural and electronic properties and chemical bonding of the B4O4 (0/-) clusters. The measured PES spectra of B4O4 (-) exhibit a major band with the adiabatic and vertical detachment energies (ADE and VDE) of 2.64 ± 0.10 and 2.81 ± 0.10 eV, respectively, as well as a weak peak with the ADE and VDE of 1.42 ± 0.08 and 1.48 ± 0.08 eV. The former band proves to correspond to the Y-shaped global minimum of Cs B4O4 (-) ((2)A″), with the calculated ADE/VDE of 2.57/2.84 eV at the CCSD(T) level, whereas the weak band is associated with the second lowest-energy, rhombic isomer of D2h B4O4 (-) ((2)B2g) with the predicted ADE/VDE of 1.43/1.49 eV. Both anion structures are planar, featuring a B atom or a B2O2 core bonded with terminal BO and/or BO2 groups. The same Y-shaped and rhombic structures are also located for the B4O4 neutral cluster, albeit with a reversed energy order. Bonding analyses reveal dual three-center four-electron (3c-4e) π hyperbonds in the Y-shaped B4O4 (0/-) clusters and a four-center four-electron (4c-4e) π bond, that is, the so-called o-bond in the rhombic B4O4 (0/-) clusters. This work is the first experimental study on a molecular system with an o-bond.

Simple, affordable and sustainable borehole observatories for complex monitoring objectives

NASA Astrophysics Data System (ADS)

Kopf, A.; Freudenthal, T.; Ratmeyer, V.; Bergenthal, M.; Lange, M.; Fleischmann, T.; Hammerschmidt, S.; Seiter, C.; Wefer, G.

2014-12-01

Seafloor drill rigs are remotely operated systems that provide a cost effective means to recover sedimentary records of the upper sub-seafloor deposits. Recent increases in their payload included downhole logging tools or autoclave coring systems. We here report on another milestone in using seafloor rigs: the development and installation of shallow borehole observatories. Three different systems have been developed for the MARUM-MeBo seafloor drill, which is operated by MARUM, University of Bremen, Germany. A simple design, the MeBoPLUG, separates the inner borehole from the overlying ocean by using o-ring seals at the conical threads of the drill pipe. The systems are self-contained and include data loggers, batteries, thermistors and a differential pressure sensor. A second design, the so-called MeBoCORK, is more sophisticated and also hosts an acoustic modem for data transfer and, if desired, fluid sampling capability using osmotic pumps. Of these MeBoCORKs, two systems have to be distinguished: the CORK-A (A = autonomous) can be installed by the MeBo alone and monitors pressure and temperature inside and above the borehole (the latter for reference). The CORK-B (B = bottom) has a higher payload and can additionally be equipped with geochemical, biological or other physical components. Owing to its larger size, it is installed by ROV and utilises a hotstab connection in the upper portion of the drill string. Either design relies on a hotstab connection from beneath which coiled tubing with a conical drop weight is lowered to couple to the formation. These tubes are fluid-saturated and either serve to transmit pore pressure signals or collect pore water in the osmo-sampler. The third design, the MeBoPUPPI (Pop-Up Pore Pressure Instrument), is similar to the MeBoCORK-A and monitors pore pressure and temperature in a self-contained manner. Instead of transferring data upon command using an acoustic modem, the MeBoPUPPI contains a pop-up telemetry with Iridium link. After a predefined period, the data unit with satellite link is released, ascends to the sea surface, and remains there for up to two weeks while sending the long-term data sets to shore. In summer 2012, two MeBoPLUGs, one MeBoCORK-A and one MeBoCORK-B were installed with MeBo on German RV Sonne in the Nankai Trough area, Japan. We have successfully downloaded data from the CORKs, attesting that coupling to the formation worked and pressure records were elevated relative to the seafloor reference. In the near future, we will further deploy the first two MeBoPUPPIs. Recovery of all monitoring systems by ROV is planned for 2016.

Use of botulinum toxin in musculoskeletal pain

PubMed Central

Singh, Jasvinder A

2013-01-01

Chronic musculoskeletal pain is a common cause of chronic pain, which is associated with a total cost of $635 billion per year in the U.S. Emerging evidence suggests an anti-nociceptive action of botulinum toxin, independent of its muscle paralyzing action. This review provides a summary of data from both non-randomized and randomized clinical studies of botulinum toxin in back pain and various osteoarticular conditions, including osteoarthritis, tennis elbow, low back pain and hand pain. Three randomized controlled trials (RCTs) of small sizes provide evidence of short-term efficacy of a single intra-articular injection of 100 units of botulinum toxin A (BoNT/A) for the relief of pain and the improvement of both function and quality of life in patients with chronic joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis elbow with one showing a significant improvement in pain relief compared with placebo, another one showing no difference from placebo, and the third finding that pain and function improvement with BoNT/A injection were similar to those obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain found improvement in pain and function compared to placebo. Single RCTs using local injections of BoNT in patients with either temporomandibular joint (TMJ) pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found improvement in pain in both BoNT/B and placebo groups, but no significant difference between groups. Most evidence is based on small studies, but the use of BoNT is supported by a single, and sometimes up to three, RCTs for several chronic musculoskeletal pain conditions. This indicates that botulinum toxin may be a promising potential new treatment for chronic refractory musculoskeletal pain. Well-designed large clinical trials are needed. PMID:24715952

Refinement of the crystal structures of synthetic nickel- and cobalt-bearing tourmalines

NASA Astrophysics Data System (ADS)

Rozhdestvenskaya, I. V.; Setkova, T. V.; Vereshchagin, O. S.; Shtukenberg, A. G.; Shapovalov, Yu. B.

2012-01-01

The crystal structures of synthetic tourmalines with a unique composition containing 3 d elements (Ni, Fe, and Co) have been refined: (Ca0.12▭0.88)(Al1.69Ni{0.81/2+}Fe{0.50/2+})(Al5.40Fe{0.60/3+})(Si5.82Al0.18O18)(BO3)3(OH)3.25O0.75 I, a = 15.897(5), c = 7.145(2) Å, V = 1564(1) Å; Na0.91(Ni{1.20/2+}Cr{0.96/3+}Al0.63Fe{0.18/2+}Mg0.03)(Al4.26Ni{1.20/2+}Cr{0.48/3+}Ti0.06)(Si5.82Al0.18)O18(BO3)3(OH)3.73O0.27 II, a = 15.945(5), c = 7.208(2) Å, V = 1587(1) Å3 and Na0.35(Al1.80Co{1.20/2+})(Al5.28Co{0.66/2+}Ti0.06)(Si5.64B0.36)O18(BO3)3(OH)3.81O0.19 III, a = 15.753(8), c = 7.053(3) Å, V = 1516(2) Å3. The reliability factors are R 1 = 0.038-0.057 and wR 2 = 0.041-0.060. It is found that 3 d elements occupy both Y- and Z positions in all structures. The excess positive charge is compensated for due to the incorporation of divalent oxygen anions into the O3(V)+O1(W) positions.

US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments.

PubMed

Wedam, Suparna B; Beaver, Julia A; Amiri-Kordestani, Laleh; Bloomquist, Erik; Tang, Shenghui; Goldberg, Kirsten B; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Kluetz, Paul; McKee, Amy; Pazdur, Richard

2018-04-20

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

Molecular assembly of Clostridium botulinum progenitor M complex of type E

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eswaramoorthy, Subramaniam; Sun, Jingchuan; Li, Huilin

2015-12-07

Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. Furthermore, the similarity of the general architecture betweenmore » the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.« less

Synthesis, structure characterization, photoluminescence properties and TD-DFT calculations for two new borates.

PubMed

Hadjadj, Nasreddine; Dems, Mohamed AbdEsselem; Merazig, Hocine; Bendjeddou, Lamia

2018-04-01

Due to their rich structural chemistry and wide variety of applications, borate materials have provided a rich area of research. In a continuation of this research, diethylammonium bis(2-oxidobenzoato-κ 2 O 1 ,O 2 )borate, C 4 H 12 N + ·BO 4 (C 7 H 4 O) 2 - , (1), and propylammonium bis(2-oxidobenzoato-κ 2 O 1 ,O 2 )borate, C 3 H 10 N + ·BO 4 (C 7 H 4 O) 2 - , (2), have been synthesized by the reaction of boric acid with salicylic acid under ambient conditions. In both structures, the B atom exhibits a slightly distorted tetrahedral environment formed by the bidentate coordination of two salicylate anions via the O atoms of the central carboxylate and oxide groups. In the crystals of salts (1) and (2), mixed cation-anion layers lying parallel to the (101) plane are formed through N-H...O, C-H...O and C-H...π/N-H...O hydrogen-bonding interactions, resulting, in each case, in a two-dimensional supramolecular architecture in the solid state. The photoluminescence properties of the salts were studied using the as-synthesized samples and reveal that salts (1) and (2) both display a strong blue-light emission, with maxima at 489 and 491 nm, respectively. In DFT/TD-DFT (time-dependent density functional theory) studies, the blue emission appears to be derived from an intramolecular charge transfer (ICT) excited state. In addition, IR and UV-Vis spectroscopies were used to investigate the title salts.

Study of vaporization of sodium metaborate by transpiration thermogravimetry and Knudsen effusion mass spectrometry.

PubMed

Narasimhan, T S Lakshmi; Viswanathan, R; Nalini, S

2011-11-17

The vaporization of solid sodium metaborate NaBO(2)(s) was studied by transpiration thermogravimetry (TTG) and Knudsen effusion mass spectrometry (KEMS). The transpiration measurements, performed for the first time on NaBO(2)(s), involved use of argon as the carrier gas for vapor transport and derivation of vapor pressure of NaBO(2)(g) (by assuming it as the sole vapor species) through many flow-dependence runs and temperature-dependence runs in the temperature range 1075-1218 K. The KEMS measurements performed in the temperature range 1060-1185 K confirmed NaBO(2)(g) as the principal vapor species over NaBO(2)(s), in accord with the previously reported KEMS studies. The values of p(NaBO(2)) obtained by both TTG and KEMS are consistent within the uncertainties associated with each method and so are the second- and third-law values of enthalpy of sublimation, the latter aspect consistently missing in all previous vaporization studies. The results of both TTG and KEMS were combined to recommend the following thermodynamic parameters pertinent to the sublimation reaction, NaBO(2)(s) = NaBO(2)(g): Log{p(NaBO(2))/Pa} = -(17056 ± 441)/(T/K) + (14.73 ± 0.35) for the temperature range 1060-1218 K; Δ(r)H°(m)(298.15 K) = (346.3 ± 9.4) kJ·mol(-1); and Δ(r)S°(m)(298.15 K) = (210.2 ± 6.8) J·mol(-1)·K(-1).

Duality, phase structures, and dilemmas in symmetric quantum games

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ichikawa, Tsubasa; Tsutsui, Izumi

Symmetric quantum games for 2-player, 2-qubit strategies are analyzed in detail by using a scheme in which all pure states in the 2-qubit Hilbert space are utilized for strategies. We consider two different types of symmetric games exemplified by the familiar games, the Battle of the Sexes (BoS) and the Prisoners' Dilemma (PD). These two types of symmetric games are shown to be related by a duality map, which ensures that they share common phase structures with respect to the equilibria of the strategies. We find eight distinct phase structures possible for the symmetric games, which are determined by themore » classical payoff matrices from which the quantum games are defined. We also discuss the possibility of resolving the dilemmas in the classical BoS, PD, and the Stag Hunt (SH) game based on the phase structures obtained in the quantum games. It is observed that quantization cannot resolve the dilemma fully for the BoS, while it generically can for the PD and SH if appropriate correlations for the strategies of the players are provided.« less

Bovine herpesvirus 1 modified live virus vaccines for cattle reproduction: Balancing protection with undesired effects.

PubMed

Chase, Christopher C L; Fulton, Robert W; O'Toole, Donal; Gillette, Benjamin; Daly, Russell F; Perry, George; Clement, Travis

2017-07-01

Bovine herpesvirus 1 (BoHV-1) has long been associated with reproductive failure in cattle following infection of the ovary and/or fetus. Vaccination prior to breeding has been an effective approach to lessen the impact of BoHV-1 on reproduction. Prior studies in the 1980s and 1990s established the susceptibility of the ovary and particularly the corpus luteum (CL) to BoHV-1 infection. A series of studies at breeding time established that: (1) in naïve animals, the CL was the major target of BoHV-1 pathology; (2) CL lesions occurred within 4-9 days after estrus; (3) similar lesions was seen with BoHV-1 MLV vaccines; (4) ovarian lesions varied by the vaccine strain used; (5) progesterone decreased with or without CL lesions; and (6) following reactivation of BoHV-1 latent infection, ovaries could become reinfected in the face of BoHV-1 immunity. Large scale field studies demonstrated that conception was highest in animals previously vaccinated and boostered with inactivated vaccine compared to animals revaccinated with MLV. In the early 2000s, to get a label claim to vaccinate calves nursing pregnant cows, safety study outlines were approved by USDA-APHIS CVB. These studies were designed to determine the effect of revaccination with MLV during pregnancy on previously vaccinated cows and were not rigorous enough to confirm complete fetal safety. As designed these studies showed no difference in reproductive loss between the previously vaccinated animals and the animals revaccinated ∼4, 7 and 9 months later, leading to the label approval for MLV vaccination in pregnant cows. Subsequent investigations by diagnostic laboratories found an increase in BoHV-1 reproductive loss after the approval for use in pregnant animals. A method was developed to differentiate IBR vaccine strains from field strains. Analysis of viruses from 31 cases from 2009-2016 indicated that all 31 isolates matched with vaccine strains. Going forward, it will be necessary to develop vaccine approaches that use non-abortifacient, nonlatent BoHV-1 vaccines that develop lifelong immunity, protecting the animal while doing no harm to the fetus. Copyright © 2017 Elsevier B.V. All rights reserved.

Ca3La2(BO3)4 crystal: a new candidate host material for the ytterbium ion

NASA Astrophysics Data System (ADS)

Wang, Yeqing; You, Zhenyu; Zhu, Zhaojie; Xu, Jinlong; Li, Jianfu; Wang, Yan; Wang, Hongyan; Tu, Chaoyang

2013-10-01

A disordered laser crystal Yb3+-doped Ca3La2(BO3)4 crystal was grown by the Czochralski technique. The characterized room temperature polarized spectra, re-absorption possibility and laser performance showed that this crystal should be a promising gain material, not only suitable for diode pumping, but also a good candidate for the generation of tunable and short pulse lasers. End pumped by a diode laser at 976 nm in plano-concave and plano-plano cavity, a 3.65 W output power with a slope efficiency of 65% was achieved by using a c-cut Yb3+:Ca3La2(BO3)4 crystal. The output laser wavelength shifted from 1042 to 1062 nm.

Combustion synthesis and luminescence properties of yellow-emitting phosphors Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Zhiguo, E-mail: xiazg426@yahoo.com.cn; Liao, Libing, E-mail: lbliao@cugb.edu.cn; Zhang, Zepeng

2012-02-15

Graphical abstract: A yellow-emitting phosphor Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+} was firstly synthesized by the solution-combustion method. The photoluminescence excitation and emission spectra, temperature dependence of luminescence intensity, and luminescence lifetime of the phosphor were investigated. Highlights: Black-Right-Pointing-Pointer Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+} phosphor was synthesized by a solution-combustion method. Black-Right-Pointing-Pointer Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+} showed an intense yellow emission band centered at 569 nm with the CIE coordinate of (0.453, 0.526). Black-Right-Pointing-Pointer The temperature dependent luminescence property and mechanism of Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+} were studied. -- Abstract: Yellow-emitting phosphor Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+} was synthesized by a solution-combustion method. Themore » phase structure and microstructure were determined by the X-ray diffraction (XRD) and scanning electron microscope (SEM) analysis, respectively. The as-prepared Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+} phosphor absorbed near ultraviolet and blue light of 320-500 nm, and showed an intense yellow emission band centered at 569 nm with the CIE coordinate of (0.453, 0.526). The lifetime of Eu{sup 2+} ions in Ca{sub 2}BO{sub 3}Cl:Eu{sup 2+} phosphor was measured, furthermore the temperature dependent luminescence property and mechanism were studied, which also testified that the present phosphor had a promising potential for white light-emitting diodes.« less

Combinatorial Effects of the Glucocorticoid Receptor and Krüppel-Like Transcription Factor 15 on Bovine Herpesvirus 1 Transcription and Productive Infection.

PubMed

El-Mayet, Fouad S; Sawant, Laximan; Thunuguntla, Prasanth; Jones, Clinton

2017-11-01

Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes lifelong latency in sensory neurons. Latently infected calves consistently reactivate from latency following a single intravenous injection of the synthetic corticosteroid dexamethasone. The immediate early transcription unit 1 (IEtu1) promoter, which drives bovine ICP0 (bICP0) and bICP4 expression, is stimulated by dexamethasone because it contains two glucocorticoid receptor (GR) response elements (GREs). Several Krüppel-like transcription factors (KLF), including KLF15, are induced during reactivation from latency, and they stimulate certain viral promoters and productive infection. In this study, we demonstrate that the GR and KLF15 were frequently expressed in the same trigeminal ganglion (TG) neuron during reactivation and cooperatively stimulated productive infection and IEtu1 GREs in mouse neuroblastoma cells (Neuro-2A). We further hypothesized that additional regions in the BoHV-1 genome are transactivated by the GR or stress-induced transcription factors. To test this hypothesis, BoHV-1 DNA fragments (less than 400 bp) containing potential GR and KLF binding sites were identified and examined for transcriptional activation by stress-induced transcription factors. Intergenic regions within the unique long 52 gene (UL52; a component of the DNA primase/helicase complex), bICP4, IEtu2, and the unique short region were stimulated by KLF15 and the GR. Chromatin immunoprecipitation studies revealed that the GR and KLF15 interacted with sequences within IEtu1 GREs and the UL52 fragment. Coimmunoprecipitation studies demonstrated that KLF15 and the GR were associated with each other in transfected cells. Since the GR stimulates KLF15 expression, we suggest that these two transcription factors form a feed-forward loop that stimulates viral gene expression and productive infection following stressful stimuli. IMPORTANCE Bovine herpesvirus 1 (BoHV-1) is an important viral pathogen that causes respiratory disease and suppresses immune responses in cattle; consequently, life-threatening bacterial pneumonia can occur. Following acute infection, BoHV-1 establishes lifelong latency in sensory neurons. Reactivation from latency is initiated by the synthetic corticosteroid dexamethasone. Dexamethasone stimulates lytic cycle viral gene expression in sensory neurons of calves latently infected with BoHV-1, culminating in virus shedding and transmission. Two stress-induced cellular transcription factors, Krüppel-like transcription factor 15 (KLF15) and the glucocorticoid receptor (GR), cooperate to stimulate productive infection and viral transcription. Additional studies demonstrated that KLF15 and the GR form a stable complex and that these stress-induced transcription factors bind to viral DNA sequences, which correlates with transcriptional activation. The ability of the GR and KLF15 to synergistically stimulate viral gene expression and productive infection may be critical for the ability of BoHV-1 to reactivate from latency following stressful stimuli. Copyright © 2017 American Society for Microbiology.

Combinatorial Effects of the Glucocorticoid Receptor and Krüppel-Like Transcription Factor 15 on Bovine Herpesvirus 1 Transcription and Productive Infection

PubMed Central

El-mayet, Fouad S.; Sawant, Laximan; Thunuguntla, Prasanth

2017-01-01

ABSTRACT Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes lifelong latency in sensory neurons. Latently infected calves consistently reactivate from latency following a single intravenous injection of the synthetic corticosteroid dexamethasone. The immediate early transcription unit 1 (IEtu1) promoter, which drives bovine ICP0 (bICP0) and bICP4 expression, is stimulated by dexamethasone because it contains two glucocorticoid receptor (GR) response elements (GREs). Several Krüppel-like transcription factors (KLF), including KLF15, are induced during reactivation from latency, and they stimulate certain viral promoters and productive infection. In this study, we demonstrate that the GR and KLF15 were frequently expressed in the same trigeminal ganglion (TG) neuron during reactivation and cooperatively stimulated productive infection and IEtu1 GREs in mouse neuroblastoma cells (Neuro-2A). We further hypothesized that additional regions in the BoHV-1 genome are transactivated by the GR or stress-induced transcription factors. To test this hypothesis, BoHV-1 DNA fragments (less than 400 bp) containing potential GR and KLF binding sites were identified and examined for transcriptional activation by stress-induced transcription factors. Intergenic regions within the unique long 52 gene (UL52; a component of the DNA primase/helicase complex), bICP4, IEtu2, and the unique short region were stimulated by KLF15 and the GR. Chromatin immunoprecipitation studies revealed that the GR and KLF15 interacted with sequences within IEtu1 GREs and the UL52 fragment. Coimmunoprecipitation studies demonstrated that KLF15 and the GR were associated with each other in transfected cells. Since the GR stimulates KLF15 expression, we suggest that these two transcription factors form a feed-forward loop that stimulates viral gene expression and productive infection following stressful stimuli. IMPORTANCE Bovine herpesvirus 1 (BoHV-1) is an important viral pathogen that causes respiratory disease and suppresses immune responses in cattle; consequently, life-threatening bacterial pneumonia can occur. Following acute infection, BoHV-1 establishes lifelong latency in sensory neurons. Reactivation from latency is initiated by the synthetic corticosteroid dexamethasone. Dexamethasone stimulates lytic cycle viral gene expression in sensory neurons of calves latently infected with BoHV-1, culminating in virus shedding and transmission. Two stress-induced cellular transcription factors, Krüppel-like transcription factor 15 (KLF15) and the glucocorticoid receptor (GR), cooperate to stimulate productive infection and viral transcription. Additional studies demonstrated that KLF15 and the GR form a stable complex and that these stress-induced transcription factors bind to viral DNA sequences, which correlates with transcriptional activation. The ability of the GR and KLF15 to synergistically stimulate viral gene expression and productive infection may be critical for the ability of BoHV-1 to reactivate from latency following stressful stimuli. PMID:28794031

Identification of a novel MLPK homologous gene MLPKn1 and its expression analysis in Brassica oleracea.

PubMed

Gao, Qiguo; Shi, Songmei; Liu, Yudong; Pu, Quanming; Liu, Xiaohuan; Zhang, Ying; Zhu, Liquan

2016-09-01

M locus protein kinase, one of the SRK-interacting proteins, is a necessary positive regulator for the self-incompatibility response in Brassica. In B. rapa, MLPK is expressed as two different transcripts, MLPKf1 and MLPKf2, and either isoform can complement the mlpk/mlpk mutation. The AtAPK1B gene has been considered to be the ortholog of BrMLPK, and AtAPK1B has no role in self-incompatibility (SI) response in A. thaliana SRK-SCR plants. Until now, what causes the MLPK and APK1B function difference during SI response in Brassica and A. thaliana SRKb-SCRb plants has remained unknown. Here, in addition to the reported MLPKf1/2, we identified the new MLPKf1 homologous gene MLPKn1 from B. oleracea. BoMLPKn1 and BoMLPKf1 shared nucleotide sequence identity as high as 84.3 %, and the most striking difference consisted in two fragment insertions in BoMLPKn1. BoMLPKn1 and BoMLPKf1 had a similar gene structure; both their deduced amino acid sequences contained a typical plant myristoylation consensus sequence and a Ser/Thr protein kinase domain. BoMLPKn1 was widely expressed in petal, sepal, anther, stigma and leaf. Genome-wide survey revealed that the B. oleracea genome contained three MLPK homologous genes: BoMLPKf1/2, BoMLPKn1 and Bol008343n. The B. rapa genome also contained three MLPK homologous genes, BrMLPKf1/2, BraMLPKn1 and Bra040929. Phylogenetic analysis revealed that BoMLPKf1/2 and BrMLPKf1/2 were phylogenetically more distant from AtAPK1A than Bol008343n, Bra040929, BraMLPKn1 and BoMLPKn1, Synteny analysis revealed that the B. oleracea chromosomal region containing BoMLPKn1 displayed high synteny with the A. thaliana chromosomal region containing APK1B, whereas the B. rapa chromosomal region containing BraMLPKn1 showed high synteny with the A. thaliana chromosomal region containing APK1B. Together, these results revealed that BoMLPKn1/BraMLPKn1, and not the formerly reported BoMLPKf1/2 (BrMLPKf1/2), was the orthologous genes of AtAPK1B, and no ortholog of BoMLPKf1/2 (BrMLPKf1/2) was found in the A. thaliana genome. We speculated that Brassica MLPKf1/2 might have emerged after speciation of Brassica and A. thailiana, and that it was recruited to the SRK-triggered SI signaling cascade in Brassica.

High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex.

PubMed

Lee, Kwangkook; Lam, Kwok-Ho; Kruel, Anna Magdalena; Perry, Kay; Rummel, Andreas; Jin, Rongsheng

2014-04-04

Botulinum neurotoxins (BoNTs) are produced as progenitor toxin complexes (PTCs) by Clostridium botulinum. The PTCs are composed of BoNT and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver BoNT through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich PTC on the intestinal lumen preceding its transport across the epithelial barriers. Here, we report the crystal structure of HA33 of type B PTC (HA33/B) in complex with lactose at 1.46Å resolution. The structural comparisons among HA33 of serotypes A-D reveal two different HA33-glycan interaction modes. The glycan-binding pockets on HA33/A and B are more suitable to recognize galactose-containing glycans in comparison to the equivalent sites on HA33/C and D. On the contrary, HA33/C and D could potentially recognize Neu5Ac as an independent receptor, whereas HA33/A and B do not. These findings indicate that the different oral toxicity and host susceptibility observed among different BoNT serotypes could be partly determined by the serotype-specific interaction between HA33 and host carbohydrate receptors. Furthermore, we have identified a key structural water molecule that mediates the HA33/B-lactose interactions. It provides the structural basis for development of new receptor-mimicking compounds, which have enhanced binding affinity with HA33 through their water-displacing moiety. Copyright © 2014 Elsevier Inc. All rights reserved.

Jackson Bar Training Structure Study

DTIC Science & Technology

2015-05-01

comparison of the one-dimensional bridge hydraulic routines from: HEC - RAS , HEC -2, and WSPRO. Davis, CA: U.S. Army Corps of Engineers, Hydrologic Engineering...ER D C/ CH L TR -1 5- 4 Jackson Bar Training Structure Study Co as ta l a nd H yd ra ul ic s La bo ra to ry Jeremy A. Sharp and...The hydrodynamic model was validated with gage data from the U.S. Geological Survey 02470050 Tombigbee River at Steamplant near Leroy, AL, gage

Non-Born-Oppenheimer electronic and nuclear densities for a Hooke-Calogero three-particle model: non-uniqueness of density-derived molecular structure.

PubMed

Ludeña, E V; Echevarría, L; Lopez, X; Ugalde, J M

2012-02-28

We consider the calculation of non-Born-Oppenheimer, nBO, one-particle densities for both electrons and nuclei. We show that the nBO one-particle densities evaluated in terms of translationally invariant coordinates are independent of the wavefunction describing the motion of center of mass of the whole system. We show that they depend, however, on an arbitrary reference point from which the positions of the vectors labeling the particles are determined. We examine the effect that this arbitrary choice has on the topology of the one-particle density by selecting the Hooke-Calogero model of a three-body system for which expressions for the one-particle densities can be readily obtained in analytic form. We extend this analysis to the one-particle densities obtained from full Coulomb interaction wavefunctions for three-body systems. We conclude, in view of the fact that there is a close link between the choice of the reference point and the topology of one-particle densities that the molecular structure inferred from the topology of these densities is not unique. We analyze the behavior of one-particle densities for the Hooke-Calogero Born-Oppenheimer, BO, wavefunction and show that topological transitions are also present in this case for a particular mass value of the light particles even though in the BO regime the nuclear masses are infinite. In this vein, we argue that the change in topology caused by variation of the mass ratio between light and heavy particles does not constitute a true indication in the nBO regime of the emergence of molecular structure.

