The <i>agr</i> inhibitors solonamide B and analogues alter immune responses to <i>Staphylococccus aureus</i> but do not exhibit adverse effects on immune cell functions

Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization

Identification and Engineering of Transporters for Efficient Melatonin Production in Escherichia coli

Transporter discovery and engineering play an important role in cell factory development. Decreasing the intracellular concentration of the product reduces product inhibition and/or toxicity. Lowering intracellular concentrations is especially beneficial for achieving a robust strain at high titers. However, the identification of transporters for xenobiotic chemicals in the host strain is challenging. Here we present a high-throughput workflow to discover Escherichia coli transporters responsible for the efflux of the inhibitory xenobiotic compound melatonin. We took advantage of the Keio collection and screened about 400 transporter knockouts in the presence of a high concentration of melatonin. We found five transporters that when knocked out showed decreased tolerance to melatonin, indicating they are exporters of melatonin. We overexpressed these five genes individually in the production strain and found that one of them, yhjV, encoding a transporter with unknown substrates, resulted in a 27% titer increase in cultivation mimicking fed-batch fermentation. This study demonstrates how microbial cell factories can be improved through transporter identification and engineering. Further, these results lay the foundation for the scale-up of melatonin production in E. coli

PENGARUH PENGGUNAAN MEDIA POSTER TERHADAP AKTIVITAS DAN HASIL BELAJAR SISWA (Penelitian Kuasi Eksperimen Kelas V SD Negeri Bojongasih 01 Kecamatan Dayeuhkolot Kabupaten Bandung)

Penelitian ini berjudul “Pengaruh Penggunaan Media Poster Terhadap Aktivitas dan Hasil Belajar Siswa”. Penelitian ini dilakukan di kelas V SD Negeri Bojongasih 01. Penelitian ini dilatar belakangi oleh rendahnya aktivitas dan hasil belajar siswa. Penelitian ini didasari temuan dalam kegiatan observasi pembelajaran dimana pembelajaran kurang melibatkan siswa, kemudian minimnya media pembelajaran yang digunakan ketika kegiatan pembelajaran berlangsung. Metode yang digunakan pada penelitian ini adalah kuasi eksperimen, dimana satu kelas merupakan kelas kontrol, dan satu kelas merupakan kelas eksperimen. Pada kelas eksperimen dilakukan tindakan dengan menggunakan media poster sebagai media pembelajaran. Instrumen yang digunakan pada penelitian ini adalah lembar observasi dan soal tes tertulis. Lembar observasi digunakan untuk mengukur aktivitas siswa di dalam kelas, sedangkan soal tes tertulis digunakan untuk mengukur hasil belajar siswa. Pembelajaran dengan menggunakan media poster dapat meningkatkan aktivitas siswa. Aktivitas siswa pada pembelajaran dengan menggunakan media poster dikategorikan baik, hal tersebut dapat dilihat dari banyaknya jumlah siswa aktif pada saat pembelajaran berlangsung. Kemudian hasil belajar siswa dengan menggunakan media poster menujukkan rata-rata sebesar 79.1 dimana sebanyak 78% siswa dikatakan tuntas. Berdasarkan data yang sudah diperoleh, maka dapat disimpulkan bahwa pembelajaran dengan menggunakan media poster dapat meningkatkan aktivitas dan hasil belajar siswa SD Negeri Bojongasih 01. Kata kunci : Media poster, aktivitas belajar, hasil belaja

COVID-19-krisen: Forløb og bekymringer: Artikel 1a

Denne artikel leverer en oversigt over og en gennemgang af de konkrete politiske indgreb, som den danske regering foretog med henblik på at opdæmme smittespredning i de første måneder af COVID-19-pandemien i Danmark 2020

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up lschaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CON-SORT) statement and provides clear and open reporting. Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Peer reviewe

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up lschaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CON-SORT) statement and provides clear and open reporting. Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Peer reviewe

Tidslinje : Artikel 1b

Dette er en oversigt over Coronasygdommens første måneder i Danmark

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Forord til temanummeret om COVID-19, religion og trivsel i Danmark