TMEM16 scramblases thin the membrane to enable lipid scrambling

TMEM16 scramblases dissipate the plasma membrane lipid asymmetry to activate multiple eukaryotic cellular pathways. It was proposed that lipid headgroups move between leaflets through a membrane-spanning hydrophilic groove. Direct information on lipid-groove interactions is lacking. We report the 2.3 Å resolution cryoEM structure of the Ca2+-bound afTMEM16 scramblase in nanodiscs showing how rearrangement of individual lipids at the open pathway results in pronounced membrane thinning. Only the groove’s intracellular vestibule contacts lipids, and mutagenesis suggests scrambling does not entail specific protein-lipid interactions with the extracellular vestibule. Further, we find scrambling can occur outside a closed groove in thinner membranes and is inhibited in thicker membranes despite an open pathway. Our results show how afTMEM16 thins the membrane to enable scrambling and that an open hydrophilic pathway is not a structural requirement to allow rapid transbilayer movement of lipids. This mechanism could be extended to other scramblases lacking a hydrophilic groove.

Processing of the Mandarin polarity item renhe ‘any’

The Mandarin renhe is similar to the English any in terms of polarity sensitivity (Wang 1993; Wang & Hsieh 1996; Kuo 2003; Cheng & Giannakidou 2013; Shyu 2016). However, the following phenomena regarding any in relative clause environments have not been surveyed with respect to renhe: (a) the NPI illusion effect reported in studies like Parker & Phillips (2011; 2016); (b) the subtrigging effect discussed in LeGrand (1975) and Dayal (1998; 2004). We conducted two untimed, offline acceptability judgment experiments and the results suggest that: (i) NPI illusion does not appear in Mandarin in untimed offline processing, (ii) the subtrigging effect of renhe holds, and (iii) renhe can be licensed by certain types of declarative verbs like tongyi ‘agree’ and zancheng ‘approve’. The results confirm the strict structural requirement of the c-commanding relation between a negation licensor and renhe (Wang 1993) and the licensing of renhe in non-veridical contexts (Cheng & Giannakidou 2013), and further suggest additional licensing environments for renhe: relative clauses and declarative verbs. This requires reconsideration of positing non-veridicality as a necessary licensing condition for renhe and calls for future research on how renhe is licensed under these two licensing environments.

HSV-1 UL34 mutants that affect membrane budding regulation and nuclear lamina disruption

Nuclear envelope budding in herpesvirus nuclear egress may be negatively regulated, since the pUL31/pUL34 nuclear egress complex heterodimer can induce membrane budding without capsids when expressed ectopically or on artificial membranes in vitro, but not in the infected cell. We have previously described a pUL34 mutant that contained alanine substitutions at R158 and R161, and that showed impaired growth, impaired pUL31/pUL34 interaction, and unregulated budding. Here we determine the phenotypic contributions of the individual substitutions to these phenotypes. Neither substitution alone was able to reproduce the impaired growth or NEC interaction phenotypes. Either substitution, however, could fully reproduce the unregulated budding phenotype, suggesting that mis-regulated budding may not substantially impair virus replication. Additionally, the R158A substitution caused re-localization of the NEC to intranuclear punctate structures and recruited lamin A/C to those structures, suggesting that this residue might be important for recruitment of kinases for dispersal of nuclear lamins. Importance Herpesvirus nuclear egress is a complex, regulated process coordinated by two virus proteins that are conserved among the herpesviruses that form a heterodimeric nuclear egress complex (NEC). The NEC drives budding of capsids at the inner nuclear membrane, and recruits other viral and host cell proteins for disruption of the nuclear lamina, membrane scission and fusion. The structural basis of individual activities of the NEC, apart from membrane budding, are not clear, nor is the basis of the regulation of membrane budding. Here we explore the properties of NEC mutants that have an unregulated budding phenotype, determine the significance of that regulation for virus replication, and also characterize a structural requirement for nuclear lamina disruption.

What Is It Like to Be a Bot?

This chapter seeks to further develop, define, and differentiate human-technics alterity relations within postphenomenological philosophy of technology. A central case study of the Alexa digital assistant establishes that digital assistants require the adoption of the intentional stance, and illustrates that this structural requirement is different from anthropomorphic projection of mindedness onto technical objects. Human-technics alterity relations based on projection are then more generally differentiated from human-technics alterity relations based on actual encoded pseudo-mental contents, where there are matters of fact that directly correspond to user conceptualizations of “intentions” or “knowledge” in technical systems or objects. Finally, functions and user benefits to different alterity relations are explored, establishing that there is a meaningful set of cases where the projection of a mind in human-technics alterity relations positively impacts technical functions and user experiences.

A β-hairpin epitope as novel structural requirement for protein arginine rhamnosylation

For bacterial arginine rhamnosylation, the rhamnosyltransferase EarP specifically recognizes a β-hairpin structure in the acceptor substrate.

Application of Biophysical Techniques to Investigate the Interaction of Antimicrobial Peptides With Bacterial Cells

Gaining new understanding on the mechanism of action of antimicrobial peptides is the basis for the design of new and more efficient antibiotics. To this aim, it is important to detect modifications occurring to both the peptide and the bacterial cell upon interaction; this will help to understand the peptide structural requirement, if any, at the base of the interaction as well as the pathways triggered by peptides ending in cell death. A limited number of papers have described the interaction of peptides with bacterial cells, although most of the studies published so far have been focused on model membrane-peptides interactions. Investigations carried out with bacterial cells highlighted the limitations connected to the use of oversimplified model membranes and, more importantly, helped to identify molecular targets of antimicrobial peptides and changes occurring to the bacterial membrane. In this review, details on the mechanism of action of antimicrobial peptides, as determined by the application of spectroscopic techniques, as well as scattering, microscopy, and calorimetry techniques, to complex systems such as peptide/bacteria mixtures are discussed.

Recently isolated lycodine-type Lycopodium alkaloids and their total synthesis: a review

Background Since long back, several plants species belonging to family Lycopodiaceae or Huperziaceae are being traditionally used in treatment of diseases like Alzheimer’s disease and myasthenia gravis. In 1986, huperzine A, structurally lycodine type of alkaloid was isolated and established as potent acetylcholine esterase inhibitor. Hence, further, in pursuit of similar compounds, several hundreds of different types of lycopodium alkaloids have been isolated from different Lycopodiaceae or Huperziaceae plants species. Main body For few of these recently isolated alkaloids, the possible mechanisms of their biosynthesis have been proposed while few of them were tried for their laboratory total asymmetric synthesis. This review summarized lycodine-type Lycopodium alkaloids, whose isolation, biosynthesis, and total synthesis have been reported after 2000. It also includes structure–activity relationship. Short conclusion More than 40 lycodine-type alkaloids have been isolated and structurally elucidated since 2000. Their biosynthetic pathway suggested that they got biosynthesized from lysine, while structure–activity relationship established the structural requirement of lycodine-type alkaloids to possess potent acetylcholine esterase inhibitory activity.