Graphene-Based Sulfur Cathodes and Dual Salt-Based Sparingly Solvating Electrolytes: A Perfect Marriage for High Performing,Safe, and Long Cycle Life Lithium-Sulfur Prototype Batteries

The growing requirements for electrified  applications entail exploring alternative battery systems. Lithium-sulfur batteries (LSBs) have emerged as a promising, cost-effective, and sustainable solution; however, their practical commercialization is impeded by several intrinsic challenges. With the aim of surpassing these challenges, the implementation of a holistic LSB concept is proposed. To this end, the effectiveness of coupling a high-performing 2D graphene-based sulfur cathode with a well-suited sparingly solvating electrolyte (SSE) is reported. The incorporation of bis(fluorosulfonyl)imide (LiFSI) salt to tune sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropylether based SSE enables the formation of a robust and compact lithium fluoride-rich solid electrolyte interphase. Consequently, the lithium compatibility is improved, achieving a high Coulombic efficiency (CE) of 98.8% in the Li||Cu cells and enabling thin and dense lithium depositions. When combined with a high-performing 2D graphene-based sulfur cathode, a symbiotic effect is shown, leading to high discharge capacities, remarkable rate capability (2.5 mAh cm⁻² at C/2), enhanced cell stability, and wide temperature applicability. Furthermore, the scalability of this strategy is successfully demonstrated by assembling high-performing monolayer prototype cells with a total capacity of 93 mAh, notable capacity retention of 70% after 100 cycles, and a high average CE of 99%.     

Quantitative determination of the topological propensities of amyloidogenic peptides

One of the interesting puzzles of amyloid beta-peptide of Alzheimer's disease (Abeta) is that it appears to polymerize into amyloid fibrils in a parallel beta sheet topology, while smaller subsets of the peptide produce anti-parallel beta sheets. In order to target potential weak points of amyloid fibrils in a rational drug design effort, it would be helpful to understand the forces that drive this change. We have designed two peptides CHQKLVFFAEDYNGKDEAFFVLKQHW and CHQKLVFFAEDYNGKHQKLVFFAEDW that join the significant amyloidogenic Abeta (14-23) sequence HQKLVFFAED in parallel and anti-parallel topologies, respectively. (Here, the word "parallel" refers only to residue sequence and not backbone topology). The N-termini of the hairpins were labeled with the fluorescent dye 5-((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid (IAEDANS), forming a fluorescence energy transfer donor-acceptor pair with the C-terminus tryptophan. Circular dichroism results show that the anti-parallel hairpin adopts a beta-sheet conformation, while the parallel hairpin is disordered. Fluorescent Resonance Energy Transfer (FRET) results show that the distance between the donor and the acceptor is significantly shorter in the anti-parallel topology than in the parallel topology. The fluorescence intensity of anti-parallel hairpin also displays a linear concentration dependence, indicating that the FRET observed in the anti-parallel hairpin is from intra-molecular interactions. The results thus provide a quantitative estimate of the relative topological propensities of amyloidogenic peptides. Our FRET and CD results show that beta sheets involving the essential Abeta (14-23) fragment, strongly prefer the anti-parallel topology. Moreover, we provide a quantitative estimate of the relative preference for these two topologies. Such analysis can be repeated for larger subsets of Abeta to determine quantitatively the relative degree of preference for parallel/anti-parallel topologies in given fragments of Abeta.     