Non-Born-Oppenheimer electronic and nuclear densities for a Hooke-Calogero three-particle model: Non-uniqueness of density-derived molecular structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ludena, E. V.; Echevarria, L.; Lopez, X.

2012-02-28

We consider the calculation of non-Born-Oppenheimer, nBO, one-particle densities for both electrons and nuclei. We show that the nBO one-particle densities evaluated in terms of translationally invariant coordinates are independent of the wavefunction describing the motion of center of mass of the whole system. We show that they depend, however, on an arbitrary reference point from which the positions of the vectors labeling the particles are determined. We examine the effect that this arbitrary choice has on the topology of the one-particle density by selecting the Hooke-Calogero model of a three-body system for which expressions for the one-particle densities canmore » be readily obtained in analytic form. We extend this analysis to the one-particle densities obtained from full Coulomb interaction wavefunctions for three-body systems. We conclude, in view of the fact that there is a close link between the choice of the reference point and the topology of one-particle densities that the molecular structure inferred from the topology of these densities is not unique. We analyze the behavior of one-particle densities for the Hooke-Calogero Born-Oppenheimer, BO, wavefunction and show that topological transitions are also present in this case for a particular mass value of the light particles even though in the BO regime the nuclear masses are infinite. In this vein, we argue that the change in topology caused by variation of the mass ratio between light and heavy particles does not constitute a true indication in the nBO regime of the emergence of molecular structure.« less

The minimal incubation period from the onset of Barrett's oesophagus to symptomatic adenocarcinoma.

PubMed

den Hoed, C M; van Blankenstein, M; Dees, J; Kuipers, E J

2011-07-12

The interval between the onset of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) can be termed the incubation period. However, the unrecorded onset of BO precludes its direct observation. Determining the range of intervals between BO diagnosis and OAC within the longest observational BO follow-up study. Exclusion criteria were presence of high-grade dysplasia (HGD) or OAC at baseline, death within <2 years of BO diagnosis, oesophagectomy without HGD/OAC and loss to follow-up. A total of 133 patients (M/F 73/60) were taken into account. In 1967 person years of follow-up there were 13 cases of HGD/OAC, (0.66% p.a.; 95% CI 0.58-0.74), 96 patients died without HGD/OAC and 24 survived without HGD/OAC. The mean intervals between BO diagnosis and either HGD/OAC, death or end of follow-up were 10.8, 12.6 and 25.5 years, respectively, and the mean ages at endpoint were 72.5, 80.0 and 68.3 years, respectively. The survivors without HGD/OAC had a lower age at BO diagnosis (mean 42.8 vs 61.2 and 67.4 years, P<0.001). Baseline presence of low-grade dysplasia was associated with progression to HGD/OAC (log rank P<0.001). The Rotterdam BO follow-up cohort revealed a long incubation period between onset of BO and development of HGD/OAC, in patients without HGD/OAC at baseline as illustrated by 24 patients diagnosed with BO at a young age and followed for a mean period of 25.5 years. Their tumour-free survival established a minimum incubation period, suggesting a true incubation period of three decades or more.

Luminescence characteristics of Dy3+ activated Na 2Sr 2Mg (BO 3)2F 2: Dy 3+ phosphor

NASA Astrophysics Data System (ADS)

Wani, Javaid A.; Dhoble, N. S.; Dhoble, S. J.

2012-11-01

In this paper, we have reported a new Na 2Sr 2Mg (BO 3)2F 2:Dy 3+ thermoluminescence (TL) phosphor prepared via the wet chemical method. Prepared phosphor was characterized by X-ray powder diffraction, photoluminescence (PL), TL and scanning electronmicroscopy techniques. The scanning electronmicroscopic image of Na 2Sr 2Mg (BO 3)2F 2:Dy 3+ phosphor confirms the micron size of particles. Under the PL study, the characteristic emission spectrum of Dy 3+ corresponding to 4F 9/2→6H 15/2 (481 nm) and 4F 9/2→6H 13/2 (576 nm) transitions was observed. The TL property of the as prepared phosphor was also found to be good. TL intensity of Na 2Sr2Mg(BO 3)F 2:Dy 3+ phosphors at 0.99 kGy exposure of γ-irradiations was compared with standard CaSO 4:Dy phosphor. It was seen that TL intensity of Na 2Sr 2Mg (BO 3)2F 2: Dy 3+ phosphors is 1.1 times less compared with the standard CaSO 4:Dy TL dosimeter phosphor. The kinetic parameters are also discussed in detail. The values of activation energy E (eV) and frequency factor S (s -1) were found to be 0.57 eV and 1.25×106 s-1, respectively.

The Bovine Herpesvirus 4 Bo10 Gene Encodes a Nonessential Viral Envelope Protein That Regulates Viral Tropism through both Positive and Negative Effects▿

PubMed Central

Machiels, Bénédicte; Lété, Céline; de Fays, Katalin; Mast, Jan; Dewals, Benjamin; Stevenson, Philip G.; Vanderplasschen, Alain; Gillet, Laurent

2011-01-01

All gammaherpesviruses encode a glycoprotein positionally homologous to the Epstein-Barr virus gp350 and the Kaposi's sarcoma-associated herpesvirus (KSHV) K8.1. In this study, we characterized the positional homologous glycoprotein of bovine herpesvirus 4 (BoHV-4), encoded by the Bo10 gene. We identified a 180-kDa gene product, gp180, that was incorporated into the virion envelope. A Bo10 deletion virus was viable but showed a growth deficit associated with reduced binding to epithelial cells. This seemed to reflect an interaction of gp180 with glycosaminoglycans (GAGs), since compared to the wild-type virus, the Bo10 mutant virus was both less infectious for GAG-positive (GAG+) cells and more infectious for GAG-negative (GAG−) cells. However, we could not identify a direct interaction between gp180 and GAGs, implying that any direct interaction must be of low affinity. This function of gp180 was very similar to that previously identified for the murid herpesvirus 4 gp150 and also to that of the Epstein-Barr virus gp350 that promotes CD21+ cell infection and inhibits CD21− cell infection. We propose that such proteins generally regulate virion attachment both by binding to cells and by covering another receptor-binding protein until they are displaced. Thus, they regulate viral tropism both positively and negatively depending upon the presence or absence of their receptor. PMID:21068242

Pharmacophore Refinement Guides the Design of Nanomolar-Range Botulinum Neurotoxin Serotype A Light Chain Inhibitors

PubMed Central

2010-01-01

Botulinum neurotoxins (BoNTs) are the deadliest of microbial toxins. The enzymes’ zinc(II) metalloprotease, referred to as the light chain (LC) component, inhibits acetylcholine release into neuromuscular junctions, resulting in the disease botulism. Currently, no therapies counter BoNT poisoning postneuronal intoxication; however, it is hypothesized that small molecules may be used to inhibit BoNT LC activity in the neuronal cytosol. Herein, we describe the pharmacophore-based design and chemical synthesis of potent [non-zinc(II) chelating] small molecule (nonpeptidic) inhibitors (SMNPIs) of the BoNT serotype A LC (the most toxic of the BoNT serotype LCs). Specifically, the three-dimensional superimpositions of 2-[4-(4-amidinephenoxy)phenyl]indole-6-amidine-based SMNPI regioisomers [Ki = 0.600 μM (±0.100 μM)], with a novel lead bis-[3-amide-5-(imidazolino)phenyl]terephthalamide (BAIPT)-based SMNPI [Ki = 8.52 μM (±0.53 μM)], resulted in a refined four-zone pharmacophore. The refined model guided the design of BAIPT-based SMNPIs possessing Ki values = 0.572 (±0.041 μM) and 0.900 μM (±0.078 μM). PMID:21116458

Random mutagenesis of BoNT/E Hc nanobody to construct a secondary phage-display library.

PubMed

Shahi, B; Mousavi Gargari, S L; Rasooli, I; Rajabi Bazl, M; Hoseinpoor, R

2014-08-01

To construct secondary mutant phage-display library of recombinant single variable domain (VHH) against botulinum neurotoxin E by error-prone PCR. The gene coding for specific VHH derived from the camel immunized with binding domain of botulinum neurotoxin E (BoNT/E) was amplified by error-prone PCR. Several biopanning rounds were used to screen the phage-displaying BoNT/E Hc nanobodies. The final nanobody, SHMR4, with increased affinity recognized BoNT/E toxin with no cross-reactivity with other antigens especially with related BoNT toxins. The constructed nanobody could be a suitable candidate for VHH-based biosensor production to detect the Clostridium botulinum type E. Diagnosis and treatment of botulinum neurotoxins are important. Generation of high-affinity antibodies based on the construction of secondary libraries using affinity maturation step leads to the development of reagents for precise diagnosis and therapy. © 2014 The Society for Applied Microbiology.

[Bovine herpesvirus 4 (BoHV-4): general aspects of the biology and status in Argentina].

PubMed

Morán, Pedro E; Pérez, Sandra E; Odeón, Anselmo C; Verna, Andrea E

2015-01-01

Bovine herpesvirus 4 (BoHV-4) has been isolated from cattle with respiratory infections, vulvovaginitis, mastitis, abortions, endometritis and from apparently healthy animals throughout the world. Although it has not yet been established as causal agent of a specific disease entity, it is primarily associated with reproductive disorders of cattle. This virus can infect a wide range of species, either in vivo or in vitro. Two groups of prototype strains were originated from the first isolates: the DN599-type strains (American group) and the Movar-type strains (European group). In Argentina, BoHV-4 was isolated and characterized in 2007 from vaginal discharge samples taken from cows that had aborted. So far, more than 40 isolates, mainly associated with aborting bovine females have been registered in our country. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Utilizing Ayurvedic literature for the identification of novel phytochemical inhibitors of botulinum neurotoxin A.

PubMed

Yalamanchili, Chinni; Manda, Vamshi K; Chittiboyina, Amar G; Guernieri, Rebecca L; Harrell, William A; Webb, Robert P; Smith, Leonard A; Khan, Ikhlas A

2017-02-02

Ayurveda, an ancient holistic system of health care practiced on the Indian subcontinent, utilizes a number of multi-plant formulations and is considered by many as a potential source for novel treatments, as well as the identification of new drugs. Our aim is to identify novel phytochemicals for the inhibition of bacterial exotoxin, botulinum neurotoxin A (BoNT/A) based on Ayurvedic literature. BoNT/A is released by Clostridium species, which when ingested, inhibits the release of acetylcholine by concentrating at the neuromuscular junction and causes flaccid paralysis, resulting in a condition termed as botulism, and may also lead to death due to respiratory arrest. Fifteen plants were selected from the book 'Diagnosis and treatment of diseases in Ayurveda' by Vaidya Bhagwan Dash and Lalitesh Kashyap, based on their frequency of use in the formulations used for the treatment of six diseases with neuromuscular symptoms similar to botulism. Phytochemicals from these plants were screened using in silico, and in vitro methods. Structures of 570 reported phytochemicals from 14 plants were docked inside six reported BoNT/A light chain crystal structures using ensemble docking module in Maestro (Schrödinger, LLE). From the docking scores and structural diversity, nine compounds including acoric acid 1, three flavonoids, three coumarins derivatives, one kava lactone were selected and screened using an in vitro HPLC-based protease assay. The bioassay results showed that several compounds possess BoNT/A LC inhibition of 50-60% when compared to positive controls NSC 84094 and CB7967495 (80-95%). Further testing of the active compounds identified from Ayurvedic literature and structure-activity studies of acoric acid 1 using more sensitive bioassays is under way. The identification of acoric acid 1, a novel scaffold against BoNT/A, exemplifies the utility of Ayurvedic literature for the discovery of novel drug leads. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ultrasound-Guided Injection of Botulinum Toxin Type A for Piriformis Muscle Syndrome: A Case Report and Review of the Literature

PubMed Central

Santamato, Andrea; Micello, Maria Francesca; Valeno, Giovanni; Beatrice, Raffaele; Cinone, Nicoletta; Baricich, Alessio; Picelli, Alessandro; Panza, Francesco; Logroscino, Giancarlo; Fiore, Pietro; Ranieri, Maurizio

2015-01-01

Piriformis muscle syndrome (PMS) is caused by prolonged or excessive contraction of the piriformis muscle associated with pain in the buttocks, hips, and lower limbs because of the close proximity to the sciatic nerve. Botulinum toxin type A (BoNT-A) reduces muscle hypertonia as well as muscle contracture and pain inhibiting substance P release and other inflammatory factors. BoNT-A injection technique is important considering the difficult access of the needle for deep location, the small size of the muscle, and the proximity to neurovascular structures. Ultrasound guidance is easy to use and painless and several studies describe its use during BoNT-A administration in PMS. In the present review article, we briefly updated current knowledge regarding the BoNT therapy of PMS, describing also a case report in which this syndrome was treated with an ultrasound-guided injection of incobotulinumtoxin A. Pain reduction with an increase of hip articular range of motion in this patient with PMS confirmed the effectiveness of BoNT-A injection for the management of this syndrome. PMID:26266421

Botulinum neurotoxin: a marvel of protein design.

PubMed

Montal, Mauricio

2010-01-01

Botulinum neurotoxin (BoNT), the causative agent of botulism, is acknowledged to be the most poisonous protein known. BoNT proteases disable synaptic vesicle exocytosis by cleaving their cytosolic SNARE (soluble NSF attachment protein receptor) substrates. BoNT is a modular nanomachine: an N-terminal Zn(2+)-metalloprotease, which cleaves the SNAREs; a central helical protein-conducting channel, which chaperones the protease across endosomes; and a C-terminal receptor-binding module, consisting of two subdomains that determine target specificity by binding to a ganglioside and a protein receptor on the cell surface and triggering endocytosis. For BoNT, functional complexity emerges from its modular design and the tight interplay between its component modules--a partnership with consequences that surpass the simple sum of the individual component's action. BoNTs exploit this design at each step of the intoxication process, thereby achieving an exquisite toxicity. This review summarizes current knowledge on the structure of individual modules and presents mechanistic insights into how this protein machine evolved to this level of sophistication. Understanding the design principles underpinning the function of such a dynamic modular protein remains a challenging task.

N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A.

PubMed

Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan; Lam, Kwok-Ho; Stern, Daniel; Bagramyan, Karine; Perry, Kay; Kalkum, Markus; Rummel, Andreas; Dong, Min; Jin, Rongsheng

2016-07-01

Botulinum neurotoxin serotype A1 (BoNT/A1), a licensed drug widely used for medical and cosmetic applications, exerts its action by invading motoneurons. Here we report a 2.0-Å-resolution crystal structure of the BoNT/A1 receptor-binding domain in complex with its neuronal receptor, glycosylated human SV2C. We found that the neuronal tropism of BoNT/A1 requires recognition of both the peptide moiety and an N-linked glycan on SV2. This N-glycan-which is conserved in all SV2 isoforms across vertebrates-is essential for BoNT/A1 binding to neurons and for its potent neurotoxicity. The glycan-binding interface on SV2 is targeted by a human BoNT/A1-neutralizing antibody currently licensed as an antibotulism drug. Our studies reveal a new paradigm of host-pathogen interactions, in which pathogens exploit conserved host post-translational modifications, thereby achieving highly specific receptor binding while also tolerating genetic changes across multiple isoforms of receptors.

N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A

PubMed Central

Yao, Guorui; Zhang, Sicai; Mahrhold, Stefan; Lam, Kwok-ho; Stern, Daniel; Bagramyan, Karine; Perry, Kay; Kalkum, Markus; Rummel, Andreas; Dong, Min; Jin, Rongsheng

2016-01-01

Botulinum neurotoxin serotype A1 (BoNT/A1) is one of the most dangerous potential bioterrorism agents, and exerts its action by invading motoneurons. It is also a licensed drug widely used for medical and cosmetic applications. Here we report a 2.0 Å resolution crystal structure of BoNT/A1 receptor-binding domain in complex with its neuronal receptor, the glycosylated human SV2C. We find that the neuronal tropism of BoNT/A1 requires recognition of both the peptide moiety and an N-linked glycan on SV2. This N-glycan—conserved in all SV2 isoforms across vertebrates—is essential for BoNT/A1 binding to neurons and its potent neurotoxicity. The glycan-binding interface on SV2 is targeted by a human BoNT/A1-neutralizing antibody currently licensed as an anti-botulism drug. Our studies reveal a new paradigm of host-pathogen interactions, in which pathogens exploit conserved host post-translational modifications to achieve highly specific receptor binding while also tolerating genetic changes across multiple isoforms of receptors. PMID:27294781

Quantitative Interaction Effects of Carbon Dioxide, Sodium Chloride, and Sodium Nitrite on Neurotoxin Gene Expression in Nonproteolytic Clostridium botulinum Type B

PubMed Central

Lövenklev, Maria; Artin, Ingrid; Hagberg, Oskar; Borch, Elisabeth; Holst, Elisabet; Rådström, Peter

2004-01-01

The effects of carbon dioxide, sodium chloride, and sodium nitrite on type B botulinum neurotoxin (BoNT/B) gene (cntB) expression in nonproteolytic Clostridium botulinum were investigated in a tryptone-peptone-yeast extract (TPY) medium. Various concentrations of these selected food preservatives were studied by using a complete factorial design in order to quantitatively study interaction effects, as well as main effects, on the following responses: lag phase duration (LPD), growth rate, relative cntB expression, and extracellular BoNT/B production. Multiple linear regression was used to set up six statistical models to quantify and predict these responses. All combinations of NaCl and NaNO2 in the growth medium resulted in a prolonged lag phase duration and in a reduction in the specific growth rate. In contrast, the relative BoNT/B gene expression was unchanged, as determined by the cntB-specific quantitative reverse transcription-PCR method. This was confirmed when we measured the extracellular BoNT/B concentration by an enzyme-linked immunosorbent assay. CO2 was found to have a major effect on gene expression when the cntB mRNA levels were monitored in the mid-exponential, late exponential, and late stationary growth phases. The expression of cntB relative to the expression of the 16S rRNA gene was stimulated by an elevated CO2 concentration; the cntB mRNA level was fivefold greater in a 70% CO2 atmosphere than in a 10% CO2 atmosphere. These findings were also confirmed when we analyzed the extracellular BoNT/B concentration; we found that the concentrations were 27 ng · ml−1 · unit of optical density−1 in the 10% CO2 atmosphere and 126 ng · ml−1 · unit of optical density−1 in the 70% CO2 atmosphere. PMID:15128553

Simple, affordable, and sustainable borehole observatories for complex monitoring objectives

NASA Astrophysics Data System (ADS)

Kopf, A.; Freudenthal, T.; Ratmeyer, V.; Bergenthal, M.; Lange, M.; Fleischmann, T.; Hammerschmidt, S.; Seiter, C.; Wefer, G.

2015-05-01

Seafloor drill rigs are remotely operated systems that provide a cost-effective means to recover sedimentary records of the upper sub-seafloor deposits. Recent increases in their payload included downhole logging tools or autoclave coring systems. Here we report on another milestone in using seafloor rigs: the development and installation of shallow borehole observatories. Three different systems have been developed for the MARUM-MeBo (Meeresboden-Bohrgerat) seafloor drill, which is operated by MARUM, University of Bremen, Germany. A simple design, the MeBoPLUG, separates the inner borehole from the overlying ocean by using o-ring seals at the conical threads of the drill pipe. The systems are self-contained and include data loggers, batteries, thermistors and a differential pressure sensor. A second design, the so-called MeBoCORK (Circulation Obviation Retrofit Kit), is more sophisticated and also hosts an acoustic modem for data transfer and, if desired, fluid sampling capability using osmotic pumps. In these MeBoCORKs, two systems have to be distinguished: the CORK-A (A stands for autonomous) can be installed by the MeBo alone and monitors pressure and temperature inside and above the borehole (the latter for reference); the CORK-B (B stands for bottom) has a higher payload and can additionally be equipped with geochemical, biological or other physical components. Owing to its larger size, it is installed by a remotely operated underwater vehicle (ROV) and utilises a hot-stab connection in the upper portion of the drill string. Either design relies on a hot-stab connection from beneath in which coiled tubing with a conical drop weight is lowered to couple to the formation. These tubes are fluid-saturated and either serve to transmit pore pressure signals or collect porewater in the osmo-sampler. The third design, the MeBoPUPPI (Pop-Up Pore Pressure Instrument), is similar to the MeBoCORK-A and monitors pore pressure and temperature in a self-contained manner. Instead of transferring data on command using an acoustic modem, the MeBoPUPPI contains a pop-up telemetry with iridium link. After a predefined period, the data unit with satellite link is released, ascends to the sea surface, and remains there for up to 2 weeks while sending the long-term data sets to shore. In summer 2012, two MeBoPLUGs, one MeBoCORK-A and one MeBoCORK-B were installed with MeBo on RV Sonne, Germany, in the Nankai Trough area, Japan. We have successfully downloaded data from the CORKs, attesting that coupling to the formation worked, and pressure records were elevated relative to the seafloor reference. In the near future, we will further deploy the first two MeBoPUPPIs. Recovery of all monitoring systems by a ROV is planned for 2016.

Egg yolk antibodies for detection and neutralization of Clostridium botulinum type A neurotoxin.

PubMed

Trott, D L; Yang, M; Gonzalez, J; Larson, A E; Tepp, W H; Johnson, E A; Cook, M E

2009-05-01

The objective of this research project was to determine the usefulness of an egg antibody platform for producing materials for the detection and neutralization of botulinum type A neurotoxin. Yield estimates for detection and neutralizing antibodies produced using methods described were calculated. Antibody specific to botulinum toxoid A (aToxoid) and toxin A (aBoNT/A) was produced by immunizing hens with botulinum toxoid A (toxoid) followed by increasing amounts of botulinum neurotoxin A (BoNT/A) in Freund incomplete adjuvant. Egg yolks were extracted with polyethylene glycol (PEG) for antibody detection and neutralization experiments. A model aToxoid/toxoid immunoassay using only egg yolk antibody was developed and had a detection limit of 1 pg/ml of toxoid. In an indirect enzyme-linked immunosorbent assay of BoNT/A-specific antibody, the aBoNT/A contained more BoNT/A-specific antibody than did the aToxoid, and aBoNT/A was as effective as commercial rabbit antibody. The aToxoid provided no protection against BoNT/A in a standard mouse neutralization assay; however, 1 mg of PEG-extracted aBoNT/A neutralized 4,000 lethal doses of BoNT/A injected intraperitoneally. Based on these results, we calculated that in 1 month one hen could produce more than 100 liters of antibody detection reagents or enough antibody to neutralize approximately 11.6 million mouse lethal doses of botulinum toxin. Utilization of an egg antibody platform is potentially rapid (28 to 70 days) and scalable to kilogram quantities using current egg production facilities with as few as 1,000 hens.

Bag of Lines (BoL) for Improved Aerial Scene Representation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sridharan, Harini; Cheriyadat, Anil M.

2014-09-22

Feature representation is a key step in automated visual content interpretation. In this letter, we present a robust feature representation technique, referred to as bag of lines (BoL), for high-resolution aerial scenes. The proposed technique involves extracting and compactly representing low-level line primitives from the scene. The compact scene representation is generated by counting the different types of lines representing various linear structures in the scene. Through extensive experiments, we show that the proposed scene representation is invariant to scale changes and scene conditions and can discriminate urban scene categories accurately. We compare the BoL representation with the popular scalemore » invariant feature transform (SIFT) and Gabor wavelets for their classification and clustering performance on an aerial scene database consisting of images acquired by sensors with different spatial resolutions. The proposed BoL representation outperforms the SIFT- and Gabor-based representations.« less

Residual Limb Hyperhidrosis and RimabotulinumtoxinB: A Randomized Placebo-Controlled Study.

PubMed

Pasquina, Paul F; Perry, Briana N; Alphonso, Aimee L; Finn, Sacha; Fitzpatrick, Kevin F; Tsao, Jack W

2016-05-01

To investigate the use of rimabotulinumtoxinB (BoNT/B [Myobloc]) compared with placebo in treating hyperhidrosis in the residual limbs of individuals with amputation. Randomized, double-blind, placebo-controlled pilot study. Military medical center. Male participants (N=9) with 11 major amputations of the lower limbs and who complained of excessive sweating in their residual limbs were enrolled in the study between September 24, 2008 to October 28, 2011. Participants' lower limbs were randomly assigned to receive injections of either BoNT/B (n=7) or placebo (n=4). BoNT/B. The primary efficacy variable was a minimum of 50% reduction in sweat production 4 weeks after the injection as measured via gravimetric sweat analysis after 10 minutes of physical exertion. Secondary analyses were performed on prosthetic function and pain. All volunteers (100%; 7) in the BoNT/B group achieved a minimum of 50% reduction in sweat production as compared with only 50% (2) in the placebo group. The percent reduction was significantly greater for the BoNT/B group than for the placebo group (-72.7%±15.7% vs -32.7%±39.2%; P<.05). Although both groups subjectively self-reported significant sweat reduction and improved prosthetic function (P<.05 for both), objective gravimetric sweat analyses significantly decreased only for the BoNT/B group (2.3±2.3g vs 0.7±1.1g; P<.05). Neither group reported a change in phantom limb pain or residual limb pain (P>.05 for both). BoNT/B successfully reduces sweat production in individuals with residual limb hyperhidrosis, but does not affect pain. No differences were found in perceived effect on prosthetic use between BoNT/B and placebo groups. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of nested PCR and qPCR for the detection and quantitation of BoHV6 DNA.

PubMed

Kubiś, Piotr; Materniak, Magdalena; Kuźmak, Jacek

2013-12-01

Nested PCR and qPCR (quantitative PCR) tests based on glycoprotein B (gB) gene were designed for detecting Bovine herpesvirus 6 (BoHV6) in bovine whole blood samples and wild ruminant blood clots (deer and roe-deer). This virus, commonly known as BLHV (bovine lymphotropic herpesvirus) belongs to the Herpesviridae family, subfamily Gammaherpesvirinae and Macavirus genus. DNA isolated from 92 dairy cow blood samples and 69 wild ruminant clots were examined for the presence of BoHV6 using nested PCR and qPCR tests. Viral DNA was detected by using nested PCR in 59 out of 92 bovine blood samples (64.1%), and by qPCR in 68 out of 92 bovine blood samples (73.9%), but none out of 69 DNA samples isolated from wild ruminant blood clots, was positive in both assays. The specificity of nested PCR and qPCR was confirmed by using BoHV1, BoHV4, BoHV6, BFV, BIV, and BLV DNA. The sensitivity of nested PCR and qPCR was determined using a serially 10-fold diluted vector pCR2.1HgB (2 × 10(0)-2 × 10(6)copies/reaction). In this testing, qPCR was more sensitive than the nested PCR, detecting two copies of BoHV6 whilst the limit of detection for nested PCR was 20 copies. In all qPCR assays, the coefficients of determination (R(2)) ranged between 0.990 and 0.999, and the calculated amplification efficiencies (Eff%) within the range of 89.7-106.9. The intra- and inter-assay CV (coefficient of variation) values did not exceed 4%. Copyright © 2013 Elsevier B.V. All rights reserved.

