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There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. [ABSTRACT FROM AUTHOR]

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette–Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rβ1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection. [ABSTRACT FROM AUTHOR]

Among the several alcohol dehydrogenases, PQQ-dependent enzymes are mainly found in the α, β, and γ-proteobacteria. These proteins are classified into three main groups. Type I ADHs are localized in the periplasm and contain one Ca2+-PQQ moiety, being the methanol dehydrogenase (MDH) the most representative. In recent years, several lanthanide-dependent MDHs have been discovered exploding the understanding of the natural role of lanthanide ions. Type II ADHs are localized in the periplasm and possess one Ca2+-PQQ moiety and one heme c group. Finally, type III ADHs are complexes of two or three subunits localized in the cytoplasmic membrane and possess one Ca2+-PQQ moiety and four heme c groups, and in one of these proteins, an additional [2Fe-2S] cluster has been discovered recently. From the bioinorganic point of view, PQQ-dependent alcohol dehydrogenases have been revived recently mainly due to the discovery of the lanthanide-dependent enzymes. Here, we review the three types of PQQ-dependent ADHs with special focus on their structural features and electron transfer processes. [ABSTRACT FROM AUTHOR]

Expansins are encoded by some phytopathogenic bacteria and evidence indicates that they act as virulence factors for host infection. Here we analysed the expression of exl1 by Pectobacterium brasiliense and Pectobacterium atrosepticum. In both, exl1 gene appears to be under quorum sensing control, and protein Exl1 can be observed in culture medium and during plant infection. Expression of exl1 correlates with pathogen virulence, where symptoms are reduced in a Δexl1 mutant strain of P. atrosepticum. As well as Δexl1 exhibiting less maceration of potato plants, fewer bacteria are observed at distance from the inoculation site. However, bacteria infiltrated into the plant tissue are as virulent as the wild type, suggesting that this is due to alterations in the initial invasion of the tissue. Additionally, swarming from colonies grown on MacConkey soft agar was delayed in the mutant in comparison to the wild type. We found that Exl1 acts on the plant tissue, probably by remodelling of a cell wall component or altering the barrier properties of the cell wall inducing a plant defence response, which results in the production of ROS and the induction of marker genes of the JA, ET and SA signalling pathways in Arabidopsis thaliana. Exl1 inactive mutants fail to trigger such responses. This defence response is protective against Pectobacterium brasiliense and Botrytis cinerea in more than one plant species. [ABSTRACT FROM AUTHOR]

Dye-sensitized solar cells (DSSCs) have been highlighted as the promising alternative to generate clean energy based on low pay-back time materials. These devices have been designed to mimic solar energy conversion processes from photosynthetic organisms (the most efficient energy transduction phenomenon observed in nature) with the aid of low-cost materials. Recently, light-harvesting complexes (LHC) have been proposed as potential dyes in DSSCs based on their higher light-absorption efficiencies as compared to synthetic dyes. In this work, photo-electrochemical hybrid devices were rationally designed by adding for the first time Leu and Lys tags to heterologously expressed light-harvesting proteins from Chlamydomonas reinhardtii, thus allowing their proper orientation and immobilization on graphene electrodes. The light-harvesting complex 4 from C. reinhardtii (LHC4) was initially expressed in Escherichia coli, purified via affinity chromatography and subsequently immobilized on plasma-treated thin-film graphene electrodes. A photocurrent density of 40.30 ± 9.26 μA/cm2 was measured on devices using liquid electrolytes supplemented with a phosphonated viologen to facilitate charge transfer. Our results suggest that a new family of graphene-based thin-film photovoltaic devices can be manufactured from rationally tagged LHC proteins and opens the possibility to further explore fundamental processes of energy transfer for biological components interfaced with synthetic materials. [ABSTRACT FROM AUTHOR]

