A widespread riboswitch candidate that controls bacterial genes involved in molybdenum cofactor and tungsten cofactor metabolism

We have identified a highly conserved RNA motif located upstream of genes encoding molybdate transporters, molybdenum cofactor (Moco) biosynthesis enzymes, and proteins that utilize Moco as a coenzyme. Bioinformatics searches have identified 176 representatives in γ-Proteobacteria, δ-Proteobacteria, Clostridia, Actinobacteria, Deinococcus-Thermus species and DNAs from environmental samples. Using genetic assays, we demonstrate that a Moco RNA in Escherichia coli associated with the Moco biosynthetic operon controls gene expression in response to Moco production. In addition, we provide evidence indicating that this conserved RNA discriminates against closely related analogues of Moco. These results, together with extensive phylogenetic conservation and typical gene control structures near some examples, indicate that representatives of this structured RNA represent a novel class of riboswitches that sense Moco. Furthermore, we identify variants of this RNA that are likely to be triggered by the related tungsten cofactor (Tuco), which carries tungsten in place of molybdenum as the metal constituent

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2′,2′-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (P< 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P=0.044) and overall survival (P=0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P=0.049), time to progression (9.9 vs 2.3 months; P=0.003) and overall survival (15.4 vs 3.6; P=0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy

Analysis of Pre-Seismic Ionospheric Disturbances Prior to 2020 Croatian Earthquakes

International audienceWe study the sub-ionospheric VLF transmitter signals recorded by the Austrian Graz station in the year 2020. Those radio signals are known to propagate in the Earth-ionosphere waveguide between the ground and lower ionosphere. The Austrian Graz facility (geographic coordinates: 15.46 • E, 47.03 • N) can receive such sub-ionospheric transmitter signals, particularly those propagating above earthquake (EQ) regions in the southern part of Europe. We consider in this work the transmitter amplitude variations recorded a few weeks before the occurrence of two EQs in Croatia at a distance less than 200 km from Graz VLF facility. The selected EQs happened on 22 March 2020 and 29 December 2020, with magnitudes of M w 5.4 and M w 6.4, respectively, epicenters localized close to Zagreb (16.02 • E, 45.87 • N; 16.21 • E, 45.42 • N), and with focuses of depth smaller than 10 km. In our study we emphasize the anomaly fluctuations before/after the sunrise times, sunset times, and the cross-correlation of transmitter signals. We attempt to evaluate and to estimate the latitudinal and the longitudinal expansions of the ionospheric disturbances related to the seismic preparation areas