The risk of oesophageal adenocarcinoma in a prospectively recruited Barrett's oesophagus cohort.

PubMed

Theron, B T; Padmanabhan, H; Aladin, H; Smith, P; Campbell, E; Nightingale, P; Cooper, B T; Trudgill, N J

2016-12-01

Varying rates of oesophageal adenocarcinoma (OAC) complicating Barrett's oesophagus (BO) have been reported. Recent studies and meta-analyses suggest a lower incidence, questioning the value of endoscopic surveillance. We aimed to retrospectively examine the rate of OAC, risk factors and causes of death in a prospectively recruited BO cohort. Data from patients with BO from a cohort from 1982-2007 were studied. Patients were subdivided into surveyed, failed to attend surveillance and unfit for surveillance. Standardised mortality ratios (SMR) were calculated for common causes of death. Cox proportional hazards models were used to determine which factors were associated with progression to OAC. In total, 671 BO patients (61% male) were studied; 37 (76% male) were diagnosed with OAC. OAC incidence was 0.47% per annum and stable across three decades (1982-1991 0.56%, 1992-2001 0.46%, 2002-2012 0.41% ( p  = 0.8)). All-cause mortality was increased for the whole cohort (SMR 163(95% CI 145-183)). Mortality from OAC appeared higher in patients who failed to attend surveillance (SMR 3216(95% CI 1543-5916)) compared with surveyed (SMR 1753(95% CI 933-2998)) and those unfit for surveillance due to co-morbidity (SMR 440(95% CI 143-1025)). Multivariable analysis identified low-grade dysplasia (HR 4.4(95% CI 1.56-12.43), p  = 0.005) and length of BO (HR 1.2(95% (1.1-1.3)), p  < 0.001)) as associated with OAC. Progression to OAC appeared stable over three decades at 0.47% per annum. Patients with BO had a modest increase in all-cause mortality and a large increase in OAC mortality, particularly if fit for surveillance. Low-grade dysplasia and the length of the BO segment were associated with developing OAC.

All-in-one light-tunable borated phosphors with chemical and luminescence dynamical control resolution.

PubMed

Lin, Chun Che; Liu, Yun-Ping; Xiao, Zhi Ren; Wang, Yin-Kuo; Cheng, Bing-Ming; Liu, Ru-Shi

2014-06-25

Single-composition white-emitting phosphors with superior intrinsic properties upon excitation by ultraviolet light-emitting diodes are important constituents of next-generation light sources. Borate-based phosphors, such as NaSrBO3:Ce(3+) and NaCaBO3:Ce(3+), have stronger absorptions in the near-ultraviolet region as well as better chemical/physical stability than oxides. Energy transfer effects from sensitizer to activator caused by rare-earth ions are mainly found in the obtained photoluminescence spectra and lifetime. The interactive mechanisms of multiple dopants are ambiguous in most cases. We adjust the doping concentration in NaSrBO3:RE (RE = Ce(3+), Tb(3+), Mn(2+)) to study the energy transfer effects of Ce(3+) to Tb(3+) and Mn(2+) by comparing the experimental data and theoretical calculation. The vacuum-ultraviolet experimental determination of the electronic energy levels for Ce(3+) and Tb(3+) in the borate host regarding the 4f-5d and 4f-4f configurations are described. Evaluation of the Ce(3+)/Mn(2+) intensity ratios as a function of Mn(2+) concentration is based on the analysis of the luminescence dynamical process and fluorescence lifetime measurements. The results closely agree with those directly obtained from the emission spectra. Density functional calculations are performed using the generalized gradient approximation plus an on-site Coulombic interaction correction scheme to investigate the forbidden mechanism of interatomic energy transfer between the NaSrBO3:Ce(3+) and NaSrBO3:Eu(2+) systems. Results indicate that the NaSrBO3:Ce(3+), Tb(3+), and Mn(2+) phosphors can be used as a novel white-emitting component of UV radiation-excited devices.

Effects of membrane curvature and pH on proton pumping activity of single cytochrome bo3 enzymes.

PubMed

Li, Mengqiu; Khan, Sanobar; Rong, Honglin; Tuma, Roman; Hatzakis, Nikos S; Jeuken, Lars J C

2017-09-01

The molecular mechanism of proton pumping by heme-copper oxidases (HCO) has intrigued the scientific community since it was first proposed. We have recently reported a novel technology that enables the continuous characterisation of proton transport activity of a HCO and ubiquinol oxidase from Escherichia coli, cytochrome bo 3 , for hundreds of seconds on the single enzyme level (Li et al. J Am Chem Soc 137 (2015) 16055-16063). Here, we have extended these studies by additional experiments and analyses of the proton transfer rate as a function of proteoliposome size and pH at the N- and P-side of single HCOs. Proton transport activity of cytochrome bo 3 was found to decrease with increased curvature of the membrane. Furthermore, proton uptake at the N-side (proton entrance) was insensitive to pH between pH6.4-8.4, while proton release at the P-side had an optimum pH of ~7.4, suggesting that the pH optimum is related to proton release from the proton exit site. Our previous single-enzyme experiments identified rare, long-lived conformation states of cytochrome bo 3 where protons leak back under turn-over conditions. Here, we analyzed and found that ~23% of cytochrome bo 3 proteoliposomes show ΔpH half-lives below 50s after stopping turnover, while only ~5% of the proteoliposomes containing a non-pumping mutant, E286C cytochrome bo 3 exhibit such fast decays. These single-enzyme results confirm our model in which HCO exhibit heterogeneous pumping rates and can adopt rare leak states in which protons are able to rapidly flow back. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental demonstration of optical data links using a hybrid CAP/QAM modulation scheme.

PubMed

Wei, J L; Ingham, J D; Cheng, Q; Cunningham, D G; Penty, R V; White, I H

2014-03-15

The first known experimental demonstrations of a 10  Gb/s hybrid CAP-2/QAM-2 and a 20  Gb/s hybrid CAP-4/QAM-4 transmitter/receiver-based optical data link are performed. Successful transmission over 4.3 km of standard single-mode fiber (SMF) is achieved, with a link power penalty ∼0.4  dBo for CAP-2/QAM-2 and ∼1.5  dBo for CAP-4/QAM-4 at BER=10(-9).

Efficacy of an inactivated, recombinant bovine herpesvirus type 5 (BoHV-5) vaccine.

PubMed

Campos, F S; Dezen, D; Antunes, D A; Santos, H F; Arantes, T S; Cenci, A; Gomes, F; Lima, F E S; Brito, W M E D; Filho, H C K; Batista, H B C R; Spilki, F R; Franco, A C; Rijsewijk, F A M; Roehe, P M

2011-02-24

Bovine herpesvirus type 5 (BoHV-5) is the causative agent of bovine herpetic encephalitis. In countries where BoHV-5 is prevalent, attempts to vaccinate cattle to prevent clinical signs from BoHV-5-induced disease have relied essentially on vaccination with BoHV-1 vaccines. However, such practice has been shown not to confer full protection to BoHV-5 challenge. In the present study, an inactivated, oil adjuvanted vaccine prepared with a recombinant BoHV-5 from which the genes coding for glycoprotein I (gI), glycoprotein E (gE) and membrane protein US9 were deleted (BoHV-5 gI/gE/US9(-)), was evaluated in cattle in a vaccination/challenge experiment. The vaccine was prepared from a virus suspension containing a pre-inactivation antigenic mass equivalent to 10(7.69) TCID(50)/dose. Three mL of the inactivated vaccine were administered subcutaneously to eight calves serologically negative for BoHV-5 (vaccinated group). Four other calves were mock-vaccinated with an equivalent preparation without viral antigens (control group). Both groups were boostered 28 days later. Neither clinical signs of disease nor adverse effects were observed during or after vaccination. A specific serological response, revealed by the development of neutralizing antibodies, was detected in all vaccinated animals after the first dose of vaccine, whereas control animals remained seronegative. Calves were subsequently challenged on day 77 post-vaccination (pv) with 10(9.25) TCID(50) of the wild-type BoHV-5 (parental strain EVI 88/95). After challenge, vaccinated cattle displayed mild signs of respiratory disease, whereas the control group developed respiratory disease and severe encephalitis, which led to culling of 2/4 calves. Searches for viral DNA in the central nervous system (CNS) of vaccinated calves indicated that wild-type BoHV-5 did not replicate, whereas in CNS tissues of calves on the control group, viral DNA was widely distributed. BoHV-5 shedding in nasal secretions was significantly lower in vaccinated calves than in the control group on days 2, 3, 4 and 6 post-challenge (pc). In addition, the duration of virus shedding was significantly shorter in the vaccinated (7 days) than in controls (12 days). Attempts to reactivate latent infection by administration of dexamethasone at 147 days pv led to recrudescence of mild signs of respiratory disease in both vaccinated and control groups. Infectious virus shedding in nasal secretions was detected at reactivation and was significantly lower in vaccinated cattle than in controls on days 11-13 post-reactivation (pr). It is concluded that the inactivated vaccine prepared with the BoHV-5 gI/gE/US9(-) recombinant was capable of conferring protection to encephalitis when vaccinated cattle were challenged with a large infectious dose of the parental wild type BoHV-5. However, it did not avoid the establishment of latency nor impeded dexamethasone-induced reactivation of the virus, despite a significant reduction in virus shedding after challenge and at reactivation on vaccinated calves. Copyright © 2010 Elsevier B.V. All rights reserved.

Development of an analytical method for the determination of the misuse in sports of boldenone through the analysis of urine by on-line coupling liquid chromatography-gas chromatography-combustion-isotope ratio mass spectrometry.

PubMed

Toledano, R M; Díaz-Plaza, E M; Cortes, J M; Aragón, A; Vázquez, A M; Villén, J; Muñoz-Guerra, J

2014-11-28

Boldenone (Bo), androsta-1,4-dien-17β-ol-3-one, is an anabolic androgenic steroid not clinically approved for human application. Despite this, many cases are reported every year of athletes testing positive for Bo or its main metabolite 5β-androst-1-en-17β-ol-3-one (BoM). Recently the capability of different human intestinal bacteria to produce enzymes able to modify endogenous steroids in Bo has been demonstrated. When a urinary concentration of Bo and/or BoM between 5 and 30 ng/mL is measured a complementary analysis by gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) must be carried out to discriminate the endogenous or exogenous origin. In the present work, a novel analytical method that couples LC-GC by means of the TOTAD interface with C-IRMS is described. The method is based on a first RPLC separation of unacetyled steroids, followed by acetylation and automated on-line LC-GC-C-IRMS, which includes a second RPLC clean-up of acetyl Bo and BoM, isolation of the two fractions in a fraction collector and their consecutive analysis by GC-C-IRMS. The method has been applied to the analysis of urine samples fortified at 5 and 10 ng/mL, where it has shown a good performance. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions

PubMed Central

Wagatsuma, Nobuhiko; Sakai, Ko

2017-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional modulations for time-courses were induced by selective enhancement of early-level features due to interactions between V1 and PP. Our proposed model suggests fundamental roles of surrounding suppression/facilitation based on feedforward inputs as well as the interactions between early and parietal visual areas with respect to the ambiguity dependence of the neural dynamics in intermediate-level vision. PMID:28163688

Modeling the Time-Course of Responses for the Border Ownership Selectivity Based on the Integration of Feedforward Signals and Visual Cortical Interactions.

PubMed

Wagatsuma, Nobuhiko; Sakai, Ko

2016-01-01

Border ownership (BO) indicates which side of a contour owns a border, and it plays a fundamental role in figure-ground segregation. The majority of neurons in V2 and V4 areas of monkeys exhibit BO selectivity. A physiological work reported that the responses of BO-selective cells show a rapid transition when a presented square is flipped along its classical receptive field (CRF) so that the opposite BO is presented, whereas the transition is significantly slower when a square with a clear BO is replaced by an ambiguous edge, e.g., when the square is enlarged greatly. The rapid transition seemed to reflect the influence of feedforward processing on BO selectivity. Herein, we investigated the role of feedforward signals and cortical interactions for time-courses in BO-selective cells by modeling a visual cortical network comprising V1, V2, and posterior parietal (PP) modules. In our computational model, the recurrent pathways among these modules gradually established the visual progress and the BO assignments. Feedforward inputs mainly determined the activities of these modules. Surrounding suppression/facilitation of early-level areas modulates the activities of V2 cells to provide BO signals. Weak feedback signals from the PP module enhanced the contrast gain extracted in V1, which underlies the attentional modulation of BO signals. Model simulations exhibited time-courses depending on the BO ambiguity, which were caused by the integration delay of V1 and V2 cells and the local inhibition therein given the difference in input stimulus. However, our model did not fully explain the characteristics of crucially slow transition: the responses of BO-selective physiological cells indicated the persistent activation several times longer than that of our model after the replacement with the ambiguous edge. Furthermore, the time-course of BO-selective model cells replicated the attentional modulation of response time in human psychophysical experiments. These attentional modulations for time-courses were induced by selective enhancement of early-level features due to interactions between V1 and PP. Our proposed model suggests fundamental roles of surrounding suppression/facilitation based on feedforward inputs as well as the interactions between early and parietal visual areas with respect to the ambiguity dependence of the neural dynamics in intermediate-level vision.

Determination of (13)C/(12)C ratios of urinary excreted boldenone and its main metabolite 5beta-androst-1-en-17beta-ol-3-one.

PubMed

Piper, Thomas; Geyer, Hans; Gougoulidis, Vassilios; Flenker, Ulrich; Schänzer, Wilhelm

2010-05-01

Boldenone (androsta-1,4-dien-17beta-ol-3-one, Bo) is an anabolic steroid known to have been used in cattle breeding or equine sport as a doping agent for many years. Although not clinically approved for human application, Bo or its main metabolite 5beta-androst-1-en-17beta-ol-3-one (BM1) were detected in several doping control samples. For more than 15 years the possibility of endogenous Bo production in human beings has been discussed. This is a challenging issue for doping control laboratories as Bo belongs to the list of prohibited substances of the World Anti-Doping Agency and therefore the chance for false positive testing is significant. By GC/C/IRMS (gas chromatography/combustion/isotope ratio mass spectrometry) it should be possible to analyze the (13)C/(12)C ratio of either Bo or BM1 and to distinguish whether their source is endogenous or exogenous. Therefore a method was developed to determine the (13)C/(12)C ratios of Bo, BM1, pregnanediol, androsterone, etiocholanolone, and testosterone from a single urine specimen. The validity of the method was ensured by repeated processing of urine fortified with 2-50 ng/mL Bo and BM1. The specificity of the method was ensured by gas chromatography/mass spectrometry determinations. Out of 23 samples investigated throughout the last four years, 11 showed (13)C/(12)C ratios of Bo or BM1 inconsistent with an exogenous origin. Two of these samples were collected from the same athlete within a one-month interval, strongly indicating the chance of endogenous Bo production by this athlete.

Polarized spectral properties and 1.5-1.6 μm laser operation of Er:Sr3Yb2(BO3)4 crystal

NASA Astrophysics Data System (ADS)

Lin, F. L.; Huang, J. H.; Chen, Y. J.; Gong, X. H.; Lin, Y. F.; Luo, Z. D.; Huang, Y. D.

2013-10-01

Undoped and Er3+-doped Sr3Yb2(BO3)4 crystals were grown by the Czochralski method. Room temperature polarized spectral properties of the Er:Sr3Yb2(BO3)4 crystal were investigated. The efficiency of the energy transfer from Yb3+ to Er3+ ions in this crystal was calculated to be about 95%. End-pumped by a diode laser at 970 nm in a hemispherical cavity, a 0.75 W quasi-CW laser at 1.5-1.6 μm with a slope efficiency of 7% and an absorbed pump threshold of 3.8 W was achieved in a 0.5-mm-thick Z-cut crystal glued on a 5-mm-thick pure YAG crystal with UV-curable adhesive.

75 FR 7571 - Board of Visitors, United States Military Academy (USMA)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

.... Purpose of the Meeting: This is the 2010 Organizational Meeting of the USMA Board of Visitors (BoV... Excellence, Energy Costs and Initiatives, Wastewater Privatization, A- 76 Commercial Activities, and...

Synthesis and characterization of polycrystalline brownmillerite cobalt doped Ca{sub 2}Fe{sub 2}O{sub 5}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhankhar, Suchita; Baskar, K.; Singh, Shubra, E-mail: shubra6@gmail.com

2016-05-23

Brownmillerite compounds with general formula A{sub 2}BB’O{sub 5} (BB’ = Mn, Al, Fe, Co) have attracted attention in wide range of applications such as in solid oxide fuel cell, oxygen separation membrane and photocatalysis. Brownmillerite compounds have unique structure with alternate layers of BO{sub 6} octahedral layers and BO{sub 4} tetrahedral layers. Presence of dopants like Co in place of Fe increases oxygen vacancies. In the present work we have synthesized polycrystalline Ca{sub 2}Fe{sub 2}O{sub 5} and Ca{sub 2}Fe{sub 1-x}Co{sub x}O{sub 5} (x = 0.01, 0.03) by citrate combustion route. The as prepared samples were characterized by XRD using PANalyticalmore » X’Pert System, DRS (Diffuse reflectance spectroscopy) and SEM (Scanning electron microscopy).« less

Effect of temperature on magnetic and impedance properties of Fe3BO6 of nanotubular structure with a bonded B2O3 surface layer

NASA Astrophysics Data System (ADS)

Kumari, Kalpana; Ram, S.; Kotnala, R. K.

2018-03-01

In this investigation, we explore a facile synthesis of Fe3BO6 in the form of small crystallites in the specific shape of nanotubes crystallized from a supercooled liquid Fe2O3-B2O3 precursor. This study includes high resolution transmission electron microscopy (HRTEM) images, magnetic, optical, and impedance properties of the sample. HRTEM images reveal small tubes of Fe3BO6 of 20 nm diameter. A well resolved hysteresis loop appears at 5 K in which the magnetization does not saturate even up to as high field as 50 kOe. It means that the Fe3BO6 nanotubes behave as highly antiferromagnetic in nature in which the surface spins do not align along the field so easily. The temperature dependent impedance describes an ionic Fe3BO6 conductor with a reasonably small activation energy Ea ˜ 0.33 eV. Impedance formalism in terms of a Cole-Cole plot shows a deviation from an ideal Debye-like behavior. We have also reported that electronic absorption spectra are over a spectral range 200-800 nm of wavelengths in order to find out how a bonded surface layer present on the Fe3BO6 crystallites tunes the 3d → 3d electronic transitions in Fe3+ ions.

Photoelectron spectroscopy of B{sub 4}O{sub 4}{sup −}: Dual 3c-4e π hyperbonds and rhombic 4c-4e o-bond in boron oxide clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Wen-Juan; Chen, Qiang; Ou, Ting

2015-04-07

Gas-phase anion photoelectron spectroscopy (PES) is combined with global structural searches and electronic structure calculations at the hybrid Becke 3-parameter exchange functional and Lee-Yang-Parr correlation functional (B3LYP) and single-point coupled-cluster with single, double, and perturbative triple excitations (CCSD(T)) levels to probe the structural and electronic properties and chemical bonding of the B{sub 4}O{sub 4}{sup 0/−} clusters. The measured PES spectra of B{sub 4}O{sub 4}{sup −} exhibit a major band with the adiabatic and vertical detachment energies (ADE and VDE) of 2.64 ± 0.10 and 2.81 ± 0.10 eV, respectively, as well as a weak peak with the ADE and VDEmore » of 1.42 ± 0.08 and 1.48 ± 0.08 eV. The former band proves to correspond to the Y-shaped global minimum of C{sub s} B{sub 4}O{sub 4}{sup −} ({sup 2}A″), with the calculated ADE/VDE of 2.57/2.84 eV at the CCSD(T) level, whereas the weak band is associated with the second lowest-energy, rhombic isomer of D{sub 2h} B{sub 4}O{sub 4}{sup −} ({sup 2}B{sub 2g}) with the predicted ADE/VDE of 1.43/1.49 eV. Both anion structures are planar, featuring a B atom or a B{sub 2}O{sub 2} core bonded with terminal BO and/or BO{sub 2} groups. The same Y-shaped and rhombic structures are also located for the B{sub 4}O{sub 4} neutral cluster, albeit with a reversed energy order. Bonding analyses reveal dual three-center four-electron (3c-4e) π hyperbonds in the Y-shaped B{sub 4}O{sub 4}{sup 0/−} clusters and a four-center four-electron (4c-4e) π bond, that is, the so-called o-bond in the rhombic B{sub 4}O{sub 4}{sup 0/−} clusters. This work is the first experimental study on a molecular system with an o-bond.« less

Comparison of the Expression Changes after Botulinum Toxin Type A and Minocycline Administration in Lipopolysaccharide-Stimulated Rat Microglial and Astroglial Cultures.

PubMed

Piotrowska, Anna; Popiolek-Barczyk, Katarzyna; Pavone, Flaminia; Mika, Joanna

2017-01-01

Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of SNARE proteins, which prevents cells from releasing neurotransmitters from vesicles, while the effects of minocycline are related to the inhibition of p38 activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their direct impact on glial cells is not fully known. Therefore, the aim of the present study was to determine the effects of those drugs on microglial and astroglial activity after lipopolysaccharide (LPS) stimulation and their potential synergistic action. Our results show that BoNT/A and minocycline influenced primary microglial cells by inhibiting intracellular signaling pathways, such as p38, ERK1/2, NF-κB, and the release of pro-inflammatory factors, including IL-1β, IL-18, IL-6, and NOS2. We have revealed that, in contrast to minocycline, BoNT/A treatment did not decrease LPS-induced release of pro-inflammatory factors in the astroglia. In addition, BoNT/A decreased SNAP-23 in both types of glial cells and also SNAP-25 expressed only in astrocytes. Moreover, BoNT/A increased TLR2 and its adaptor protein MyD88, but not TLR4 exclusively in microglial cells. Furthermore, we have shown the impact of BoNT/A on microglial and astroglial cells, with a particular emphasis on its molecular target, TLR2. In contrast, minocycline did not affect any of those factors. We have revealed that despite of different molecular targets, minocycline, and BoNT/A reduced the release of microglia-derived pro-inflammatory factors. In conclusion, we have shown that BoNT/A and minocycline are effective drugs for the management of neuroinflammation by dampening the activation of microglial cells, with minocycline also affecting astroglial activity.

Comparison of the Expression Changes after Botulinum Toxin Type A and Minocycline Administration in Lipopolysaccharide-Stimulated Rat Microglial and Astroglial Cultures

PubMed Central

Piotrowska, Anna; Popiolek-Barczyk, Katarzyna; Pavone, Flaminia; Mika, Joanna

2017-01-01

Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of SNARE proteins, which prevents cells from releasing neurotransmitters from vesicles, while the effects of minocycline are related to the inhibition of p38 activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their direct impact on glial cells is not fully known. Therefore, the aim of the present study was to determine the effects of those drugs on microglial and astroglial activity after lipopolysaccharide (LPS) stimulation and their potential synergistic action. Our results show that BoNT/A and minocycline influenced primary microglial cells by inhibiting intracellular signaling pathways, such as p38, ERK1/2, NF-κB, and the release of pro-inflammatory factors, including IL-1β, IL-18, IL-6, and NOS2. We have revealed that, in contrast to minocycline, BoNT/A treatment did not decrease LPS-induced release of pro-inflammatory factors in the astroglia. In addition, BoNT/A decreased SNAP-23 in both types of glial cells and also SNAP-25 expressed only in astrocytes. Moreover, BoNT/A increased TLR2 and its adaptor protein MyD88, but not TLR4 exclusively in microglial cells. Furthermore, we have shown the impact of BoNT/A on microglial and astroglial cells, with a particular emphasis on its molecular target, TLR2. In contrast, minocycline did not affect any of those factors. We have revealed that despite of different molecular targets, minocycline, and BoNT/A reduced the release of microglia-derived pro-inflammatory factors. In conclusion, we have shown that BoNT/A and minocycline are effective drugs for the management of neuroinflammation by dampening the activation of microglial cells, with minocycline also affecting astroglial activity. PMID:28491822

A randomised controlled trial of ablation of Barrett's oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results

PubMed Central

Sharma, P; Wani, S; Weston, A P; Bansal, A; Hall, M; Mathur, S; Prasad, A; Sampliner, R E

2006-01-01

Background Many modalities have been used to ablate Barrett's oesophagus (BO). However, long term results and comparative effectiveness are unknown. Aims Our aim was to compare the long term efficacy of achieving complete reversal (endoscopic and histological) between multipolar electrocoagulation (MPEC) and argon plasma coagulation (APC) in BO patients and assess factors influencing successful ablation. Methods Patients with BO, 2–6 cm long, underwent 24 hour pH testing on proton pump inhibitor (PPI) therapy. Patients were then randomised by BO length to undergo ablation with MPEC or APC every 4–8 weeks until endoscopic reversal or maximal of six treatment sessions. Results Thirty five BO patients have been followed for at least two years following endoscopic ablation, 16 treated with MPEC and 19 with APC. There was complete reversal of BO in 24 patients (69%); 75% with MPEC and 63% with APC (p = 0.49). There was no difference in the number of sessions required in the two groups. There was no difference in age, pH results, BO length, PPI dose, or hiatal hernia size between patients with and without complete reversal. One patient developed an oesophageal stricture but there were no major complications such as bleeding or perforation. Conclusions In BO patients treated with MPEC or APC in combination with acid suppression, at long term follow up, complete reversal of BO can be maintained in approximately 70% of patients, irrespective of the technique. There are no predictors associated with achieving complete reversal of BO. Continued surveillance is still indicated in the post ablative setting. As yet, these techniques are not ready for clinical application (other than for high grade dysplasia or early oesophageal adenocarcinoma) and cannot be offered outside the research arena. PMID:16905695

Creating a Body of Knowledge for cartography

NASA Astrophysics Data System (ADS)

Fairbairn, David

2018-05-01

The nature of knowledge is considered, in particular its creation and formalisation, and some of the issues which re-late to disciplinary knowledge in particular. It is suggested that cartography has particular needs addressing its disciplinary boundaries, the role of uncertain and `troublesome' knowledge in its subject-matter, and the enhancement of its subject-specific knowledge, with more generic supporting material, including skills and attitudes. An overview of Bodies of Knowledge (BoK) in other disciplines has been undertaken, and models of BoK structure, content and usage have been assessed. BoKs in closely related subjects, including civil engineering, GIS and software engineering, give examples of good practice. The paper concentrates on the work done to date to create the cartography BoK, and the adoption of the `Delphi' method of consultation to develop it. The Delphi method is intended to yield consensus on the scope, content, context and use of the BoK. It is regarded as a rigorous process, iterative (and therefore time consuming), involving questionnaire survey, opinion gathering, discourse analysis, and feedback. The participants are expected to be experts, from a range of different sectors, but `volunteer amateurs' are also important consultants.

Molecular bases of protective immune responses against botulinum neurotoxin A--how antitoxin antibodies block its action.