Palladium catalyzed cross coupling between 3β-acetoxy-bisnorchol-5-en-22-oic acid and phenylboronic acid produced the hereto unknown 22-phenyl-3β-acetoxy-bisnorchol-5-en-22-one which crystallizes in the monoclinic system with space group P2. The presence of 17β-substituent that bears both the C21 methyl group and the introduced phenylketone moiety provides a twisted conformation on C13-C14 for the D ring with asymmetry parameters (Altona et al., Tetrahedron 24:13-32, ): ∆ = 711.4, τ = 47.3 (2), ∆C(C13-C14) = 5.7 (3), ∆C(C13) = 14.0 (3) and ∆C(C14) = 21.6 (3)°. The angle 77.20 (8)° between planes of the steroid-ABCD framework and phenyl ring evidences the relative orthogonal positions of these fragments. The H and C NMR characterization of the obtained compound are described. Graphical Abstract: The crystal structure and NMR characterization of 22-phenyl-3β-acetoxy-bisnorchol-5-en-22-one are described.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The title new compound, cis-[Cr( tmpcH)Cl][ZnCl]·MeOH (1) was prepared by using 1,4,8,11- tetrakis-(2-Methylpyridyl)-1,4,8,11-tetraazacyclotetradecane ( tmpc) with Cr(III) and its structure and electronic transition bands were determined. The compound crystallizes in monoclinic crystal system, space group P2/ n with a/Å = 16.9284(12), b/Å = 12.9024(9), c/Å = 20.0535(15), β/º = 109.6790(10), Z = 4. In the X-ray structure of the complex, it was found that the ligand bonds with Cr(III) through exo-coordination to form an octahedral geometry. The electronic spectral data also show that even in the solution state, the compound preserves a six coordinated structure around the metal ion as two bands were observed in the visible region of the spectra. The presence of cis-geometrical configuration in the compound was confirmed by the IR spectral studies. Graphical Abstract: [Cr( tmpcH)Cl][ZnCl]·MeOH, which was prepared by using 1,4,8,11- tetrakis-(2-methylpyridyl)-1,4,8,11-tetraazacyclo- tetradecane ( tmpc) with Cr(III), exhibits cis-geometrical configuration, where the ligand bonded with Cr(III) through exo-coordination to form an octahedral geometry [Figure not available: see fulltext.]. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause of visual impairment in the elderly population, with severe disease affecting nearly 10% of individuals of European descent over the age of 75 years. It is a complex disease in which genetic and environmental factors contribute to susceptibility. Complement factor H (CFH) has recently been identified as a major AMD susceptibility gene, and the Y402H polymorphism has been proposed as the likely causative factor. We genotyped polymorphisms spanning the cluster of CFH and five CFH-related genes on chromosome 1q23 in 173 individuals with severe neovascular AMD and 170 elderly controls with no signs of AMD. Detailed analysis showed a common haplotype associated with decreased risk of AMD that was present on 20% of chromosomes of controls and 8% of chromosomes of individuals with AMD. We found that this haplotype carried a deletion of CFHR1 and CFHR3, and the proteins encoded by these genes were absent in serum of homozygotes. The protective effect of the deletion haplotype cannot be attributed to linkage disequilibrium with Y402H and was replicated in an independent sample. [ABSTRACT FROM AUTHOR]

The crystal structure of the ligand 1,4,8,11-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane ( tpmc) has been determined. The compound crystallizes in triclinic space group P $$\overline 1$$ with a = 6.1927(3), b = 11.3771(3), c = 11.8229(3) Å α = 84.368(2), β = 98.77(1), γ = 78.533(2)° V = 810.84(5) Å3; and Z = 1. [ABSTRACT FROM AUTHOR]

The recent finding that the inhibition of Ca2+-stimulated respiration by ruthenium red is mainlydue to a binuclear ruthenium complex (Ru360) present in the commercial samples of the classicalinhibitor ruthenium red (Ying et. al., 1991), showed that this complex is the more potent andspecific inhibitor of the mitochondrial calcium uniporter. This work was aimed to provideinsights into the mechanism by which Ru360 and other ruthenium-related compounds inhibitscalcium uptake. Ruthenium red and a synthesized analog (Rrphen) were compared with Ru360.The inhibition by this binuclear complex was noncompetitive, with a K i of 9.89 n M. Thenumber of specific binding sites for Ru360 was 6.2 pmol/mg protein. Ruthenium red and Ru360were mutually exclusive inhibitors. Bound La3+ was not displaced by Ru360. Rrphen was theleast effective for inhibiting calcium uptake. The results support the notion of a specific bindingsite in the uniporter for the polycationic complexes and a negative charged region from thephospholipids in the membrane, closely associated with the uniporter inhibitor-binding site. [ABSTRACT FROM AUTHOR]

A correction to the article "A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration" that was published in the previous issue is presented.