In a Cosy Little Homestead On the Old New England Shore

https://digitalcommons.library.umaine.edu/mmb-me/1105/thumbnail.jp

Group contribution modeling of activity coefficients in associating solutions containing water, alcohols and carboxylic acids

A modified UNIFAC group contribution model for the prediction of activity coefficients in associating solutions (A-UNIFAC) is applied to calculate phase equilibria in binary and ternary mixtures of associating and non-associating species, including alcohols, water, carboxylic acids, esters, alkanes, aromatic hydrocarbons and alkyl chlorides. Self- and cross-association in these mixtures is adequately described by the definition of a single hydrogen-bonding group. The new model is able to give good predictions of vapor-liquid equilibria, liquid-liquid equilibria and infinite dilution activity coefficients, using a single set of group-interaction parameters.The authors are grateful to the Argentinian National Research Council (CONICET) and to Universidad Nacional del Sur (UNS) for financial support. M.O. Ferreira acknowledges financial support from the PRAXIS program, FCT, Lisbon, Portugal

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

Mesenchymal stem/stromal cells (MSCs) have been widely studied in the field of regenerative medicine for applications in the treatment of several disease settings. The therapeutic potential of MSCs has been evaluated in studies in vitro and in vivo, especially based on their anti-inflammatory and pro-regenerative action, through the secretion of soluble mediators. In many cases, however, insufficient engraftment and limited beneficial effects of MSCs indicate the need of approaches to enhance their survival, migration and therapeutic potential. Genetic engineering emerges as a means to induce the expression of different proteins and soluble factors with a wide range of applications, such as growth factors, cytokines, chemokines, transcription factors, enzymes and microRNAs. Distinct strategies have been applied to induce genetic modifications with the goal to enhance the potential of MCSs. This review aims to contribute to the update of the different genetically engineered tools employed for MSCs modification, as well as the factors investigated in different fields in which genetically engineered MSCs have been tested

Protease-sensitive synthetic prions

Prions arise when the cellular prion protein (PrP(C)) undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc). Frequently, PrP(Sc) is protease-resistant but protease-sensitive (s) prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec) PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164), denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174) did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc) and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc). These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc)

Molecular, Biochemical and Genetic Characteristics of BSE in Canada

The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrPres). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrPres, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrPres from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrPres subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide

CHEMICAL CONTROL OF THE REDBAY AMBROSIA BEETLE, XYLEBORUS GLABRATUS, AND OTHER SCOLYTINAE (COLEOPTERA: CURCULIONIDAE)