PubMed

Atassi, M Zouhair; Dolimbek, Behzod Z; Steward, Lance E; Aoki, K Roger

2007-01-01

In studies from this laboratory, we localized the regions on the H chain of botulinum neurotoxin A (BoNT/A) that are recognized by anti-BoNT/A antibodies (Abs) and block the activity of the toxin in vivo. These Abs were obtained from cervical dystonia patients who had been treated with BoNT/A and had become unresponsive to the treatment, as well as blocking Abs raised in mouse, horse, and chicken. We also localized the regions involved in BoNT/A binding to mouse brain synaptosomes (snp). Comparison of spatial proximities in the three-dimensional structure of the Ab-binding regions and the snp binding showed that except for one, the Ab-binding regions either coincide or overlap with the snp regions. It should be folly expected that protective Abs when bound to the toxin at sites that coincide or overlap with snp binding would prevent the toxin from binding to nerve synapse and therefore block toxin entry into the neuron. Thus, analysis of the locations of the Ab-binding and the snp-binding regions provides a molecular rationale for the ability of protecting Abs to block BoNT/A action in vivo.

AmeriFlux US-Bo1 Bondville

DOE Data Explorer

Meyers, Tilden [NOAA/ARL

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-Bo1 Bondville. Site Description - Agriculture, continuous no-till since 1986, Annual rotation between corn (C4) and soybeans (C3). The field was planted with corn during 2005 and 2007, with soybeans during 2006 and 2008.

Type-I non-critically phase-matched second-harmonic generation in Gd1-xYxCa4O(BO3)3

NASA Astrophysics Data System (ADS)

Burmester, P. B. W.; Kellner, T.; Petermann, K.; Huber, G.; Uecker, R.; Reiche, P.

Second-harmonic generation was z-cut observed Gd1-xYxCa4O(BO3)3 (Gd1-xYxCOB) and the dependence of the phase-matching wavelength on the mixing ratio x has been investigated. The dependence on both temperature and angle tuning was examined as well. We found the suitable composition for noncritical frequency doubling at 930 nm, which is the lasing wavelength of Nd:YAlO3 on the 4F3/2?4I9/2 transition.

75 FR 3901 - Board of Visitors, United States Military Academy (USMA)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-25

... Organizational Meeting of the USMA Board of Visitors (BoV). Members of the Board will be provided updates on..., Technology, Engineering & Math (STEM) Center of Excellence, Energy Costs and Initiatives, Wastewater...

Molecular Structures and Functional Relationships in Clostridial Neurotoxins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaminathan S.

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structuresmore » have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here.« less

Structural and photoluminescence studies on europium-doped lithium tetraborate (Eu:Li2B4O7) single crystal grown by microtube Czochralski (μT-Cz) technique

NASA Astrophysics Data System (ADS)

A, Kumaresh; R, Arun Kumar; N, Ravikumar; U, Madhusoodanan; B, S. Panigrahi; K, Marimuthu; M, Anuradha

2016-05-01

Rare earth europium (Eu3+)-doped lithium tetraborate (Eu:Li2B4O7) crystal is grown from its stoichiometric melt by microtube Czochralski pulling technique (μT-Cz) for the first time. The grown crystals are subjected to powder x-ray diffraction (PXRD) analysis which reveals the tetragonal crystal structure of the crystals. UV-vis-NIR spectral analysis is carried out to study the optical characteristics of the grown crystals. The crystal is transparent in the entire visible region, and the lower cutoff is observed to be at 304 nm. The existence of BO3 and BO4 bonding structure and the molecular associations are analyzed by Fourier transform infrared (FTIR) spectroscopy. The results of excitation and emission-photoluminescence spectra of europium ion incorporated in lithium tetraborate (LTB) single crystal reveal that the observations of peaks at 258, 297, and 318 nm in the excitation spectra and peaks at 579, 591, 597, 613, and 651 nm are observed in the emission spectra. The chromaticity coordinates are calculated from the emission spectra, and the emission intensity of the grown crystal is characterized through a CIE 1931 (Commission International d’Eclairage) color chromaticity diagram. Project supported by the Department of Science and Technology-Science and Engineering Research Board (Grant No. SR/S2/LOP-0012/2011), the Government of India for Awarding Major Research Project, the University Grants Commission-Department of Atomic Research-Consortium for Scientific Research (Grant No. CSR-KN/CSR-63/2014-2015/503), and the Kalpakkam and Indore, India.

Effect of boron oxide addition on the viscosity-temperature behaviour and structure of phosphate-based glasses.

PubMed

Sharmin, Nusrat; Hasan, Muhammad S; Rudd, Chris D; Boyd, Daniel; Werner-Zwanziger, Ulrike; Ahmed, Ifty; Parsons, Andrew J

2017-05-01

In this study, nine phosphate-based glass formulations from the system P 2 O 5 -CaO-Na 2 O-MgO-B 2 O 3 were prepared with P 2 O 5 content fixed as 40, 45 and 50 mol%, where Na 2 O was replaced by 5 and 10 mol% B 2 O 3 and MgO and CaO were fixed to 24 and 16 mol%, respectively. The effect of B 2 O 3 addition on the viscosity-temperature behaviour, fragility index and structure of the glasses was investigated. The composition of the glasses was confirmed by ICP-AES. The viscosity-temperature behaviour of the glasses were measured using beam-bending and parallel -plate viscometers. The viscosity of the glasses investigated was found to shift to higher temperature with increasing B 2 O 3 content. The kinetic fragility parameter, m and F 1/2 , estimated from the viscosity curve were found to decease with increasing B 2 O 3 content. The structural analysis was achieved by a combination of Fourier transform infrared spectroscopy and solid state nuclear magnetic resonance. 31 P solid-state magic-angle-spinning nuclear magnetic resonance (MAS-NMR) showed that the local structure of the glasses changes with increasing B 2 O 3 content. As B 2 O 3 was added to the glass systems, the phosphate connectivity increases as the as the Q 1 units transforms into Q 2 units. The 11 B NMR results confirmed the presence of tetrahedral boron (BO 4 ) units for all the compositions investigated. Structural analysis indicates an increasing level of cross-linking with increasing B 2 O 3 content. Evidence of the presence of P-O-B bonds was also observed from the FTIR and 31 P NMR analysis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 764-777, 2017. © 2016 Wiley Periodicals, Inc.

Enantioselective syntheses of lignin models: an efficient synthesis of B-O-4 dimers and trimers by using the Evans chiral auxiliary

Treesearch

Costyl N. Njiojob; Joseph J. Bozell; Brian K. Long; Thomas Elder; Rebecca E. Key; William T. Hartwig

2016-01-01

We describe an efficient five-step, enantioselective synthesis of (R,R)- and (S,S)-lignin dimer models possessing a B-O-4 linkage, by using the Evans chiral aldol reaction as a key step. Mitsunobu inversion of the (R,R)- or (S,S)-isomers generates the corresponding (R,S)- and (S,R)-diastereomers. We further extend this approach to the...

Growth and laser properties of Nd:Ca 4YO(BO 3) 3 crystal

NASA Astrophysics Data System (ADS)

Zhang, H. J.; Meng, X. L.; Zhu, L.; Wang, C. Q.; Cheng, R. P.; Yu, W. T.; Zhang, S. J.; Sun, L. K.; Chow, Y. T.; Zhang, W. L.; Wang, H.; Wong, K. S.

1999-02-01

Nd:Ca 4YO(BO 3) 3 (Nd:YCOB) crystal was grown by the Czochralski method, and its structure was measured by using a four circle X-ray diffractometer. The transparent spectrum from 200 to 2600 nm was measured at room temperature. The fluorescence spectrum near 1.06 μm showed that the main emission wavelength of Nd:YCOB crystal was centered at 1060.8 nm. Laser output at 1.06 μm has been demonstrated when it was pumped by a Ti:sapphire laser at the wavelength of 794 nm, the highest output power was 68 mW under pumping power of 311 mW, the pumping threshold was 163 mW and slope efficiency was 46.9%. The self-frequency doubled green light has been observed when it was pumped by a Ti:sapphire or a laser diode (LD). A 14.5 mm Nd:YCOB crystal sample cut at ( θ, φ)=(90°, 33°) was used for type I second-frequency generation (SHG) of the 1.06 μm laser pulse. The SHG conversion efficiency was 22%.

Phase relations in the pseudo ternary system In2O3-TiO2-BO (B: Zn, Co and Ni) at 1200 °C in air

NASA Astrophysics Data System (ADS)

Brown, Francisco; Jacobo-Herrera, Ivan Edmundo; Alvarez-Montaño, Victor Emmanuel; Kimizuka, Noboru; Hirano, Tomonosuke; Sekine, Ryotaro; Denholme, Saleem J.; Miyakawa, Nobuaki; Kudo, Akihiko; Iwase, Akihide; Michiue, Yuichi

2018-02-01

Phase relations in the pseudo ternary systems In2O3-TiO2-ZnO, In2O3-TiO2-CoO and In2O3-TiO2-NiO at 1200 °C in air were determined by means of a classic quenching method. In6Ti6BO22 (B: Zn, Co and Ni) which has the monoclinic In(Fe1/4Ti3/4)O27/8-type of structure with a 4-dimensional super space group exists in a stable form. There exist homologous phases In1+x(Ti1/2Zn1/2)1-xO3(ZnO)m (m: natural number, 0

Quantitative Analysis of Levels of Serum Immunoglobulin G against Botulinum Neurotoxin Type D and Association with Protection in Natural Outbreaks of Cattle Botulism

PubMed Central

Steinman, A.; Chaffer, M.; Elad, D.; Shpigel, N. Y.

2006-01-01

The recent outbreaks of cattle botulism in vaccinated Israeli dairy cattle prompted us to determine vaccine efficacy and reasons for vaccine failure. Analysis of clinical signs, feeding practice, vaccination history, and epidemic curves enabled us to define a study population in two outbreaks, where high doses of Clostridium botulinum neurotoxin type D (BoNT/D) were evenly consumed by the affected animal groups. Attack rates among unvaccinated 6- to 24-month-old heifers were 96% (55/57) and 85% (53/62). The attack rates in vaccinated parity 1, 2, and ≥3 cows were 40.4% (21/52), 14.3% (4/28), and 5.6% (3/54), respectively. Vaccine efficacies for these cow groups were 52.5%, 83.2%, and 93.4%, respectively. In younger, unvaccinated 2- to 6-month-old calves, presumably protected by maternal antibodies, the attack rate was 24% (17/71). These differences correlated with significant differences in levels of specific anti-BoNT/D antibody in serum by an enzyme-linked immunosorbent assay (ELISA). The ELISA performance for predicting protection was analyzed by receiver operating characteristic analysis and was found to be highly significant, with an area under the curve of 0.941 (standard error, 0.034; 95% confidence interval, 0.875 to 1.008; P < 0.000). No animals with serum ELISA unit levels above 0.33 were affected in these exposed groups. At this cutoff level, the specificity of the ELISA was 100%, sensitivity was 67%, and accuracy was 92%. We concluded that botulinum toxoids can confer adequate protection against natural exposure to lethal doses of BoNT/D; however, the vaccination protocols should be optimized. Our in-house ELISA system will enable us to optimize vaccination protocols in the animal population. PMID:16893985

Magnetic properties of Co 2 2+ Co 1 - x 3+ Fe x 3+ BO5 ( x = 0.10) single crystals with a ludwigite structure

NASA Astrophysics Data System (ADS)

Knyazev, Yu. V.; Kazak, N. V.; Bayukov, O. A.; Platunov, M. S.; Velikanov, D. A.; Bezmaternykh, L. N.; Ivanova, N. B.; Ovchinnikov, S. G.

2017-04-01

The investigation of mixed Co-Fe ludwigite single crystals shows that their magnetic properties are close to the magnetic properties of Fe3BO5 despite the predominance of cobalt ions. The magnetic properties of Co3 - x Fe x BO5 single crystals with x = 0.10 are studied in detail. Magnetometric measurements demonstrate a strong magnetic anisotropy with easy magnetization axis b, and the orbital magnetic moment of cobalt is in a frozen state. The detected temperature dependence of the absorption of Mössbauer spectra allowed us to determine the magnetic ordering temperature, which agrees with the results of magnetization measurements ( T C = 84 K).

Structure, spectra and thermal, mechanical, Faraday rotation properties of novel diamagnetic SeO2-PbO-Bi2O3-B2O3 glasses

NASA Astrophysics Data System (ADS)

Chen, Qiuling; Su, Kai; Li, Yantao; Zhao, Zhiwei

2018-06-01

Faraday rotation diamagnetic glass has attracted research attentions in photonics, sensing and magneto optical devices due to their high refractive index, wide transmittance in UV and Fourier transform infrared (FT-IR) range and temperature independent Faraday rotation. Selenite modified heavy metal oxides glasses with composition of xSeO2-(10-x) B2O3-45PbO-45Bi2O3 (x = 0, 1, 5 and 10mol%) and 15%SeO2-40%PbO-45%Bi2O3 have been fabricated by melt-quenching method in present study. The influence of SeO2 on glass forming ability, thermal, mechanical properties and Faraday rotation were evaluated through X-ray Diffraction (XRD), Fourier transforms infrared spectra (FT-IR), Raman, X-ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), Vicker's hardness and Verdet constant measurements. XRD spectra reveal that the good vitrification was achieved for glass with SeO2 amounts ≤10% even without B2O3. FT-IR, Raman and XPS spectra ascertain the existence of characteristic vibration of SeO4, SeO3, PbO4, BiO3 and BO3 units. The incorporation of SeO2 increases the connectivity of glassy network by increasing the Tg, thermal stability and mechanical hardness. The small band gap, high polarizable Se4+ ions and isolated SeO3 units contribute to Faraday rotation improvement.

Antioxidant capacity of BO-653, 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, and uric acid as evaluated by ORAC method and inhibition of lipid peroxidation.

PubMed

Niki, Etsuo; Fukuhara, Akiko; Omata, Yo; Saito, Yoshiro; Yoshida, Yasukazu

2008-04-01

The role of radical-scavenging antioxidant against oxidative stress has received much attention. The antioxidant capacity has been assessed by various methods. Above all, oxygen radical absorbance capacity (ORAC) has been frequently employed [Prior et.al., J. Agric. Food Chem.2005, 53, 4290]. In the present study, the antioxidant capacity of 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653) and uric acid was assessed by ORAC method using pyranine as a reference probe and compared with that against lipid peroxidation of human plasma. It was found that BO-653 was assessed to be much less potent than uric acid by ORAC method, whereas BO-653 exerted much higher antioxidant activity than uric acid against plasma lipid peroxidation. The reason for such discrepancy is discussed. The results suggest that ORAC method is suitable for the assessment of free radical scavenging capacity, but not for the assessment of antioxidant capacity against lipid peroxidation in plasma.

Effect of 3d-transition metal doping on the shielding behavior of barium borate glasses: a spectroscopic study.

PubMed

ElBatal, H A; Abdelghany, A M; Ghoneim, N A; ElBatal, F H

2014-12-10

UV-visible and FT infrared spectra were measured for prepared samples before and after gamma irradiation. Base undoped barium borate glass of the basic composition (BaO 40%-B2O3 60mol.%) reveals strong charge transfer UV absorption bands which are related to unavoidable trace iron impurities (Fe(3+)) within the chemical raw materials. 3d transition metal (TM)-doped glasses exhibit extra characteristic absorption bands due to each TM in its specific valence or coordinate state. The optical spectra show that TM ions favor generally the presence in the high valence or tetrahedral coordination state in barium borate host glass. Infrared absorption bands of all prepared glasses reveal the appearance of both triangular BO3 units and tetrahedral BO4 units within their characteristic vibrational modes and the TM-ions cause minor effects because of the low doping level introduced (0.2%). Gamma irradiation of the undoped barium borate glass increases the intensity of the UV absorption together with the generation of an induced broad visible band at about 580nm. These changes are correlated with suggested photochemical reactions of trace iron impurities together with the generation of positive hole center (BHC or OHC) within the visible region through generated electrons and positive holes during the irradiation process. Copyright © 2014 Elsevier B.V. All rights reserved.

Extraction and Inhibition of Enzymatic Activity of Botulinum Neurotoxins/A1, /A2, and /A3 by a Panel of Monoclonal Anti-BoNT/A Antibodies

DTIC Science & Technology

2009-04-01

triplicate and results were averaged. MS Detection A master mix was created consisting of 9 parts matrix solution (alpha-cyano-4-hydroxy cinnamic acid ...thus, do not inhibit the catalytic activity. Another feature of BoNT/A is that it exhibits genetic and amino acid variance within the toxin type, or...less amino acid variance [23] and this variance has been reported to affect binding of the toxin to anti-BoNT/A mAbs [24]. For these reasons, it is

Investigating burnout situations, nurses' stress perception and effect of a post-graduate education program in health care organizations of northern Italy: a multicenter study.

PubMed

Arrigoni, Cristina; Caruso, Rosario; Campanella, Francesca; Berzolari, Francesca Gigli; Miazza, Daniela; Pelissero, Gabriele

2015-01-01

Burnout (BO) is increasingly considered a public health problem: it is not only harmful to the individual, but also for the organization. Therefore, in recent years, research has given particular attention to the study of the phenomenon and its antecedents among the nursing profession. In the last ten years, the literature shows the prevalence of BO in different clinical settings, but there are few recent data describing the phenomenon and its relationship with educational preventive programs. The aims of this study are: a) to describe the prevalence of nurses' risk of BO in the northern Italy area b) to describe nurses' coping and their perception of the BO antecedents. c) to describe the effects of education on the nurses' coping and their recognition of BO antecedents. The study is structured into two main parts. The first was cross-sectional, the second was prospective. Burnout Potential Inventory (BPI) questionnaire was used in the cross-sectional part to survey risk of BO in three big hospitals in Northern Italy. The Health Profession Stress and Coping Scale (HPSCS) was used in the prospective part to survey the nurses' stress perception and their coping mechanisms in a post-graduate educational program. Nurses' BO risk is within the normal range, although the BPI highlighted three borderline subscales: poor team work, work overload and poor feedback. Post-graduate education had a positive effect on the stress perception, but it is not sufficient to improve coping mechanisms. The study revealed the more stressful work situations and the effect of post-graduate education to prevent the effects of stress. This topic needs further investigation in the light of the result of this study.

The role of BoFLC2 in cauliflower (Brassica oleracea var. botrytis L.) reproductive development.

PubMed

Ridge, Stephen; Brown, Philip H; Hecht, Valérie; Driessen, Ronald G; Weller, James L

2015-01-01

In agricultural species that are sexually propagated or whose marketable organ is a reproductive structure, management of the flowering process is critical. Inflorescence development in cauliflower is particularly complex, presenting unique challenges for those seeking to predict and manage flowering time. In this study, an integrated physiological and molecular approach was used to clarify the environmental control of cauliflower reproductive development at the molecular level. A functional allele of BoFLC2 was identified for the first time in an annual brassica, along with an allele disrupted by a frameshift mutation (boflc2). In a segregating F₂ population derived from a cross between late-flowering (BoFLC2) and early-flowering (boflc2) lines, this gene behaved in a dosage-dependent manner and accounted for up to 65% of flowering time variation. Transcription of BoFLC genes was reduced by vernalization, with the floral integrator BoFT responding inversely. Overall expression of BoFT was significantly higher in early-flowering boflc2 lines, supporting the idea that BoFLC2 plays a key role in maintaining the vegetative state. A homologue of Arabidopsis VIN3 was isolated for the first time in a brassica crop species and was up-regulated by two days of vernalization, in contrast to findings in Arabidopsis where prolonged exposure to cold was required to elicit up-regulation. The correlations observed between gene expression and flowering time in controlled-environment experiments were validated with gene expression analyses of cauliflowers grown outdoors under 'natural' vernalizing conditions, indicating potential for transcript levels of flowering genes to form the basis of predictive assays for curd initiation and flowering time. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Identification of full length bovine TLR1 and functional characterization of lipopeptide recognition by bovine TLR2/1 heterodimer

PubMed Central

Farhat, Katja; Riekenberg, Sabine; Jung, Günther; Wiesmüller, Karl-Heinz; Jungi, Thomas W.; Ulmer, Artur J.

2010-01-01

Toll-like receptors (TLR) are highly conserved pattern recognition receptors of the innate immune system. Toll-like receptor 2 (TLR2) recognizes bacterial lipopeptides in a heterodimeric complex with TLR6 or TLR1, thereby discriminating between di- or triacylated lipopeptides, respectively. Previously, we found that HEK293 cells transfected with bovine TLR2 (boTLR2) were able to respond to diacylated lipopeptides but did not recognize triacylated lipopeptides, even after cotransfection with the so far published sequence of boTLR1. In this study we now could show that primary bovine cells were in general able to detect triacylated lipopetides. A closer investigation of the boTLR1 gene locus revealed an additional ATG 195 base pairs upstream from the published start codon. Its transcription would result in an N-terminus with high identity to human and murine TLR1 (huTLR1, muTLR1). Cloning and cotransfection of this longer boTLR1 with boTLR2 now resulted in the recognition of triacylated lipopeptides by HEK293 cells, thereby resembling the ex vivo observation. Analysis of the structure-activity relationship showed that the ester-bound acid chains of these lipopeptides need to consist of at least 12 carbon atoms to activate the bovine heterodimer showing similarity to the recognition by huTLR2/huTLR1. In contrast, HEK293 cell cotransfected with muTLR2 and muTLR1 could already be activated by lipopeptides with shorter fatty acids of only 6 carbon atoms. Thus, our data indicate that the additional N-terminal nucleotides belong to the full length and functionally active boTLR1 (boTLR1-fl) which participates in a species-specific recognition of bacterial lipopeptides. PMID:20167196

Light chain separated from the rest of the type a botulinum neurotoxin molecule is the most catalytically active form.

PubMed

Gul, Nizamettin; Smith, Leonard A; Ahmed, S Ashraf

2010-09-22

Botulinum neurotoxins (BoNT) are the most potent of all toxins. The 50 kDa N-terminal endopeptidase catalytic light chain (LC) of BoNT is located next to its central, putative translocation domain. After binding to the peripheral neurons, the central domain of BoNT helps the LC translocate into cytosol where its proteolytic action on SNARE (soluble NSF attachment protein receptor) proteins blocks exocytosis of acetyl choline leading to muscle paralysis and eventual death. The translocation domain also contains 105 Å -long stretch of ∼100 residues, known as "belt," that crosses over and wraps around the LC to shield the active site from solvent. It is not known if the LC gets dissociated from the rest of the molecule in the cytosol before catalysis. To investigate the structural identity of the protease, we prepared four variants of type A BoNT (BoNT/A) LC, and compared their catalytic parameters with those of BoNT/A whole toxin. The four variants were LC + translocation domain, a trypsin-nicked LC + translocation domain, LC + belt, and a free LC. Our results showed that K(m) for a 17-residue SNAP-25 (synaptosomal associated protein of 25 kDa) peptide for these constructs was not very different, but the turnover number (k(cat)) for the free LC was 6-100-fold higher than those of its four variants. Moreover, none of the four variants of the LC was prone to autocatalysis. Our results clearly demonstrated that in vitro, the LC minus the rest of the molecule is the most catalytically active form. The results may have implication as to the identity of the active, toxic moiety of BoNT/A in vivo.

The role of BoFLC2 in cauliflower (Brassica oleracea var. botrytis L.) reproductive development

PubMed Central

Ridge, Stephen; Brown, Philip H.; Hecht, Valérie; Driessen, Ronald G.; Weller, James L.

2015-01-01

In agricultural species that are sexually propagated or whose marketable organ is a reproductive structure, management of the flowering process is critical. Inflorescence development in cauliflower is particularly complex, presenting unique challenges for those seeking to predict and manage flowering time. In this study, an integrated physiological and molecular approach was used to clarify the environmental control of cauliflower reproductive development at the molecular level. A functional allele of BoFLC2 was identified for the first time in an annual brassica, along with an allele disrupted by a frameshift mutation (boflc2). In a segregating F2 population derived from a cross between late-flowering (BoFLC2) and early-flowering (boflc2) lines, this gene behaved in a dosage-dependent manner and accounted for up to 65% of flowering time variation. Transcription of BoFLC genes was reduced by vernalization, with the floral integrator BoFT responding inversely. Overall expression of BoFT was significantly higher in early-flowering boflc2 lines, supporting the idea that BoFLC2 plays a key role in maintaining the vegetative state. A homologue of Arabidopsis VIN3 was isolated for the first time in a brassica crop species and was up-regulated by two days of vernalization, in contrast to findings in Arabidopsis where prolonged exposure to cold was required to elicit up-regulation. The correlations observed between gene expression and flowering time in controlled-environment experiments were validated with gene expression analyses of cauliflowers grown outdoors under ‘natural’ vernalizing conditions, indicating potential for transcript levels of flowering genes to form the basis of predictive assays for curd initiation and flowering time. PMID:25355864

Modeling Tropical Cyclone Storm Surge and Wind Induced Risk Along the Bay of Bengal Coastline Using a Statistical Copula

NASA Astrophysics Data System (ADS)

Bushra, N.; Trepanier, J. C.; Rohli, R. V.

2017-12-01

High winds, torrential rain, and storm surges from tropical cyclones (TCs) cause massive destruction to property and cost the lives of many people. The coastline of the Bay of Bengal (BoB) ranks as one of the most susceptible to TC storm surges in the world due to low-lying elevation and a high frequency of occurrence. Bangladesh suffers the most due to its geographical setting and population density. Various models have been developed to predict storm surge in this region but none of them quantify statistical risk with empirical data. This study describes the relationship and dependency between empirical TC storm surge and peak reported wind speed at the BoB using a bivariate statistical copula and data from 1885-2011. An Archimedean, Gumbel copula with margins defined by the empirical distributions is specified as the most appropriate choice for the BoB. The model provides return periods for pairs of TC storm surge and peak wind along the BoB coastline. The BoB can expect a TC with peak reported winds of at least 24 m s-1 and surge heights of at least 4.0 m, on average, once every 3.2 years, with a quartile pointwise confidence interval of 2.7-3.8 years. In addition, the BoB can expect peak reported winds of 62 m s-1 and surge heights of at least 8.0 m, on average, once every 115.4 years, with a quartile pointwise confidence interval of 55.8-381.1 years. The purpose of the analysis is to increase the understanding of these dangerous TC characteristics to reduce fatalities and monetary losses into the future. Application of the copula will mitigate future threats of storm surge impacts on coastal communities of the BoB.

77 FR 14006 - Board of Visitors, United States Military Academy (USMA)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

... Organizational Meeting of the USMA Board of Visitors (BoV). Members of the Board will be provided updates on... Harassment/Assault Response and Prevention, Supporting US Army Strategies, and the DAIG Cemetery Inspection...

Effects on craniofacial growth and development of unilateral botulinum neurotoxin injection into the masseter muscle.

PubMed

Tsai, Chi-Yang; Chiu, Wan Chi; Liao, Yi-Hsuan; Tsai, Chih-Mong

2009-02-01

The effects of botulinum neurotoxin type A (BoNT/A) on masseter muscles, when injected for cosmetic purposes (volumetric reduction) or treatment of excessive muscle activity (bruxism), have been investigated. However, the full anatomic effects of treatment are not known, particularly with respect to the mandible and relevant anthropometric measurements. The intent of this study was to use unilaterial BoNT/A injections to induce localized masseter atrophy and paresis and then to measure the effects of muscle influence on craniofacial growth and development. Growing male Wistar rats, 30 days old, were studied. The experimental group consisted of 8 rats. One side of the masseter muscle was injected with BoNT/A and the other side of the masseter muscle was injected with saline. The side with BoNT/A belonged to 1 group and the side with saline was the sham group. Three rats without injections was the control. After 45 days, the masseter muscles were dissected and weighed. Dry skulls were prepared, and anthropometric measurements determined. One-way ANOVA showed that the animals maintained their weight in both groups; however, the muscles injected with BoNT/A were smaller than the sham or control muscles. Anthropometric measurements of the bony structures attached to the masseter muscle showed a significant treatment effect. After localized masseter muscle atrophy induced by BoNT/A injection, alterations of craniofacial bone growth and development were seen. The results agree with the functional matrix theory that soft tissues regulate bone growth.

