Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR)

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects.     

Exposure to Dishwashing Liquid Assessed in University Students from Brest City: A Preliminary Study—A First Approach to Household Products Exposure in France

In recent years, more attention has been paid to exposure of the general population to household products. In order to assess exposure, it is necessary to generate exposure data. For this reason, a preliminary study of dishwashing liquid contact on Brest university students was performed. Dishwashing liquid is frequently used and when it is improperly mixed it can liberate harmful molecules. As for university students, they may have a repetitive contact with dishwashing liquid during their academic studies. Relevant parameters as frequency of dishwashing, duration, and amount of dishwashing liquid were assessed from questionnaires and laboratory tests. Tests revealed that overall no difference between the sexes and the type of residential household on dishwashing was present on this population. Amount of washed items and duration was significantly correlated, which could seem logical but remarkable considering the lack of correlation between other parameters. Values of 1.39 and 58.8 μg/kg bw/day for the 95th percentile of dermal and inhalation probabilistic exposure were found, respectively. Dermal exposure coincides with deterministic published data. In the case of inhalation exposure no published data are available. Higher inhalation exposure value may show that dermal exposure is diminished by high dilution of dishwashing liquid in water.     

Domains of BclA,the major surface glycoprotein of the B. cereus exosporium: glycosylation patterns and role in spore surface properties

The role of the BclA domains of B. cereus ATCC 14579 was investigated in order to understand the phenomena involved in the interfacial processes occurring between spores and inert surfaces. This was done by (i) creating deletions in the collagen-like region (CLR) and the C-terminal domain (CTD) of BclA, (ii) building BclA proteins with various lengths in the CLR and (iii) modifying the hydrophobic upper surface in the CTD. First, it was demonstrated that the CLR was substituted by three residues already reported in the CLR of B. anthracis, viz. rhamnose, 3-O-methyl-rhamnose, and GalNH₂ residues, while the CTD was also substituted by two additional glycosyl residues, viz. 2-O-methyl-rhamnose and 2,4-O-methyl-rhamnose. Regarding the properties of the spores, both CLR and CTD contributed to the adhesion of the spores, which was estimated by measuring the resistance to detachment of spores adhered to stainless steel plates). CLR and CTD also impacted the hydrophobic character and isoelectric point of the spores. It was then shown that the resistance to detachment of the spores was not affected by the physicochemical properties, but by the CLR length and the presence of hydrophobic amino acids on the CTD.     

Long‐term dynamics in microbial eukaryotes communities: a palaeolimnological view based on sedimentary DNA

Assessing the extent to which changes in lacustrine biodiversity are affected by anthropogenic or climatic forces requires extensive palaeolimnological data. We used high‐throughput sequencing to generate time‐series data encompassing over 2200 years of microbial eukaryotes (protists and Fungi) diversity changes from the sedimentary DNA record of two lakes (Lake Bourget in French Alps and Lake Igaliku in Greenland). From 176 samples, we sequenced a large diversity of microbial eukaryotes, with a total 16 386 operational taxonomic units distributed within 50 phylogenetic groups. Thus, microbial groups, such as Chlorophyta, Dinophyceae, Haptophyceae and Ciliophora, that were not previously considered in lacustrine sediment record analyses appeared to be potential biological markers of trophic status changes. Our data suggest that shifts in relative abundance of extant species, including shifts between rare and abundant taxa, drive ecosystem responses to local and global environmental changes. Community structure shift events were concomitant with major climate variations (more particularly in Lake Igaliku). However, this study shows that the impacts of climatic fluctuations may be overpassed by the high‐magnitude eutrophication impacts, as observed in the eutrophicated Lake Bourget. Overall, our data show that DNA preserved in sediment constitutes a precious archive of information on past biodiversity changes.     

Domains of BclA, the major surface glycoprotein of the B. cereus exosporium: glycosylation patterns and role in spore surface properties

The role of the BclA domains of B. cereus ATCC 14579 was investigated in order to understand the phenomena involved in the interfacial processes occurring between spores and inert surfaces. This was done by (i) creating deletions in the collagen-like region (CLR) and the C-terminal domain (CTD) of BclA, (ii) building BclA proteins with various lengths in the CLR and (iii) modifying the hydrophobic upper surface in the CTD. First, it was demonstrated that the CLR was substituted by three residues already reported in the CLR of B. anthracis, viz. rhamnose, 3-O-methyl-rhamnose, and GalNH(2) residues, while the CTD was also substituted by two additional glycosyl residues, viz. 2-O-methyl-rhamnose and 2,4-O-methyl-rhamnose. Regarding the properties of the spores, both CLR and CTD contributed to the adhesion of the spores, which was estimated by measuring the resistance to detachment of spores adhered to stainless steel plates). CLR and CTD also impacted the hydrophobic character and isoelectric point of the spores. It was then shown that the resistance to detachment of the spores was not affected by the physicochemical properties, but by the CLR length and the presence of hydrophobic amino acids on the CTD.