Binding mode of SARS-CoV-2 fusion peptide to human cellular membrane

Infection of human cells by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) relies on its binding to a specific receptor and subsequent fusion of the viral and host cell membranes. The fusion peptide (FP), a short peptide segment in the spike protein, plays a central role in the initial penetration of the virus into the host cell membrane, followed by the fusion of the two membranes. Here, we use an array of molecular dynamics simulations that take advantage of the highly mobile membrane mimetic model to investigate the interaction of the SARS-CoV2 FP with a lipid bilayer representing mammalian cellular membranes at an atomic level and to characterize the membrane-bound form of the peptide. Six independent systems were generated by changing the initial positioning and orientation of the FP with respect to the membrane, and each system was simulated in five independent replicas, each for 300 ns. In 73% of the simulations, the FP reaches a stable, membrane-bound configuration, in which the peptide deeply penetrated into the membrane. Clustering of the results reveals three major membrane-binding modes (binding modes 1–3), in which binding mode 1 populates over half of the data points. Taking into account the sequence conservation among the viral FPs and the results of mutagenesis studies establishing the role of specific residues in the helical portion of the FP in membrane association, the significant depth of penetration of the whole peptide, and the dense population of the respective cluster, we propose that the most deeply inserted membrane-bound form (binding mode 1) represents more closely the biologically relevant form. Analysis of FP-lipid interactions shows the involvement of specific residues, previously described as the “fusion-active core residues,” in membrane binding. Taken together, the results shed light on a key step involved in SARS-CoV2 infection, with potential implications in designing novel inhibitors.     

Neurobiology of glaucomatous optic neuropathy: diverse cellular events in neurodegeneration and neuroprotection

Although glaucomatous optic nerve degeneration is a leading cause of worldwide blindness, neither the precise cellular mechanisms underlying neurodegeneration in glaucoma, nor effective strategies for neuroprotection are yet clear. This review focuses on diverse cellular events associated with glaucomatous neurodegeneration whose balance is critical for determination of ultimate cell fate. An improved understanding of the site of primary injury to optic nerve, the mediator pathways of apoptotic cell death and intrinsic protection mechanisms in retinal ganglion cells, the role of glial activation on the survival and death of retinal ganglion cell bodies and their axons, and the protective and destructive consequences of immune system involvement can facilitate development of effective neuroprotective strategies in glaucoma.     

Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis

Clathrin-mediated endocytosis of surface receptors and their bound ligands (i.e., cargo) is highly regulated, including by the cargo itself. One of the possible sources of the observed heterogeneous dynamics of clathrin-coated pits (CCPs) might be the different cargo content. Consistent with this, we show that CCP size and dynamic behavior varies with low density lipoprotein receptor (LDLR) expression levels in a manner dependent on the LDLR-specific adaptors, Dab2 and ARH. In Dab2-mCherry–expressing cells, varying LDLR expression leads to a progressive increase in CCP size and to the appearance of nonterminal endocytic events. In LDLR and ARH-mCherry–expressing cells in addition to an increase in CCP size, turnover of abortive CCPs increases, and the rate of CCP maturation decreases. Altogether, our results underscore the highly dynamic and cargo-responsive nature of CCP assembly and suggest that the observed heterogeneity is, in part, related to compositional differences (e.g., cargo and adaptors) between CCPs.     

Nuclear Pore Complex Number and Distribution throughout the Saccharomyces cerevisiae Cell Cycle by Three-Dimensional Reconstruction from Electron Micrographs of Nuclear Envelopes

The number of nuclear pore complexes (NPCs) in individual nuclei of the yeast Saccharomyces cerevisiae was determined by computer-aided reconstruction of entire nuclei from electron micrographs of serially sectioned cells. Nuclei of 32 haploid cells at various points in the cell cycle were modeled and found to contain between 65 and 182 NPCs. Morphological markers, such as cell shape and nuclear shape, were used to determine the cell cycle stage of the cell being examined. NPC number was correlated with cell cycle stage to reveal that the number of NPCs increases steadily, beginning in G₁-phase, suggesting that NPC assembly occurs continuously throughout the cell cycle. However, the accumulation of nuclear envelope observed during the cell cycle, indicated by nuclear surface area, is not continuous at the same rate, such that the density of NPCs per unit area of nuclear envelope peaks in apparent S-phase cells. Analysis of the nuclear envelope reconstructions also revealed no preferred NPC-to-NPC distance. However, NPCs were found in large clusters over regions of the nuclear envelope. Interestingly, clusters of NPCs were most pronounced in early mitotic nuclei and were found to be associated with the spindle pole bodies, but the functional significance of this association is unknown.     

Cryptic habitats and cryptic diversity: unexpected patterns of connectivity and phylogeographical breaks in a Mediterranean endemic marine cave mysid

The marine cave‐dwelling mysid Hemimysis margalefi is distributed over the whole Mediterranean Sea, which contrasts with the poor dispersal capabilities of this brooding species. In addition, underwater marine caves are a highly fragmented habitat which further promotes strong genetic structuring, therefore providing highly informative data on the levels of marine population connectivity across biogeographical regions. This study investigates how habitat and geography have shaped the connectivity network of this poor disperser over the entire Mediterranean Sea through the use of several mitochondrial and nuclear markers. Five deeply divergent lineages were observed among H. margalefi populations resulting from deep phylogeographical breaks, some dating back to the Oligo‐Miocene. Whether looking at the intralineage or interlineage levels, H. margalefi populations present a high genetic diversity and population structuring. This study suggests that the five distinct lineages observed in H. margalefi actually correspond to as many separate cryptic taxa. The nominal species, H. margalefi sensu stricto, corresponds to the westernmost lineage here surveyed from the Alboran Sea to southeastern Italy. Typical genetic breaks such as the Almeria‐Oran Front or the Siculo‐Tunisian Strait do not appear to be influential on the studied loci in H. margalefi sensu stricto. Instead, population structuring appears more complex and subtle than usually found for model species with a pelagic dispersal phase. The remaining four cryptic taxa are all found in the eastern basin, but incomplete lineage sorting is suspected and speciation might still be in process. Present‐day population structure of the different H. margalefi cryptic species appears to result from past vicariance events started in the Oligo‐Miocene and maintained by present‐day coastal topography, water circulation and habitat fragmentation.     

A natural macroalgae consortium for biosorption of copper from aqueous solution: Optimization,modeling and design studies

In this study, the capacity of a natural macroalgae consortium consisting of Chaetomorpha sp., Polysiphonia sp., Ulva sp. and Cystoseira sp. species for the removal of copper ions from aqueous environment was investigated at different operating conditions, such as solution pH, copper ion concentration and contact time. These environmental parameters affecting the biosorption process were optimized on the basis of batch experiments. The experimentally obtained data for the biosorption of copper ions onto the macroalgae-based biosorbent were modeled using the isotherm models of Freundlich, Langmuir, Sips and Dubinin–Radushkevich and the kinetic models of pseudo-first-order, pseudo-second-order, Elovich and Weber and Morris. The pseudo-first-order and Sips equations were the most suitable models to describe the copper biosorption from aqueous solution. The thermodynamic data revealed the feasibility, spontaneity and physical nature of biosorption process. Based on the data of Sips isotherm model, the biosorption capacity of biosorbent for copper ions was calculated as 105.370 mg g^?1 under the optimum operating conditions. A single-stage batch biosorption system was developed to predict the real-scale-based copper removal performance of biosorbent. The results of this investigation showed the potential utility of macroalgae consortium for the biosorption of copper ions from aqueous medium.