Nonallergic Eyelid Edema After Botulinum Toxin Type A Injection

PubMed Central

Chang, Yin-Shuo; Chang, Chang-Cheng; Shen, Jen-Hsiang; Chen, Yu-Tsung; Chan, Karen Kar-Wun

2015-01-01

Abstract Periocular botulinum toxin type A (BoNTA) injections are generally safe. Ptosis is the most common adverse effect, whereas eyelid edema is rarely reported. There is no consensus on the latter's incidence, clinical course, or treatment strategy. Here we managed a 59-year-old woman who received BoNTA injections to her forehead, glabella, and eye corner. At 3-day follow-up, she presented with painless, nonpruritic, bilateral periorbital edema, and erythema. Preliminary diagnosis was a local allergic reaction, and topical corticosteroid was administered, but upon lack of improvement, edema secondary to venous and lymphatic congestion was hypothesized, and she was advised to apply hot pads over her eyes, blink frequently, and massage the area. Her eyelid edema resolved 2 weeks later. At 4-month follow-up, the patient requested and received another course of BoNTA at half the dose. Frequent blinking was instructed, and the patient reported a satisfactory outcome with no adverse effects. In our literature review, incidence of BoNTA-induced eyelid edema was 1.4% and showed Asian tendency. Although rare, BoNTA-induced periorbital edema is self-limiting, and normally resolves in 2 to 4 weeks without medical treatment. Patients at risk for edema, including Asian ethnicity, dermatochalasis, and poor periocular muscle tone, are advised to receive injections at half the dosage. Examination of the function and tone of the orbicularis oculi and levator palpebrae superioris muscles before treatment is recommended, and application of hot pads over the eyes, frequent blinking in the morning, and self-massage of the affected area to increase venous return have demonstrated to improve outcome. PMID:26402825

Corrosion-Control (CC) Program: Pilot Powder Coating Station Service Test.

DTIC Science & Technology

1986-03-14

o CL oU C4 CL00 z ;,S Go 0 m~ CL - C9 uj4 U..~D o . ZC.F Go zz 2 0 I- - c t < m U, cc V V4 cg c ~ D GD...Spray Booth# Curing Oven and A2-58 UNIT TOTAL is_18 A2-1 1WOW - o 0 -1 Q S re. 10 U c Z. 2E E. a.E 8 tE 20 4AU ==- %A a 4 $AO - Lo 48 0 w 0 -IL .. 0.... 0...Laa 00 3-r Q’ IA E zo 0..0 -< 4o C a) Ia - o x c bi. l c *4 ’a a~~* coLo. 0V Ua- 41 w - a V 2 2 .8 h A a U to bo co i ac

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

PubMed

Lagergren, Katarina; Ek, Weronica E; Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Casson, Alan G; Risch, Harvey A; Shaheen, Nicholas J; Bird, Nigel C; Reid, Brian J; Corley, Douglas A; Hardie, Laura J; Wu, Anna H; Fitzgerald, Rebecca C; Pharoah, Paul; Caldas, Carlos; Romero, Yvonne; Vaughan, Thomas L; MacGregor, Stuart; Whiteman, David; Westberg, Lars; Nyren, Olof; Lagergren, Jesper

2015-01-01

The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Variations of trace gases over the Bay of Bengal during the summer monsoon

NASA Astrophysics Data System (ADS)

Girach, I. A.; Ojha, Narendra; Nair, Prabha R.; Tiwari, Yogesh K.; Kumar, K. Ravi

2018-02-01

In situ measurements of near-surface ozone (O3), carbon monoxide (CO), and methane (CH4) were carried out over the Bay of Bengal (BoB) as a part of the Continental Tropical Convergence Zone (CTCZ) campaign during the summer monsoon season of 2009. O3, CO and CH4 mixing ratios varied in the ranges of 8-54 ppbv, 50-200 ppbv and 1.57-2.15 ppmv, respectively during 16 July-17 August 2009. The spatial distribution of mean tropospheric O3 from satellite retrievals is found to be similar to that in surface O3 observations, with higher levels over coastal and northern BoB as compared to central BoB. The comparison of in situ measurements with the Monitoring Atmospheric Composition & Climate (MACC) global reanalysis shows that MACC simulations reproduce the observations with small mean biases of 1.6 ppbv, -2.6 ppbv and 0.07 ppmv for O3, CO and CH4, respectively. The analysis of diurnal variation of O3 based on observations and the simulations from Weather Research and Forecasting coupled with Chemistry (WRF-Chem) at a stationary point over the BoB did not show a net photochemical build up during daytime. Satellite retrievals show limitations in capturing CH4 variations as measured by in situ sample analysis highlighting the need of more shipborne in situ measurements of trace gases over this region during monsoon.

Growth, improved thermal stability and spectral properties of Yb3+-ions doped high temperature phase α-Ba3Gd(BO3)3 crystals co-doped by Sr2+, Ca2+ and La3+ ions

NASA Astrophysics Data System (ADS)

Pan, Shangke; Zhang, Jianyu; Pan, Jianguo

2018-02-01

To investigate the cause of the thermal instability of Yb3+-ions doped Ba3Gd(BO3)3 crystal grown from Czochralski technique, the low temperature phase β-Ba3Gd(BO3)3 powder was synthesized at the temperature of 800 °C. To inhibit the phase transition of high temperature phase Yb:α-Ba3Gd(BO3)3 during the crystal growth process, co-doping ions Sr2+, Ca2+ and La3+ ions were introduced in Yb:α-Ba3Gd(BO3)3 crystal. The melting point increased and the thermal stability of Yb:α-Ba3Gd(BO3)3 crystal was improved by co-doping ions. The absorption peaks of co-doped crystals centered at 976 nm with FWHM of 11, 11 and 12 nm and the absorption cross sections were 3.40 × 10-21 cm2, 4.00 × 10-21 cm2 and 2.66 × 10-21 cm2, respectively. The emission cross sections at 1040 nm were 2.19 × 10-21 cm2, 2.53 × 10-21 cm2 and 1.93 × 10-21 cm2, respectively. The fluorescence times of co-doped by Sr2+, Ca2+ and La3+ ions were shorter than that of Yb:α-Ba3Gd(BO3)3 crystal. So Yb:α-Ba3Gd(BO3)3 crystals co-doped by Sr2+, Ca2+ and La3+ ions will be more suitable for LD-pumping laser.

Molecular structures and functional relationships in clostridial neurotoxins.

PubMed

Swaminathan, Subramanyam

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structures have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here. Journal compilation © 2011 FEBS. No claim to original US government works.

Treatment of phantom limb pain with botulinum toxin type A.

PubMed

Jin, Lingjing; Kollewe, Katja; Krampfl, Klaus; Dengler, Reinhard; Mohammadi, Bahram

2009-03-01

Phantom limb pain and sensations are common in amputees. The pathophysiology remains unclear and the treatment difficult and often unsuccessful. Opioids are frequently used when non-narcotics have failed, but are not effective in many cases. We report on three phantom and stump pain patients, refractive to previous treatments, who were successfully treated with botulinum toxin A (BoNT-A). Three patients who had previously undergone amputation of their leg due to accident (N = 2) or injury by a landmine (N = 1) were treated with BoNT-A (Dysport). We injected a total dose of up to 500 units (U) BoNT-A under EMG-control. Global clinical improvement was based on a 0-3 scale (0 = no effect; 3 = marked improvement) and on a questionnaire rating pain intensity (based on the visual analog scale), intake of pain medication and phantom limb sensations. All three patients evaluated the clinical global improvement with 3 (marked improvement). The pain intensity and pain medication was reduced significantly in all three cases. No side effects were reported. The duration of response lasted up to 11 weeks. These three successfully treated phantom and stump pain patients show that therapy with BoNT-A may be worth studying as an effective and safe treatment option for this kind of pain.

Effects of Y/Gd Ratio and Boron Excess on Vacuum Ultraviolet Characteristics and Morphology of (Y,Gd)BO3:Eu Phosphor Particles Prepared by Spray Pyrolysis

NASA Astrophysics Data System (ADS)

Koo, Hye Young; Jung, Dae Soo; Hong, Seung Kwon; Kang, Yun Chan; Jung, Kyeong Youl

2007-06-01

(Y1-xGdx)BO3:Eu (0≤ x≤ 1) phosphor particles were prepared by spray pyrolysis. The optimal amount of boric acid for the high photoluminescence intensity of there particles differed depending on the molar ratio of Y to Gd. With decreasing Y/Gd molar ratio, an increasing amount of excess boric acid was required. The difference in excess quantity of boric acid, which was demanded for the highest photoluminescence intensity according to the Y/Gd ratio, influenced the morphology and mean size of the (Y,Gd)BO3:Eu phosphor particles. The (Y1-xGdx)BO3:Eu (0≤ x≤ 1) phosphor particles had a regular morphology. The mean sizes of the GdBO3:Eu and YBO3:Eu phosphor particles were 1.4 and 1 μm, respectively. The high reactivity of boron and yttrium components produced YBO3:Eu phosphor particles with high photoluminescence intensities by spray pyrolysis using a spray solution with a stoichiometric amount of boric acid.

Anorganic bovine bone and a silicate-based synthetic bone activate different microRNAs.

PubMed

Annalisa, Palmieri; Furio, Pezzetti; Ilaria, Zollino; Anna, Avantaggiato; Luca, Scapoli; Marcella, Martinelli; Marzia, Arlotti; Elena, Masiero; Carinci, Francesco

2008-09-01

Bio-Oss (BO), composed of anorganic bovine bone, is widely used in several bone regeneration procedures in oral surgery. PerioGlas (PG) is an alloplastic material that has been used for grafting of periodontal osseous defects since the 1990s. However, how these biomaterials alter osteoblast activity to promote bone formation is poorly understood. We attempted to address this question by using microRNA microarray techniques to investigate differences in translational regulation in osteoblasts exposed to BO and PG. By using miRNA microarrays containing 329 probes designed from human miRNA sequences, we investigated miRNAs whose expression was significantly modified in an osteoblast-like cell line (MG-63) cultured with BO vs PG. Three up-regulated miRNAs (mir-337, mir-200b, mir-377) and 4 down-regulated miRNAs (mir-130a, mir-214, mir-27a, mir-93) were identified. Our results indicated that BO and PG act on different miRNAs. Globally, PG causes activation of bone-forming signaling, whereas BO also activates cartilage-related pathways.

Co-circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in Italy.

PubMed

Zappa, Alessandra; Canuti, Marta; Frati, Elena; Pariani, Elena; Perin, Silvana; Ruzza, Maria Lorena; Farina, Claudio; Podestà, Alberto; Zanetti, Alessandro; Amendola, Antonella; Tanzi, Elisabetta

2011-01-01

The discovery of human Metapneumovirus (hMPV) and human Bocavirus (hBoV) identified the etiological causes of several cases of acute respiratory tract infections in children. This report describes the molecular epidemiology of hMPV and hBoV infections observed following viral surveillance of children hospitalized for acute respiratory tract infections in Milan, Italy. Pharyngeal swabs were collected from 240 children ≤3 years of age (130 males, 110 females; median age, 5.0 months; IQR, 2.0-12.5 months) and tested for respiratory viruses, including hMPV and hBoV, by molecular methods. hMPV-RNA and hBoV-DNA positive samples were characterized molecularly and a phylogenetical analysis was performed. PCR analysis identified 131/240 (54.6%) samples positive for at least one virus. The frequency of hMPV and hBoV infections was similar (8.3% and 12.1%, respectively). Both infections were associated with lower respiratory tract infections: hMPV was present as a single infectious agent in 7.2% of children with bronchiolitis, hBoV was associated with 18.5% of pediatric pneumonias and identified frequently as a single etiological agent. Genetically distinct hMPV and hBoV strains were identified in children examined with respiratory tract infections. Phylogenetic analysis showed an increased prevalence of hMPV genotype A (A2b sublineage) compared to genotype B (80% vs. 20%, respectively) and of the hBoV genotype St2 compared to genotype St1 (71.4% vs. 28.6%, respectively). Interestingly, a shift in hMPV infections resulting from A2 strains has been observed in recent years. In addition, the occurrence of recombination events between two hBoV strains with a breakpoint located in the VP1/VP2 region was identified. © 2010 Wiley-Liss, Inc.

Synthesis and luminescence of Ca 4YO(BO 3) 3:Eu 3+ for fluorescent lamp application

NASA Astrophysics Data System (ADS)

Kuo, Te-Wen; Chen, Teng-Ming

2010-07-01

The red-emitting Ca 4YO(BO 3) 3:Eu 3+ phosphor has been prepared at 1200 °C by the simple solid-state reaction. This preparation temperature is much lower than Y 2O 3:Eu 3+ (1400-1500 °C) for conventional solid-state reaction method. In particular, the complete process to produce high-quality phosphor particles was carried out through the single-step heat treatment of the mixture of corresponding oxide-type metal sources. For this material, the XRD, PL, PL excitation (PLE) and SEM features have also been investigated. The X-ray diffraction data indicate that pure phase of Ca 4YO(BO 3) 3:Eu 3+ can be successfully obtained. Among the different emission transitions 5D 0 → 7F J=0, 1, 2, 3, 4 of this phosphor, one particular transition ( 5D 0 → 7F 2) at 610 nm has been found. Besides carrying out these essential measurements, we have also made an attempt to observe a strong red emission performance displayed by this phosphor for use as coating material on compact fluorescent lamps (CFLs). The results clearly indicate that the life time based on Ca 4YO(BO 3) 3:Eu 3+ was found to be much longer than that using Y 2O 3:Eu 3+. The good performances of the CFLs demonstrate that this phosphor may be suitable for application on short ultraviolet fluorescent lamp.

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

PubMed

Axell, Richard G; Giblett, Joel P; White, Paul A; Klein, Andrew; Hampton-Til, James; O'Sullivan, Michael; Braganza, Denise; Davies, William R; West, Nick E J; Densem, Cameron G; Hoole, Stephen P

2017-06-06

We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P <0.001) and BO (end-diastolic pressure [mm Hg]: 8.1 ± 4.0 versus 8.7±4.0, P =0.03). Impairment of systolic and diastolic function after BO remained at 15-minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P <0.01; end-diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P <0.01). Persistent diastolic dysfunction was also evident in the RP group at 15-minutes recovery (end-diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P =0.03) and there was also sustained impairment of load-independent indices of systolic function at 15 minutes after RP (end-systolic elastance and ventriculo-arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P <0.01). RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Demographics of patients affected by surgical disease in rural hospitals in two sub-Saharan African countries: a retrospective analysis.

PubMed

Grimes, Caris E; Billingsley, Michael L; Dare, Anna J; Day, Nigel; Mabey, Imogen; Naraghi, Sara; George, Peter M; Murowa, Michael; Kamara, Thaim B; Mkandawire, Nyengo C; Leather, Andy; Lavy, Christopher B D

2015-04-27

Awareness is growing of both the importance of surgical disease as a major cause of death and disability in low-income and middle-income countries (LMICs) and the cost-effectiveness of fairly simple surgical interventions. We hypothesised that surgical disease predominantly affects young adults and is therefore significant in both the macroeconomic effect of untreated disease and the microeconomic effects on patients and families in low-resource settings. We retrospectively reviewed all admission data from two rural government district hospitals, Bo District Hospital in Sierra Leone and Thyolo District Hospital in Malawi. Both hospitals serve a rural population of roughly 600 000. We analysed data from 3 months in the wet season and 3 months in the dry season for each hospital by careful analysis of all hospital logbook data. For the purposes of this study, a surgical diagnosis was defined as a diagnosis in which the patient should be managed by a surgically trained provider. We analysed all surgical admissions with respect to patient demographics (age and sex), diagnoses, and the procedures undertaken. In Thyolo, 835 (12·9%) of 6481 hospital admissions were surgical admissions. In Bo, 427 (19·8%) of 2152 hospital admissions were surgical admissions. In Thyolo, if all patients who had undergone a procedure in theatre were admitted overnight, the total number of admissions would have been 6931, with 1344 (19·4%) hospital admissions being surgical and 1282 (18·5%) hospital patients requiring a surgical procedure. In Bo, 133 patients underwent a surgical procedure. This corresponded to 6·18% of all hospital admissions; although notably many of the obstetric admissions were referred to a nearby Médecins Sans Frontières (MSF) hospital for treatment. Analysis of the admission data showed that younger than 16-year-olds accounted for 10·5% of surgical admissions in Bo, and 17·9% of surgical admissions in Thyolo. 16-35-year-olds accounted for 57·3% of all surgical admissions in Bo and 53·5% of all surgical admissions in Thyolo. Men accounted for 53·7% of surgical admissions in Bo and 46·0% of surgical admissions in Thyolo. Analysis of the procedure data showed that younger than 16-year-olds accounted for 7·0% of procedures in Bo and 4·5% of procedures in Thyolo, with 16-35-year-olds accounting for 65·6% of all procedures in Bo and 84·4% of all procedures in Thyolo. Men underwent 63% of all surgical procedures in Bo, but only 7·7% of surgical procedures in Thyolo. This discrepancy is explained by the high rate of maternal surgery in Thyolo, which was not present in Bo because this service was provided at the nearby MSF hospital. Most people affected by disease requiring surgery are young adults. It would be expected that failure to provide surgical care could have long-term adverse effects on both individual and national wealth. The Sir Ratanji Dalal Scholarship from the Royal College of Surgeons of England. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anatomical recommendations for safe botulinum toxin injection into temporalis muscle: a simplified reproducible approach.

PubMed

Lee, Won-Kang; Bae, Jung-Hee; Hu, Kyung-Seok; Kato, Takafumi; Kim, Seong-Taek

2017-03-01

The objective of this study was to simplify the anatomically safe and reproducible approach for BoNT injection and to generate a detailed topographic map of the important anatomical structures of the temporal region by dividing the temporalis into nine equally sized compartments. Nineteen sides of temporalis muscle were used. The topographies of the superficial temporal artery, middle temporal vein, temporalis tendon, and the temporalis muscle were evaluated. Also evaluated was the postural relations among the foregoing anatomical structures in the temporalis muscle, pivoted upon a total of nine compartments. The temporalis above the zygomatic arch exhibited an oblique quadrangular shape with rounded upper right and left corners. The distance between the anterior and posterior margins of the temporalis muscle was equal to the width of the temporalis rectangle, and the distance between the reference line and the superior temporalis margin was equal to its height. The mean ratio of width to height was 5:4. We recommend compartments Am, Mu, and Pm (coordinates of the rectangular outline) as areas in the temporal region for BoNT injection, because using these sites will avoid large blood vessels and tendons, thus improving the safety and reproducibility of the injection.

The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport®) injections for oromandibular, lingual, and truncal-axial dystonias.

PubMed

Rosales, Raymond L; Ng, Arlene R; Santos, Mary Mildred Delgado-Delos; Fernandez, Hubert H

2011-01-01

While the majority of chemodenervation clinics worldwide typically use botulinum toxins for the treatment of common conditions such as blepharopsams, cervical dystonia, limb dystonia, and spasticity, the unusually high concentration of X-linked dystonia-parkinsonism (XDP) has allowed us to collect and describe our experience in the use of botulinum toxin type A (BoNT-A) on rarer dystonic patterns. BoNT-A (Dysport®) was injected in a total 109 dystonias of XDP. Our cohort included: 50 cases in the oromandibular area (jaw opening: 32 cases, jaw closing: 12 cases, and jaw deviation: 6 cases); 35 cases in the lingual area (tongue protrusion: 27 cases and tongue curling: 8 cases); and, 24 cases in the truncal-axial area (flexor: 12 cases, extensor: 7 cases, and lateral-extensor: 5 cases). Interestingly, pain, often a nonprominent symptom of dystonias, was frequently reported in 40/50 XDP cases with oromandibular dystonia and 18/24 XDP cases with truncal-axial dystonia. All BoNT-A procedures were performed under electromyography guidance. A "high potency, low dilution" BoNT-A protocol was applied for oromandibular, lingual, cranial, cervical, and distal limb dystonias; whereas for dystonias of the abdominal, paraspinal, and proximal limb muscles, a "low potency, high dilution" BoNT-A injection protocol was applied. Outcomes measures included: the global dystonia rating scale (DRS) and pain visual analog scale (VAS) reduction at week 4; duration of BoNT-A effects; and, side effect profile. The median DRS score after 4 weeks was 3 ("substantial improvement") for oromandibular and lingual dystonias and 2 ("moderate improvement") for truncal-axial dystonias. Pain reduction was significantly reduced (75%-80% in oromandibular; 30%-80% in truncal-axial dystonias). The median duration of BoNT-A effect was 16 weeks for oromandibular, 12 weeks for lingual, and 11 weeks for truncal-axial dystonias. Compared to a generally safe and well-tolerated BoNT-A injections for truncal-axial dystonias, the oromandibular-lingual dystonias had the following frequency of adverse events: oromandibular--19% in jaw opening and 17% in jaw closing dystonias; lingual--19% in tongue protrusion and 13% in tongue curling dystonias. The most frequent adverse events were mouth dryness and dysphagia. Thus, BoNT-A injection working protocols may be adopted in XDP dystonia that adheres to cost minimization (e.g., lower dose end per selected muscle), while achieving some benefit, and potentially reduce the adverse event profile.

In search of the X{sub 2}BO and X{sub 2}BS (X = H, F) free radicals: Ab initio studies of their spectroscopic signatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clouthier, Dennis J., E-mail: dclaser@uky.edu

2014-12-28

The F{sub 2}BO free radical is a known, although little studied, species but similar X{sub 2}BY (X = H, D, F; Y = O, S) molecules are largely unknown. High level ab initio methods have been used to predict the molecular structures, vibrational frequencies (in cm{sup −1}), and relative energies of the ground and first two excited electronic states of these free radicals, as an aid to their eventual spectroscopic identification. The chosen theoretical methods and basis sets were tested on F{sub 2}BO and found to give good agreement with the known experimental quantities. In particular, complete basis set extrapolationsmore » of coupled-cluster single and doubles with perturbative triple excitations/aug-cc-pVXZ (X = 3, 4, 5) energies gave excellent electronic term values, due to small changes in geometry between states and the lack of significant multireference character in the wavefunctions. The radicals are found to have planar C{sub 2v} geometries in the X{sup ~2}B{sub 2} ground state, the low-lying A{sup ~2}B{sub 1} first excited state, and the higher B{sup ~2}A{sub 1} state. Some of these radicals have very small ground state dipole moments hindering microwave measurements. Infrared studies in matrices or in the gas phase may be possible although the fundamentals of H{sub 2}BO and H{sub 2}BS are quite weak. The most promising method of identifying these species in the gas phase appears to be absorption or laser-induced fluorescence spectroscopy through the allowed B{sup ~}-X{sup ~} transitions which occur in the visible-near UV region of the electromagnetic spectrum. The ab initio results have been used to calculate the Franck-Condon profiles of the absorption and emission spectra, and the rotational structure of the B{sup ~}-X{sup ~}0{sub 0}{sup 0} bands has been simulated. The calculated single vibronic level emission spectra provide a unique, readily recognizable fingerprint of each particular radical, facilitating the experimental identification of new X{sub 2}BY species in the gas phase.« less

Synthesis, structure characterization and optical properties of a new tripotassium cadmium pentaborate, K{sub 3}CdB{sub 5}O{sub 10}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Hongwei; Graduate school of Chinese Academy of Sciences, Beijing 100049; Pan Shilie, E-mail: slpan@ms.xjb.ac.cn

A new ternary borate oxide, K{sub 3}CdB{sub 5}O{sub 10}, has been synthesized by solid-state reaction at 580 deg. C. The compound crystallizes in the monoclinic space group P2{sub 1}/n with a=7.6707 (7) A, b=19.1765 (17) A, c=7.8784 (6) A, {beta}=115.6083 (49){sup o}, and Z=4. The crystal structure consists of a two-dimensional infinite [CdB{sub 5}O{sub 10}] layer, which forms by connecting isolated double ring [B{sub 5}O{sub 10}] groups and CdO{sub 4} tetrahedra. K atoms filling in the interlayer and intralayer link the layers together and balance charge. The IR spectrum has been studied and confirmed the presence of both BO{sub 3}more » and BO{sub 4} groups, and the UV-vis-IR diffuse reflectance spectrum exhibits a band gap of about 3.4 eV. The DSC analysis proves that K{sub 3}CdB{sub 5}O{sub 10} is a congruent melting compound. - Graphical abstract: A new phase, K{sub 3}CdB{sub 5}O{sub 10}, has been discovered in the ternary K{sub 2}O-CdO-B{sub 2}O{sub 3} system. The crystal structure consists of a two-dimensional infinite [CdB{sub 5}O{sub 10}] layer. Highlights: > The compound, K{sub 3}CdB{sub 5}O{sub 10}, was synthesized and characterized for the first time. {yields}K{sub 3}CdB{sub 5}O{sub 10} is a congruent melting compound, which means the large single crystals could be grown from the melt using the Czochralski pulling method. {yields}The crystal structure consists of a two-dimensional infinite [CdB{sub 5}O{sub 10}].« less

Embryonic Stem Cell-Derived Neurons are a Novel, Highly Sensitive Tissue Culture Platform for Botulinum Research

DTIC Science & Technology

2011-01-01

and acceleration of toxin degradation may be more amenable to therapeutic intervention, the neuronal response to intoxication and the molecular ...References [1] L.L. Simpson, Identification of the major steps in botulinum toxin action, Annu. Rev. Pharmacol. Toxicol. 44 (2004) 167–193. [2] J.C...BoNT) therapeutics: time to think outside the BoNT?, Botulinum J 1 (2009) 261–269. [6] L.L. Simpson, The origin, structure , and pharmacological

Nonallergic Eyelid Edema After Botulinum Toxin Type A Injection: Case Report and Review of Literature.

PubMed

Chang, Yin-Shuo; Chang, Chang-Cheng; Shen, Jen-Hsiang; Chen, Yu-Tsung; Chan, Karen Kar-Wun

2015-09-01

Periocular botulinum toxin type A (BoNTA) injections are generally safe. Ptosis is the most common adverse effect, whereas eyelid edema is rarely reported. There is no consensus on the latter's incidence, clinical course, or treatment strategy. Here we managed a 59-year-old woman who received BoNTA injections to her forehead, glabella, and eye corner. At 3-day follow-up, she presented with painless, nonpruritic, bilateral periorbital edema, and erythema. Preliminary diagnosis was a local allergic reaction, and topical corticosteroid was administered, but upon lack of improvement, edema secondary to venous and lymphatic congestion was hypothesized, and she was advised to apply hot pads over her eyes, blink frequently, and massage the area. Her eyelid edema resolved 2 weeks later. At 4-month follow-up, the patient requested and received another course of BoNTA at half the dose. Frequent blinking was instructed, and the patient reported a satisfactory outcome with no adverse effects. In our literature review, incidence of BoNTA-induced eyelid edema was 1.4% and showed Asian tendency. Although rare, BoNTA-induced periorbital edema is self-limiting, and normally resolves in 2 to 4 weeks without medical treatment. Patients at risk for edema, including Asian ethnicity, dermatochalasis, and poor periocular muscle tone, are advised to receive injections at half the dosage. Examination of the function and tone of the orbicularis oculi and levator palpebrae superioris muscles before treatment is recommended, and application of hot pads over the eyes, frequent blinking in the morning, and self-massage of the affected area to increase venous return have demonstrated to improve outcome.

