The Rhizosphere Bacterial Communities Differ Among Domesticated Maize Landraces – An Experimental Confirmation

The plant-associated microbiome has been shown to vary considerably between species and across environmental gradients. The effects of genomic variation on the microbiome within single species are less clearly understood, with results often confounded by the larger effects of climatic and edaphic variation. In this study, the effect of genomic variation on the rhizosphere bacterial communities of maize was investigated by comparing different genotypes grown within controlled environments. Rhizosphere bacterial communities were profiled by metabarcoding the universal bacterial 16S rRNA v3-v4 region. Initially, plants from the inbred B73 line and the Ancho - More 10 landrace were grown for 12-weeks and compared. The experiment was then repeated with an additional four Mexican landraces (Apachito - Chih 172, Tehua - Chis 204, Serrano - Pueb 180 and Hairnoso de Ocho) that were grown alongside additional B73 and Ancho - More 10 genotypes. In both experiments there were significant genotypic differences in the rhizosphere bacteria. Additionally, the bacterial communities were significantly correlated with genomic distance between genotypes, with the more closely related landraces being more similar in rhizosphere bacterial communities. Despite limited sampling numbers, here we confirm that genomic variation in maize landraces is associated with differences in the rhizosphere bacterial communities. Further studies that go beyond correlations to identify the mechanisms that determine the genotypic variation of the rhizosphere microbiome are required.

Evaluation of the Robustness of Therapeutic Drug Monitoring Coupled with Bayesian Forecasting of Busulfan with Regard to Inaccurate Documentation

Background Inaccurate documentation of sampling and infusion times is a potential source of error in personalizing busulfan doses using therapeutic drug monitoring (TDM). Planned times rather than the actual times for sampling and infusion time are often documented. Therefore, this study aimed to evaluate the robustness of a limited sampling TDM of busulfan with regard to inaccurate documentation. Methods A pharmacometric analysis was conducted in NONMEM® 7.4.3 and “R” by performing stochastic simulation and estimation with four, two and one sample(s) per patient on the basis of a one-compartment- (1CMT) and two-compartment (2CMT) population pharmacokinetic model. The dosing regimens consisted of i.v. busulfan (0.8 mg/kg) every 6 h (Q6H) or 3.2 mg/kg every 24 h (Q24H) with a 2 h- and 3 h infusion time, respectively. The relative prediction error (rPE) and relative root-mean-square error (rRmse) were calculated in order to determine the accuracy and precision of the individual AUC estimation. Results A noticeable impact on the estimated AUC based on a 1CMT-model was only observed if uncertain documentation reached ± 30 min (1.60% for Q24H and 2.19% for Q6H). Calculated rPEs and rRmse for Q6H indicate a slightly lower level of accuracy and precision when compared to Q24H. Spread of rPE’s and rRmse for the 2CMT-model were wider and higher compared to estimations based on a 1CMT-model. Conclusions The estimated AUC was not affected substantially by inaccurate documentation of sampling and infusion time. The calculated rPEs and rRmses of estimated AUC indicate robustness and reliability for TDM of busulfan, even in presence of erroneous records.

In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients

Purpose Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. Methods Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t1/2), time to 1% (Time1%), and calculated weekly dose (Dose1%). Bias and precision of these estimates were assessed to determine which LSS was adequate. Results For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: −5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time1%, except for t1/2 (range: 27.1% to 44.7%) and Dose1% (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose1% using LSS with the last sample taken on day 3 (LSS 6 and 10). Conclusion Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively.

Low-Coverage Whole Genomes Reveal the Higher Phylogeny of Green Lacewings

Green lacewings are one of the largest families within Neuroptera and are widely distributed all over the world. Many species within this group are important natural predators that are widely used for the biological control of pests in agricultural ecosystems. Several proposed phylogenetic relationships among the three subfamilies of Chrysopidae have been extensively debated. To further understand the higher phylogeny as well as the evolutionary history of Chrysopidae, we newly sequenced and analyzed the low-coverage genomes of 5 species (Apochrysa matsumurae, Chrysopa pallens, Chrysoperla furcifera, Italochrysa pardalina, Nothochrysa sinica), representing 3 subfamilies of Chrysopidae. There are 2213 orthologs selected to reconstruct the phylogenetic tree. Phylogenetic reconstruction was performed using both concatenation and coalescent-based approaches, based on different data matrices. All the results suggested that Chrysopinae were a monophyletic sister group to the branch Apochrysinae + Nothochrysinae. These results were completely supported, except by the concatenation analyses of the nt data matrix, which suggested that Apochrysinae were a sister group to Chrysopinae + Nothchrysinae. The different topology from the nt data matrix may have been caused by the limited sampling of Chrysopidae. The divergence time showed that Chrysopinae diverged from Apochrysinae + Nothochrysinae during the Early Cretaceous period (144–151 Ma), while Aporchrysinae diverged from Nothochrysinae around 117–133 Ma. These results will improve our understanding of the higher phylogeny of Chrysopidae and lay a foundation for the utilization of natural predators.

The Brewer–Dobson circulation in CMIP6

The Brewer–Dobson circulation (BDC) is a key feature of the stratosphere that models need to accurately represent in order to simulate surface climate variability and change adequately. For the first time, the Climate Model Intercomparison Project includes in its phase 6 (CMIP6) a set of diagnostics that allow for careful evaluation of the BDC. Here, the BDC is evaluated against observations and reanalyses using historical simulations. CMIP6 results confirm the well-known inconsistency in the sign of BDC trends between observations and models in the middle and upper stratosphere. Nevertheless, the large uncertainty in the observational trend estimates opens the door to compatibility. In particular, when accounting for the limited sampling of the observations, model and observational trend error bars overlap in 40 % of the simulations with available output. The increasing CO2 simulations feature an acceleration of the BDC but reveal a large spread in the middle-to-upper stratospheric trends, possibly related to the parameterized gravity wave forcing. The very close connection between the shallow branch of the residual circulation and surface temperature is highlighted, which is absent in the deep branch. The trends in mean age of air are shown to be more robust throughout the stratosphere than those in the residual circulation.

The Coume Ouarnède System, a Hotspot of Subterranean Biodiversity in Pyrenees (France)

Located in Northern Pyrenees, in the Arbas massif, France, the system of the Coume Ouarnède, also known as Réseau Félix Trombe—Henne Morte, is the longest and the most complex cave system of France. The system, developed in massive Mesozoic limestone, has two distinct resurgences. Despite relatively limited sampling, its subterranean fauna is rich, composed of a number of local endemics, terrestrial as well as aquatic, including two remarkable relictual species, Arbasus caecus (Simon, 1911) and Tritomurus falcifer Cassagnau, 1958. With 38 stygobiotic and troglobiotic species recorded so far, the Coume Ouarnède system is the second richest subterranean hotspot in France and the first one in Pyrenees. This species richness is, however, expected to increase because several taxonomic groups, like Ostracoda, as well as important subterranean habitats, like MSS (“Milieu Souterrain Superficiel”), have not been considered so far in inventories. Similar levels of subterranean biodiversity are expected to occur in less-sampled karsts of central and western Pyrenees.