Differentiation of Foot-and-Mouth Disease-Infected pigs from Vaccinated Pigs Using Antibody-Detecting Sandwich ELISA

The presence of serum antibodies for nonstructural proteins of the foot-and-mouth disease virus (FMDV) can differentiate FMDV-infected animals from vaccinated animals. In this study, a sandwich ELISA was developed for rapid detection of the foot-and-mouth disease (FMD) antibodies; it was based on an Escherichia coli-expressed, highly conserved region of the 3ABC nonstructural protein of the FMDV O/TW/99 strain and a monoclonal antibody derived from the expressed protein. The diagnostic sensitivity of the assay was 98.4%, and the diagnostic specificity was 100% for naïve and vaccinated pigs; the detection ability of the assay was comparable those of the PrioCHECK and UBI kits. There was 97.5, 93.4 and 66.6% agreement between the results obtained from our ELISA and those obtained from the PrioCHECK, UBI and CHEKIT kits, respectively. The kappa statistics were 0.95, 0.87 and 0.37, respectively. Moreover, antibodies for nonstructural proteins of the serotypes A, C, Asia 1, SAT 1, SAT 2 and SAT 3 were also detected in bovine sera. Furthermore, the absence of cross-reactions generated by different antibody titers against the swine vesicular disease virus and vesicular stomatitis virus (VSV) was also highlighted in this assay's specificit

PmoB subunit of particulate methane monooxygenase (pMMO) in Methylococcus capsulatus (Bath): The Cu^I sponge and its function

In this study, we describe efforts to clarify the role of the copper cofactors associated with subunit B (PmoB) of the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath) (M. capsulatus). This subunit exhibits strong affinity toward Cu^I ions. To elucidate the high copper affinity of the subunit, the full-length PmoB, and the N-terminal truncated mutants PmoB_(33–414) and PmoB_(55–414), each fused to the maltose-binding protein (MBP), are cloned and over-expressed into Escherichia coli (E. coli) K12 TB1 cells. The Y374F, Y374S and M300L mutants of these protein constructs are also studied. When this E. coli is grown with the pmoB gene in 1.0 mM Cu^(II), it behaves like M. capsulatus (Bath) cultured under high copper stresswith abundant membrane accumulation and high CuI content. The recombinantPmoB proteins are verified by Western blotting of antibodies directed against the MBP sub-domain in each of the copper-enriched PmoB proteins. Cu K-edge X-rayabsorption near edge spectroscopy (XANES) of the copper ions confirms that all the PmoB recombinants are Cu^I proteins. All the PmoB proteins show evidence of a “dicopper site” according to analysis of the Cu extended X-ray absorption edge fine structure (EXAFS) of the membranes. No specific activities toward methane and propene oxidation are observed with the recombinant membrane-bound PmoB proteins. However, significant production of hydrogen peroxide is observed in the case of the PmoB_(33–414) mutant. Reaction of the dicopper site with dioxygenproduces hydrogen peroxide and leads to oxidation of the CuI ions residing in the C-terminal sub-domain of the PmoB subunit

Nanocontact Disorder in Nanoelectronics for Modulation of Light and Gas Sensitivities

To fabricate reliable nanoelectronics, whether by top-down or bottom-up processes, it is necessary to study the electrical properties of nanocontacts. The effect of nanocontact disorder on device properties has been discussed but not quantitatively studied. Here, by carefully analyzing the temperature dependence of device electrical characteristics and by inspecting them with a microscope, we investigated the Schottky contact and Mott\u27s variable-range-hopping resistances connected in parallel in the nanocontact. To interpret these parallel resistances, we proposed a model of Ti/TiOx in the interface between the metal electrodes and nanowires. The hopping resistance as well as the nanocontact disorder dominated the total device resistance for high-resistance devices, especially at low temperatures. Furthermore, we introduced nanocontact disorder to modulate the light and gas responsivities of the device; unexpectedly, it multiplied the sensitivities compared with the intrinsic sensitivity of the nanowires. Our results improve the collective understanding of electrical contacts to low-dimensional semiconductor devices and will aid performance optimization in future nanoelectronics

Chemically coupling SnO2 quantum dots and MXene for efficient CO2 electroreduction to formate and Zn–CO2 battery

Electrochemical conversion of CO2 into formate is a promising strategy for mitigating the energy and environmental crisis, but simultaneously achieving high selectivity and activity of electrocatalysts remains challenging. Here, we report low-dimensional SnO2 quantum dots chemically coupled with ultrathin Ti3C2Tx MXene nanosheets (SnO2/MXene) that boost the CO2 conversion. The coupling structure is well visualized and verified by high-resolution electron tomography together with nanoscale scanning transmission X-ray microscopy and ptychography imaging. The catalyst achieves a large partial current density of -57.8 mA cm-2 and high Faradaic efficiency of 94% for formate formation. Additionally, the SnO2/MXene cathode shows excellent Zn-CO2 battery performance, with a maximum power density of 4.28 mW cm-2, an open-circuit voltage of 0.83 V, and superior rechargeability of 60 h. In situ X-ray absorption spectroscopy analysis and first-principles calculations reveal that this remarkable performance is attributed to the unique and stable structure of the SnO2/MXene, which can significantly reduce the reaction energy of CO2 hydrogenation to formate by increasing the surface coverage of adsorbed hydrogen

PmoB subunit of particulate methane monooxygenase (pMMO) in Methylococcus capsulatus (Bath): The Cu^I sponge and its function