Synthesis of the O-linked pentasaccharide in glycoproteins of Trypanosoma cruzi and selective sialylation by recombinant trans-sialidase

The mucin-like glycoproteins of Trypanosoma cruzi have novel O-linked oligosaccharides that are acceptors of sialic acid in the trans-sialidase (TcTS) reaction. The transference of sialic acid from host glycoconjugates to the mucins is involved in infection and pathogenesis. The synthesis of the pentasaccharide, beta-D-Galp-(1-->2)-[beta-D-Galp-(1-->3)]-beta-D-Galp-(1-->6)-[beta-D-Galf-(1-->4)]-D-GlcpNAc and the corresponding alditol, previously isolated by reductive beta-elimination of the mucins, is described. The key step was the 6-O-glycosylation of a easily accessible derivative of beta-D-Galf-(1-->4)-D-GlcpNAc with a beta-D-Galp-(1-->2)-[beta-D-Galp-(1-->3)]-D-Galp donor using the trichloroacetimidate method. The beta-linkage was diastereoselectively obtained by the nitrile effect. The pentasaccharide is the major oligosaccharide in the mucins of T. cruzi, G strain and presents two terminal beta-D-Galp residues for possible sialylation by TcTS. A preparative sialylation reaction was performed with its benzyl glycoside and the sialylated product was isolated and characterized. NMR spectroscopic analysis showed that selective monosialylation occurred at the terminal (1-->3) linked galactopyranose.     

Computational RNA secondary structure design: empirical complexity and improved methods

Background  

We investigate the empirical complexity of the RNA secondary structure design problem, that is, the scaling of the typical difficulty of the design task for various classes of RNA structures as the size of the target structure is increased. The purpose of this work is to understand better the factors that make RNA structures hard to design for existing, high-performance algorithms. Such understanding provides the basis for improving the performance of one of the best algorithms for this problem, RNA-SSD, and for characterising its limitations.     

Conformational Effects of a Common Codon 399 Polymorphism on the BRCT1 Domain of the XRCC1 Protein

The X-ray cross-complementing-1 (XRCC1) protein functions as a scaffold that coordinates the activity of the cellular machinery involved in base excision repair (BER) of DNA damage. The BRCT1 domain of XRCC1 is responsible for interacting with several of the key components of the BER machinery, and it is also the site of a common genetic polymorphism in XRCC1 at amino acid residue 399 (Arg → Gln). Experimental and epidemiologic evidence suggest that this polymorphism may alter BER capacity and increase cancer risk. The aim of this study was to investigate whether these effects could be attributable to conformational changes in XRCC1 induced by the polymorphism. Molecular dynamics techniques were used to predict the structure of the wild-type and polymorphic forms of the BRCT1 domain of XRCC1, and differences in structure produced by the polymorphic substitution were determined. The results indicate that, although the general configuration of both proteins is similar and there is little actual deviation at the site of the polymorphism itself, the substitution produces significant conformational changes at several other sites in the BRCT1 domain, including the loss of secondary structural features such as α helices that may be critical for protein–protein interactions. These results provide support for the hypothesis that this polymorphism in XRCC1 could affect DNA repair capability by altering the structure of the BRCT1 domain and thus the ability of XRCC1 to coordinate BER.     

Immunoproteomic analysis of the protective response obtained from vaccination with Candida albicans ecm33 cell wall mutant in mice

Systemic candidiasis remains a major cause of disease and death, particularly among immunocompromised patients. The cell wall of Candida albicans defines the interface between host and pathogen and surface proteins are major elicitors of host immune responses during candidiasis. The C. albicans ecm33 mutant (RML2U) presents an altered cell wall, which entails an increase in the outermost protein layer. Vaccination of BALB/c mice with RML2U mutant protected them from a subsequent lethal infection with virulent strain SC5314 in a systemic candidiasis model. Using immunoproteomics (2-DE followed by Immunoblotting) we detected 29 immunoreactive proteins specifically recognized by antibodies from vaccinated mice sera, six of which are described as immunogenic for the first time (Gnd1p, Cit1p, Rpl10Ep, Yst1p, Cys4p, Efb1p). Furthermore, identification of wild type and mutant cell surface proteome (surfome), confirmed us that the mutant surfome presented a larger number of proteins than the wild type. Interestingly, proteins exclusively identified in the mutant surfome (Met6p, Eft2p, Tkl1p, Rpl10Ep, Atp1p, Atp2p) were also detected as immunogenic, supporting the idea that their surface location enhances their immunoprotective capacity.