Ribosome engineering to promote new crystal forms

Truncation of ribosomal protein L9 in T. thermophilus allows the generation of new crystal forms and the crystallization of ribosome–GTPase complexes

Производительность труда на предприятии: оценка и направления повышения (на примере ОАО «Гомельский завод станочных узлов»)

Penicillin-binding proteins (PBPs) are enzymes responsible for the polymerization of the glycan strand and the cross-linking between glycan chains as well as the target proteins for beta-lactam antibiotics. Mutational alterations in PBPs can confer resistance either by reducing binding of the antibiotic to the active site or by evolving a beta-lactamase activity that degrades the antibiotic. As no systematic studies have been performed to examine the potential of all PBPs present in one bacterial species to evolve increased resistance against beta-lactam antibiotics, we explored the ability of fifteen different defined or putative PBPs in Salmonella enterica to acquire increased resistance against penicillin G. We could after mutagenesis and selection in presence of penicillin G isolate mutants with amino-acid substitutions in the PBPs, FtsI, DacB and DacC (corresponding to PBP3, PBP4 and PBP6) with increased resistance against b-lactam antibiotics. Our results suggest that: (i) most evolved PBPs became 'generalists" with increased resistance against several different classes of b-lactam antibiotics, (ii) synergistic interactions between mutations conferring antibiotic resistance are common and (iii) the mechanism of resistance of these mutants could be to make the active site more accessible for water allowing hydrolysis or less binding to b-lactam antibiotics

Arbeidsplassbasert barnehagelærerutdanning : studenters erfaringer med veiledning under studiet

The purpose of this article is to increase insight into how mentoring in the workplace is experienced by students in work-based early childhood teacher education. Kindergarten plays a key role as a learning environment in the course of the students, and the goal of the mentoring given here is to support the students’ learning process. The results are based on qualitative data from focus group interviews, and show that students perceive mentoring as a meaningful contribution to their learning process. However, we find large variations in the way things are organized, and the clarification of roles is a topic rarely articulated between students and mentors. In particular, the absence of such clarification in the transition to the student role seems to create challenges for the students.Artikkelens hensikt er å bidra til økt innsikt i hvordan veiledning på egen arbeidsplass erfares av studenter på arbeidsplassbasert barnehagelærerutdanning. Barnehagen er en viktig læringsarena i studietiden, og veiledning i egen barnehage skal støtte studentenes læringsprosess. Resultatene er basert på kvalitative data fra fokusgruppeintervju, og viser at studentene opplever veiledning som et betydningsfullt bidrag til egen læring. Imidlertid finner vi store variasjoner i organisering, og at rolleavklaring mellom studenter og veiledere har vært et lite artikulert tema. Spesielt synes fraværet av rolleavklaring i overgangen til studentrollen å skape utfordringer for studenten.publishedVersio

"Jeg føler jeg står litt sånn imellom". Studenters grensekryssinger i arbeidsplassbasert barnehagelærerutdanning

Artikkelens hensikt er å bidra til økt innsikt i faktorer som har betydning for at barnehagen skal fungere som læringsarena for studenter ved arbeidsplassbasert barnehagelærerutdanning (ABLU). ABLU-studenter arbeider i barnehage parallelt med studiene. Gjennom utdanningsløpet opplever de kontinuerlige grensekryssinger mellom å være student og assistent, samt en grensekryssing fra assistent til barnehagelærerrollen. Resultatene baseres på kvalitative data fra fokusgruppeintervju. Problemstillingen er: Hvordan kan barnehagen være en støttende læringsarena i ABLU-studenters grensekryssinger? Funnene viser til utfordringer studentene møter underveis i grensekryssingene, primært knyttet til å synliggjøre og bruke fagkunnskapen sin på egen arbeidsplass under utdanningsløpet. Støtte og forventningsavklaringer fremtrer som nødvendige faktorer for at barnehagen skal fungere optimalt som læringsarena når studentene utvikler profesjonsidentitet og krysser grenser mellom ulike praksisfellesskap i praksislandskapet.publishedVersio

Structure and function of FusB: an elongation factor G-binding fusidic acid resistance protein active in ribosomal translocation and recycling

Fusidic acid (FA) is a bacteriostatic antibiotic that locks elongation factor G (EF-G) to the ribosome after GTP hydrolysis during elongation and ribosome recycling. The plasmid pUB101-encoded protein FusB causes FA resistance in clinical isolates of Staphylococcus aureus through an interaction with EF-G. Here, we report 1.6 and 2.3 Å crystal structures of FusB. We show that FusB is a two-domain protein lacking homology to known structures, where the N-terminal domain is a four-helix bundle and the C-terminal domain has an alpha/beta fold containing a C4 treble clef zinc finger motif and two loop regions with conserved basic residues. Using hybrid constructs between S. aureus EF-G that binds to FusB and Escherichia coli EF-G that does not, we show that the sequence determinants for FusB recognition reside in domain IV and involve the C-terminal helix of S. aureus EF-G. Further, using kinetic assays in a reconstituted translation system, we demonstrate that FusB can rescue FA inhibition of tRNA translocation as well as ribosome recycling. We propose that FusB rescues S. aureus from FA inhibition by preventing formation or facilitating dissociation of the FA-locked EF-G–ribosome complex

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

Background: Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment. Objectives: To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy. Methods: We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits. Results: We included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5–8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34). Conclusions: In this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.publishedVersio

Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment.publishedVersio

“The people who are out of ‘right’ English”: Japanese university students' social evaluations of English language diversity and the internationalisation of Japanese higher education

Previous research indicates that evaluations of speech forms reflect stereotypes of, and attitudes towards, the perceived group(s) of speakers of the language/variety under consideration. This study, employing both implicit and explicit attitude measures, investigates 158 Japanese university students' perceptions of forms of UK, US, Japanese, Chinese, Thai and Indian English speech. The results show a general convergence between students' explicit and implicit attitudes, for instance, regarding US and UK English as the most correct, and solidarity with Japanese speakers of English. The findings are discussed in relation to intergroup relations between the traditional Japanese cohort and specific groups of overseas students, particularly in light of recent internationalisation policies adopted by many Japanese universities, and the resultant increase in international students from South and East Asia

Identification of known and novel recurrent viral sequences in data from multiple patients and multiple cancers

Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified