CRABS CLAW Acts as a Bifunctional Transcription Factor in Flower Development

One of the crucial steps in the life cycle of angiosperms is the development of carpels. They are the most complex plant organs, harbor the seeds, and, after fertilization, develop into fruits and are thus an important ecological and economic trait. CRABS CLAW (CRC), a YABBY protein and putative transcription factor, is one of the major carpel developmental regulators in A. thaliana that includes a C2C2 zinc finger and a domain with similarities to an HMG box. CRC is involved in the regulation of processes such as carpel fusion and growth, floral meristem termination, and nectary formation. While its genetic interactions with other carpel development regulators are well described, its biochemical properties and molecular way of action remain unclear. We combined Bimolecular Fluorescence Complementation, Yeast Two-Hybrid, and Yeast One-Hybrid analyzes to shed light on the molecular biology of CRC. Our results showed that CRC dimerizes, also with other YABBY proteins, via the YABBY domain, and that its DNA binding is mainly cooperative and is mediated by the YABBY domain. Further, we identified that CRC is involved in floral meristem termination via transcriptional repression while it acts as a transcriptional activator in nectary development and carpel fusion and growth control. This work increases our understanding on how YABBY transcription factors interact with other proteins and how they regulate their targets

Semi-homogeneous vector bundles on abelian varieties: moduli spaces and their tropicalization

We construct a moduli space of semi-homogeneous vector bundles with a fixed N\'eron-Severi class $H$ on an abelian variety $A$ over an algebraically closed field of characteristic zero. When $A$ has totally degenerate reduction over a non-Archimedean field, we describe our moduli space from the perspective of non-Archimedean uniformization and show that the essential skeleton may be identified with a tropical analogue of this moduli space. For $H=0$ our moduli space may be identified with the moduli space $M_{0,r}(A)$ of semistable vector bundles with vanishing Chern classes on $A$. In this case we construct a surjective analytic morphism from the character variety of the analytic fundamental group of $A$ onto $M_{0,r}(A)$, which naturally tropicalizes. One may view this construction as a non-Archimedean uniformization of $M_{0,r}(A)$.Comment: v2: added further explanation to Section 1, 31 pages, comments very welcome

Mating still disrupted: Future elevated CO2 concentrations are likely to not interfere with Lobesia botrana and Eupoecilia ambiguella mating disruption in vineyards in the near future

The successful, area-wide application of the mating disruption (MD) technique, an insect sex pheromone-based biotechnological pest control method, against the European grapevine moth Lobesia botrana and the European grape berry moth Eupoecilia ambiguella, has led to drastic reductions in insecticide application in vineyards. However, since insect pheromone perception and emission can be affected by abiotic conditions, the future success of MD may be affected by climate change. At the same time, politics and society are calling for drastic and sustainable reductions in pesticide application, making highly specific, efficient, and environmentally friendly pest control techniques like MD more important than ever. To anticipate whether climate change factors will interfere with the MD of L. botrana and E. ambiguella in vineyards, we conducted field experiments in the Geisenheim VineyardFACE (Free-Air Carbon dioxide Enrichment) facility. The insects were raised at ambient or elevated temperatures in the lab and male moths were released in cages installed in the VineyardFACE facility. Trap recapture rates obtained by pheromone lures or female moths under elevated or ambient CO2 in areas with and without MD were evaluated. Our results did not indicate a reduced efficacy of L. botrana or E. ambiguella MD at elevated CO2 concentrations, irrespective of the temperature the moths were raised under. From a practical point of view-and especially from an ecological one-our results are good news. They indicate that MD will not be negatively affected by future elevated CO2 concentrations

Altered volatile emission of pear trees under elevated atmospheric CO2 levels has no relevance to pear psyllid host choice

The impact of climate change drivers on cultivated plants and pest insects has come into research focus. One of the most significant drivers is atmospheric carbon dioxide, which is converted into primary plant metabolites by photosynthesis. Increased atmospheric CO2 concentrations therefore affect plant chemistry. The chemical composition of non-volatile and volatile organic compounds of plants is used by insects to locate and identify suitable host plants for feeding and reproduction. We investigated whether elevated CO2 concentrations in the atmosphere affect the plant-pest interaction in a fruit crop of high economic importance in Europe. Therefore, potted pear trees were cultivated under specified CO2 conditions in a Free-Air Carbon dioxide Enrichment (FACE) facility at Geisenheim University in Germany for up to 14 weeks, beginning from bud swelling. We compared emitted volatiles from these pear trees cultivated for 7 and 14 weeks under two different CO2 levels (ambient: ca. 400 ppm and elevated: ca. 450 ppm CO2) and their impact on pest insect behavior. In total, we detected and analyzed 76 VOCs from pear trees. While we did not detect an overall change in VOC compositions, the relative release of single compounds changed in response to CO2 increase. Differences in VOC release were inconsistent over time (phenology stages) and between study years, indicating interactions with other climate parameters, such as temperature. Even though insect-plant interaction can rely on specific volatile compounds and specific mixtures of compounds, respectively, the changes of VOC patterns in our field study did not impact the host choice behavior of C. pyri females. In olfactometer trials, 64% and 60% of the females preferred the odor of pear trees cultivated under elevated CO2 for 7 and 14 weeks, respectively, over the odor from pear trees cultivated under ambient CO2. In binary-choice oviposition assays, C. pyri females laid most eggs on pears during April 2020; on average, 51.9 (+/- 51.3) eggs were laid on pears cultivated under eCO(2) and 60.3 (+/- 48.7) eggs on aCO(2.

