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Abstract Point-of-use diagnostics based on allosteric transcription factors (aTFs) are promising tools for environmental monitoring and human health. However, biosensors relying on natural aTFs rarely exhibit the sensitivity and selectivity needed for real-world applications, and traditional directed evolution struggles to optimize multiple biosensor properties at once. To overcome these challenges, we develop a multi-objective, machine learning (ML)-guided cell-free gene expression workflow for engineering aTF-based biosensors. Our approach rapidly generates high-quality sequence-to-function data, which we transform into an augmented paired dataset to train an ML model using directional labels that capture how aTF mutations alter performance. We apply our workflow to engineer the aTF PbrR as a point-of-use diagnostic for lead contamination in water. We tune the sensitivity of PbrR to sense at the U.S. Environmental Protection Agency (EPA) action level for lead and modify the selectivity away from zinc, a common metal found in water supplies. Finally, we show that the engineered PbrR functions in freeze-dried cell-free reactions, enabling a diagnostic capable of detecting lead in drinking water down to ~5.7 ppb. Our ML-driven, multi-objective framework powered by directional tokens can generalize to other biosensors and proteins, accelerating the development of synthetic biology tools for biotechnology applications. 

ABSTRACT Microgastroid parasitoids lay eggs in other insects and harbor bracoviruses (BVs), which evolved from a nudivirus. BV genomes are endogenized in the wasp germline and consist of nudivirus-like genes plus proviral segments with virulence genes. Nudivirus genes produce virions in the ovary calyx cells, which wasps use to transfer virulence genes to hosts. Here, we report a chromosome-scale genome assembly forMicroplitis demolitor,which harbors Microplitis demolitor bracovirus (MdBV). The assembly identified the locations of all MdBV nudivirus-like genes and proviral segments. Like nudiviruses and related baculoviruses, BVs express nudivirus-like genes in a temporally ordered cascade. Early genes include subunits of an RNA polymerase (RNApol) that transcribes late genes encoding virion components. Promoter motifs in BV relatives did not predict MdBV early and late genes. In contrast, RNA interference experiments showed that knockdown of the MdBV RNApol downregulated most of the known nudivirus-like late genes. We identified 60 genes with no homology with known nudivirus genes, with features indicating that they were also inherited from the BV ancestor. We named these candidate, new nudivirus-like genes. Each was expressed as a late gene, 39 encoded virion components, and orthologs were identified in wasps that are closely related toM. demolitor. Finally, we identified a new 20 bp motif in most MdBV late genes. This motif was present in the nudivirus-like genes of another BV but was largely absent in nudivirus and baculovirus genes. Altogether, the results identified several new features of BVs that are important for virion formation.IMPORTANCEBracoviruses (BVs) provide a dramatic example of cooption and repurposing of a virus by eukaryotes for new functions. This study further characterizes the gene content and organization of the MdBV genome. Our results support the conclusion that the MdBV RNApol retains conserved functions by primarily transcribing viral late genes. Reported results also present a strategy for identifying BV genes that share no homology with known nudiviruses. 

Why do people fall for misinformation, and what can be done about it? The current article reviews a programme of research that has used a signal-detection framework to identify three distinct factors in truth judgements of true and false information: (a) accurate discernment of true and false information (truth sensitivity); (b) a general tendency to judge information as true versus false (overall threshold); and (c) a tendency to accept information that is congruent versus incongruent with one’s views (myside bias). A first level of analysis addresses whether people accept false information as true due to low truth sensitivity, low overall threshold, or myside bias. A second level of analysis addresses the psychological determinants of truth sensitivity, overall threshold, and myside bias. The current article reviews key findings at each level of analysis and discusses their implications for why people fall for misinformation and what could be done about it. 

People overaccept information that supports their identity and underaccept information that opposes their identity—a phenomenon known as partisan bias. Although partisan-bias effects in judgments of misinformation are robust and pervasive, there is ongoing debate about whether partisan-bias effects arise from identity-protective motivated reasoning or differential knowledge of identity-congenial versus identity-uncongenial information. Prior empirical work has been unable to differentiate the two accounts because of a reliance on groups with pre-existing differences in knowledge (e.g., Democrats and Republicans). The current research addresses this issue by using randomly assigned rather than pre-existing identities. Across two experiments (N = 1,411), adult U.S. Prolific workers showed lower thresholds for accepting information that is congenial versus uncongenial to a randomly assigned identity, despite having no differences in prior knowledge. These results support theories that emphasize identity protection as a factor underlying partisan bias in the acceptance of misinformation, with important practical implications for misinformation interventions. 