Estimation of nasal shedding and seroprevalence of organisms known to be associated with bovine respiratory disease in Australian live export cattle.

PubMed

Moore, S Jo; O'Dea, Mark A; Perkins, Nigel; O'Hara, Amanda J

2015-01-01

The prevalence of organisms known to be associated with bovine respiratory disease (BRD) was investigated in cattle prior to export. A quantitative reverse transcription polymerase chain reaction assay was used to detect nucleic acids from the following viruses and bacteria in nasal swab samples: Bovine coronavirus (BoCV; Betacoronavirus 1), Bovine herpesvirus 1 (BoHV-1), Bovine viral diarrhea virus 1 (BVDV-1), Bovine respiratory syncytial virus (BRSV), Bovine parainfluenza virus 3 (BPIV-3), Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida. Between 2010 and 2012, nasal swabs were collected from 1,484 apparently healthy cattle destined for export to the Middle East and Russian Federation. In addition, whole blood samples from 334 animals were tested for antibodies to BoHV-1, BRSV, BVDV-1, and BPIV-3 using enzyme-linked immunosorbent assay. The nasal prevalence of BoCV at the individual animal level was 40.1%. The nasal and seroprevalence of BoHV-1, BRSV, BVDV-1, and BPIV-3 was 1.0% and 39%, 1.2% and 46%, 3.0% and 56%, and 1.4% and 87%, respectively. The nasal prevalence of H. somni, M. bovis, M. haemolytica, and P. multocida was 42%, 4.8%, 13.4%, and 26%, respectively. Significant differences in nasal and seroprevalence were detected between groups of animals from different geographical locations. The results of the current study provide baseline data on the prevalence of organisms associated with BRD in Australian live export cattle in the preassembly period. This data could be used to develop strategies for BRD prevention and control prior to loading. © 2014 The Author(s).

Newly Designed Quinolinol Inhibitors Mitigate the Effects of Botulinum Neurotoxin A in Enzymatic, Cell-Based, and ex Vivo Assays.

PubMed

Bremer, Paul T; Adler, Michael; Phung, Cecilia H; Singh, Ajay K; Janda, Kim D

2017-01-12

Botulinum neurotoxin A (BoNT/A) is one of the most deadly toxins and is the etiological agent of the potentially fatal condition, botulism. Herein, we investigated 8-hydroxyquinoline (quinolin-8-ol) as a potential inhibitor scaffold for preventing the deadly neurochemical effects of the toxin. Quinolinols are known chelators that can disrupt the BoNT/A metalloprotease zinc-containing active site, thus impeding its proteolysis of the endogenous protein substrate, synaptosomal-associated protein 25 (SNAP-25). By use of this information, the structure-activity relationship (SAR) of the quinolinol-5-sulfonamide scaffold was explored through preparation of a crude sulfonamide library and evaluation of the library in a BoNT/A LC enzymatic assay. Potency optimization of the sulfonamide hit compounds was undertaken as informed by docking studies, granting a lead compound with a submicromolar K i . These quinolinol analogues demonstrated inhibitory activity in a cell-based model for SNAP-25 cleavage and an ex vivo assay for BoNT/A-mediated muscle paralysis.

Botulinum neurotoxin serotype D attacks neurons via two carbohydrate-binding sites in a ganglioside-dependent manner.

PubMed

Strotmeier, Jasmin; Lee, Kwangkook; Völker, Anne K; Mahrhold, Stefan; Zong, Yinong; Zeiser, Johannes; Zhou, Jie; Pich, Andreas; Bigalke, Hans; Binz, Thomas; Rummel, Andreas; Jin, Rongsheng

2010-10-15

The extraordinarily high toxicity of botulinum neurotoxins primarily results from their specific binding and uptake into neurons. At motor neurons, the seven BoNT (botulinum neurotoxin) serotypes A-G inhibit acetylcholine release leading to flaccid paralysis. Uptake of BoNT/A, B, E, F and G requires a dual interaction with gangliosides and the synaptic vesicle proteins synaptotagmin or SV2 (synaptic vesicle glycoprotein 2), whereas little is known about the cell entry mechanisms of the serotypes C and D, which display the lowest amino acid sequence identity compared with the other five serotypes. In the present study we demonstrate that the neurotoxicity of BoNT/D depends on the presence of gangliosides by employing phrenic nerve hemidiaphragm preparations derived from mice expressing the gangliosides GM3, GM2, GM1 and GD1a, or only GM3 [a description of our use of ganglioside nomenclature is given in Svennerholm (1994) Prog. Brain Res. 101, XI-XIV]. High-resolution crystal structures of the 50 kDa cell-binding domain of BoNT/D alone and in complex with sialic acid, as well as biological analyses of single-site BoNT/D mutants identified two carbohydrate-binding sites. One site is located at a position previously identified in BoNT/A, B, E, F and G, but is lacking the conserved SXWY motif. The other site, co-ordinating one molecule of sialic acid, resembles the second ganglioside-binding pocket (the sialic-acid-binding site) of TeNT (tetanus neurotoxin).

The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin*

PubMed Central

Romes, Erin M.; Sobhany, Mack; Stanley, Robin E.

2016-01-01

The synthesis of eukaryotic ribosomes is a complex, energetically demanding process requiring the aid of numerous non-ribosomal factors, such as the PeBoW complex. The mammalian PeBoW complex, composed of Pes1, Bop1, and WDR12, is essential for the processing of the 32S preribosomal RNA. Previous work in Saccharomyces cerevisiae has shown that release of the homologous proteins in this complex (Nop7, Erb1, and Ytm1, respectively) from preribosomal particles requires Rea1 (midasin or MDN1 in humans), a large dynein-like protein. Midasin contains a C-terminal metal ion-dependent adhesion site (MIDAS) domain that interacts with the N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 as well as the UBL domain of Rsa4/Nle1 in a later step in the ribosome maturation pathway. Here we present the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at 1.7 Å resolution and demonstrate that human midasin binds to WDR12 as well as Nle1 through their respective UBL domains. Midasin contains a well conserved extension region upstream of the MIDAS domain required for binding WDR12 and Nle1, and the interaction is dependent upon metal ion coordination because removal of the metal or mutation of residues that coordinate the metal ion diminishes the interaction. Mammalian WDR12 displays prominent nucleolar localization that is dependent upon active ribosomal RNA transcription. Based upon these results, we propose that release of the PeBoW complex and subsequent release of Nle1 by midasin is a well conserved step in the ribosome maturation pathway in both yeast and mammalian cells. PMID:26601951

Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B.

PubMed

Masuyer, Geoffrey; Beard, Matthew; Cadd, Verity A; Chaddock, John A; Acharya, K Ravi

2011-04-01

Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inhibiting neurotransmission at cholinergic nerve terminals. BoNTs consist of three essential domains for toxicity: the cell binding domain (Hc), the translocation domain (Hn) and the catalytic domain (LC). A functional derivative (LHn) of the parent neurotoxin B composed of Hn and LC domains was recombinantly produced and characterised. LHn/B crystallographic structure at 2.8Å resolution is reported. The catalytic activity of LHn/B towards recombinant human VAMP was analysed by substrate cleavage assay and showed a higher specificity for VAMP-1, -2 compared to VAMP-3. LHn/B also showed measurable activity in living spinal cord neurons. Despite lacking the Hc (cell-targeting) domain, LHn/B retained the capacity to internalize and cleave intracellular VAMP-1 and -2 when added to the cells at high concentration. These activities of the LHn/B fragment demonstrate the utility of engineered botulinum neurotoxin fragments as analytical tools to study the mechanisms of action of BoNT neurotoxins and of SNARE proteins. Copyright © 2010 Elsevier Inc. All rights reserved.

Recombinant Botulinum Neurotoxin Hc Subunit (BoNT Hc) and Catalytically Inactive Clostridium botulinum Holoproteins (ciBoNT HPs) as Vaccine Candidates for the Prevention of Botulism

PubMed Central

Webb, Robert P.; Smith, Theresa J.; Smith, Leonard A.; Wright, Patrick M.; Guernieri, Rebecca L.; Brown, Jennifer L.; Skerry, Janet C.

2017-01-01

There are few available medical countermeasures against botulism and the discontinuation of the pentavalent botulinum toxoid vaccine by the Centers for Disease Control and Prevention in 2011 has resulted in the need for a safe and effective prophylactic alternative. Advances in genetic engineering have resulted in subsequent vaccine efforts being primarily focused on the production of highly purified recombinant protein antigens representing one or more domains of the botulinum neurotoxin. Recombinant subunit vaccines based on the carboxy one-third of the toxin (Hc) developed in our lab against serotypes A-F have been shown to be safe and effective. However, in response to the identification of an ever increasing number of BoNT subtypes with significant amino acid heterogeneity, we have developed catalytically inactive BoNT holoproteins (ciBoNT HPs) in an attempt to elicit greater protective immunity to address these toxin variants. Here we report the production of ciBoNT/B1 HP, ciBoNT/C1 HP, ciBoNT/E1 HP and ciBoNT/F1 HP and compare the immunological and protective abilities of ciBoNT HPs and BoNT/A Hc, BoNT/B Hc, BoNT/C Hc, BoNT/E Hc and BoNT/F Hc vaccines when challenged with homologous and heterologous toxins. Our results suggest the ciBoNT HP vaccines exhibit superior potency after single vaccinations but multiple vaccinations with BoNT/Hc antigens resulted in increased survival rates at the toxin challenge levels used. PMID:28869522

Structural and luminescence studies on Dy3+ doped lead boro-telluro-phosphate glasses

NASA Astrophysics Data System (ADS)

Selvi, S.; Venkataiah, G.; Arunkumar, S.; Muralidharan, G.; Marimuthu, K.

2014-12-01

This paper reports results obtained on the structural and luminescence properties of Dy3+doped lead boro-telluro-phosphate glasses prepared following the melt quenching technique. FTIR spectra exhibit the presence of B-O vibrations, P-O-P symmetric vibrations and Te-O stretching modes of TeO3 and TeO6 units. The metal-ligand bond was identified through UV-vis-NIR absorption spectra and to determine the band tailing parameter, direct and indirect band gap energy of the prepared glasses. The Judd-Ofelt (JO) intensity parameters (Ω2, Ω4 and Ω6), experimental and theoretical oscillator strengths were also determined and reported. Luminescence measurements were made to determine the transition probability (A), stimulated emission cross-section (σPE) and branching ratio (βR) for the transitions that include 4F9/2→6H11/2, 6H13/2 and 6H15/2 bands. The effect of Dy3+ ion concentration on the intensity ratio of yellow to blue emission bands has also been studied and reported. The lifetime corresponding to the 4F9/2 level of the title glasses has been found to decrease with the increase in Dy3+ ion concentration. The chromaticity coordinates (x,y) have been estimated from the luminescence spectra and the suitability of title glasses for white light applications has been analyzed using CIE chromaticity diagram. The variation of optical properties with the concentration of dysprosium oxide content in the glasses have been studied and reported.

Mapping giant mass transport deposits (MTDs) for delineating the extended Continental Shelf of Spain to the West of Canary Islands according UNCLOS Art. 76

NASA Astrophysics Data System (ADS)

Somoza, Luis; Medialdea, Teresa; León, Ricardo; Vázquez, Juan T.; González, Javier; Palomino, Desiree; González-Aller, Daniel; Fernández-Salas, Luis M.; Espinosa, Salvador

2017-04-01

On 19 December 2014, Spain presented a third partial submission for the delineation of the Extended Continental in the area west of the Canary Islands to the Commission on the Limits of the Continental Shelf (CLCS) according to the United Nations Convention on the Law of Sea (UNCLOS). The Canary Islands are located within a NE-SW 1,350 km long ridge of hotspot-inferred volcanic islands and seamounts (composed by more of 100, from Lars to Tropic seamounts). This submission has been documented with an extensive dataset specifically obtained for the project during ten oceanographic cruises between 2010 and 2014 aboard the Spanish research vessels Hespérides, Sarmiento de Gamboa and Miguel Oliver. This new dataset allows to investigate an area of 440,000 km2 with acoustic backscatter images and multibeam echosounder bathymetric (MBES) data (Simrad EM-12, EM-120 and EM-302, and Atlas HYDROSWEEP DS), a dense network of 65,800 km of very-high resolution (VHR) seismic lines (including chirp parametric source TOPAS PS-18 and Atlas PARASOUND P-35) and 4,471 km of multichannel seismic reflection lines (MCS) acquired with an array of air-guns yielding a total volume of 4,600 inch3 (75.38 L) and a 3,500 m long streamer composed of 280 channels. In order to determine the Foot of Slope (FoS), the Base of Slope (BoS) region has been traced following geomorphological arguments based on the morphology of the mass transport deposits (MTDs) extended downslope west of the Canary Islands. Based on backscatter and MBEs mapping, and VHR lines, the BoS has been traced by means of a detailed mapping of the debris flow deposits widespread along the slope. Therefore, the seaward limit of the BoS has been traced following the termination of the debris flow sourced from the Canary Island. Otherwise, the landward limit of the BoS has been defined following the morphological changes in the debris flow forced by the breaking in the slope gradient, which form distributary lobes downslope. Finally, the Foot of Slope (FoS) has been determined on the basis of MBES profiles at the maximum change in gradient (MCG) within the BoS region, according to Art. 76(4b). Some FoS points coincide with morphological features formed at the end of the debris flow lobes, but MCG have been only determined after calculation of the second derivative of the MBES bathymetry. The database and mapping carried out for this submission offers new insights on the morphology of deep-water giant submarine landslides triggered by hotspot-induced massive collapse/volcanic events in the central eastern Atlantic Ocean. Acknowledgments: Project for the Extension of the Spanish Continental according UNCLOS (CTM2010-09496-E) and Projects CGL2012-39524-C02 and CTM2016-75947-R.

Soy Biodiesel Emissions Have Reduced Inflammatory Effects ...

EPA Pesticide Factsheets

Toxicity of exhaust from combustion of petroleum diesel (BO), soy-based biodiesel (B100), or a 20% biodiesel/80% petrodiesel mix (B20) was compared in healthy and house dust mite (HDM)-allergic mice. Fuel emissions were diluted to target fine particulate matter (PM2.5) conrentrations of 50, 150, or 500 µg/m(3). Studies in healthy mice showed greater levels of neutrophils and MIP-2 in bronchoaeolar lavage (BAL) fluid 2 h after a single 4-h exposure to BO compared with mice exposed to B20 or B100. No consistent differences in BAL cells and biochemistry, or hematological parameters, were observed after 5 d or 4 weeks of exposure to any of the emissions. Air-exposed HDM-allergc mice had significantly increased responsiveness to methacholine aerosol challenge compared with non-allergic mice. Exposure to any of the emissions for 4 weeks did not further increase responsiveness in either non-allergic or HDM­ allergic mice, and few parameters of allergic inflammation in BAL fluid were altered. Lung and nasal pathology were not significantly different among BO-, B20-, or B100-exposed groups. In HDM-allergic mice, exposure to BO, but not B20 or B100, significantly increased resting peribronchiolar lymph node cell proliferation and production of TH2 cytokines (IL-4, IL-5, and IL-13) and IL-17 in comparison with air-exposed allergic mice. These results suggest that diesel exhaust at a relatively high concentration (500 µg/m(3)) can induce inflammation acutely in healthy m

The influence of physical therapy and anti-botulinum toxin antibody on the efficacy of botulinum toxin-A injections in children with spastic cerebral palsy.

PubMed

Jang, Dae-Hyun; Sung, In Young

2014-12-01

To identify factors associated with the efficacy of botulinum toxin-A (BoNT-A) injections. Thirty-eight children with spastic cerebral palsy (CP) received BoNT-A injections into the gastrocnemius. The baseline anti-botulinum antibodies were checked. The Static dorsiflexion range of motion (ROM), Modified Tardieu Scale (MTS) and Physician Rating Scale (PRS) were assessed at pre-injection as well as 4- and 12-week post-injection. No samples contained anti-botulinum antibodies. Greater baseline MTS dynamic range was associated with greater changes in MTS dynamic ranges at 4-week post-injection. More frequent physical therapy was associated with greater changes in static dorsiflexion ROM at 4-week post-injection and greater changes in PRS at 4- and 12-week post-injection. The improvement in PRS at 12-week post-injection was associated with the frequency of physical therapy. Therefore, intensive physical therapy programs may be necessary to maintain the beneficial effects of BoNT-A injections in children with CP.

Effect of Fill Temperature on Clostridium botulinum Type A Toxin Activity during the Hot Filling of Juice Bottles.

PubMed

Skinner, Guy E; Fleischman, Gregory J; Balster, Fran; Reineke, Karl; Reddy, N Rukma; Larkin, John W

2015-08-01

The potential threat of terrorist attacks against the United States food supply using neurotoxin produced by Clostridium botulinum (BoNT) has resulted in the need for studying the effect of various food process operations on the bioavailability of this toxin. The objective of this study was to evaluate C. botulinum type A neurotoxin bioavailability after a simulated hot fill juice bottling operation. C. botulinum type A acid mud toxin (∼10(6) mouse lethal dose [MLD50]/ml) was deposited into juice bottles at an experimentally determined fastest cooling spot. Bottles (12 or 20 oz [355 and 592 ml]) were filled with either apple juice or an orange drink, at 80 or 85°C, in either upright or inverted orientations. Toxicity of the juice was evaluated as a function of holding time (1 to 2 min) by the mouse bioassay. The fastest cooling point in the upright orientation was determined to be at a bottle's bottom rim. In the inverted orientation, the fastest cooling point was in the bottle cap region. With respect to these two points, the upright bottle cooled faster than the inverted bottle, which was reflected in a higher inactivation of BoNT in the latter. For the orange drink (pH 2.9) toxicity was reduced by 0.5 × 10(6) MLD50/ml to a nondetectable level after 1 min in all bottle sizes, orientations, and temperatures as measured by the mouse bioassay. This indicates that there was at least a 0.5 × 10(6) MLD50/ml reduction in activity. Inactivation in apple juice (pH 4.0), to the same degree as in the orange drink, was found only for the inverted orientation at 85°C. Complete inactivation in apple juice for all conditions was found at a lower added toxin level of 0.25 × 10(5) MLD50/ml. In general, bottle inversion and filling at 85°C provided complete inactivation of BoNT to the 0.5 × 10(6) MLD50/ml level. All experiments resulted in the inactivation of 2.5 × 10(4) MLD50/ml of BoNT regardless of juice type, fill temperature, or bottle orientation and size.

Time-dependent wellbore breakout growth caused by drilling-induced pore pressure transients: Implications for estimations of far field stress magnitude

NASA Astrophysics Data System (ADS)

Olcott, K. A.; Saffer, D. M.; Elsworth, D.

2013-12-01

One method used to constrain principal stress orientations and magnitudes in the crust combines estimates of rock strength with observations of wellbore failures, including drilling-induced tensile fractures (DITF) and compressional borehole breakouts (BO). This method has been applied at numerous Integrated Ocean Drilling Program (IODP) boreholes drilled into sediments in a wide range of settings, including the Gulf of Mexico, the N. Japan and Costa Rican subduction margins, and the Nankai Trough Accretionary Prism. At Nankai and N. Japan, BO widths defined by logging-while-drilling (LWD) resistivity images have been used to estimate magnitudes of far-field horizontal tectonic stresses. At several drillsites (C0010, C0002, and C0011), sections of the borehole were relogged with LWD after the hole was left open for times ranging from ~30 min to 3 days; times between acquisition were associated with pipe connections (~30 min), cleaning and circulating the hole (up to ~3 hr), and evacuation of the site for weather (~3 days). Relogged portions exhibit widening of BO, hypothesized to reflect time-dependent re-equilibration of instantaneous changes in pore fluid pressure (Pf) induced by opening the borehole. In this conceptual model, Pf decrease caused by initial excavation of the borehole and resulting changes in the state of stress at the borehole wall lead to an initial strengthening of the sediment. Re-equilibration of Pf results in time-dependent weakening of the sediment and subsequent BO growth. If correct, this hypothesis implies that stress magnitudes estimated by BO widths could be significantly underestimated. We test this idea using a finite-element model in COMSOL multiphysics that couples fluid flow and deformation in a poroelastic medium. We specify far-field horizontal principal stresses (SHmax and Shmin) in the model domain. At the start of simulations/at the time of borehole opening, we impose a decreased stress at the borehole wall. We consider a range of sediment permeability from 10-18 m2 to 10-14 m2. We find Pf initially increases at the borehole wall over a range of azimuths +/-~60° from Shmin, with a maximum increase of 10 MPa (4.4% of the maximum principal stress (σ1) at the borehole wall) and would lead to weakening of the rock. Pf decreases over a range of azimuths +/- ~30° from SHmax, with a maximum decrease of 10 MPa (8.8% of σ1), leading to initial strengthening of the rock. Evolution of Pf depends strongly on sediment permeability: Pf is 90% equilibrated at the borehole wall in ~43 minutes for a permeability of 10-18 m2, whereas for a permeability of 10-14 m2, Pf equilibrates nearly instantaneously. Since BO form parallel to Shmin, BO growth driven by drilling-induced Pf changes require that the initial BO be wider than ~120°, or outside the zone of initially increased Pf. This is not consistent with observations of BO growth, where initial BO are 0-25° and grow up to 125°. In contrast, our results imply that analyses based on BO measured immediately after drilling could overestimate far-field stresses because the BO are formed in sediments weakened by poroelastic pressure changes. Future work will focus on systematic investigation of the role of far field stresses and different sediment rheologies on the distribution of pore pressure change around the wellbore.

Pilot Study of Topical Acetyl Hexapeptide-8 in Treatment of Blepharospasm in Patients Receiving Botulinum Neurotoxin Therapy

PubMed Central

Lungu, Codrin; Considine, Elaine; Zahir, Sana; Ponsati, Berta; Arrastia, Silvia; Hallett, Mark

2016-01-01

Background Injectable botulinum neurotoxin (BoNT) is the principal effective treatment for blepharospasm (BSP). This trial explores the safety and efficacy of topical Acetyl Hexapeptide-8 (AH8), a competitive SNAP25 inhibitor, as a potential new therapy in BSP. Methods Double-blind, placebo-controlled, randomized trial of daily topical application of AH8 in 24 patients with BSP. The primary outcome was time to return to baseline Jankovic Rating Scale (JBRS) after a BoNT injection simultaneously with initiation of AH8. Patients displaying a strictly regular pattern of response to 3-monthly injections of BoNT were included. Results There were no significant adverse events. There was a trend for longer time until return to baseline JBRS after injection in the active group compared to placebo (3.7 vs 3.0 months), and for better scores in the active group. One third (4/12) of the patients in the active group had a significant extension of symptom control after BoNT (range: 3.3-7.1 months). Conclusions Topical AH8 is safe and promising for extending the duration of action of BoNT therapy for BSP. PMID:23146065

BoLA class I polymorphism and in vitro immune response to M. bovis antigens.

PubMed

Longeri, M; Polli, M; Ponti, W; Zanotti, M

1993-01-12

From a sample of 119 Friesian calves, serologically typed for BoLA class I, 47 subjects were chosen expressing 9 different MHC types (A6, A6.9, A10, A11, A14, A15, A30, W16, M103) with the same age and reared in the same farm conditions. The animals were s.c. injected with a water in oil suspension of killed M. bovis and the treatment was repeated two days later. Before the treatment and 21 days later, calves were bled and on PBM (peripheral blood mononuclear leucocytes) were performed the following tests: 1. Lymphocyte Stimulation with bovine and avian PPDs (Purified protein derivative of Mycobacterium bovis and Mycobacterium avium, respectively). 2. Phagocytic activity towards M. bovis. 3. Class II molecules expression on cell surface. 4. Percentage of leucocyte populations and subpopulations. In the in vitro Lymphocyte Stimulation test, all the animals and classes were responders. Animals bearing A10 BoLA class I presented c.p.m. (counts per minute) and index values higher than the other cattle; these values were significantly positively related both to bovine and avian PPDs (P < .01). By variance analysis A14 BoLA type showed a slight positive significant correlation with more efficient phagocytic activity. BoLA class I type did not seem to significantly affect percentage of class II positive cells and leucocyte percentages on PBM. ZUSAMMENFASSUNG: Der BoLA Klasse I Polymorphismus und in vitro immunologische Antwort gegen die Antigene von M. bovis Aus einer Stichprobe von 119 für BoLA Klasse I serologisch typisierten Friesian Kälber, wurden 47 Subjekte ausgewählt, die 9 verschiedene MHC Typen ausdrückten (A6, A6.9, A10, A11, A14, A15, A30, W16, M103). Alle waren gleich alt und in gleichen Haltungsbedingungen. Die Tiere wurden mit einer Wasser-in-Ol Suspension abgetöteter M. bovis subkutan injiziert und die Behandlung nach zwei Tagen wiederholt. Vor und 21 Tage nach Behandlung wurden die folgenden Tests ausgeführt: 1. Lymphozyten-Stimulationstest mit bovinen und Geflügel PPDs. 2. Phagozyten Aktivität gegen M. bovis. 3. Zeil-Oberflächen, Expression der Klasse II Moleküle. 4. Anteile der Lymphozyten Populationen und Subpopulationen. Im in vitro Lymphozyten-Stimulationstest waren alle Tiere und Klassen responder. Tiere mit A10 BoLA I zeigten höhere c.p.m. und Indexwerte als die anderen; diese Werte waren in signifikant positiver Beziehung mit der PPD von M. bovis und auch mit M. avium (P < .01). BoLA Typ A14 zeigte leicht signifikant positive Korrelation mit wirksamerer Phagozyten Aktivität. BoLA Klasse I Typ scheint nicht den Prozentsatz der positiven Zellen der Klasse II und der Leukozyten der PBM signifikant zu beeinflussen. RESUMEN: Polimorfismo de BoLA clase I y immunidad a los antigenos del M. bovis Se escojeron 47 novillos dentro de un grupo de 119 animales que segun analisis previamente hecha tenian BoLA de clase I. Estos 47 novillos fueron escojidos de manera que tuvieran 9 distintos tipos de MHC (A6, A6.9, A10, A11, A14, A15, A30, W16, M103), la misma edad, las mismas condiciones de cria. Estos animales fueron inoculados subcutaneo con M. bovis matados en una suspension oleosa y la misma inoculacion fue repetida una secunda vez despues de dos dias. Por cada animal se tomaron muestras de sangre antes y 21 dias despues de la inoculacion de arriba. Las muestras de sangre fueron pruebaoas con: 1. Stimulacion Lymhocitaria con PPD bovina y avicola. 2. Actividad phagocitaria a M. bovis. 3. Expresion sobre la superficie celular de moleculas de clase II. 4. Porcentaje de poblaciones y de subpob-laciones de leucocitos. Todos los animales y todos los tipos de MHC dieron respuestas positivas en las pruebas de Stimulacion Lymphocitaria. Los animales que tenian la BoLA A10 presentaron valores de c.p.m. y indices mas altos de los demas animales. Estos valores se encontraron significativamente y positivamente relacionados sea a la PPD bovina que a la PPD avicola. Por medio de la analisis de varianzas se encontro que el tipo BoLA A14 muestraba una correlacion significativa y algo positiva con una mejor actividad fagocitaria. Los tipos de clase BoLA I no parecieron que influenzaran de manera appreciable el porcentaje de positividad por la clase II y el porcentaje de leucocitos en la sangre PBM. 1993 Blackwell Verlag GmbH.