Common garden versus common practice – Phenotypic changes in Trifolium pratense L. in response to repeated mowing

Plants react to various biotic and abiotic factors by adjusting their growth pattern. This process, called phenotypic plasticity, can also be observed in the agronomical important fodder plant Trifolium pratense L. (red clover) which is grown worldwide for its high pro-tein content and soil improving ability. After cutting it changes its growth pattern due to phenotypic plasticity and initiates a second growth phase. Here, we analyze the regrowth dynamics of red clover in response to grazing or mowing by recording the plant’s architecture, leaf morphology, and growth performance in different cutting experiments. As previous studies were limited in the number of individuals and carried out via common garden experiments, we analyzed the regrowth reaction of T. pratense under standard agricul-tural field conditions. T. pratense forms smaller and rounder leaflets after repeated cutting, compensated by the production of more bio-mass. Nitrogen contents were subjected to seasonal changes, rather than by changes through cutting. As middle to late cut plants had higher regrowth capacities and regrew more biomass than early cut plants, an optimal time point for biomass harvest can be suggested to maximize the total yield of red clover biomass

A physiologically based pharmacokinetic model of clopidogrel in populations of European and Japanese ancestry: An evaluation of CYP2C19 activity

Treatment response to clopidogrel is associated with CYP2C19 activity through the formation of the active H4 metabolite. The aims of this study were to develop a physiologically based pharmacokinetic (PBPK) model of clopidogrel and its metabolites for populations of European ancestry, to predict the pharmacokinetics in the Japanese population by CYP2C19 phenotype, and to investigate the effect of clinical and demographic factors. A PBPK model was developed and verified to describe the two metabolic pathways of clopidogrel (H4 metabolite, acyl glucuronide metabolite) for a population of European ancestry using plasma data from published studies. Subsequently, model predictions in the Japanese population were evaluated. The effects of CYP2C19 activity, fluvoxamine coadministration (CYP2C19 inhibitor), and population-specific factors (age, sex, BMI, body weight, cancer, hepatic, and renal dysfunction) on the pharmacokinetics of clopidogrel and its metabolites were then characterized. The predicted/observed ratios for clopidogrel and metabolite exposure parameters were acceptable (twofold acceptance criteria). For all CYP2C19 phenotypes, steady-state AUC0-τ of the H4 metabolite was lower for the Japanese (e.g., EM, 7.69 [6.26–9.45] ng·h/ml; geometric mean [95% CI]) than European (EM, 24.8 [20.4–30.1] ng·h/ml, p <.001) population. In addition to CYP2C19-poor metabolizer phenotype, fluvoxamine coadministration, hepatic, and renal dysfunction were found to reduce H4 metabolite but not acyl glucuronide metabolite concentrations. This is the first PBPK model describing the two major metabolic pathways of clopidogrel, which can be applied to populations of European and Japanese ancestry by CYP2C19 phenotype. The differences between the two populations appear to be determined primarily by the effect of varying CYP2C19 liver activity

Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis

Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD

Interinstitutional variations in mode of birth after a previous caesarean section : a cross-sectional study in six German hospitals

Aims: Regional and interinstitutional variations have been recognized in the increasing incidence of caesarean section. Modes of birth after previous caesarean section vary widely, ranging from elective repeat caesarean section (ERCS) and unplanned repeat caesarean section (URCS) after trial of labour to vaginal birth after caesarean section (VBAC). This study describes interinstitutional variations in mode of birth after previous caesarean section in relation to regional indicators in Germany. Material and methods: A cross-sectional study using the birth registers of six maternity units (n=12,060) in five different German states (n=370,209). Indicators were tested by χ2 and relative deviations from regional values were expressed as relative risks and 95% confidence intervals. Results: The percentages of women in the six units with previous caesarean section ranged from 11.9% to 15.9% (P=0.002). VBAC was planned for 36.0% to 49.8% (P=0.003) of these women, but actually completed in only 26.2% to 32.8% (P=0.66). Depending on the indicator, the units studied deviated from the regional data by up to 32% [relative risk 0.68 (0.47–0.97)] in respect of completed VBAC among all initiated VBAC. Conclusions: There is substantial interinstitutional variation in mode of birth following previous caesarean section. This variation is in addition to regional patterns

Platform trial design for neurofibromatosis type 1, NF2-related schwannomatosis and non-NF2-related schwannomatosis:A potential model for rare diseases

Background Neurofibromatosis type 1, NF2-related schwannomatosis and non-NF2-related schwannomatosis (grouped under the abbreviation "NF") are rare hereditary tumor predisposition syndromes. Due to the low prevalence, variability in the range, and severity of manifestations, as well as limited treatment options, these conditions require innovative trial designs to accelerate the development of new treatments.Methods Within European Patient-Centric Clinical Trial Platforms (EU-PEARL), we designed 2 platform-basket trials in NF. The trials were designed by a team of multidisciplinary NF experts and trial methodology experts.Results The trial will consist of an observational and a treatment period. The observational period will serve as a longitudinal natural history study. The platform trial design and randomization to a sequence of available interventions allow for the addition of interventions during the trial. If a drug does not meet the predetermined efficacy endpoint or reveals unacceptable toxicities, participants may stop treatment on that arm and re-enter the observational period, where they can be re-randomized to a different treatment arm if eligible. Intervention-specific eligibility criteria and endpoints are listed in intervention-specific-appendices, allowing the flexibility and adaptability needed for highly variable and rare conditions like NF.Conclusions These innovative platform-basket trials for NF may serve as a model for other rare diseases, as they will enhance the chance of identifying beneficial treatments through optimal learning from a small number of patients. The goal of these trials is to identify beneficial treatments for NF more rapidly and at a lower cost than traditional, single-agent clinical trials