{"Abstract":["This data product contains physical, chemical, and biological data ranging from the minute to daily to weekly scale in six artificial ponds (400 square meter surface area, 2m depth) in central Iowa (USA) 2020. Ponds were paired into three sets of treatment and reference with treatment ponds receiving two nutrient pulses designed to increase ambient phosphorus concentrations ~ 3 - 5%. Nitrogen and phosphorus were added as NH4NO3 and H3PO4, respectively, at a 24:1 molar ratio. The first nutrient pulse occurred on Julian day of year (DOY) 176 corresponding to a 3% increase and the second nutrient pulse occurred on DOY 211 to a 5% increase. Each treatment-reference set had a different food web structure established ranging between low, intermediate, and high complexity based on trophic connectivity and food chain length. \n \n Added to this data package is a document titled "2020 Iowa State University Horticultural Farm Experimental Ponds Nutrient Addition Experiment". For experimental set up, context, and a summary table of the data tables archived herein with available variables please review this document. It is added to aid in successful interpretation and to increase ease-of-use. Please email Tyler Butts (tyler.james.butts@gmail.com) for any and all questions regarding context or use of this dataset!"]} 

Unsubstituted carbatripyrrins have previously been shown to be useful intermediates in the synthesis of benzocarbaporphyrins and related core- modified analogues. However, the absence of substituents often resulted in the formation of poorly soluble products. In this study, four examples alkyl substituted carbatripyrrins were constructed by base-catalyzed condensation of dihydrofulvenes with pyrrole aldehydes. Further reaction with a pyrrole dialdehyde in the presence of trifluoroacetic acid afforded a series of carbaporphyrins, while reactions with 2,5-furandicarboxaldehyde generated oxacarbaporphyrins. These results demonstrate that alkyl substituted carba- tripyrrins are promising precursors to new carbaporphyrinoid structures. 

Elucidating the factors limiting quantum coherence in real materials is essential to the development of quantum technologies. Here we report a strategic approach to determine the effect of lattice dynamics on spin coherence lifetimes using oxygen deficient double perovskites as host materials. In addition to obtaining millisecond T1 spin-lattice lifetimes at T ~ 10 K, measurable quantum superpositions were observed up to room temperature. We determine that T2 enhancement in Sr2CaWO6-δ over previously studied Ba2CaWO6-δ is caused by a dynamically-driven increase in effective site symmetry around the dominant paramagnetic site, assigned as W5+ via electron paramagnetic resonance spectroscopy. Further, a combination of experimental and computational techniques enabled quantification of the relative strength of spin-phonon coupling of each phonon mode. This analysis demonstrates the effect of thermodynamics and site symmetry on the spin lifetimes of W5+ paramagnetic defects, an important step in the process of reducing decoherence to produce longer-lived qubits. 

Abstract Adult neural stem cells (NSCs) in the mammalian dentate gyrus (DG) of the hippocampus rely on multiple signals for their preservation throughout the lifespan. While several studies have suggested that vascular endothelial growth factor (VEGF), in particular VEGF synthesized by NSCs themselves, is critical for NSC maintenance and adult neurogenesis, conflicting studies have left it uncertain how VEGF signals to NSCs. Here, we identified a VEGF-VEGFR2 intracrine signaling mechanism within adult DG NSCs that prevents NSC exhaustion and supports their proximity to local blood vessels. Using cell culture assays, we show that while intracellular VEGF stimulated receptor signaling cascades, extracellular VEGF did not. We found that this primary reliance on intracellular VEGF receptor signaling was most likely due to sheddase-mediated cleavage of extracellular VEGFR2 ligand binding domains, as phospho-signaling in response to extracellular VEGF could be restored using sheddase inhibitors. Using cultured adult DG NSCs and intact mice, we further show that NSC-VEGF loss caused cell-autonomous exhaustion of adult DG NSCs, along with impaired migration in cultured NSCs and reduced proximity of NSCs to local blood vessels in mouse DG. Our findings support an exclusively intracellular mechanism for VEGF signaling in adult DG NSCs, thereby providing resolution to previously conflicting studies and suggesting that cellular source can dictate the functional impact of soluble ligands in DG NSCs.