Aqueous two-phase extraction of proteins and enzymes using tetraalkylammonium-based ionic liquids

Within the scope of this thesis, the application of ionic liquids (IL) for the generation of aqueous two-phase systems (IL-based ATPS) and their use for the purification of catalytically active enzymes was evaluated. By studying the partitioning of different model proteins, a deeper understanding of the mechanisms influencing the partition process is provided. The IL AmmoengTM 110 in combination with an inorganic salt (K2HPO4/KH2PO4) can be used to establish an IL-based ATPS for the selective purification of two alcohol dehydrogenases. The presence of IL within the system was found to be advantageous due to its stability enhancing effect on both enzymes and its solubility enhancing effect on hydrophobic substrates

Consequences of the progression law in the FET phase: a case study

The progression law, which restricts grade repetition to once within each of the four phasesof basic education, has only been enforced in the Further Education and Training (FET)phase since 2013. The first cohort of progressed learners reached grade 12 in 2014. Weinvestigate the extent of progression in 2014 in various school quintiles and the observedand speculated future consequences of the progression law in the FET phase. Our mainlyquantitative data includes numbers and pass rates for the entire Free State (FS) province,with a focus on the Motheo district. We also draw on some qualitative data in the forms ofquestionnaires and reports from teachers and mentors working in 22 low quintile schools inMotheo. Our findings show marked differences in extents and impacts of progressionbetween the school quintiles, with low quintile schools acutely impacted and withdifficulties likely to escalate in the next few years

Binding between the neural cell adhesion molecules axonin-1 and Nr- CAM/Bravo is involved in neuron-glia interaction

Neural cell adhesion molecules of the immunoglobulin superfamily mediate cellular interactions via homophilic binding to identical molecules and heterophilic binding to other family members or structurally unrelated cell-surface glycoproteins. Here we report on an interaction between axonin-1 and Nr-CAM/Bravo. In search for novel ligands of axonin-1, fluorescent polystyrene microspheres conjugated with axonin-1 were found to bind to peripheral glial cells from dorsal root ganglia. By antibody blockage experiments an axonin-1 receptor on the glial cells was identified as Nr-CAM. The specificity of the interaction was confirmed with binding studies using purified axonin-1 and Nr-CAM. In cultures of dissociated dorsal root ganglia antibodies against axonin-1 and Nr-CAM perturbed the formation of contacts between neurites and peripheral glial cells. Together, these results implicate a binding between axonin-1 of the neuritic and Nr-CAM of the glial cell membrane in the early phase of axon ensheathment in the peripheral nervous system

Lipids in local anesthetic toxicity

INTRODUCTION: With the advent of long-lasting local anesthetics, local and regional anesthesia gained considerable impetus and the use of these techniques has become increasingly widespread. New block techniques have been described and regional anesthesia is frequently associated with general anesthesia to provide postoperative analgesia. In contrast, large doses of local anesthetics are required with the risk of accidents due to inadvertent intravascular injection, which is a severe complication without a specific treatment until a few years ago. In 1998, the use of lipid emulsions was proposed in animals. Since 2006, many studies have demonstrated an interest in these solutions in cases of local anesthetic-induced toxicity with a decrease in morbidity and mortality. The aim of this review article was to research the methodology, reviewing mechanisms, interests, limitations and currently recommended treatment. METHOD: Some historical references on local anesthetics, articles published during the last 30 years in journals indexed in Medline and in two textbooks were reviewed. Articles on local anesthetic toxicity, lipid emulsion therapy, review articles on the topic and treatment adopted in diverse services and countries were selected, producing a summary. CONCLUSIONS: It is no longer necessary to show the effectiveness and interest in lipid emulsion therapy for local anesthetic toxicity. Various specialty societies have already published their guidelines and advice about stocking these products in any setting in which local and regional anesthetic techniques are practiced.INTRODUÇÃO: Com o advento dos anestésicos locais de longa duração, a anestesia locorregional ganhou grande impulso sendo cada vez mais utilizada. Novas técnicas de bloqueios foram descritas e a técnica é frequentemente associada à anestesia geral com o objetivo de proporcionar analgesia pós-operatória. A contra-partida é a necessidade da utilização de grandes doses com risco de acidentes por injeção intravascular inadvertida; trata-se de complicação grave sem tratamento específico até há alguns anos. Em 1998 foi proposta a utilização de emulsões lipídicas em animais e a partir de 2006 vários trabalhos demonstraram o interesse dessas soluções nos casos de intoxicações por anestésicos locais com diminuição da morbi-mortalidade. O objetivo desta revisão foi fazer um levantamento da metodologia, revisando os mecanismos, interesses, limites e as condutas preconizadas atualmente. MÉTODO: Foram revistas algumas referências históricas sobre anestésicos locais, artigos publicados nos últimos 30 anos em revistas indexadas no Medline e em dois livros-texto. Foram selecionados os artigos que tratavam da intoxicação por anestésicos locais, da terapia com emulsões lipídicas, os de revisão sobre o assunto e as condutas adotadas em diversos serviços e países, sendo realizada uma síntese. CONCLUSÕES: A eficiência e interesse da terapia com emulsões lipídicas nas intoxicações por anestésicos locais não é mais a demonstrar; várias sociedades da especialidade já publicaram suas diretrizes e aconselham que se disponha desses produtos nos locais onde se pratica a anestesia locorregional.16917

