Brain methylation and epileptogenesis: The case of methionine sulfoximine

A brief review of the neurochemical effects of the convulsant agent L -methionine- dl -sulfoximine (MSO) on cerebral methylation reactions is presented. Our findings point to the involvement of a number of endogenous methyl acceptor molecules, including histamine, membrane phospholipids, and membrane proteins, in the mediation of the convulsant effect. Our findings also associate the inhibition of methylations by high levels of S -adenosyl- L -homocysteine in brain with protection against MSO-induced seizures. We propose that MSO acts by eliciting the acceleration of a regulatory methylation-demethylation sequence at key molecular sites, including the benzodiazepine receptor complex, which creates an imbalance in this sequence's normal mediation of convulsant–anticonvulsant mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50309/1/410160717_ftp.pd

Effect of methionine sulfoximine on methylation of guanine residues in astroglial transfer ribonucleic acids

Culture-grown astrocytes derived from 3-day-old rat brain were incubated in the presence of [ 3 H]guanosine and of the convulsant agent l -methionine- dl -sulfoximine (MSO). The resulting [ 3 H]tRNA was purified from control and MSO-exposed cells at several time points during the incubation and was hydrolyzed to [ 3 H]guanine and four [ 3 H]methyl guanines which were separated by high pressure liquid chromatography. Three of the four [ 3 H]methyl guanines were more highly labeled in the [ 3 H]tRNA of the MSO-exposed cells, relative to that of the control cells throughout the entire incubation period. The findings extend to cultured astrocytes, the stimulatory effect of MSO on the methylation of neural tRNA guanines, previouly observed both in vitro using [ 14 C] S -adenosyl- l -methionine and in vivo using [ methyl 3 -H] l -methionine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45427/1/11064_2004_Article_BF00964832.pd

An immigrant nurse is our colleague : how to develop the language and culture in multicultural nursing

The number of personnel of foreign origin working in Finnish healthcare has tripled when comparing the year 2000 to 2012. In the future, there is also a need of increased working force in Finnish healthcare, caused by the retirement of the baby boomer generation. The purpose of this thesis was to create an educational video about increasing cultural competence when working with immigrant nurses. The target audience was Finnish nursing students studying at Tampere University of Applied Sciences. The objective of the thesis was to raise awareness and cultural competence of future nurses, when they are working with immigrant nurses. This study was executed in a form of a functional bachelor’s thesis. A literature review was conducted to acquire information regarding the theoretical starting points of the thesis. The theoretical starting points were; challenges of an immigrant nurse, professional interaction, collegiality in nursing, language and cultural differences in nursing and foreign nurses’ experiences in Finland. The results indicated that the main challenge the immigrant nurses face is the Finnish language. Immigrants need support from their colleagues and resources for familiarisation from the employer. Other main difficulties are cultural differences, discrimination and lack of social networks. Increase in the education of nurses and nursing managers’ cultural competence as well as open discussion is needed in the working communities to confront these issues. The educational video has three main themes concerning language, culture and interaction. Each of the themes are presented with three scenes that elaborate the subject by the means of drama. The video can be seen at the address https://youtu.be/Hkp30u0aidc.Suomalaisessa sosiaali- ja terveydenhuollossa työskentelevien ulkomaalaistaustaisten työntekijöiden määrä on noin kolminkertaistunut verrattaessa vuotta 2000 vuoteen 2012. Maahanmuuton sekä työvoiman tarpeen lisääntyessä eläköitymisestä johtuen on tulevaisuudessa yhä todennäköisempää, että useammalla suomalaisella sairaanhoitajalla on ulkomaalaistaustainen työtoveri. Tämän opinnäytetyön tarkoitus oli tehdä opetusvideo työskentelystä monikulttuurisessa työyhteisössä Tampereen ammattikorkeakoululle. Kohdeyleisönä videolle olivat suomalaiset sairaanhoitajaopiskelijat. Opinnäytetyön tavoitteena oli lisätä tietoisuutta ja kulttuurista osaamista tulevissa sairaanhoitajissa, jotka työskentelevät ulkomaalaistaustaisten työtovereiden kanssa. Opinnäytetyö tehtiin toiminnallisena opinnäytetyönä, jonka tuote oli video. Videon käsikirjoittamista varten tehtiin kirjallisuuskatsaus teoreettisista lähtökohdista, jotka olivat maahanmuuttajahoitajan haasteet, ammatillinen vuorovaikutus työyhteisössä, kollegiaalisuus, kieli- ja kulttuurierot hoitotyössä sekä ulkomaalaistaustaisten hoitajien kokemukset Suomessa. Kirjallisuuskatsauksen tuloksista oli nähtävissä, että maahanmuuttajien suurin vaikeus työyhteisöön sopeutumisessa olivat ongelmat suomen kielen osaamisessa. Maahanmuuttajat tarvitsevat tukea ammattikielen oppimiseen sekä kollegoiltaan että työnantajaltaan. Muita suuria ongelmia olivat kulttuurierot, syrjintä ja sosiaalisten tukiverkostojen puute. Avoin keskustelu kulttuurieroista sekä kulttuurisen kompetenssin kohentamiseksi lisäkoulutuksen tarve niin sairaanhoitajille kuin hoitotyön johtajille nousivat esiin. Valmiissa videossa on kolme teemaa: kieli, kulttuuri ja vuorovaikutus. Jokaisesta teemasta on videolla kolme lyhyttä kohtausta, jotka draaman keinoin valaisevat maahanmuuttajahoitajien jokapäiväisiä ongelmia. Video on nähtävissä osoitteessa https://youtu.be/Hkp30u0aidc

Aggregation prediction; A bioinformatics method for studying the effects of missense variations on pathogenicity

