The ectodomain of the human T-cell leukemia virus type 1 TM glycoprotein is involved in postfusion events.

To examine the contribution of the transmembrane envelope glycoprotein (TM) to the infectivity of the human T-cell leukemia virus type 1 (HTLV-1), single amino acid substitutions were introduced throughout its ectodomain. The mutated envelopes were tested for intracellular maturation and for functions, including ability to elicit syncytium formation and ability to mediate cell-to-cell transmission of the virus. Three major phenotypes, defining three functionally distinct regions, were identified. (i) Mutations causing defects in intracellular maturation of the envelope precursor are mostly distributed in the central portion of the TM ectodomain, containing the immunosuppressive peptide. This region, which includes vicinal cysteines thought to form an intramolecular disulfide bridge, is probably essential for correct folding of the protein. (ii) Mutations resulting in reduced syncytium-forming ability despite correct intracellular maturation are clustered in the amino-terminal part of the TM ectodomain, within the leucine zipper-like motif. Similar motifs with a propensity to form coiled-coil structures have been implicated in the fusion process driven by other viral envelope proteins, and HTLV-1 may thus conform to this general rule for viral fusion. (iii) Mutants with increased syncytium-forming ability define a region immediately amino-terminal to the membrane-spanning domain. Surprisingly, these mutants exhibited severe defects in infectivity, despite competence for fusion. Existence of this phenotype indicates that capacity for cell-to-cell fusion is not sufficient to ensure viral entry, even in cell-to-cell transmission. The ectodomain of the TM glycoprotein thus may be involved in postfusion events required for full infectivity of HTLV-1, which perhaps represents a unique feature of this poorly infectious retrovirus.     

Immunogenicity of the Shigella flexneri Serotype Y (SFL124) Vaccine Strain Expressing Cloned Glucosyl Transferase Gene of Converting Bacteriophage SfX

The glucosyl transferase gene (gtr) from bacteriophage phage X (SfX) caused partial conversion of serotype Y (group antigen 3, 4) to X (group antigen 7, 8) when introduced into a candidate vaccine strain of Shigella flexneri serotype Y (SFL124). The gtr gene caused conversion of O-antigens but did not eliminate the adsorption of the corresponding phage SfX. The hybrid strain expressing both group antigens 7, 8 and 3, 4 showed 75% protection when immunized guinea pigs were challenged with a wild-type S. flexneri serotype X strain. No protection was observed against serotype Y challenge, although group antigen 3, 4 was detected in the LPS of the hybrid strain. This suggests the importance of O-antigen immunity in the host defense against shigellosis.     

Human T-cell leukemia virus type I envelope protein maturation process: requirements for syncytium formation.

The human T-cell leukemia virus type I (HTLV-I) envelope protein is synthesized as a gp61 precursor product cleaved into two mature proteins, a gp45 exterior protein and a gp20 anchoring the envelope at the cell membrane. Using N-glycosylation inhibitors and site-directed mutagenesis of the potential glycosylation sites, we have studied the HTLV-I envelope intracellular maturation requirements for syncytium formation. We show here that experimental conditions resulting in the absence of precursor cleavage (tunicamycin, monensin treatments, and use of inhibitors of the reticulum steps of the N glycosylations) also result in no cell surface expression of envelope protein. The lack of syncytium formation observed in these cases is thus explained by incorrect intracellular transport. When the precursor is cleaved in the Golgi stack (no treatment or treatment with inhibitors of the Golgi steps of the N glycosylations), it is transported to the cell surface in all the cases examined. Syncytium formation is markedly reduced, however, when Golgi glycosylations are incorrect, which shows that the sugar moieties are involved in the envelope functions. Site-directed mutagenesis demonstrates that each of the five potential glycosylation sites is actually glycosylated. Glycosylation of sites 1 and 5 is required for normal maturation, whereas that of sites 2, 3, and 4 is dispensable. Glycosylation of each site, however, is required for normal syncytium formation. Altogether, the restraints exerted by the cell for the HTLV-I envelope to be transported and functional are very high, which might play a role in the observed conservation of the envelope amino acid sequence between various strains.     

Development of Dopant‐Free Organic Hole Transporting Materials for Perovskite Solar Cells

There has been considerable progress over the last decade in development of the perovskite solar cells (PSCs), with reported performances now surpassing 25.2% power conversion efficiency. Both long‐term stability and component costs of PSCs remain to be addressed by the research community, using hole transporting materials (HTMs) such as 2,2′,7,7′‐tetrakis(N,N′‐di‐pmethoxyphenylamino)‐9,9′‐spirbiuorene(Spiro‐OMeTAD) and poly[bis(4‐phenyl)(2,4,6‐trimethylphenyl)amine] (PTAA). HTMs are essential for high‐performance PSC devices. Although effective, these materials require a relatively high degree of doping with additives to improve charge mobility and interlayer/substrate compatibility, introducing doping‐induced stability issues with these HTMs, and further, additional costs and experimental complexity associated with using these doped materials. This article reviews dopant‐free organic HTMs for PSCs, outlining reports of structures with promising properties toward achieving low‐cost, effective, and scalable materials for devices with long‐term stability. It summarizes recent literature reports on non‐doped, alternative, and more stable HTMs used in PSCs as essential components for high‐efficiency cells, categorizing HTMs as reported for different PSC architectures in addition to use of dopant‐free small molecular and polymeric HTMs. Finally, an outlook and critical assessment of dopant‐free organic HTMs toward commercial application and insight into the development of stable PSC devices is provided.     

Enantiopure ethyl 2,3-dibromopropionate: Enantioselective synthesis vs preparative HPLC enantioseparation of racemate on multigram scale

Racemic ethyl 2,3-dibromopropionate, commercially available at low price, is a key intermediate used in the synthesis of several heterocycle fragments, which are present in many biologically active compounds. Surprisingly, the enantiomers are not commercially available and have never been described in the literature. In this work, we undertook two different strategies to obtain these enantiomers, which are enantioselective synthesis and preparative HPLC enantioseparation of commercially available racemate on multigram scale. The first strategy has proved inadequate because racemization occurred during the synthesis (ee ≈ 9-50%). Conversely, the second strategy produced a very good enantioseparation of commercially available racemate (ee > 99.5% for both enantiomers) on multigram scale.     

Off-the-shelf mesenchymal stem cells from human umbilical cord tissue can significantly improve symptoms in COVID-19 patients: An analysis of evidential relations

Coronavirus disease-2019 (COVID-19) has affected more than 200 countries worldwide. This disease has hugely affected healthcare systems as well as the economy to an extent never seen before. To date, COVID-19 infection has led to about 165000 deaths in 150 countries. At present, there is no specific drug or efficient treatment for this disease. In this analysis based on evidential relationships of the biological characteristics of MSCs, especially umbilical cord (UC)-derived MSCs as well as the first clinical trial using MSCs for COVID-19 treatment, we discuss the use of UC-MSCs to improve the symptoms of COVID-19 in patients.