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Population Genomics of Human Viruses
2018
Viruses, and a few RNA viruses in particular, represent one of the greatest threats for human health. High mutation rates, large population sizes, and short generation times contribute to their typically fast evolutionary rates. However, many additional processes operate on their genomes, often in opposite directions, driving their evolution and allowing them to adapt to diverse host populations and antiviral drugs. Until recently, the high levels of genetic variation of most viruses have been explored only at a few genes or genome regions. The recent advent and increasing affordability of next-generation sequencing techniques have allowed obtaining complete genome sequences of large number…
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
2016
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…
Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity.
2020
The memory CD8 T-cell pool must select for clones that bind immunodominant epitopes with high affinity to efficiently counter reinfection. At the same time, it must retain a level of clonal diversity to allow recognition of pathogens with mutated epitopes. How the level of diversity within the memory pool is controlled is unclear, especially in the context of a selective drive for antigen affinity. We find that preservation of clones that bind the activating antigen with low affinity depends on expression of the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the prosurvival protein…
Regulation of yeast fatty acid desaturase in response to iron deficiency
2017
Unsaturated fatty acids (UFA) are essential components of phospholipids that greatly contribute to the biophysical properties of cellular membranes. Biosynthesis of UFAs relies on a conserved family of iron-dependent fatty acid desaturases, whose representative in the model yeast Saccharomyces cerevisiae is Ole1. OLE1 expression is tightly regulated to adapt UFA biosynthesis and lipid bilayer properties to changes in temperature, and in UFA or oxygen availability. Despite iron deficiency being the most extended nutritional disorder worldwide, very little is known about the mechanisms and the biological relevance of fatty acid desaturases regulation in response to iron starvation. In this re…
Block Sorting-Based Transformations on Words: Beyond the Magic BWT
2018
The Burrows-Wheeler Transform (BWT) is a word transformation introduced in 1994 for Data Compression and later results have contributed to make it a fundamental tool for the design of self-indexing compressed data structures. The Alternating Burrows-Wheeler Transform (ABWT) is a more recent transformation, studied in the context of Combinatorics on Words, that works in a similar way, using an alternating lexicographical order instead of the usual one. In this paper we study a more general class of block sorting-based transformations. The transformations in this new class prove to be interesting combinatorial tools that offer new research perspectives. In particular, we show that all the tra…
Impact of poplar-based phytomanagement on soil properties and microbial communities in a metal-contaminated site
2016
Despite a long history of use in phytomanagement strategies, the impacts of poplar trees on the structure and function of microbial communities that live in the soil remain largely unknown. The current study combined fungal and bacterial community analyses from different management regimes using Illumina-based sequencing with soil analysis. The poplar phytomanagement regimes led to a significant increase in soil fertility and a decreased bioavailability of Zn and Cd, in concert with changes in the microbial communities. The most notable changes in the relative abundance of taxa and operational taxonomic units unsurprisingly indicated that root and soil constitute distinct ecological microbi…
Targeting Bacterial Sortase A with Covalent Inhibitors: 27 New Starting Points for Structure-Based Hit-to-Lead Optimization.
2019
Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of
FLYCOP: metabolic modeling-based analysis and engineering microbial communities
2018
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Guidelines for the use of flow cytometry and cell sorting in immunological studies
2017
The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and some…
Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease
2020
Abstract Background Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD. Methods To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for > 170,000 photographs from UKBB. We searched for early AMD loc…