 Background and Aims: Aggregation has been shown to be an intrinsic property of many proteins including proteins not involved in amyloid diseases. The most common types of protein aggregates are amyloid fibrils and amorphous aggregates characterized by an increase in the level of β-structure. Missense variations have the potential to change the propensity of a property to aggregate. Variation research in recent times has focused on obtaining information about the effects of sequence variations on proteins. Experimental study of the possible disease association of variants is laborious and time-consuming. Computational methods on the other hand give rapid automated results for large amounts of data sets but are less reliable. To use aggregation as mechanism to study the effects of missense variations on pathogenicity, it is important to predict the change in aggregation of proteins upon aggregation. There are several aggregation prediction methods available on the Internet making it difficult to find the best methods. This study evaluates the performance of five widely used aggregation prediction methods. Results from the aggregation prediction can then be used for pathogenicity prediction to determine how they correlate. Methods: Aggrescan, AmylPred consensus, Average Packing Density, TANGO and Hexapeptide Conformational Energy were the evaluated methods. The methods were tested with a dataset of 365 missense variations. Matthews correlation Coefficient, Sensitivity, Specificity, Accuracy, Precision and Negative Predictive Value were the measures used to evaluate the performance of the prediction methods. Results: Aggrescan performed best in MCC, accuracy, sensitivity and NPV show that is the best method. Tango performed best in precision (0.92) and specificity (0.95). Conclusion: From the results, all the methods showed good MCC values of above 0.59. It is easy to conclude that Aggrescan was the best amongst all the five methods followed by Tango. It is on the other hand difficult to recommend a specific method since all the methods depend on physicochemical properties and side chains in β-sheet aggregates making the algorithms in the methods give different results. It is therefore advisable for the end user to know much about the algorithms used before choosing a particular method for prediction. Asiasanat:Aggregation, Missense variations,Pathogenicity, Amyloid fibril

Aggregation prediction; A bioinformatics method for studying the effects of missense variations on pathogenicity

 Background and Aims: Aggregation has been shown to be an intrinsic property of many proteins including proteins not involved in amyloid diseases. The most common types of protein aggregates are amyloid fibrils and amorphous aggregates characterized by an increase in the level of β-structure. Missense variations have the potential to change the propensity of a property to aggregate. Variation research in recent times has focused on obtaining information about the effects of sequence variations on proteins. Experimental study of the possible disease association of variants is laborious and time-consuming. Computational methods on the other hand give rapid automated results for large amounts of data sets but are less reliable. To use aggregation as mechanism to study the effects of missense variations on pathogenicity, it is important to predict the change in aggregation of proteins upon aggregation. There are several aggregation prediction methods available on the Internet making it difficult to find the best methods. This study evaluates the performance of five widely used aggregation prediction methods. Results from the aggregation prediction can then be used for pathogenicity prediction to determine how they correlate. Methods: Aggrescan, AmylPred consensus, Average Packing Density, TANGO and Hexapeptide Conformational Energy were the evaluated methods. The methods were tested with a dataset of 365 missense variations. Matthews correlation Coefficient, Sensitivity, Specificity, Accuracy, Precision and Negative Predictive Value were the measures used to evaluate the performance of the prediction methods. Results: Aggrescan performed best in MCC, accuracy, sensitivity and NPV show that is the best method. Tango performed best in precision (0.92) and specificity (0.95). Conclusion: From the results, all the methods showed good MCC values of above 0.59. It is easy to conclude that Aggrescan was the best amongst all the five methods followed by Tango. It is on the other hand difficult to recommend a specific method since all the methods depend on physicochemical properties and side chains in β-sheet aggregates making the algorithms in the methods give different results. It is therefore advisable for the end user to know much about the algorithms used before choosing a particular method for prediction. Asiasanat:Aggregation, Missense variations,Pathogenicity, Amyloid fibril

Régulation du métabolisme du glycogène cérébral sous l'effet de la méthionine sulfoximine

La raison pour laquelle les neurones synchronisent leurs activités pour générer l épilepsie est toujours inconnue. Au cours de l épilepsie expérimentale et humaine, le métabolisme énergétique cérébral subit de profondes altérations. Nous recherchons un lien éventuel entre ces altérations et l épileptogenèse. Pour cela, nous avons utilisé le modèle d épilepsie induit par la méthionine sulfoximine. Sous l effet de ce convulsivant, le taux de glycogène augmente dans l encéphale d une série de lignées de souris, mais, la chronologie et l amplitude de cette augmentation varient d une ligne e à l autre. Un mécanisme pouvant expliquer cette augmentation pourrait être la baisse du taux de sérotonine observée dans l encéphale. En stimulant les récepteurs 5-HT1A par un dérivé pyridinergique présentant une forte affinité pour ces récepteurs, le taux de sérotonine augmente. Ce dérivé pourrait alors antagoniser les effets de la méthionine sulfoximine. Étant donné que la sérotonine peut cibler un certain nombre de protéines régulant le taux de glycogène, les transcrits de ces protéines ont été étudiés. Le taux de transcrits de la principale protéine régulatrice, la Protein Targeting to Glycogen n augmente pas. Il en est de même des transcrits de la glycogénine, de la glycogène synthase et de la phosphorylase. Il ressort de l ensemble de nos résultats que la méthionine sulfoximine augmente le taux de glycogène en agissant directement sur les astrocytes et en modulant le taux de sérotonine. Il reste à montrer si ce sont les altérations du métabolisme du glycogène et/ou les altérations de la neurotransmission sérotoninergique qui jouent un rôle prépondérant dans l épileptogenèse.ORLEANS-BU Sciences (452342104) / SudocSudocFranceF

Early, middle, and late stages of neural cells from ovine embryo in primary cultures

International audienc