Pivmecillinam, a pro-drug of mecillinam, has been used extensively in Scandinavia for the treatment of acute lower urinary tract infections (UTIs) caused by Enterobacterales. It is still an attractive first-line drug for the empirical treatment of UTIs owing to the low prevalence of resistance as well as its favourable impact on the intestinal microbiota as a pro-drug and good in vitro efficacy ...

Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive‐CRP (hs‐CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA‐<i>life</i>), a prospective population‐based cohort study, 7,356 men were included. Prediagnostic WBC and hs‐CRP were assessed ...

Despite the fact that the transcription factor ATOH1 is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependent oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, which is one of the most ...

The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease. Our understanding of the mitochondrial signals that trigger their recognition and targeting by mitophagy is limited. Here, we show that the mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog ...

Accumulating evidence suggests that constitutively active Nrf2 has a pivotal role in cancer as it induces pro-survival genes that promote cancer cell proliferation and chemoresistance. The mechanisms of Nrf2 dysregulation and functions in cancer have not been fully characterized. Here, we jointly analyzed the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Atlas (TCGA) ...

A new study shows that the oligomerization of p62/Sequestosome-1 (SQSTM1) — a selective autophagy receptor and signaling adapter — is regulated directly by vault RNA. This riboregulation negatively affects the aggregation state of p62 and thereby its autophagic degradation and its role as a selective autophagy receptor.

Mammalian homologs of yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains ill‐defined. Syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was recently shown to bind mAtg8s. Here, we identified LC3‐interacting regions (LIRs) in several SNAREs that broaden the landscape of the mAtg8‐SNARE interactions. We found that Syntaxin 16 (Stx16) and its cognate ...

The mammalian ATG8 proteins (LC3A-C/GABARAP, GABARAPL1, and GABARAPL2) are small ubiquitin-like proteins critically involved in macroautophagy. Their processed C-termini are posttranslationally conjugated to a phosphatidylethanolamine moiety, enabling their insertion into the lipid bilayers of both the inner and outer membranes of the forming autophagosomes. The ATG8s bind a diverse selection of ...

Based on the cabozantinib scaffold, novel c‐Met inhibitors were rationalized from the limited knowledge of structure‐activity relationships for the quinoline 6‐position. Emphasis was given to modifications capable of engaging in additional polar interactions with the c‐Met active site. In addition, <i>ortho</i>‐fluorinations of the terminal benzene ring were explored. Fifteen new molecules were ...

<i>Background</i> - Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of ...