A BSTRACT The redbay ambrosia beetle (RAB), Xyleborus glabratus Eichhoff (Coleoptera: Curculionidae: Scolytinae), is an adventive pest of Lauraceae in the southeastern U.S. This wood-boring insect vectors a lethal fungus, Raffaelea lauricola T. C. Harr., Fraedrich & Aghayeva , the causal agent of laurel wilt (LW) disease. The vector-pathogen complex is responsible for extensive mortality of native Persea trees in South Carolina, Georgia, and northern Florida, and now poses an imminent threat to the avocado ( Persea americana Mill.) industry in south Florida. While chemical control of the vector is not viewed as the primary solution, control tactics should be made available to Florida avocado growers. Field and laboratory tests were conducted using avocado bolts, potted avocado trees, and field grown swampbay trees ( Persea palustris (Raf.) Sarg.) treated with contact and systemic insecticides. Zeta-cypermethrin + bifenthrin and lambda-cyhalothrin + thiamethoxam provided the most consistent control of Scolytinae as contact insecticides, while methomyl, malathion, bifenthrin, and endosulfan were more variable in effectiveness. Avocado trees treated with fenpropathrin, cryolite Na Al fluoride, and lambda-cyhalothrin+thiametoxam had similar numbers of beetle entrance holes on treated trees as on the untreated control trees. No statistical differences were observed in disease severity on treated versus non-treated avocados or swampbay. Linear regressions between the number of RAB entrance holes per tree ( x) and LW disease severity ( y a ) and between RAB entrance holes per tree ( x) and recovery of R. lauricola ( y b ) were both significant. Key Words: Redbay ambrosia beetle, avocado, Persea , Xyleborus , Xylosandrus , Hypothenemus , chemical control R ESUMEN El cucarroncito de ambrosia del laurel, Xyleborus glabratus Eichhoff (Coleoptera: Curculionidae), es una plaga exótica de la familia Lauraceae que ha invadido el suroriente de los Estados Unidos. Este insecto barrenador es el vector del hongo, Raffaelea lauricola T.C. Harr., Fraedrich & Aghayeva, agente causal de la enfermedad del secamiento del laurel. El complejo vector-patógeno es responsable de una extensa mortalidad de arboles nativos del genero Persea en Carolina del Sur, Georgia y en el norte de Florida y representa una amenaza inminente para la industria del aguacate ( Persea americana Mill.) de Florida. Aunque el control químico no es la única solución a este problema, se estima que este tipo de opción de tác-ticas se debe ofrecer a los productores de aguacate. Se condujeron experimentos tanto en campo como en laboratorio utilizando troncos de aguacate, arboles de aguacate y arboles del laurel de la ciénaga ( P. palustris (Raf.) Sarg.), los cuales se trataron con insecticidas de contacto y sistémicos. En general, zetaciypermetrina + bifenthrina y lambda-cyalotrina + tiametoxam dieron un control consistente de los Scolytinae como insecticidas de contacto, mientras que metomíl, malatión y bifentrina y endosulfan dieron resultados variables. No hubo diferencias significativas en los orificios de entrada de los cucarroncitos cuando se trataron los arboles de aguacate con fenpropatrina, floruro de cryolita NA Al y lambda-cyalotrina-tiametoxam comparado con los arboles testigo. No se observaron diferencias estadísticas en cuanto a la severidad de la enfermedad entre árboles tratados y aquellos no tratados. Sin embargo, modelos de regresión lineal entre el número de orificios por árbol ( x

Transmissibility of Atypical Scrapie in Ovine Transgenic Mice: Major Effects of Host Prion Protein Expression and Donor Prion Genotype

Atypical scrapie or Nor98 has been identified as a transmissible spongiform encephalopathy (TSE) that is clearly distinguishable from classical scrapie and BSE, notably regarding the biochemical features of the protease-resistant prion protein PrPres and the genetic factors involved in susceptibility to the disease. In this study we transmitted the disease from a series of 12 French atypical scrapie isolates in a transgenic mouse model (TgOvPrP4) overexpressing in the brain ∼0.25, 1.5 or 6× the levels of the PrPARQ ovine prion protein under the control of the neuron-specific enolase promoter. We used an approach based on serum PrPc measurements that appeared to reflect the different PrPc expression levels in the central nervous system. We found that transmission of atypical scrapie, much more than in classical scrapie or BSE, was strongly influenced by the PrPc expression levels of TgOvPrP4 inoculated mice. Whereas TgOvPrP4 mice overexpressing ∼6× the normal PrPc level died after a survival periods of 400 days, those with ∼1.5× the normal PrPc level died at around 700 days. The transmission of atypical scrapie in TgOvPrP4 mouse line was also strongly influenced by the prnp genotypes of the animal source of atypical scrapie. Isolates carrying the AF141RQ or AHQ alleles, associated with increased disease susceptibility in the natural host, showed a higher transmissibility in TgOvPrP4 mice. The biochemical analysis of PrPres in TgOvPrP4 mouse brains showed a fully conserved pattern, compared to that in the natural host, with three distinct PrPres products. Our results throw light on the transmission features of atypical scrapie and suggest that the risk of transmission is intrinsically lower than that of classical scrapie or BSE, especially in relation to the expression level of the prion protein