Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

This work was supported by grants of the German Research Foundation (DFG: KR 4073/11-1; SFBTRR219, 322900939; and CRU344, 428857858, and CRU5011 InteraKD 445703531), a grant of the European Research Council (ERC-StG 677448), the Federal Ministry of Research and Education (BMBF NUM-COVID19, Organo-Strat 01KX2021), the Dutch Kidney Foundation (DKF) TASK FORCE consortium (CP1805), the Else Kroener Fresenius Foundation (2017_A144), and the ERA-CVD MENDAGE consortium (BMBF 01KL1907) all to R.K.; DFG (CRU 344, Z to I.G.C and CRU344 P2 to R.K.S.); and the BMBF eMed Consortium Fibromap (to V.G.P, R.K., R.K.S., and I.G.C.). R.K.S received support from the KWF Kankerbestrijding (11031/2017–1, Bas Mulder Award) and a grant by the ERC (deFiber; ERC-StG 757339). J.J. is supported by the Netherlands Organisation for Scientific Research (NWO Veni grant no: 091 501 61 81 01 36) and the DKF (grant no. 19OK005). B.S. is supported by the DKF (grant: 14A3D104) and the NWO (VIDI grant: 016.156.363). R.P.V.R. and G.J.O. are supported by the NWO VICI (grant: 16.VICI.170.090). P.B. is supported by the BMBF (DEFEAT PANDEMIcs, 01KX2021), the Federal Ministry of Health (German Registry for COVID-19 Autopsies-DeRegCOVID, www.DeRegCOVID.ukaachen.de; ZMVI1-2520COR201), and the German Research Foundation (DFG; SFB/TRR219 Project-IDs 322900939 and 454024652). S.D. received DFG support (DJ100/1-1) as well as support from VGP and TBH (SFB1192). M.d.B,R.R., N.S., and A.A. are supported by an ERC Advanced Investigator grant (H2020-ERC-2017-ADV-788982-COLMIN) to N.S. A.A. is supported by the NWO (VI.Veni.192.094). We thank Saskia de Wildt, Jeanne Pertijs (Radboudumc, Department of Pharmacology), and Robert M. Verdijk (Erasmus Medical Center, Department of Pathology) for providing tissue controls (Erasmus MC Tissue Bank) and Christian Drosten (Charite´ Universitatsmedizin Berlin, Institute of € Virology) and Bart Haagmans (Erasmus Medical Center, Rotterdam) for providing the SARS-CoV-2 isolate. We thank Kioa L. Wijnsma (Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children’s Hospital, Radboud University Medical Center) for support with statistical analysis regarding the COVID-19 patient cohort.Peer reviewedPublisher PD

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field