Synthesis and photoluminescence characteristics of (Y,Gd)BO3:RE (RE = Eu(3+), Ce(3+), Dy(3+) and Tb(3+)) phosphors for blue chip and near-UV white LEDs.

PubMed

Rangari, V V; Singh, V; Dhoble, S J

2016-03-01

A series of Eu(3+)-, Ce(3+)-, Dy(3+)- and Tb(3+)-doped (Y,Gd)BO3 phosphors was synthesized by a solid-state diffusion method. X-Ray diffraction confirmed their hexagonal structure and the scanning electron microscopy results showed crystalline particles. The excitation spectra revealed that (Y,Gd)BO3 phosphors doped with Eu(3+), Ce(3+), Dy(3+) and Tb(3+) are effectively excited with near UV-light of 395 nm/blue light, 364, 351 and 314 nm, respectively. Photoluminescence spectra of Eu(3+)-, Ce(3+)- and Tb(3+)/Dy(3+)-doped phosphor showed intense emission of reddish orange, blue and white light, respectively. The phosphor Y0.60Gd0.38BO3:Ce0.02 showed CIE 1931 color coordinates of (0.158, 0.031) and better color purity compared with commercially available blue BAM:Eu(2+) phosphor. The phosphor (Y,Gd)BO3 doped with Eu(3+), Dy(3+) and Tb(3+) showed CIE 1931 color coordinates of (0.667, 0.332), (0.251, 0.299) and (0.333, 0.391) respectively. Significant photoluminescence characteristics of the prepared phosphors indicate that they might serve as potential candidates for blue chip and near-UV white light-emitting diode applications. Copyright © 2015 John Wiley & Sons, Ltd.

The thioredoxin reductase--Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles.

PubMed

Pirazzini, Marco; Azarnia Tehran, Domenico; Zanetti, Giulia; Lista, Florigio; Binz, Thomas; Shone, Clifford C; Rossetto, Ornella; Montecucco, Cesare

2015-12-01

Botulinum neurotoxins (BoNTs) are Janus toxins, as they are at the same time the most deadly substances known and one of the safest drugs used in human therapy. They specifically block neurotransmission at peripheral nerves through the proteolysis of SNARE proteins, i.e. the essential proteins which are the core of the neuroexocytosis machinery. Even if BoNTs are traditionally known as seven main serotypes, their actual number is much higher as each serotype exists in many different subtypes, with individual biological properties and little antigenic relations. Since BoNTs can be used as biological weapons, and the only currently available therapy is based on immunological approaches, the existence of so many different subtypes is a major safety problem. Nevertheless, all BoNT isoforms are structurally similar and intoxicate peripheral nerve endings via a conserved mechanism. They consist of two chains linked by a unique disulphide bond which must be reduced to enable their toxicity. We found that thioredoxin 1 and its reductase compose the cell redox system responsible for this reduction, and its inhibition via specific chemicals significantly reduces BoNTs activity, in vitro as well as in vivo. Such molecules can be considered as lead compounds for the development of pan-inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Repeated onabotulinumtoxin-a injections provide better results than single injection in treatment of painful bladder syndrome.

PubMed

Kuo, Hann-Chorng

2013-01-01

Onabotulinumtoxin-A (BoNT-A) is effective for the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS). However, long-term follow-up does not show successful outcome after a single injection. To evaluate the efficacy and safety of repeated intravesical BoNT-A injections for treatment of IC/PBS and compare the success rates among patient groups receiving different injection numbers. Prospective interventional study. Tertiary medical center. Intravesical injection of 100 U of BoNT-A was performed in 81 patients every 6 months for up to 4 times or until patients' symptoms significantly improved. Patients who received a single injection served as active controls. Measured parameters included O'Leary-Sant symptom indexes (ICSI) and problem indexes (ICPI), visual analogue score (VAS) for pain, voiding diary variables, urodynamic parameters, maximal bladder capacity under anesthesia, glomerulation grade, and global response assessment. Multiple measurements and Kaplan-Meier analysis were used for comparison of consecutive data and success rates among groups. Among 81 patients, 20 received single injections, 19 received 2 injections, 12 received 3 injections, and 30 received 4 injections. The mean (± standard deviation) of ICSI, ICPI, total scores, VAS, functional bladder capacity, and daytime frequency all showed significant improvement after repeated BoNT-A treatment with different injections. Significantly better success rates were noted in patients who received 4 repeated injections (P = 0.0242) and 3 injections (P = 0.050), compared to those who received a single injection. However, there was no significant difference of long-term success rates among patients who received 2, 3, and 4 injections. Lack of placebo control group is the main limitation. Repeated intravesical BoNT-A injections were safe and effective for pain relief and they increased bladder capacity and provided a better long-term success rate than a single injection did for treatment of IC/PBS.

Prognostic influence of Barrett's oesophagus and Helicobacter pylori infection on healing of erosive gastro-oesophageal reflux disease (GORD) and symptom resolution in non-erosive GORD: report from the ProGORD study.

PubMed

Malfertheiner, P; Lind, T; Willich, S; Vieth, M; Jaspersen, D; Labenz, J; Meyer-Sabellek, W; Junghard, O; Stolte, M

2005-06-01

Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase. Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett's oesophagus (BO). Data from 6215 patients were included in the "intention to treat" analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4-8 weeks for endoscopic healing while NERD patients received 20 mg for 2-4 weeks for resolution of heartburn symptoms. Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in Helicobacter pylori negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only H pylori infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for H pylori positive and H pylori negative, respectively; p = 0.03). The presence of Barrett's mucosa, as well as severe mucosal damage, exerts a negative impact on healing. H pylori infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.

THE α-GLYCEROPHOSPHATE CYCLE IN DROSOPHILA MELANOGASTER

PubMed Central

O'Brien, Stephen J.; Shimada, Yoshio

1974-01-01

"Null" mutations previously isolated at the αGpdh-1 locus of Drosophila melanogaster, because of disruption of the energy-producing α-glycerophosphate cycle, severely restrict the flight ability and relative viability of affected individuals. Two "null" alleles, αGpdh-1 BO-1-4, and αGpdh-1 BO-1-5, when made hemizygous with a deficiency of the αGpdh-1 locus, Df(2L)GdhA, were rendered homozygous by recombination with and selective elimination of the Df(2L)GdhA chromosome. After over 25 generations, a homozygous αGpdh-1 BO-1-4 stock regained the ability to fly despite the continued absence of measurable αGPDH activity. Inter se heterozygotes of three noncomplementing αGpdh-1 "null" alleles and the "adapted" αGpdh-1 BO-1-4 homozygotes were examined for metabolic enzymatic activities related to the energy-producing and pyridine nucleotide-regulating functions of the α-glycerophosphate cycle in Drosophila. The enzyme functions tested included glyceraldehyde-3-phosphate dehydrogenase, cytoplasmic and soluble malate dehydrogenase, lactate dehydrogenase, mitochondrial NADH oxidation, oxidative phosphorylation, and respiratory control with the substrates α-glycerophosphate, succinate, and pyruvate. These activities in any of the mutant genotypes in early adult life were indistinguishable from those in the wild type. There was, however, a premature deterioration and atrophy of the ultrastructural integrity of flight muscle sarcosomes observed by electron microscopy in the "null" mutants. These observations were correlated with a decrease in state 3 mitochondrial oxidation with α-glycerophosphate, succinate, and pyruvate, as well as with loss of respiratory control in adults as early as 2 wk after eclosion. Such observations, which normally are seen in aged dipterans, were accompanied by premature mortality of the mutant heterozygotes. The adapted αGpdh-1 BO-1-4 was identical with wild type in each of the aging characters with the single exception of lowered rates of mitochondrial oxidative phosphorylation. PMID:4154945

Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.

PubMed

Cheng, Luisa W; Henderson, Thomas D

2011-07-01

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.

Colorless chlorophyll catabolites in senescent florets of broccoli (Brassica oleracea var. italica).

PubMed

Roiser, Matthias H; Müller, Thomas; Kräutler, Bernhard

2015-02-11

Typical postharvest storage of broccoli (Brassica oleracea var. italica) causes degreening of this common vegetable with visible loss of chlorophyll (Chl). As shown here, colorless Chl-catabolites are generated. In fresh extracts of degreening florets of broccoli, three colorless tetrapyrrolic Chl-catabolites accumulated and were detected by high performance liquid chromatography (HPLC): two "nonfluorescent" Chl-catabolites (NCCs), provisionally named Bo-NCC-1 and Bo-NCC-2, and a colorless 1,19-dioxobilin-type "nonfluorescent" Chl-catabolite (DNCC), named Bo-DNCC. Analysis by nuclear magnetic resonance spectroscopy and mass spectrometry of these three linear tetrapyrroles revealed their structures. In combination with a comparison of their HPL-chromatographic properties, this allowed their identification with three known catabolites from two other brassicacea, namely two NCCs from oil seed rape (Brassica napus) and a DNCC from degreened leaves of Arabidopsis thaliana.

Investigation of Extensions to the Distorted Born Approximation in Strong Fluctuation Theory

DTIC Science & Technology

1988-10-01

9316I * where D = 3/4[bop+b# J+ l/4b;) D = 1/4[ bpp +bo | (35)n12 b -bo( I D 13 =l/ 2 [Cppzz +C4zzI n Here -1 0~ o , bus(z,z)= (271) u I dl )acs (zl) am...that FXW = 1- 2X + 32. + 1 2(X) = 2 - 23 + + ... (-5 F (X) = 2 3 3 42 3 ’ + VX +.. D5 F3 (X) = 2/X + 3 gn X + ... Using (D-4) and (D-5) as guides for...showed that the rational approximations to Fir F2, F3 have maximum errors of .06%, .03%, and .06%, respectively. The integrals in (C-5) are completely

Air-Sea and Lateral Exchange Processes in East Indian Coastal Current off Sri Lanka

DTIC Science & Technology

2015-09-30

moorings to shed light on the spatial structure of the upper layer currents in the area associated with southwest monsoons. C. CTD and ADCP...thermohaline profiles (Fig. 4a). Figure 3. The weekly composite (June 30 – July 3) image of the BoB ocean color, showing enhanced chlorophyll ...measurements. The depth- averaged (between z = 21 and 141m) velocity magnitude is shown by black line; a polynomial approximation of these fluctuations is in

Naturally tuned quantum critical point in the S =1 kagomé YCa3(VO) 3(BO3)4

NASA Astrophysics Data System (ADS)

Silverstein, Harlyn J.; Sinclair, Ryan; Sharma, Arzoo; Qiu, Yiming; Heinmaa, Ivo; Leitmäe, Alexander; Wiebe, Christopher R.; Stern, Raivo; Zhou, Haidong

2018-04-01

Although S =1 /2 kagomé systems have been intensely studied theoretically, and within the past decade been realized experimentally, much less is known about the S =1 analogs. While the theoretical ground state is still under debate, it has been found experimentally that S =1 kagomé systems either order at low temperatures or enter a spin glass state. In this work, YCa3(VO) 3(BO3)4 (YCVBO) is presented, with trivalent vanadium. Owing to its unusual crystal structure, the metal-metal bonding is highly connected along all three crystallographic directions, atypical of other kagomé materials. Using neutron scattering it is shown that YCVBO fails to order down to at least 50 mK and exhibits broad and dispersionless excitations. 11B NMR provides evidence of fluctuating spins at low temperatures while dc magnetization shows critical scaling that is also observed in systems near a quantum critical point such as Herbertsmithite, despite its insulating nature and S =1 magnetism. The evidence shown indicates that YCVBO is naturally tuned to be a quantum disordered magnet in the limit of T =0 K.

Crystallographic control on the boron isotope paleo-pH proxy

NASA Astrophysics Data System (ADS)

Noireaux, J.; Mavromatis, V.; Gaillardet, J.; Schott, J.; Montouillout, V.; Louvat, P.; Rollion-Bard, C.; Neuville, D. R.

2015-11-01

When using the boron isotopic composition (δ11B) of marine carbonates as a seawater pH proxy, it is assumed that only the tetrahedral borate ion is incorporated into the growing carbonate crystals and that no boron isotope fractionation occurs during uptake. However, the δ11B of the calcium carbonate from most modern foraminifera shells or corals skeletons is not the same as the δ11B of seawater borate, which depends on pH, an observation commonly attributed to vital effects. In this study, we combined previously published high-field 11B MAS NMR and new δ11B measurements on the same synthetic calcite and aragonite samples precipitated inorganically under controlled environments to avoid vital effects. Our results indicate that the main controlling factors of δ11B are the solution pH and the mineralogy of the precipitated carbonate mineral, whereas the aqueous boron concentration of the solution, CaCO3 precipitation rate and the presence or absence of growth seeds all appear to have negligible influence. In aragonite, the NMR data show that boron coordination is tetrahedral (BO4), in addition, its δ11B is equal to that of aqueous borate, thus confirming the paleo-pH hypothesis. In contrast, both trigonal BO3 and tetrahedral BO4 are present in calcite, and its δ11B values are higher than that of aqueous borate and are less sensitive to solution pH variations compared to δ11B in aragonite. These observations are interpreted in calcite as a reflection of the incorporation of decreasing amounts of boric acid with increasing pH. Moreover, the fraction of BO3 measured by NMR in calcite is higher than that inferred from δ11B which indicates a coordination change from BO4 to BO3 upon boron incorporation in the solid. Overall, this study shows that although the observed differences in δ11B between inorganic and biological aragonite are compatible with a pH increase at calcification sites, the B speciation and isotope composition of biological calcites call for a more complex mechanism of boron incorporation.

Genetics and fine mapping of a purple leaf gene, BoPr, in ornamental kale (Brassica oleracea L. var. acephala).

PubMed

Liu, Xiao-Ping; Gao, Bao-Zhen; Han, Feng-Qing; Fang, Zhi-Yuan; Yang, Li-Mei; Zhuang, Mu; Lv, Hong-Hao; Liu, Yu-Mei; Li, Zhan-Sheng; Cai, Cheng-Cheng; Yu, Hai-Long; Li, Zhi-Yuan; Zhang, Yang-Yong

2017-03-14

Due to its variegated and colorful leaves, ornamental kale (Brassica oleracea L. var. acephala) has become a popular ornamental plant. In this study, we report the fine mapping and analysis of a candidate purple leaf gene using a backcross population and an F 2 population derived from two parental lines: W1827 (with white leaves) and P1835 (with purple leaves). Genetic analysis indicated that the purple leaf trait is controlled by a single dominant gene, which we named BoPr. Using markers developed based on the reference genome '02-12', the BoPr gene was preliminarily mapped to a 280-kb interval of chromosome C09, with flanking markers M17 and BoID4714 at genetic distances of 4.3 cM and 1.5 cM, respectively. The recombination rate within this interval is almost 12 times higher than the usual level, which could be caused by assembly error for reference genome '02-12' at this interval. Primers were designed based on 'TO1000', another B. oleracea reference genome. Among the newly designed InDel markers, BRID485 and BRID490 were found to be the closest to BoPr, flanking the gene at genetic distances of 0.1 cM and 0.2 cM, respectively; the interval between the two markers is 44.8 kb (reference genome 'TO1000'). Seven annotated genes are located within the 44.8 kb genomic region, of which only Bo9g058630 shows high homology to AT5G42800 (dihydroflavonol reductase), which was identified as a candidate gene for BoPr. Blast analysis revealed that this 44.8 kb interval is located on an unanchored scaffold (Scaffold000035_P2) of '02-12', confirming the existence of assembly error at the interval between M17 and BoID4714 for reference genome '02-12'. This study identified a candidate gene for BoPr and lays a foundation for the cloning and functional analysis of this gene.

Goals Set by Patients Using the ICF Model before Receiving Botulinum Injections and Their Relation to Spasticity Distribution

PubMed Central

Choi, Kevin; Peters, Jaclyn; Tri, Andrew; Chapman, Elizabeth; Sasaki, Ayako; Ismail, Farooq; Boulias, Chris; Reid, Shannon

2017-01-01

Purpose: Goal Attainment Scaling (GAS) is used to assess functional gains in response to treatment. Specific characteristics of the functional goals set by individuals receiving botulinum toxin type A (BoNTA) injections for spasticity management are unknown. The primary objectives of this study were to describe the characteristics of the goals set by patients before receiving BoNTA injections using the International Classification of Functioning, Disability and Health (ICF) and to determine whether the pattern of spasticity distribution affected the goals set. Methods: A cross-sectional retrospective chart review was carried out in an outpatient spasticity-management clinic in Toronto. A total of 176 patients with a variety of neurological lesions attended the clinic to receive BoNTA injections and completed GAS from December 2012 to December 2013. The main outcome measures were the characteristics of the goals set by the participants on the basis of ICF categories (body functions and structures, activity and participation) and the spasticity distribution using Modified Ashworth Scale scores. Results: Of the patients, 73% set activity and participation goals, and 27% set body functions and structures goals (p<0.05). In the activity and participation category, 30% of patients set moving and walking goals, 28% set self-care and dressing goals, and 12% set changing and maintaining body position goals. In the body functions and structures category, 18% set neuromuscular and movement-related goals, and 8% set pain goals. The ICF goal categories were not related to the patterns of spasticity (upper limb vs. lower limb or unilateral vs. bilateral spasticity) or type of upper motor neuron (UMN) lesion (p>0.05). Conclusion: Our results show that patients receiving BoNTA treatment set a higher percentage of activity and participation goals than body functions and structures goals. Goal classification was not affected by type of spasticity distribution or type of UMN disorder. PMID:28539691

Activity of botulinum neurotoxin type D (strain 1873) in human neurons

PubMed Central

Pellett, Sabine; Tepp, William H.; Scherf, Jacob M.; Pier, Christina L.; Johnson, Eric A.

2015-01-01

Botulinum Neurotoxin type D (BoNT/D) causes periodic outbreaks of botulism in cattle and horses, but is rarely associated with human botulism. Previous studies have shown that humans responded poorly to peripheral injection of up to 10 U of BoNT/D. Isolated human pyramidalis muscle preparations were resistant to BoNT/D, whereas isolated human intercostal muscle preparations responded to BoNT/D similarly as to other BoNT serotypes. In vitro data indicate that BoNT/D does not cleave human VAMP1 efficiently, and differential expression of the VAMP 1 and 2 isoforms may be responsible for the above observations. Here we examined sensitivity of cultured human neurons derived from human induced pluripotent stem cells to BoNT/D. Our data indicate that BoNT/D can enter and cleave VAMP 2 in human neurons, but at significantly lower efficiency than other BoNT serotypes. In addition, BoNT/D had a short duration of action in the cultured neurons, similar to that of BoNT/E. In vivo analyses indicated a slower time to death in mice, as well as a later onset and shorter duration of action than BoNT/A1. Finally, examination of BoNT/D activity in various rodent and human cell models resulted in dramatic differences in sensitivity, indicating a unique cell entry mechanism of BoNT/D. PMID:25937339

Therapeutic Approaches of Botulinum Toxin in Gynecology.

PubMed

Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

2018-04-21

Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

Therapeutic Approaches of Botulinum Toxin in Gynecology

PubMed Central

Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

2018-01-01

Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration. PMID:29690530

A new model linking elastic properties and ionic conductivity of mixed network former glasses.

PubMed

Wang, Weimin; Christensen, Randilynn; Curtis, Brittany; Martin, Steve W; Kieffer, John

2018-01-17

Glasses are promising candidate materials for all-solid-state electrolytes for rechargeable batteries due to their outstanding mechanical stability, wide electrochemical stability range, and open structure for potentially high conductivity. Mechanical stiffness and ionic conductivity are two key parameters for solid-state electrolytes. In this study, we investigate two mixed-network former glass systems, sodium borosilicate 0.2Na 2 O + 0.8[xBO 1.5 + (1 - x)SiO 2 ] and sodium borogermanate 0.2Na 2 O + 0.8[xBO 1.5 + (1 - x)GeO 2 ] glasses. With mixed-network formers, the structure of the network changes while the network modifier mole fraction is kept constant, i.e., x = 0.2, which allows us to analyze the effect of the network structure on various properties, including ionic conductivity and elastic properties. Besides the non-linear, non-additive mixed glass former effect, we find that the longitudinal, shear and Young's moduli depend on the combined number density of tetrahedrally and octahedrally coordinated network former elements. These units provide connectivity in three dimensions, which is required for the networks to exhibit restoring forces in response to isotropic and shear deformations. Moreover, the activation energy for modifier cation, Na + , migration is strongly correlated with the bulk modulus, suggesting that the elastic strain energy associated with the passageway dilation for the sodium ions is governed by the bulk modulus of the glass. The detailed analysis provided here gives an estimate for the number of atoms in the vicinity of the migrating cation that are affected by elastic deformation during the activated process. The larger this number and the more compliant the glass network, the lower is the activation energy for the cation jump.

SYBR Green Real-Time PCR Method To Detect Clostridium botulinum Type A▿

PubMed Central

Fenicia, Lucia; Anniballi, Fabrizio; De Medici, Dario; Delibato, Elisabetta; Aureli, Paolo

2007-01-01

Botulinum toxins (BoNTs) are classically produced by Clostridium botulinum but rarely also from neurotoxigenic strains of Clostridium baratii and Clostridium butyricum. BoNT type A (BoNT/A), BoNT/B, BoNT/E, and very rarely BoNT/F are mainly responsible for human botulism. Standard microbiological methods take into consideration only the detection of C. botulinum. The presumptive identification of the toxigenic strains together with the typing of BoNT has to be performed by mouse bioassay. The development of PCR-based methods for the detection and typing of BoNT-producing clostridia would be an ideal alternative to the mouse bioassay. The objective of this study was to develop a rapid and robust real-time PCR method for detecting C. botulinum type A. Four different techniques for the extraction and purification of DNA from cultured samples were initially compared. Of the techniques used, Chelex 100, DNeasy tissue kit, InstaGene matrix DNA, and boiling, the boiling technique was significantly less efficient than the other three. These did not give statistically different results, and Chelex 100 was chosen because it was less expensive than the others. In order to eliminate any false-negative results, an internal amplification control was synthesized and included in the amplification mixture according to ISO 22174. The specificity of the method was tested against 75 strains of C. botulinum type A, 4 strains of C. botulinum type Ab, and 101 nontarget strains. The detection limit of the reaction was less than 6 × 101 copies of C. botulinum type A DNA. The robustness of the method was confirmed using naturally contaminated stool specimens to evaluate the tolerance of inhibitor substances. SYBR green real-time PCR showed very high specificity for the detection of C. botulinum types A and Ab (inclusivity and exclusivity, 100%). PMID:17369349

A protein chip membrane-capture assay for botulinum neurotoxin activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marconi, Severine; Universite de la Mediterranee-Aix Marseille 2, Faculte de medecine secteur nord, Bd P. Dramard, Marseille F-13916; Ferracci, Geraldine

2008-12-15

Botulinum neurotoxins A and B (BoNT/A and B) are neuromuscular blocking agents which inhibit neurotransmission by cleaving the intra-cellular presynaptic SNARE proteins SNAP-25 and VAMP2, localized respectively in plasma membrane and synaptic vesicles. These neurotoxins are both dangerous pathogens and powerful therapeutic agents with numerous clinical and cosmetic applications. Consequently there is a need for in vitro assays of their biological activity to screen for potential inhibitors and to replace the widely used in vivo mouse assay. Surface plasmon resonance (SPR) was used to measure membrane vesicle capture by antibodies against SNAP-25 and VAMP2. Substrate cleavage by BoNTs modified capturemore » providing a method to assay toxin activity. Firstly using synaptic vesicles as a substrate, a comparison of the EC{sub 50}s for BoNT/B obtained by SPR, ELISA or flow cytometry indicated similar sensitivity although SPR assays were more rapid. Sonication of brain or neuronal cultures generated plasma membrane fragments with accessible intra-cellular epitopes adapted to measurement of BoNT/A activity. SPR responses were proportional to antigen concentration permitting detection of as little as 4 pM SNAP-25 in crude lysates. BoNT/A activity was assayed using monoclonal antibodies that specifically recognize a SNAP-25 epitope generated by the proteolytic action of the toxin. Incubation of intact primary cultured neurons with BoNT/A yielded an EC{sub 50} of 0.5 pM. The SPR biosensor method was sensitive enough to monitor BoNT/A and B activity in cells cultured in a 96-well format providing an alternative to experimental animals for toxicological assays.« less

Multichannel Luminescence Properties of Mixed-Valent Eu2+/Eu3+ Coactivated SrAl3BO7 Nanocrystalline Phosphors for Near-UV LEDs.

PubMed

Liu, Xiaoming; Xie, Weijie; Lü, Ying; Feng, Jingchun; Tang, Xinghua; Lin, Jun; Dai, Yuhua; Xie, Yu; Yan, Liushui

2017-11-20

Up to now, orchestrating the coexistence of Eu 2+ and Eu 3+ activators in a single host lattice has been an extremely difficult task, especially for the appearance of the characteristic emission of Eu 2+ and Eu 3+ in order to generate white light. Nevertheless, here we demonstrate a new Eu 2+ /Eu 3+ coactivated SrAl 3 BO 7 nanocrystalline phosphor with abundant and excellent multichannel luminescence properties. A series of Eu 2+ /Eu 3+ coactivated SrAl 3 BO 7 nanocrystalline phosphors were prepared through a Pechini-type sol-gel method followed by a reduction process. With excitation of UV/NUV light, the prepared SrAl 3 BO 7 :Eu 2+ ,Eu 3+ phosphors show not only the characteristic f-f transitions of Eu 3+ ion ( 5 D J → 7 F J,J' , J, J' = 0-3), but also the 5d → 4f transitions of Eu 2+ ion with comparable intensity from 400 to 700 nm in the whole visible spectral region. The luminescence color of the SrAl 3 BO 7 :Eu 2+ ,Eu 3+ phosphor can be tuned from blue, blue-green, white, and orange to orange-red by changing the excitation wavelength, the overall doping concentration of europium ions (Eu 2+ , Eu 3+ ), and the relative ratio of Eu 2+ to Eu 3+ ions to some extent. A single-phase white-light emission has been realized in SrAl 3 BO 7 :Eu 2+ ,Eu 3+ phosphor. The obtained SrAl 3 BO 7 :Eu 2+ ,Eu 3+ phosphor has potential application in the area of NUV white-light-emitting diodes.

Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache

PubMed Central

Simpson, David M.; Hallett, Mark; Ashman, Eric J.; Comella, Cynthia L.; Green, Mark W.; Gronseth, Gary S.; Armstrong, Melissa J.; Gloss, David; Potrebic, Sonja; Jankovic, Joseph; Karp, Barbara P.; Naumann, Markus; So, Yuen T.; Yablon, Stuart A.