Efeitos hemodinâmicos da injeção endovenosa de ropivacaína e levobupivacaína em suínos

PURPOSE: To compare the hemodynamic effects following a toxic dose of either agent after intravenous injection in swines, as might accidentally occur during regional anesthesia in humans. METHODS: Large White pigs were anesthetized with thiopental, tracheal intubation was performed and mechanical ventilation was instituted. Hemodynamic variables were recorded with invasive pressure monitoring and pulmonary artery catheterization. After a 30-minute resting period, the animals were randomly divided into two groups in a double-blinded fashion and received a bolus intravenous injection of 4 mg.kg-1 of either agent. Hemodynamic results were evaluated at rest and 1, 5, 10, 15, 20 and 30 minutes after intoxication. RESULTS: Hemodynamic repressions of acute intoxication with levobupivacaine were more important and more prolonged than those of ropivacaína. CONCLUSION: In pigs, levobupivacaine was shown to be more toxic than ropivacaine when the same large doses are injected intravenously.OBJETIVO: Comparar as repercussões hemodinâmicas após a injeção endovenosa dos dois agentes em suínos simulando a intoxicação que pode ocorrer durante uma anestesia locorregional em humanos. MÉTODOS: Suínos da raça Large-White foram anestesiados com tiopental, realizada intubação traqueal e instituída ventilação controlada mecânica. As variáveis hemodinâmicas foram medidas através de monitorização invasiva da pressão arterial e cateterização de artéria pulmonar. Após período de repouso de 30 minutos os animais foram aleatoriamente e em duplo-cego divididos em dois grupos e receberam por via endovenosa 4 mg.kg-1 de um ou outro agente. Os resultados hemodinâmicos foram avaliados em repouso e 1, 5, 10, 15, 20 e 30 minutos após a intoxicação. RESULTADOS: As repercussões hemodinâmicas da intoxicação aguda com levobupivacaína foram mais importantes e mais prolongadas do que as com ropivacaína. CONCLUSÃO: Em suínos, a levobupivacaína foi mais tóxica do que a ropivacaína quando as mesmas grandes doses são injetadas por via endovenosa.29630

Register: Language Users’ Knowledge of Situational-Functional Variation

The Collaborative Research Center 1412 “Register: Language Users’ Knowledge of Situational-Functional Variation” (CRC 1412) investigates the role of register in language, focusing in particular on what constitutes a language user’s register knowledge and which situational-functional factors determine a user’s choices. The following paper is an extract from the frame text of the proposal for the CRC 1412, which was submitted to the Deutsche Forschungsgemeinschaft in 2019, followed by a successful onsite evaluation that took place in 2019. The CRC 1412 then started its work on January 1, 2020. The theoretical part of the frame text gives an extensive overview of the theoretical and empirical perspectives on register knowledge from the viewpoint of 2019. Due to the high collaborative effort of all PIs involved, the frame text is unique in its scope on register research, encompassing register-relevant aspects from variationist approaches, psycholinguistics, grammatical theory, acquisition theory, historical linguistics, phonology, phonetics, typology, corpus linguistics, and computational linguistics, as well as qualitative and quantitative modeling. Although our positions and hypotheses since its submission have developed further, the frame text is still a vital resource as a compilation of state-of-the-art register research and a documentation of the start of the CRC 1412. The theoretical part without administrative components therefore presents an ideal starter publication to kick off the CRC’s publication series REALIS. For an overview of the projects and more information on the CRC, see https://sfb1412.hu-berlin.de/

ORCID DE 2 – Konsolidierung der ORCID-Informationsinfrastruktur in Deutschland

[No abstract available

MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era.

BACKGROUND: Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. METHODS: We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009-2010; (2) MDR strains from the Nhlangano region, 2014-2017). RESULTS: MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987-1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. CONCLUSION: The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently