Sphingolipids are bioactive molecules associated with oxidative stress, inflammation, and neurodegenerative diseases, but poorly studied in the context of age-related macular degeneration (AMD), a ...prevalent sight-threatening disease of the ageing retina. Here, we found higher serum levels of hexosylceramide (HexCer) d18:1/16:0 in patients with choroidal neovascularization (CNV) and geographic atrophy (GA), two manifestations of late stage AMD, and higher ceramide (Cer) d18:1/16:0 levels in GA patients. A sensitivity analysis of genetic variants known to be associated with late stage AMD showed that rs1061170 (p.Y402H) in the complement factor H (CFH) gene influences the association of Cer d18:1/16:0 with GA. To understand the possible influence of this genetic variant on ceramide levels, we established a cell-based assay to test the modulation of genes in the ceramide metabolism by factor H-like protein 1 (FHL-1), an alternative splicing variant of CFH that also harbors the 402 residue. We first showed that malondialdehyde-acetaldehyde adducts, an oxidation product commonly found in AMD retinas, induces an increase in ceramide levels in WERI-Rb1 cells in accordance with an increased expression of ceramide synthesis genes. Then, we observed that cells exposed to the non-risk FHL-1:Y402, but not the risk associated variant FHL-1:H402 or full-length CFH, downregulated ceramide synthase 2 and ceramide glucosyltransferase gene expression. Together, our findings show that serum ceramide and hexosylceramide species are altered in AMD patients and that ceramide levels may be influenced by AMD associated risk variants.
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•The role in host selectivity of ACE2, Tmprss2 and GPR78 in SARS-CoV-2 was explored.•Differences in the SARS-CoV-2 RBD binding mode with ACE2 of secondary hosts could be associated ...with host permissiveness.•Nafamostat could be considered a good inhibitor of mammalian hosts TMPRSS2 proteins.•In silico studies confirm that the spike protein could interact with GRP78 in studied mammalian hosts.•TMPRSS2 and GRP78 do not seem to play a role in host selectivity.
Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N–O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts.
The India–France SARAL/AltiKa mission is the first Ka-band altimetric mission dedicated primarily to oceanography. The mission objectives were firstly the observation of the oceanic mesoscales but ...also global and regional sea level monitoring, including the coastal zone, data assimilation, and operational oceanography. SARAL/AltiKa proved also to be a great opportunity for inland waters applications, for observing ice sheet or icebergs, as well as for geodetic investigations. The mission ended its nominal phase after three years in orbit and began a new phase (drifting orbit) in July 2016. The objective of this paper is to highlight some of the most remarkable achievements of the SARAL/AltiKa mission in terms of scientific applications. Compared to the standard Ku-band altimetry measurements, the Ka-band provides substantial improvements in terms of spatial resolution and data accuracy. We show here that this leads to remarkable advances in terms of observation of the mesoscale and coastal ocean, waves, river water levels, ice sheets, icebergs, fine scale bathymetry features as well as for the many related applications.
The genetic diversity and phylogenetic relationships of a collection of strains of dengue virus type 1 (DV-1), isolated from different parts of the world, were investigated. Phylogenetic trees ...derived from the complete sequence of the E gene of 44 strains suggested the existence of five genetic types defined by a maximum nucleotide divergence within each group of 6%. The 22 strains from America were classified into a single genetic type that included strains associated either with classical dengue or hemorrhagic dengue episodes. Using a maximum likelihood procedure based on a single rate with dated tips model and substitution rates calculated at the third codon position, evolution of the five DV-1 genotypes was shown to conform to a molecular clock. The average rate of evolution was estimated to be approximately 16.2 × 10−4 substitutions/third codon position site/year. Using this estimate, divergence among the DV-1 genotypes was calculated to have occurred approximately 100 years ago. Very low average value of the ratio of nonsynonymous-to-synonymous nucleotide substitutions, relative to the respective sites (0.046), indicated that the evolution of the E gene of the DV-1 is subject mostly to purifying selection.
Hepatitis A virus (HAV) infection is highly prevalent in Latin America, including Venezuela. Subgenotype IA seems to circulate in an almost exclusive fashion, except in Brazil. The aim of this study ...was the molecular characterization of the HAV infection in Venezuela, in order to characterize the circulating strains and to analyze the presence of quasispecies in sporadic cases and an epidemic outbreak. A total of 125 (113 sera and 12 feces) samples positive for anti-HAV IgM from sporadic cases and epidemic outbreak, were submitted to hemi-nested RT-PCR for amplification of the VP1 N terminus or complete region of the HAV genome. Sequences obtained from 96 Venezuelan isolates were used for phylogenetic analysis. The quasispecies distribution was evaluated by cloning of HAV amplicons. Phylogenetic analysis of HAV sequences from Venezuela showed the exclusive circulation of subgenotype IA, but with co-circulation of two lineages, not found in other countries. The genetic variability found among Venezuelan strains was also analyzed by single-strand conformation polymorphism (SSCP). This technique allowed the detection of intra-strain variability, which was indeed related to the presence of quasispecies populations in the isolates. The quasispecies heterogeneity was higher in some isolates derived from sporadic cases compared to the one observed in the outbreak. The molecular characterization of HAV isolates from Venezuela showed the circulation of a unique subgenotype IA, but with the presence of diverse strains and quasispecies inside the viral populations. J. Med. Virol. 82:1829-1834, 2010.
Molecular characterization of two sewage-borne pathogens identified hepatitis A virus (HAV) subgenotype IA and Giardia duodenalis assemblages A and B as predominant genotypes circulating in an urban ...area of Venezuela. This study reveals epidemiological features of human pathogens of worldwide distribution and the efficacy of molecular methods for accurate assessment of sewage pollution.
The gene encoding the VP8* trypsin-cleavage product of the VP4 protein of porcine rotavirus strain A34 was sequenced, and the predicted amino acid (aa) sequence was compared to the homologous region ...of all known P genotypes. The aa sequence of the VP8* of strain A34 shared low identity, ranging from 39% (bovine strain B223, P811) to 76% (human strain 69M, P410), with the homologous sequences of representative strains of the remaining 21 P genotypes. Phylogenetic relationships showed that the VP8* of strain A34 shares a common evolutionary lineage with those of human 69M (P410) and equine H-2 (P412) strains. Hyperimmune sera raised to strain A34 and to a genetic reassortant strain containing the VP4 gene from strain A34, both with high homologous neutralization titer via VP4, failed to neutralize strains representative of 15 different P genotypes. These results indicate that strain A34 should be considered as prototype of a new P genotype and serotype (P1423) and provide further evidence for the vast genetic and antigenic diversity of group A rotaviruses.
Hepatitis B virus (HBV) infection is still a significant health concern in Latin America, where around 11 million persons are infected. Amerindian populations exhibit the highest prevalences of ...infection in the region. HBV exhibits a degree of variability intermediate between DNA and RNA viruses. This plasticity leads to the generation of several mutants and genotypic variability. Eight HBV genotypes (A–H) have been described, based on a minimum divergence of 8% of the complete genome sequences. HBV genotype F is the most divergent of the HBV genotypes, is autochthonous to South America and is highly predominant in the Northern region of South America. The recently described HBV genotype H is closely related to genotype F and seems to be restricted to Central and North America. Recombination among different HBV strains seems to be frequent, although it has not been described yet between American genotypes. Inside HBV genotype F, four subgenotypes have been described, which exhibit a geographic pattern of distribution. The clinical and biologic importance of the genotypic diversity of HBV is of major concern at the present moment and has been studied in Asia and Europe. In contrast, it is not known whether infection with the American HBV genotypes F and H is associated with a rapid or slow development of disease. The origin of HBV is still an open question. Depending on the model used for the phylogenetic analysis, an Asian or an American origin of HBV has been proposed. By revisiting the genotypic diversity of HBV, an alternative explanation is that human HBV genotypes might have emerged by several zoonotic introductions, both in the Old and the New World.
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