Human microbiota drives hospital-associated antimicrobial resistance dissemination in the urban environment and mirrors patient case rates

Background: The microbial community composition of urban environments is primarily determined by human activity. The use of metagenomics to explore how microbial communities are shaped in a city provides a novel input that can improve decisions on public health measures, architectural design, and urban resilience. Of note, the sewage system in a city acts as a complex reservoir of bacteria, pharmaceuticals, and antimicrobial resistant (AMR) genes that can be an important source of epidemiological information. Hospital effluents are rich in patient-derived bacteria and can thus readily become a birthplace and hotspot reservoir for antibiotic resistant pathogens which are eventually incorporated into the environment. Yet, the scope to which nosocomial outbreaks impact the urban environment is still poorly understood. Results: In this work, we extensively show that different urban waters from creeks, beaches, sewage spillways and collector pipes enclose discrete microbial communities that are characterized by a differential degree of contamination and admixture with human-derived bacteria. The abundance of human bacteria correlates with the abundance of AMR genes in the environment, with beta-lactamases being the top-contributing class to distinguish low vs.highly-impacted urban environments. Indeed, the abundance of beta-lactamase resistance and carbapenem resistance determinants in the urban environment significantly increased in a 1-year period. This was in line with a pronounced increase of nosocomial carbapenem-resistant infections reported during the same period that was mainly driven by an outbreak-causing, carbapenemase-producing Klebsiella pneumoniae (KPC) ST-11 strain. Genome-resolved metagenomics of urban waters before and after this outbreak, coupled with high-resolution whole-genome sequencing, confirmed the dissemination of the ST-11 strain and a novel KPC megaplasmid from the hospital to the urban environment. City-wide analysis showed that geospatial dissemination of the KPC megaplasmid in the urban environment inversely depended on the sewage system infrastructure. Conclusions: We show how urban metagenomics and outbreak genomic surveillance can be coupled to generate relevant information for infection control, antibiotic stewardship, and pathogen epidemiology. Our results highlight.ANII: POS_FSA_2019_1_1008860

The Tax Subsidy War: Digital Battlefront

We argue that the high revenue triggers in proposed digital taxes — including the recent Franco-German proposal for a digital advertising tax — may violate state-aid law and prohibitions on nationality discrimination in the Treaty on the Functioning of the European Union. We explain how both digital taxes adopted by particular member states and digital taxes as an EU directive may discriminate against the EU subsidiaries of US-headquartered tech companies. Our arguments depend critically on two features of proposed digital taxes: (a) their high revenue triggers, which ensure that only very large, and therefore disproportionately foreign, companies pay digital taxes; and (b) their narrow scope, which ensures that only companies operating in specific disfavored sectors face taxation. To the extent that any digital tax proposal (whether unilateral or EU) ends up sharing these features, it would face the same challenges. If those flaws were corrected, digital taxes would be less discriminatory, but also less politically palatable

Company Size Matters

Considers whether company size classification under EU Member States' tax laws may be indirect nationality discrimination and a breach of fundamental freedoms. Reviews the ECJ's approaches to discrimination in facially suspect and facially neutral classifications, the challenges of proving intention to discriminate, the justification for company size classification, and whether digital services tax amounts to indirect nationality discrimination

Transcription Factor KLF7 Is Important for Neuronal Morphogenesis in Selected Regions of the Nervous System

The Krüppel-like transcription factors (KLFs) are important regulators of cell proliferation and differentiation in several different organ systems. The mouse Klf7 gene is strongly active in postmitotic neuroblasts of the developing nervous system, and the corresponding protein stimulates transcription of the cyclin-dependent kinase inhibitor p21(waf/cip) gene. Here we report that loss of KLF7 activity in mice leads to neonatal lethality and a complex phenotype which is associated with deficits in neurite outgrowth and axonal misprojection at selected anatomical locations of the nervous system. Affected axon pathways include those of the olfactory and visual systems, the cerebral cortex, and the hippocampus. In situ hybridizations and immunoblots correlated loss of KLF7 activity in the olfactory epithelium with significant downregulation of the p21(waf/cip) and p27(kip1) genes. Cotransfection experiments extended the last finding by documenting KLF7's ability to transactivate a reporter gene construct driven by the proximal promoter of p27(kip1). Consistent with emerging evidence for a role of Cip/Kip proteins in cytoskeletal dynamics, we also documented p21(waf/cip) and p27(kip1) accumulation in the cytoplasm of differentiating olfactory sensory neurons. KLF7 activity might therefore control neuronal morphogenesis in part by optimizing the levels of molecules that promote axon outgrowth