In this study, we describe efforts to clarify the role of the copper cofactors associated with subunit B (PmoB) of the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath) (M. capsulatus). This subunit exhibits strong affinity toward Cu^I ions. To elucidate the high copper affinity of the subunit, the full-length PmoB, and the N-terminal truncated mutants PmoB_(33–414) and PmoB_(55–414), each fused to the maltose-binding protein (MBP), are cloned and over-expressed into Escherichia coli (E. coli) K12 TB1 cells. The Y374F, Y374S and M300L mutants of these protein constructs are also studied. When this E. coli is grown with the pmoB gene in 1.0 mM Cu^(II), it behaves like M. capsulatus (Bath) cultured under high copper stresswith abundant membrane accumulation and high CuI content. The recombinantPmoB proteins are verified by Western blotting of antibodies directed against the MBP sub-domain in each of the copper-enriched PmoB proteins. Cu K-edge X-rayabsorption near edge spectroscopy (XANES) of the copper ions confirms that all the PmoB recombinants are Cu^I proteins. All the PmoB proteins show evidence of a “dicopper site” according to analysis of the Cu extended X-ray absorption edge fine structure (EXAFS) of the membranes. No specific activities toward methane and propene oxidation are observed with the recombinant membrane-bound PmoB proteins. However, significant production of hydrogen peroxide is observed in the case of the PmoB_(33–414) mutant. Reaction of the dicopper site with dioxygenproduces hydrogen peroxide and leads to oxidation of the CuI ions residing in the C-terminal sub-domain of the PmoB subunit

RenalHandling of Drugsin RenalFailureI: Differential Effectsof Uranyl Nitrate-andGlycerol-induced AcuteRenalFailureon RenalExcretion of TEABandPAHin Rats

ABSTRACT Two etiologically different modelsof experimental acuterenal failurewere inducedin rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the g@merularfiItration rate(GFR)and the net tubular secretion oftetraethylammonium bromide (TEAB) andpara-amlnohippuric add (PAH). The degree of renal impairment indUCedby uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol poten tiated the renal damage. In uranyl nftrate-induced renal failure, the dedine of the net tubular secretion for TEAB and PAH was not proportional to the decreasein GFR;the secretionprocess deterioratedfasterthanthe GFR.Forexample,when0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereasthe nettUbUlar secretion wasdecreased to 30% of normal. These results suggest that the tUbUlartransport was preferentiallyaffectedby uranylnitrate.In contrast,in glyc erol-inducedrenalfailure,the declineof TEABsecretionfell in a parallel fashionwith the GFR,suggestingthat the glomeruli and the proximaltUbUleS were equallydamagedby glycerol.How ever, in this latter model,the declineof PAH secretiondid not parallelthe decreasein GFR, contradictingthe proposalthat glycerolaffectsequallythe glomeruliand the proximaltubules. This discrepancymay be due to the selectivecompetitiveinhi bffionof PAHsecretionbytheaccumtMtionof naturallyoccumng organicacids. The results that the secretionof PAH but not Clinically, it is generally assumed that the decrease of renal clearance of drugs parallels the decline of glomerular ifitration rate (GFR) in patients with renal failure, even when tubular secretion is the main route of excretion (Rowland and Tozer, 1980; The results obtained from the present study show that both the GFR and the tubular secretion of TEAB and PAH were impaired in experimental acute renal failure. However, the two different models of acute renal failure have quantitatively dif ferent effects on the passive ifitration and active secretion processes depending on whether organic cations or anions were studied. Thus, the general assumption that the decrease of renal clearance of drugs parallels the decline of the GFR in renal failure may not hold. The data of this report suggest that one should be cautious in extrapolating the relative changes in the GFR to the changes in the tubular secretion in renal failure. ABBREVIATiONS GFR giomerular filtration rate TEAB tetraethylammonium bromidePAH para-aminohippuric acidCL@, renal clearance

Intra-oral HIV-associated Burkitt’s lymphoma with mandible involvement

SummaryAlthough Burkitt’s lymphoma (BL) of the oral cavity is very uncommon in human immunodeficiency virus (HIV)-infected patients, its occurrence is highlighted as one of the earliest clinical manifestations. This report deals with the first occurrence of intra-oral HIV-associated BL with plasmacytoid differentiation and mandibular involvement. It also serves to illustrate the importance of histological and immunohistochemical analyses of oral lesions to indicate the possibility of HIV-infection

Case studies for practical food effect assessments across BCS/BDDCS class compounds using in silico, in vitro, and preclinical in vivo data

Practical food effect predictions and assessments were described using in silico, in vitro, and/or in vivo preclinical data to anticipate food effects and Biopharmaceutics Classification System (BCS)/Biopharmaceutics Drug Disposition Classification System (BDDCS) class across drug development stages depending on available data: (1) limited in silico and in vitro data in early discovery; (2) preclinical in vivo pharmacokinetic, absorption, and metabolism data at candidate selection; and (3) physiologically based absorption modeling using biorelevant solubility and precipitation data to quantitatively predict human food effects, oral absorption, and pharmacokinetic profiles for early clinical studies. Early food effect predictions used calculated or measured physicochemical properties to establish a preliminary BCS/BDDCS class. A rat-based preclinical BCS/BDDCS classification used rat in vivo fraction absorbed and metabolism data. Biorelevant solubility and precipitation kinetic data were generated via animal pharmacokinetic studies using advanced compartmental absorption and transit (ACAT) models or in vitro methods. Predicted human plasma concentration-time profiles and the magnitude of the food effects were compared with observed clinical data for assessment of simulation accuracy. Simulations and analyses successfully identified potential food effects across BCS/BDDCS classes 1-4 compounds with an average fold error less than 1.6 in most cases. ACAT physiological absorption models accurately predicted positive food effects in human for poorly soluble bases after oral dosage forms. Integration of solubility, precipitation time, and metabolism data allowed confident identification of a compound's BCS/BDDCS class, its likely food effects, along with prediction of human exposure profiles under fast and fed conditions. © 2012 American Association of Pharmaceutical Scientists