Influenza A viruses limit NLRP3‐NEK7‐complex formation and pyroptosis in human macrophages

Pyroptosis is a fulminant form of macrophage cell death, contributing to release of pro‐inflammatory cytokines. In humans, it depends on caspase 1/4‐activation of gasdermin D and is characterized by the release of cytoplasmic content. Pathogens apply strategies to avoid or antagonize this host response. We demonstrate here that a small accessory protein (PB1‐F2) of contemporary H5N1 and H3N2 influenza A viruses (IAV) curtails fulminant cell death of infected human macrophages. Infection of macrophages with a PB1‐F2‐deficient mutant of a contemporary IAV resulted in higher levels of caspase‐1 activation, cleavage of gasdermin D, and release of LDH and IL‐1β. Mechanistically, PB1‐F2 limits transition of NLRP3 from its auto‐repressed and closed confirmation into its active state. Consequently, interaction of a recently identified licensing kinase NEK7 with NLRP3 is diminished, which is required to initiate inflammasome assembly.     

Conformational study of bacterial lipopeptides: refinement of the structure of iturin A in solution by two-dimensional 1H-NMR and energy calculations

Iturin A is a lipopeptide extracted from strains of Bacillus subtilis. Seven peptide residues form a cycle closed by a β-amino acid carrying a hydrophobic tail. This compound is an antifungal and induces the formation of conducting pores in black lipid membranes. Two-dimensional ¹H-nmr was used for investigating its conformation in pyridine. A complete set of nuclear Overhauser effects (NOEs) was obtained from which interproton distances were deduced in a rather broad range of 2.2–4.2 Å. A special procedure was then used to optimize simultaneously experimental parameters and intramolecular energy calculated by semiempirical methods. A model of the conformation is proposed for the backbone for which there is an excellent coherence between NOEs, coupling constants, and intramolecular energy. The conformations of Asn, Gln, and Ser side chains appear to be much more flexible because of their interactions with the solvent. From this picture, iturin A seems to have a rather stiff ring surrounded by mobile side chains. Further studies of this lipopeptide and of other members of the family should enable us to approach some structure–activity relationships for this class of antibiotics.     

The photosensor protein Ppr of <Emphasis Type="Italic">Rhodocista centenaria</Emphasis> is linked to the chemotaxis signalling pathway

Background  

Rhodocista centenaria is a phototrophic α-proteobacterium exhibiting a phototactic behaviour visible as colony movement on agar plates directed to red light. As many phototrophic purple bacteria R. centenaria possesses a soluble photoactive yellow protein (Pyp). It exists as a long fusion protein, designated Ppr, consisting of three domains, the Pyp domain, a putative bilin binding domain (Bbd) and a histidine kinase domain (Pph). The Ppr protein is involved in the regulation of polyketide synthesis but it is still unclear, how this is connected to phototaxis and chemotaxis.     

A revision of <Emphasis Type="Italic">Gastrodia</Emphasis> (Orchidaceae: Epidendroideae,Gastrodieae) in tropical Africa

The holomycotrophic terrestrial orchids of tropical Africa are reassessed. Two new species of Gastrodia from tropical Africa are described, G. rwandensis from Rwanda and G. ballii from south-central Africa. The genus now comprises three species in tropical Africa. A key is provided to distinguish them from Gastrodia africana Kraenzl.     

Lipid biomarkers indicate different ecological niches and trophic relationships of the Arctic hyperiid amphipods Themisto abyssorum and T. libellula