2016-01-01

Objective: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. Methods: We searched the literature for relevant articles and classified them using 2004 AAN criteria. Results and recommendations: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B). PMID:27164716

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

PubMed

Invernizzi, M; Carda, S; Molinari, C; Stagno, D; Cisari, C; Baricich, A

2015-08-01

The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. Case control study. Eleven stroke survivors with spastic hemiplegia. Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. None of the variable considered showed statistically significant changes after BoNT-A injection. The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

76 FR 76068 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... GmbH Model BO-105A, BO-105C, BO-105LS A-1, BO- 105LS A-3, and BO-105S helicopters. This proposed AD... airworthy main rotor blade. Note 1: Eurocopter Deutschland GmbH Emergency Alert Service Bulletin No. BO105...

Border-ownership-dependent tilt aftereffect in incomplete figures

NASA Astrophysics Data System (ADS)

Sugihara, Tadashi; Tsuji, Yoshihisa; Sakai, Ko

2007-01-01

A recent physiological finding of neural coding for border ownership (BO) that defines the direction of a figure with respect to the border has provided a possible basis for figure-ground segregation. To explore the underlying neural mechanisms of BO, we investigated stimulus configurations that activate BO circuitry through psychophysical investigation of the BO-dependent tilt aftereffect (BO-TAE). Specifically, we examined robustness of the border ownership signal by determining whether the BO-TAE is observed when gestalt factors are broken. The results showed significant BO-TAEs even when a global shape was not explicitly given due to the ambiguity of the contour, suggesting a contour-independent mechanism for BO coding.

Border-ownership-dependent tilt aftereffect in incomplete figures.

PubMed

Sugihara, Tadashi; Tsuji, Yoshihisa; Sakai, Ko

2007-01-01

A recent physiological finding of neural coding for border ownership (BO) that defines the direction of a figure with respect to the border has provided a possible basis for figure-ground segregation. To explore the underlying neural mechanisms of BO, we investigated stimulus configurations that activate BO circuitry through psychophysical investigation of the BO-dependent tilt aftereffect (BO-TAE). Specifically, we examined robustness of the border ownership signal by determining whether the BO-TAE is observed when gestalt factors are broken. The results showed significant BO-TAEs even when a global shape was not explicitly given due to the ambiguity of the contour, suggesting a contour-independent mechanism for BO coding.

Purification and Characterization of a Novel Subtype A3 Botulinum Neurotoxin

PubMed Central

Tepp, William H.; Lin, Guangyun

2012-01-01

Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are of considerable importance due to their being the cause of human and animal botulism, their potential as bioterrorism agents, and their utility as important pharmaceuticals. Type A is prominent due to its high toxicity and long duration of action. Five subtypes of type A BoNT are currently recognized; BoNT/A1, -/A2, and -/A5 have been purified, and their properties have been studied. BoNT/A3 is intriguing because it is not effectively neutralized by polyclonal anti-BoNT/A1 antibodies, and thus, it may potentially replace BoNT/A1 for patients who have become refractive to treatment with BoNT/A1 due to antibody formation or other modes of resistance. Purification of BoNT/A3 has been challenging because of its low levels of production in culture and the need for innovative purification procedures. In this study, modified Mueller-Miller medium was used in place of traditional toxin production medium (TPM) to culture C. botulinum A3 (CDC strain) and boost toxin production. BoNT/A3 titers were at least 10-fold higher than those produced in TPM. A purification method was developed to obtain greater than 95% pure BoNT/A3. The specific toxicity of BoNT/A3 as determined by mouse bioassay was 5.8 × 107 50% lethal doses (LD50)/mg. Neutralization of BoNT/A3 toxicity by a polyclonal anti-BoNT/A1 antibody was approximately 10-fold less than the neutralization of BoNT/A1 toxicity. In addition, differences in symptoms were observed between mice that were injected with BoNT/A3 and those that were injected with BoNT/A1. These results indicate that BoNT/A3 has novel biochemical and pharmacological properties compared to those of other subtype A toxins. PMID:22367089

Purification and characterization of a novel subtype a3 botulinum neurotoxin.

PubMed

Tepp, William H; Lin, Guangyun; Johnson, Eric A

2012-05-01

Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are of considerable importance due to their being the cause of human and animal botulism, their potential as bioterrorism agents, and their utility as important pharmaceuticals. Type A is prominent due to its high toxicity and long duration of action. Five subtypes of type A BoNT are currently recognized; BoNT/A1, -/A2, and -/A5 have been purified, and their properties have been studied. BoNT/A3 is intriguing because it is not effectively neutralized by polyclonal anti-BoNT/A1 antibodies, and thus, it may potentially replace BoNT/A1 for patients who have become refractive to treatment with BoNT/A1 due to antibody formation or other modes of resistance. Purification of BoNT/A3 has been challenging because of its low levels of production in culture and the need for innovative purification procedures. In this study, modified Mueller-Miller medium was used in place of traditional toxin production medium (TPM) to culture C. botulinum A3 (CDC strain) and boost toxin production. BoNT/A3 titers were at least 10-fold higher than those produced in TPM. A purification method was developed to obtain greater than 95% pure BoNT/A3. The specific toxicity of BoNT/A3 as determined by mouse bioassay was 5.8 × 10(7) 50% lethal doses (LD(50))/mg. Neutralization of BoNT/A3 toxicity by a polyclonal anti-BoNT/A1 antibody was approximately 10-fold less than the neutralization of BoNT/A1 toxicity. In addition, differences in symptoms were observed between mice that were injected with BoNT/A3 and those that were injected with BoNT/A1. These results indicate that BoNT/A3 has novel biochemical and pharmacological properties compared to those of other subtype A toxins.

Physical, structural and spectroscopic investigations of Sm3+ doped ZnO mixed alkali borate glass

NASA Astrophysics Data System (ADS)

Sailaja, B.; Joyce Stella, R.; Thirumala Rao, G.; Jaya Raja, B.; Pushpa Manjari, V.; Ravikumar, R. V. S. S. N.

2015-09-01

Glass of 20ZnO-15 Li2O-15 Na2O-49.9 B2O3 doped with 0.1 mol% of Sm3+ (ZLNB) was prepared by the melt quenching technique. Physical properties were studied and analysed. The XRD studies confirm the amorphous nature of sample. The FT-IR spectral investigation discloses the BO3, BO4 groups, H and OH bonds. Optical absorption and emission spectra were recorded and characterized. Judd-Ofelt theory was applied to f ↔ f transitions to evaluate Judd-Ofelt intensity parameters (Ωλ). The oscillator strengths and bonding parameters were determined from absorption spectra. The trend observed was Ω4 > Ω6 > Ω2. High value of Ω4 reveals higher rigidity and covalency around the Sm3+ ion. Low value of Ω2 implies ionic nature of ligands and site symmetry around Sm3+ ion. luminescence data and Judd-Ofelt parameters Ωλ (λ = 2, 4, and 6) were used to evaluate various radiative probabilities like spontaneous radiative emission probabilities (AR), radiative lifetime (τR) and branching ratios (βR) stimulated emission cross section (σe) and CIE colour coordinates were measured, CCT temperature evaluated and the values were used to ascertain potential laser transitions at the optimum mixed alkali effect observed for the glass sample prepared. The preparedness of the material as the efficient laser active material is examined.

Analgesic Effect of Botulinum Toxin A in Myofascial Pain Syndrome Patients Previously Treated with Local Infiltration of Anesthetic and Steroids.

PubMed

Cartagena-Sevilla, Joaquín; García-Fernández, María R; Vicente-Villena, Juan P

2016-12-01

The purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P <.0001. As regards the side effects, 19 (23.2%) patients reported transient soreness at the injection site for 2 to 3 days with BoNTA. The MPS patients previously treated with a local infiltration of anesthetic and steroids who then received a single injection of BoNTA experienced significantly reduced pain for a relatively long time.

Passively Q-switched microchip Er, Yb:YAl3(BO3)4 diode-pumped laser.

PubMed

Kisel, V E; Gorbachenya, K N; Yasukevich, A S; Ivashko, A M; Kuleshov, N V; Maltsev, V V; Leonyuk, N I

2012-07-01

We report, for the first time to our knowledge, a diode-pumped cw and passively Q-switched microchip Er, Yb:YAl(3)(BO(3))(4) laser. A maximal output power of 800 mW at 1602 nm in the cw regime was obtained at an absorbed pump power of 7.7 W. By using Co(2+):MgAl(2)O(4) as a saturable absorber, a TEM(00)-mode Q-switched average output power of 315 mW was demonstrated at 1522 nm, with pulse duration of 5 ns and pulse energy of 5.25 μJ at a repetition rate of 60 kHz.

Structural and optical properties of Dy3+ doped Aluminofluoroborophosphate glasses for white light applications

NASA Astrophysics Data System (ADS)

Vijayakumar, M.; Mahesvaran, K.; Patel, Dinesh K.; Arunkumar, S.; Marimuthu, K.

2014-11-01

Dy3+ doped Aluminofluoroborophosphate glasses (BPAxD) have been prepared following conventional melt quenching technique and their structural and optical properties were explored through XRD, FTIR, optical absorption, excitation, emission and decay measurements. The coexistence of BO3 groups in borate rich domain and BO4 groups in phosphate rich domain have been confirmed through vibrational energy analysis. Negative bonding parameter (δ) values indicate that, the metal-ligand environment in the prepared glasses is of ionic in nature. The oscillator strength and the luminescent intensity Ωλ (λ = 2, 4 and 6) parameters are calculated using Judd-Ofelt theory. The radiative properties such as transition probability (A), stimulated emission cross-section (σpE) and branching ratios (β) have been calculated using JO intensity parameters and compared with the reported Dy3+ doped glasses. Concentration effect on Y/B intensity ratios and the CIE chromaticity coordinates were calculated for the generation of white light from the luminescence spectra. The color purity and the correlated color temperature were also calculated and the results are discussed in the present work. The decay of the 4F9/2 excited level is found to be single exponential for lower concentration and become non-exponential for higher concentration. The non-exponential behavior arises due to the efficient energy transfer between the Dy3+ ions through various non-radiative relaxation channels and the decay of the 4F9/2 excited level have been analyzed with IH model. Among the prepared glasses, BPA0.5D glass exhibits higher σpE, βR, σpE×σpE, σpE×Δλeff and η values for the 6H13/2 emission band which in turn specifies its suitability for white LEDs, laser applications and optical amplifiers.

Variability in ozone and its precursor gases over the Bay of Bengal during post-monsoon

NASA Astrophysics Data System (ADS)

Mallik, Chinmay; Lal, Shyam; Venkataramani, Sethuram; Naja, Manish; Ojha, Narendra

2013-04-01

O3 and precursor gases were measured during a ship campaign over the Bay of Bengal (BoB) during 28 October -17 November, 2010. The measurements revealed the large spatial heterogeneity in trace gas levels over the BoB during post-monsoon months. The heterogeneity was attributed to unique transport patterns over north and south BoB during this period. Four distinct types of air-masses influenced by heavy pollution from nearby source regions (49% time over North-West Myanmar, East Bangladesh and North-East India), mixed type (25% time over Myanmar, Thailand and Vietnam and 75% time over East BoB), affected by long-range transport of pollutants (59% time over continental South Myanmar, Vietnam and Hong-Kong region of China) and pristine marine (99% time over oceanic regions) were identified. Among these, the continental air masses were fresher compared to marine air masses. High O3 and CO levels were observed in air masses coming from South-East Asia. O3, C4H10 and alkenes were highest in air masses arriving from eastern IGP, Bangladesh, Myanmar via the North BoB. The C2H2 to CO slope of 0.004 and C3H8 to CO slope of 0.003 indicated predominance of biofuel/biomass burning in air masses from South-East Asia. The i-C4H10 to n- C4H10 value of 0.62 indicated contributions of urban/industrial sources in air masses arriving from Bangladesh, India and North-West Myanmar. 'Potential Source Contribution Function' analysis indicated fire impacted South of Myanmar and Thailand regions as potential contributors to high CO levels above 260 ppbv measured on 14 November. Observed enhancements in surface CO during 2-3 November were attributed to the faster transport of continental pollutants associated with cyclonic winds. The O3 e-fold time of 2.3 days indicated the higher rate of O3 destruction over the BoB due to higher precursor levels. Principle component analysis indicated that transport from continental source regions played a major role in determining the chemical composition of the air masses during the campaign and presence of regional sources of NOx. Diurnal variations of surface O3 revealed effects of advection, entrainment and photochemistry. Chemical box model simulations of O3 diurnal variations over the BoB were found to be very sensitive to background O3 and NO2 levels as well as dilution.

Role of bovine herpesvirus type 5 (BoHV-5) in diseases of cattle. Recent findings on BoHV-5 association with genital disease.

PubMed

Favier, P A; Marin, M S; Pérez, S E

2012-01-01

Bovine herpesvirus type 5 (BoHV-5) belongs to the family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus. This virus is a major causative agent of non-suppurative meningoencephalitis in young cattle. It was first isolated in 1962 from a neurological disease outbreak in Australia. BoHV-5 is genetically and antigenically related to bovine herpesvirus type 1 (BoHV-1), a highly prevalent virus responsible for respiratory and genital disease in cattle. Initially, BoHV-5 was considered a subtype of BoHV-1 (BoHV-1.3). However, the exclusive presentation of outbreaks of neurological disease suggested that the virus was a new agent with characteristics of neuropathogenicity. Even though both are neurotropic viruses, only BoHV-5 is capable of replicating extensively in the central nervous system and inducing neurological disease. Occasionally, encephalitis caused by BoHV-1 has been reported. Like other alpha-herpesviruses, BoHV-5 can establish latency in nervous ganglia and, by stress factors or glucocorticoid treatment, latent virus can be reactivated. During episodes of reactivation, the virus is excreted in nasal, ocular and genital secretions and transmitted to other susceptible hosts. Recently, BoHV-5 has been associated with infection of the reproductive tract. The virus has been isolated and the presence of viral DNA has been demonstrated in semen samples from Brazil and Australia and natural transmission of the virus through contaminated semen has also been described. Embryos and oocytes are permissive for BoHV-5 infection and BoHV-5 DNA has been detected in the central nervous system of aborted fetuses. The objective of this review is to compile the limited information on the recent association between BoHV-5 and reproductive disorders in cattle.

Role of bovine herpesvirus type 5 (BoHV-5) in diseases of cattle. Recent findings on BoHV-5 association with genital disease

PubMed Central

Favier, P.A.; Marin, M.S.; Pérez, S.E.

2012-01-01

Bovine herpesvirus type 5 (BoHV-5) belongs to the family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus. This virus is a major causative agent of non-suppurative meningoencephalitis in young cattle. It was first isolated in 1962 from a neurological disease outbreak in Australia. BoHV-5 is genetically and antigenically related to bovine herpesvirus type 1 (BoHV-1), a highly prevalent virus responsible for respiratory and genital disease in cattle. Initially, BoHV-5 was considered a subtype of BoHV-1 (BoHV-1.3). However, the exclusive presentation of outbreaks of neurological disease suggested that the virus was a new agent with characteristics of neuropathogenicity. Even though both are neurotropic viruses, only BoHV-5 is capable of replicating extensively in the central nervous system and inducing neurological disease. Occasionally, encephalitis caused by BoHV-1 has been reported. Like other alpha-herpesviruses, BoHV-5 can establish latency in nervous ganglia and, by stress factors or glucocorticoid treatment, latent virus can be reactivated. During episodes of reactivation, the virus is excreted in nasal, ocular and genital secretions and transmitted to other susceptible hosts. Recently, BoHV-5 has been associated with infection of the reproductive tract. The virus has been isolated and the presence of viral DNA has been demonstrated in semen samples from Brazil and Australia and natural transmission of the virus through contaminated semen has also been described. Embryos and oocytes are permissive for BoHV-5 infection and BoHV-5 DNA has been detected in the central nervous system of aborted fetuses. The objective of this review is to compile the limited information on the recent association between BoHV-5 and reproductive disorders in cattle. PMID:26623291

[Mobilization of potassium from soil by ectomycorrhizal fungi].

PubMed

Zhang, Liang; Wang, Mingxia; Zhang, Wei; Huang, Jianguo; Yuan, Ling

2014-07-04

Ectomycorrhizal fungi (ECMF), important components in forest ecosystems, could form symbionts with wooden plant roots and participate in nutrient absorption. Boletnus sp. (Bo 07), Lactarius delicious (Ld 03) and Pisolithus tinctorius (Pt 715) isolated from Southwest China and Cenococcum geophilum (Cg 04) from Daqing Mountain, Inn Mongolia, China, were cultured in liquid Pachlewsk medium at 25 +/- 1 degrees C for 28 days with soil as sole K source. Fungal biomass, K uptake, efflux of protons and organic acids, and changes of soil K pools were measured to study K mobilization from soil by ECMFs. ] The fungal biomass, K concentration and uptake of Bo 07, Ld 03 and Pt 715 were much higher than Cg 04, indicating their strong abilities to absorb K and to adapt low K environment by bio-evolution and selection. K concentrations in culture solution were increased by ECMFs compared to blank control (without ECMF). ECMFs could promote K release from the soil into culture solution. Bo 07, Ld 03 and Pt 715 increased significantly exchangeable K in soils, while structural K in soil was decreased by Bo 07 and Ld 03. They could thus mobilize unavailable K from ECMF isolates could mobilize unavailable K in soils.

Colorless Chlorophyll Catabolites in Senescent Florets of Broccoli (Brassica oleracea var. italica)

PubMed Central

2015-01-01

Typical postharvest storage of broccoli (Brassica oleracea var. italica) causes degreening of this common vegetable with visible loss of chlorophyll (Chl). As shown here, colorless Chl-catabolites are generated. In fresh extracts of degreening florets of broccoli, three colorless tetrapyrrolic Chl-catabolites accumulated and were detected by high performance liquid chromatography (HPLC): two “nonfluorescent” Chl-catabolites (NCCs), provisionally named Bo-NCC-1 and Bo-NCC-2, and a colorless 1,19-dioxobilin-type “nonfluorescent” Chl-catabolite (DNCC), named Bo-DNCC. Analysis by nuclear magnetic resonance spectroscopy and mass spectrometry of these three linear tetrapyrroles revealed their structures. In combination with a comparison of their HPL-chromatographic properties, this allowed their identification with three known catabolites from two other brassicacea, namely two NCCs from oil seed rape (Brassica napus) and a DNCC from degreened leaves of Arabidopsis thaliana. PMID:25620234

Evaluation of a Biaxial Test Fixture.

DTIC Science & Technology

1983-01-01

TD 1 a 1 I 1 ! II : ill « \\ \\ \\ X \\ 1 X X I rH 0 _ i0 2: \\ \\ 1 \\ \\ X c...i 00 o • 1—1 «4 TO x; 1 •H P X bO < c 0) 9 i—1 H Lft 03 1 C TD «4 I z <D 2: +J «-4 C fc <t H O oc «i- • & CMW w a...a, »<A T) «4 i-t C a. (0 3 o C O o S-i fn • CD < •P C £ flj M P • bO «4 ’n C ID O 0) 1 i—I H P 1 O 13 • 0> i-H

Inhalational botulism in rhesus macaques exposed to botulinum neurotoxin complex serotypes A1 and B1.

PubMed

Sanford, Daniel C; Barnewall, Roy E; Vassar, Michelle L; Niemuth, Nancy; Metcalfe, Karen; House, Robert V; Henderson, Ian; Shearer, Jeffry D

2010-09-01

A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD(50)) and to estimate 50% lethal exposure concentrations relative to time (LCt(50)) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD(50) and LCt(50) for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication.

Inhalational Botulism in Rhesus Macaques Exposed to Botulinum Neurotoxin Complex Serotypes A1 and B1▿ †

PubMed Central

Sanford, Daniel C.; Barnewall, Roy E.; Vassar, Michelle L.; Niemuth, Nancy; Metcalfe, Karen; House, Robert V.; Henderson, Ian; Shearer, Jeffry D.

2010-01-01

A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD50) and to estimate 50% lethal exposure concentrations relative to time (LCt50) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD50 and LCt50 for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication. PMID:20660138

Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins.

PubMed

Peng, Lisheng; Berntsson, Ronnie P-A; Tepp, William H; Pitkin, Rose M; Johnson, Eric A; Stenmark, Pål; Dong, Min

2012-07-01

Botulinum neurotoxins (BoNTs) are classified into seven types (A-G), but multiple subtype and mosaic toxins exist. These subtype and mosaic toxins share a high sequence identity, and presumably the same receptors and substrates with their parental toxins. Here, we report that a mosaic toxin, type D-C (BoNT/D-C), uses different receptors from its parental toxin BoNT/C. BoNT/D-C, but not BoNT/C, binds directly to the luminal domains of synaptic vesicle proteins synaptotagmin (Syt) I and II, and requires expression of SytI/II to enter neurons. The SytII luminal fragment containing the toxin-binding site can block the entry of BoNT/D-C into neurons and reduce its toxicity in vivo in mice. We also found that gangliosides increase binding of BoNT/D-C to SytI/II and enhance the ability of the SytII luminal fragment to block BoNT/D-C entry into neurons. These data establish SytI/II, in conjunction with gangliosides, as the receptors for BoNT/D-C, and indicate that BoNT/D-C is functionally distinct from BoNT/C. We further found that BoNT/D-C recognizes the same binding site on SytI/II where BoNT/B and G also bind, but utilizes a receptor-binding interface that is distinct from BoNT/B and G. Finally, we also report that human and chimpanzee SytII has diminished binding and function as the receptor for BoNT/B, D-C and G owing to a single residue change from rodent SytII within the toxin binding site, potentially reducing the potency of these BoNTs in humans and chimpanzees.

Improved soluble expression and characterization of the Hc domain of Clostridium botulinum neurotoxin serotype A in Escherichia coli by using a PCR-synthesized gene and a Trx co-expression strain.

PubMed

Chen, Rongchang; Shi, Jing; Cai, Kun; Tu, Wei; Hou, Xiaojun; Liu, Hao; Xiao, Le; Wang, Qin; Tang, Yunming; Wang, Hui

2010-05-01

Botulinum neurotoxin serotype A (BoNT/A) is an extremely potent bacterial protein toxin. The Hc fragment of BoNT/A (AHc) was shown to be non-toxic, antigenic, and capable of eliciting a protective immunity in animals challenged with homologous BoNT. In this study, we synthesized AHc gene by using T4 DNA ligase and PCR. The AHc was expressed at a high level in Escherichia coli successfully. Because of using the Trx co-expression strain, the expressed AHc is in a soluble and active form. The yield of the purified AHc was about 70mg/L, and its purity was up to 90% through one-step affinity chromatography. The AHc was positively identified by the antibodies raised against BoNT/A using immunological-dot-blot and Western blot assays. AHc was shown to bind with gangliosides and elicit immunity against BoNT/A, indicating that the expressed and purified AHc protein retains a functionally active conformation. Furthermore, the purified AHc has a strong immunogenicity and can be used as a potential subunit candidate vaccine for botulinum toxin serotype A. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Questionnaire about the adverse events and side effects following botulinum toxin A treatment in patients with cerebral palsy.

PubMed

Blaszczyk, Izabela; Foumani, Nazli Poorsafar; Ljungberg, Christina; Wiberg, Mikael

2015-11-06

Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP.

Preliminary evaluation of growth and conformation traits of local goats and Nubians upgraded by a black Boer line in Taiwan.

PubMed

Su, An-Kuo; Yang, Shen-Suan; Chen, Shui-Tsai; Cheng, Yu-Shin; Huang, Jan-Chi; Wu, Ming-Che; Poivey, Jean-Paul

2012-08-01

The goal of this research, conducted in the most southern part of Taiwan, was to create a new genotype: the "Hengchun Black Goat" (HB). Nubian (NU) goats were first crossed with a local breed, the Taiwan native (TN), then the F1 females were crossed with the imported black Boer (BO) bucks. The upgraded genotypes were then compared with the parental breeds and Kinmen (KM), another local breed, for growth traits and body conformation. The study concerned 1,136 kids born between 2005 and 2007. The analysed traits were body weight (BW), average daily gain and three linear measurements, namely height at withers, body length and chest girth. The results indicated that environmental factors, sex, birth and rearing type, dam parity and birth year had significant effects from birth to 6 months of age. The same differences persisted to 1 year. At 6 months of age, the least square means of BW were 16.2, 19.2, 25.1, 32.0, 23.9, 23.8, 23.0 and 23.9 kg, for KM, TN, NU, 1/2BO, 3/4BO, 7/8BO, BO and HB, respectively. These first results also indicate that the growth performances of the newly created line, Hengchun Black, were equivalent to those of Boer goats.

Scoring nuclear pleomorphism using a visual BoF modulated by a graph structure

NASA Astrophysics Data System (ADS)

Moncayo-Martínez, Ricardo; Romo-Bucheli, David; Arias, Viviana; Romero, Eduardo

2017-11-01

Nuclear pleomorphism has been recognized as a key histological criterium in breast cancer grading systems (such as Bloom Richardson and Nothingham grading systems). However, the nuclear pleomorphism assessment is subjective and presents high inter-reader variability. Automatic algorithms might facilitate quantitative estimation of nuclear variations in shape and size. Nevertheless, the automatic segmentation of the nuclei is difficult and still and open research problem. This paper presents a method using a bag of multi-scale visual features, modulated by a graph structure, to grade nuclei in breast cancer microscopical fields. This strategy constructs hematoxylin-eosin image patches, each containing a nucleus that is represented by a set of visual words in the BoF. The contribution of each visual word is computed by examining the visual words in an associated graph built when projecting the multi-dimensional BoF to a bi-dimensional plane where local relationships are conserved. The methodology was evaluated using 14 breast cancer cases of the Cancer Genome Atlas database. From these cases, a set of 134 microscopical fields was extracted, and under a leave-one-out validation scheme, an average F-score of 0.68 was obtained.

Aggregation of recombinant human botulinum protein antigen serotype C in varying solution conditions: implications of conformational stability for aggregation kinetics.

PubMed

Bai, Shujun; Manning, Mark Cornell; Randolph, Theodore W; Carpenter, John F

2011-03-01

Solution conditions greatly affect the aggregation rate of a protein. Elucidating these influences provides insight into the critical factors governing aggregation. In this study, recombinant human botulinum protein antigen serotype C [rBoNTC (H(c))] was employed as a model protein. rBoNTC (H(c)) aggregated irreversibly during incubation at 42°C. The aggregation rate was studied as a function of solution conditions, including varying the pH from 3.5 to 8.0 and with or without 150 mM NaCl, 7.5% (w/v) trehalose, and 0.5 M urea. Some solution conditions retarded rBoNTC (H(c)) aggregation, whereas others accelerated aggregation, particularly acidic pH and addition of NaCl or urea. To better understand the mechanism by which these solution conditions influenced aggregation rates, the structure of rBoNTC (H(c)) was characterized using circular dichroism, fluorescence, and ultraviolet absorbance spectroscopies. Conformational stability was assessed from equilibrium urea-induced unfolding studies and by using differential scanning calorimetry (DSC). The activation energy of the aggregation reaction (E(a)) was estimated from an analysis of the heating-rate dependence of the thermal transition observed during DSC heating scans. Overall, for rBoNTC (H(c)), an inverse correlation was found between conformational stability and aggregation rate, as well as between the kinetic barrier to unfolding (i.e., E(a)) and aggregation rate. Copyright © 2010 Wiley-Liss, Inc.