Small Molecules Targeting Human UDP-GlcNAc 2-Epimerase

Uridine diphosphate N-acetylglucosamine 2-epimerase (GNE) is a key enzyme in the sialic acid biosynthesis pathway. Sialic acids are primarily terminal carbohydrates on glycans and play fundamental roles in health and disease. In search of effective GNE inhibitors not based on a carbohydrate scaffold, we performed a high-throughput screening campaign of 68,640 drug-like small molecules against recombinant GNE using a UDP detection assay. We validated nine of the primary actives with an orthogonal real-time NMR assay and verified their IC50 values in the low micromolar to nanomolar range manually. Stability and solubility studies revealed three compounds for further evaluation. Thermal shift assays, analytical size exclusion, and interferometric scattering microscopy demonstrated that the GNE inhibitors acted on the oligomeric state of the protein. Finally, hydrogen-deuterium exchange mass spectrometry (HDX-MS) revealed which sections of GNE were shifted upon the addition of the inhibitors. In summary, we have identified three small molecules as GNE inhibitors with high potency in vitro, which serve as promising candidates to modulate sialic acid biosynthesis in more complex systems

Identification of low-acuity attendances in routine clinical information documented in German Emergency Departments

Abstract Introduction It has not yet been possible to ascertain the exact proportion, characterization or impact of low-acuity emergency department (ED) attendances on the German Health Care System since valid and robust definitions to be applied in German ED routine data are missing. Methods Internationally used methods and parameters to identify low-acuity ED attendances were identified, analyzed and then applied to routine ED data from two EDs of the tertiary care hospitals Charité—Universitätsmedizin Berlin, Campus Mitte (CCM) and Campus Virchow (CVK). Results Based on the three routinely available parameters `disposition´, `transport to the ED´ and `triage´ 33.2% (n = 30 676) out of 92 477 presentations to the two EDs of Charité—Universitätsmedizin Berlin (CVK, CCM) in 2016 could be classified as low-acuity presentations. Conclusion This study provides a reliable and replicable means of retrospective identification and quantification of low-acuity attendances in German ED routine data. This enables both intra-national and international comparisons of figures across future studies and health care monitoring

Zur Sache!

In den letzten Jahren ist ein verstärktes Interesse an objektbasierter Forschung vor allem in den Sozial- und Kulturwissenschaften zu beobachten. Auch die neuere Wissenschaftsgeschichte interessierte sich besonders für die materiellen Kulturen der Wissenschaft und lenkte die Aufmerksamkeit auf universitäre Sammlungen, deren Objekte Aufschluss geben über (historische) wissenschaftliche Arbeitspraktiken und die materiellen Bedingungen wissenschaftlicher Erkenntnisprozesse. Dieser Band vereint 13 Beiträge von Nachwuchswissenschaftler_innen aus den Bereichen Kunstgeschichte, Kulturanthropologie, Archäologie und Restaurierungswissenschaften sowie Ethnologie und Wissenschaftsgeschichte, die sich diesem Feld mit je unterschiedlichen Fragestellungen und Analysemethoden nähern. Eine Reflexion über forschungsleitende methodische Aspekte und theoretische Herangehensweise objektbasierter Forschung bildet einen gemeinsamen Referenzpunkt der Beiträge.Peer Reviewe

ProDeGe: a computational protocol for fully automated decontamination of genomes

Single amplified genomes and genomes assembled from metagenomes have enabled the exploration of uncultured microorganisms at an unprecedented scale. However, both these types of products are plagued by contamination. Since these genomes are now being generated in a high-throughput manner and sequences from them are propagating into public databases to drive novel scientific discoveries, rigorous quality controls and decontamination protocols are urgently needed. Here, we present ProDeGe (Protocol for fully automated Decontamination of Genomes), the first computational protocol for fully automated decontamination of draft genomes. ProDeGe classifies sequences into two classes—clean and contaminant—using a combination of homology and feature-based methodologies. On average, 84% of sequence from the non-target organism is removed from the data set (specificity) and 84% of the sequence from the target organism is retained (sensitivity). The procedure operates successfully at a rate of ~0.30 CPU core hours per megabase of sequence and can be applied to any type of genome sequence

Valorization of Marine Waste: Use of Industrial By-Products and Beach Wrack Towards the Production of High Added-Value Products

Biomass is defined as organic matter from living organisms represented in all kingdoms. It is recognized to be an excellent source of proteins, polysaccharides and lipids and, as such, embodies a tailored feedstock for new products and processes to apply in green industries. The industrial processes focused on the valorization of terrestrial biomass are well established, but marine sources still represent an untapped resource. Oceans and seas occupy over 70% of the Earth’s surface and are used intensively in worldwide economies through the fishery industry, as logistical routes, for mining ores and exploitation of fossil fuels, among others. All these activities produce waste. The other source of unused biomass derives from the beach wrack or washed-ashore organic material, especially in highly eutrophicated marine ecosystems. The development of high-added-value products from these side streams has been given priority in recent years due to the detection of a broad range of biopolymers, multiple nutrients and functional compounds that could find applications for human consumption or use in livestock/pet food, pharmaceutical and other industries. This review comprises a broad thematic approach in marine waste valorization, addressing the main achievements in marine biotechnology for advancing the circular economy, ranging from bioremediation applications for pollution treatment to energy and valorization for biomedical applications. It also includes a broad overview of the valorization of side streams in three selected case study areas: Norway, Scotland, and the Baltic Sea.</p&gt

Valorization of Marine Waste : Use of Industrial By-Products and Beach Wrack Towards the Production of High Added-Value Products

Biomass is defined as organic matter from living organisms represented in all kingdoms. It is recognized to be an excellent source of proteins, polysaccharides and lipids and, as such, embodies a tailored feedstock for new products and processes to apply in green industries. The industrial processes focused on the valorization of terrestrial biomass are well established, but marine sources still represent an untapped resource. Oceans and seas occupy over 70% of the Earth's surface and are used intensively in worldwide economies through the fishery industry, as logistical routes, for mining ores and exploitation of fossil fuels, among others. All these activities produce waste. The other source of unused biomass derives from the beach wrack or washed-ashore organic material, especially in highly eutrophicated marine ecosystems. The development of high-added-value products from these side streams has been given priority in recent years due to the detection of a broad range of biopolymers, multiple nutrients and functional compounds that could find applications for human consumption or use in livestock/pet food, pharmaceutical and other industries. This review comprises a broad thematic approach in marine waste valorization, addressing the main achievements in marine biotechnology for advancing the circular economy, ranging from bioremediation applications for pollution treatment to energy and valorization for biomedical applications. It also includes a broad overview of the valorization of side streams in three selected case study areas: Norway, Scotland, and the Baltic Sea.</p&gt