The hyperiid amphipods Themisto libellula and T. abyssorum are important components of Arctic pelagic ecosystems. Both species are carnivorous and prey on mesozooplankton. They represent a substantial food source for marine vertebrates and are a key link between zooplankton secondary production and higher trophic levels. We present data on the total lipid content, lipid class and fatty acid composition of T. libellula and T. abyssorum from northern Fram Strait and the central Arctic Ocean. Both species had moderate to high lipid contents of 14-42% of body dry mass. In T. abyssorum, total lipid content was correlated to body mass, while T. libellula showed sex-related differences in lipid content. Despite their smaller body size, females of T. libellula had higher lipid contents than males. Wax esters represented the major lipid class in both species with 41-43% of total lipid, while triacylglycerols contributed 23-32%. The fatty acid composition was dominated by the long-chain polyunsaturated moieties 20:5(n-3) and 22:6(n-3), short-chain saturated compounds (16:0 and 14:0) and monounsaturated fatty acids of varying length, i.e. 16:1(n-7), 20:1(n-9), 18:1(n-9) and 22:1(n-11). Species-specific and geographic variations in the fatty acid and alcohol patterns were apparently linked to differences in diet and life-cycle. High amounts of the fatty acids and alcohols 20:1(n-9) and 22:1(n-11) in T. libellula indicate predation on herbivorous Calanus copepodids. In addition, elevated levels of 20:5(n-3) in T. libellula indicate a close connection with ice-algal production and the importance of cryo-pelagic coupling processes (i.e. exchange processes between the sea ice and the pelagic communities) for the nutrition of this high-Arctic epipelagic species. In contrast, T. abyssorum is characterised by lower amounts of 20:5(n-3) and its biomarker ratios indicate a higher trophic level. This observation is consistent with the subarctic-boreal origin of T. abyssorum and its occurrence in deeper layers of the Arctic Ocean, where it may feed on omnivorous and/or carnivorous prey.     

A Highlights from MBoC Selection: Insulin-promoted mobilization of GLUT4 from a perinuclear storage site requires RAB10

Insulin controls glucose uptake into muscle and fat cells by inducing a net redistribution of glucose transporter 4 (GLUT4) from intracellular storage to the plasma membrane (PM). The TBC1D4-RAB10 signaling module is required for insulin-stimulated GLUT4 translocation to the PM, although where it intersects GLUT4 traffic was unknown. Here we demonstrate that TBC1D4-RAB10 functions to control GLUT4 mobilization from a trans-Golgi network (TGN) storage compartment, establishing that insulin, in addition to regulating the PM proximal effects of GLUT4-containing vesicles docking to and fusion with the PM, also directly regulates the behavior of GLUT4 deeper within the cell. We also show that GLUT4 is retained in an element/domain of the TGN from which newly synthesized lysosomal proteins are targeted to the late endosomes and the ATP7A copper transporter is translocated to the PM by elevated copper. Insulin does not mobilize ATP7A nor does copper mobilize GLUT4, and RAB10 is not required for copper-elicited ATP7A mobilization. Consequently, GLUT4 intracellular sequestration and mobilization by insulin is achieved, in part, through utilizing a region of the TGN devoted to specialized cargo transport in general rather than being specific for GLUT4. Our results define the GLUT4-containing region of the TGN as a sorting and storage site from which different cargo are mobilized by distinct signals through unique molecular machinery.     

‘One Can Always Say No.’ Enriching the Bioethical Debate on Antisocial Behaviour,Neurobiology and Prevention: Views of Juvenile Delinquents

Genomic and neuro‐scientific research into the causes and course of antisocial behaviour triggers bioethical debate. Often, these new developments are met with reservation, and possible drawbacks and negative side‐effects are pointed out. This article reflects on these scientific developments and the bioethical debate by means of an exploration of the perspectives of one important stakeholder group: juveniles convicted of a serious crime who stay in a juvenile justice institution. The views of juveniles are particularly interesting, as possible applications of current and future scientific findings are considered to be most effective if applied early in life. Based on their statements we come to the following provisional conclusions. Concerns about labelling and stigmatization are recognized and widely shared. Possible effects on one's identity are acknowledged too. Yet, a possible biological underpinning of one's antisocial behaviour is not considered to result in the development of a criminal identity. Nonetheless, psychopharmacological interventions are experienced as endangering one's current self. Concerns regarding the refusal of responsibility and the blaming of one's genes or brain can be put into perspective. Instead, participants emphasize the motive of own choice as underlying their criminal behaviour. Moreover, bioethical debate should pay attention to the role of parents of children at risk and the parent‐child relationship in families at‐risk. We argue that the short‐term and long‐term interests of children at risk, as well as their interests and those of society at large, may conflict. In order to deal appropriately with newly arising dilemmas, a normative framework needs to be developed.