Bacterial cell wall is targeted by many antibiotics. Among them are lantibiotics, which realize their function via interaction with transmembrane lipid-II molecule — a chemically conserved part of the cell wall synthesis pathway. To investigate structural and dynamic properties of this molecule, we have performed a series of nearly microsecond-long molecular dynamics simulations (MD) of lipid-II and some of its analogs in zwitterionic single component and charged mixed model phospholipid bilayers (the reference and mimic of the bacterial plasmatic membrane, respectively). Extensive analysis revealed that lipid-II forms a unique “amphiphilic pattern” exclusively on the surface of the model bacterial membrane (and not in the reference bilayer). We hypothesize that conserved features of lipid-II along with characteristic modulation of the bacterial membrane provide a recognition spot for many lantibiotics. This putative recognition mechanism opens new opportunities for studies on lantibiotics action and design of novel armament against resistant bacterial strains.
Archaeal plasma membranes appear to be extremely durable and almost impermeable to water and ions, in contrast to the membranes of Bacteria and Eucaryota. Additionally, they remain liquid within a temperature range of 0–100° С. These are the properties that have most likely determined the evolutionary fate of Archaea, and it may be possible for bionanotechnology to adopt these from nature. In this work, we use molecular dynamics simulations to assess at the atomic level the structure and dynamics of a series of model archaeal membranes with lipids that have tetraether chemical nature and “branched” hydrophobic tails. We conclude that the branched structure defines dense packing and low water permeability of archaeal-like membranes, while at the same time ensuring a liquid-crystalline state, which is vital for living cells. This makes tetraether lipid systems promising in bionanotechnology and material science, namely for design of new and unique membrane nanoobjects.
Rapid and efficient processing of external information by the brain is vital to survival in a highly dynamic environment. The key channel humans use to exchange information is language, but the neural underpinnings of its processing are still not fully understood. We investigated the spatio-temporal dynamics of neural access to word representations in the brain by scrutinising the brain’s activity elicited in response to psycholinguistically, visually and phonologically matched groups of familiar words and meaningless pseudowords. Stimuli were briefly presented on the visual-field periphery to experimental participants whose attention was occupied with a non-linguistic visual feature-detection task. The neural activation elicited by these unattended orthographic stimuli was recorded using multi-channel whole-head magnetoencephalography, and the timecourse of lexically-specific neuromagnetic responses was assessed in sensor space as well as at the level of cortical sources, estimated using individual MR-based distributed source reconstruction. Our results demonstrate a neocortical signature of automatic near-instant access to word representations in the brain: activity in the perisylvian language network characterised by specific activation enhancement for familiar words, starting as early as ~70 ms after the onset of unattended word stimuli and underpinned by temporal and inferior-frontal cortices.
Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139–159 (TM1) and 316–333 (TM2) - as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.
Attending a location in short space. Certain types of exogenous cues - such as sudden peripheral onsets - have been described as reflexive and automatic. However, it has been shown that it has been shown. However, it doesn’t automatically consider this location. It is a test of exogenous responses. We've seen such as saccadic curvature, microsaccades and pupil size. It can be measured as the result of the reaction time. There is no need for a microsaccade after the cue. It was the effect that the process of recovery was observed. It has been shown to be there in a field. Overall, we'll find it in pupil size. It is indicative of whether we see RT or facilitation or not. Microsaccades were not diagnostic in either experiment. Finally, there is no need for any response measures.