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Fertilization-induced synergid cell death by RALF12-triggered ROS production and ethylene signaling
Abstract Fertilization-dependent elimination of the persistent synergid cell is essential to block supernumerary pollen tubes and thus to avoid polyspermy in flowering plants. Little is known about the molecular mechanisms ensuring timely induction and execution of synergid cell death. We analyzed manually isolated maize synergid cells along their degeneration and show that they are gland cells expressing batteries of genes encoding small secreted proteins under control of the MYB98 transcription factor. This network is down-regulated after fertilization, while genes involved in reactive oxygen species (ROS) production, ethylene biosynthesis and response, senescence, and oxidative stress regulation are induced before synergid elimination and its ultimate fusion with the endosperm. We further show that the fertilization-induced RALF12 peptide specifically triggers mitochondrial ROS and apoptosis, while ethylene promotes synergid degeneration. In conclusion, this study sheds light on developmental programmed cell death (dPCD) in plants and provides a unique resource to discover unknown PCD regulators.
A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase reveals a role at metaphase kinetochores
Abstract Serine-threonine phosphatases have been challenging to study because of the lack of specific inhibitors. Their catalytic domains are druggable, but these are shared or very similar between individual phosphatase complexes, precluding their specific inhibition. Instead, phosphatase complexes often achieve specificity by interacting with short linear motifs (SLiMs) in substrates or their binding partners. We develop here a chemical-genetic system to rapidly inhibit these interactions within the PP2A-B56 family. Drug-inducible recruitment of ectopic SLiMs (“directSLiMs”) is used to rapidly block the SLiM-binding pocket on the B56 regulatory subunit, thereby displacing endogenous interactors and inhibiting PP2A-B56 activity within seconds. We use this system to characterise PP2A-B56 substrates during mitosis and to identify a role for PP2A-B56 in allowing metaphase kinetochores to properly sense tension and maintain microtubule attachments. The directSLiMs approach can be used to inhibit any other phosphatase, enzyme or protein that uses a critical SLiM-binding interface, providing a powerful strategy to inhibit and characterise proteins once considered “undruggable”.
Food and water intake are regulated by distinct central amygdala circuits revealed using intersectional genetics
Abstract The central amygdala (CeA) plays a crucial role in defensive and appetitive behaviours. It contains genetically defined GABAergic neuron subpopulations distributed over three anatomical subregions, capsular (CeC), lateral (CeL), and medial (CeM). The roles that these molecularly- and anatomically-defined CeA neurons play in appetitive behavior remain unclear. Using intersectional genetics in mice, we found that neurons driving food or water consumption are confined to the CeM. Separate CeM subpopulations exist for water only versus water or food consumption. In vivo calcium imaging revealed that CeMHtr2a neurons promoting feeding are responsive towards appetitive cues with little regard for their physical attributes. CeMSst neurons involved in drinking are sensitive to the physical properties of salient stimuli. Both CeM subtypes receive inhibitory input from CeL and send projections to the parabrachial nucleus to promote appetitive behavior. These results suggest that distinct CeM microcircuits evaluate liquid and solid appetitive stimuli to drive the appropriate behavioral responses.
Aberrant gene expression prediction across human tissues
Abstract Despite the frequent implication of aberrant gene expression in diseases, algorithms predicting aberrantly expressed genes of an individual are lacking. To address this need, we compile an aberrant expression prediction benchmark covering 8.2 million rare variants from 633 individuals across 49 tissues. While not geared toward aberrant expression, the deleteriousness score CADD and the loss-of-function predictor LOFTEE show mild predictive ability (1–1.6% average precision). Leveraging these and further variant annotations, we next train AbExp, a model that yields 12% average precision by combining in a tissue-specific fashion expression variability with variant effects on isoforms and on aberrant splicing. Integrating expression measurements from clinically accessible tissues leads to another two-fold improvement. Furthermore, we show on UK Biobank blood traits that performing rare variant association testing using the continuous and tissue-specific AbExp variant scores instead of LOFTEE variant burden increases gene discovery sensitivity and enables improved phenotype predictions.
Assessing the success of marine ecosystem restoration using meta-analysis
Period-doubling in the phase dynamics of a shunted HgTe quantum well Josephson junction
Abstract The fractional AC Josephson effect is a discerning property of topological superconductivity in hybrid Josephson junctions. Recent experimental observations of missing odd Shapiro steps and half Josephson frequency emission in various materials have sparked significant debate regarding their potential origin in the effect. In this study, we present microwave emission measurements on a resistively shunted Josephson junction based on a HgTe quantum well. We demonstrate that, with significant spurious inductance in the shunt wiring, the experiment operates in a nonlinear dynamic regime characterized by period-doubling. This leads to additional microwave emission peaks at half of the Josephson frequency, f J/2, which can mimic the 4π-periodicity of topological Andreev states. The observed current-voltage characteristics and emission spectra are well-described by a simple RCLSJ model. Furthermore, we show that the nonlinear dynamics of the junction can be controlled using gate voltage, magnetic field, and temperature, with our model accurately reproducing these effects without incorporating any topological attributes. Our observations urge caution in interpreting emission at f J/2 as evidence for gapless Andreev bound states in topological junctions and suggest the appropriate parameter range for future experiments.
Synthesis of nickel(II)-containing meso-edited phthalocyanine derivatives
Genome-scale CRISPRi screen identifies pcnB repression conferring improved physiology for overproduction of free fatty acids in Escherichia coli
Incoherent feedback from coupled amino acids and ribosome pools generates damped oscillations in growing E. coli
Non-reciprocal Coulomb drag between Chern insulators
Dopamine prediction error signaling in a unique nigrostriatal circuit is critical for associative fear learning
Abstract Learning by experience that certain cues in the environment predict danger is crucial for survival. How dopamine (DA) circuits drive this form of associative learning is not fully understood. Here, in male mice, we demonstrate that DA neurons projecting to a unique subregion of the dorsal striatum, the posterior tail of the striatum (TS), encode a prediction error (PE) signal during associative fear learning. These DA neurons are necessary specifically during acquisition of fear learning, but not once the fear memory is formed, and are not required for forming cue-reward associations. Notably, temporally-precise inhibition or excitation of DA terminals in TS impairs or enhances fear learning, respectively. Furthermore, neuronal activity in TS is crucial for the acquisition of associative fear learning and learning-induced activity patterns in TS critically depend on DA input. Together, our results reveal that DA PE signaling in a non-canonical nigrostriatal circuit is important for driving associative fear learning.
Mechanically deformable organic ferroelectric crystal with plasticity optimized by fluorination
β-Carotene alleviates substrate inhibition caused by asymmetric cooperativity
Abstract Enzymes are essential catalysts in biological systems. Substrate inhibition, once dismissed, is now observed in 20% of enzymes1 and is attributed to the formation of an unproductive enzyme-substrate complex, with no structural evidence of unproductivity provided to date1–6. This study uncovers the molecular mechanism of substrate inhibition in tobacco glucosyltransferase NbUGT72AY1, which transfers glucose to phenols for plant protection. The peculiarity that β-carotene strongly attenuates the substrate inhibition of NbUGT72AY1, despite being a competitive inhibitor, allows to determine the conformational changes that occur during substrate binding in both active and substrate-inhibited complexes. Crystallography reveals structurally different ternary enzyme-substrate complexes that do not conform to classical mechanisms. An alternative pathway suggests substrates bind randomly, but the reaction occurs only if a specific order is followed (asymmetric cooperativity). This unreported paradigm explains substrate inhibition and reactivation by competitive inhibitors, opening new research avenues in metabolic regulation and industrial applications.
Efficient and accurate framework for genome-wide gene-environment interaction analysis in large-scale biobanks
Using Mg isotopes to constrain the formation temperature of dolomite
Hydro-morphodynamic numerical modeling indicates risk zones for riverbed clogging
Abstract Riverbed clogging compromises the ecological functioning of gravel-bed rivers. Physical clogging affects aquatic habitats and occurs when fine sediments infiltrate coarser substrates, reducing permeability, porosity, and oxygenation. Clogging analyses mostly rely on methods or models that assess the clogging state from field data without predictive capacity. However, predictive tools are essential to optimize habitat restoration in mountain rivers. This study evaluates a two-dimensional numerical model for simulating fine sediment infiltration and mobilization around two large wood pieces in a fully controlled morphodynamic gravel-bed channel. Field data from the morphodynamic channel, collected before and after an artificial flood, were used to calibrate the model and compare its outputs with measured sediment parameters. The model reproduces fine sediment fractions in the surface and subsurface layers, especially in a shallow, high-velocity zone that underwent substantial declogging. In contrast, fine sediment fractions increased in a deeper, slower-flowing zone. Additionally, simulated suspended sediment concentration and fine sediment fraction maps highlight how a swale saturated with fine sediment on the floodplain contributed to increased fine sediment infiltration and clogging downstream. These findings demonstrate that a robust 2d model capturing fine sediment dynamics can effectively identify clogging-prone areas in gravel-bed rivers.
Inference of a plume conduit beneath the Réunion Island from 3D migration of Ps conversions from the mantle transition zone
Abstract The Réunion hotspot is the best example of a primary plume, manifested as intraplate-volcanism, a large igneous province and a geochemical anomaly. In this study, we investigate the mantle transition zone (MTZ) structure beneath the Réunion Island using 3D-migration of P-Receiver functions, to decipher the effect of the plume on the MTZ and its architecture. Results indicate a thin MTZ in the regions surrounding the Réunion, like Madagascar and its vicinity, eastern and south-eastern sides of the Réunion, suggesting high-temperature anomalies within, caused by the plume. Interestingly, we detect a depressed 410 km discontinuity exactly beneath the Réunion hotspot and a broader depression of 660 km discontinuity within and regions in its proximity. These maiden results shed-light on the high-temperature anomalies in the mid-mantle, probably sourced from the Réunion plume and provide evidence for the Majorite-garnet phase transformation at 660 km discontinuity. We postulate that an ascending Réunion plume has initially hit the 660 km discontinuity, got horizontally spread and further progressed to the 410 km discontinuity as a columnar structure.