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Ratiometric Sensing of Pnt and Yan Transcription Factor Levels Confers Ultrasensitivity to Photoreceptor Fate Transitions in Drosophila
No full textCell state transitions are often triggered by large changes in the concentrations of transcription factors and therefore large differences in their stoichiometric ratios. Whether cells can elicit transitions using modest changes in the ratios of co-expressed factors is unclear. Here, we investigate how cells in the Drosophila eye resolve state transitions by quantifying the expression dynamics of the ETS transcription factors Pnt and Yan. Eye progenitor cells maintain a relatively constant ratio of Pnt/Yan protein, despite expressing both proteins with pulsatile dynamics. A rapid and sustained twofold increase in the Pnt/Yan ratio accompanies transitions to photoreceptor fates. Genetic perturbations that modestly disrupt the Pnt/Yan ratio produce fate transition defects consistent with the hypothesis that transitions are normally driven by a twofold shift in the ratio. A biophysical model based on cooperative Yan-DNA binding coupled with non-cooperative Pnt-DNA binding illustrates how twofold ratio changes could generate ultrasensitive changes in target gene transcription to drive fate transitions. Thus, coupling cell state transitions to the Pnt/Yan ratio sensitizes the system to modest fold-changes, conferring robustness and ultrasensitivity to the developmental program
A latent Gaussian process model for the spatial distribution of liquefaction manifestation
No full textThis paper presents a model for distributing zones of liquefaction and nonliquefaction for use in regional liquefaction risk analysis. There are two broad methodologies that have been used to evaluate liquefaction risk on the regional scale: (a) application of site-specific procedures using soil properties inferred from geology, or (b) application of geospatial proxies for liquefaction. The first approach will tend to predict similar liquefaction probabilities across broad areas with similar geology, water table depths, and shaking intensities. The second approach yields the probability of liquefaction, which can be interpreted as the portion of the area affected by liquefaction (%Aliq). Neither approach, however, gives an informed prediction of the spatial distribution of liquefaction and the resulting displacements, which are particularly important for assessments of seismic risk for spatially distributed infrastructure systems. We propose a methodology for incorporating spatial correlation into a geospatial proxy for liquefaction to create maps of liquefaction and nonliquefaction for a given earthquake scenario. First, we describe a latent Gaussian process that is assumed to govern the spatial distribution of liquefaction. Next, a database of empirical observations of liquefaction is used to obtain the coefficients that describe that latent Gaussian process. The proposed model yields random realizations of maps of liquefaction and nonliquefaction conditioned on a map of (%Aliq). Such maps can be used to constrain the area over which displacements are estimated using soil properties inferred from geology and are therefore a critical component in reducing bias in assessments of liquefaction risk at the regional scale
Revised Properties and Dynamical History for the HD 17156 System
No full textFrom the thousands of known exoplanets, those that transit bright host stars provide the greatest accessibility toward detailed system characterization. The first known such planets were generally discovered using the radial-velocity technique, then later found to transit. HD 17156b is particularly notable among these initial discoveries because it diverged from the typical hot-Jupiter population, occupying a 21.2 day eccentric (e = 0.68) orbit, offering preliminary insights into the evolution of planets in extreme orbits. Here we present new data for this system, including ground- and space-based photometry, radial velocities, and speckle imaging, that further constrain the system properties and stellar/planetary multiplicity. These data include photometry from the Transiting Exoplanet Survey Satellite that cover five transits of the known planet. We show that the system does not harbor any additional giant planets interior to 10 au. The lack of stellar companions and the age of the system indicate that the eccentricity of the known planet may have resulted from a previous planet–planet scattering event. We provide the results from dynamical simulations that suggest possible properties of an additional planet that culminated in ejection from the system, leaving a legacy of the observed high eccentricity for HD 17156b
Early Results from GLASS-JWST. XVI. Discovering a Bluer z ∼ 4–7 Universe through UV Slopes
No full textWe use the GLASS-JWST Early Release Science NIRCam parallel observations to provide a first view of the UV continuum properties of NIRCam/F444W selected galaxies at 4 99% of the galaxies are blue star-forming galaxies with very low levels of dust (Avβ ∼ 0.01 ± 0.33). We find no statistically significant correlation for UV slope with redshift or UV magnitude. However, we find that in general galaxies at higher redshifts and fainter UV magnitudes have steeper UV slopes. We find a statistically significant correlation for UV slope with stellar mass, with galaxies with higher stellar mass showing shallower UV slopes. Individual fits to some of our galaxies reach the bluest UV slopes of β ∼ −3.1 allowed by stellar population models used in this analysis. Therefore, it is likely that stellar population models with a higher amount of Lyman continuum leakage, active galactic nucleus effects, and/or Population III contributions are required to accurately reproduce the rest-UV and optical properties of some of our bluest galaxies. This dust-free early view confirms that our current cosmological understanding of gradual mass + dust buildup of galaxies with cosmic time is largely accurate to describe the ∼0.7–1.5 Gyr age window of the universe. The abundance of a large population of UV faint dust-poor systems may point to a dominance of low-mass galaxies at z > 6 playing a vital role in cosmic reionization
Milton, Boccaccio, and Demogorgon
No full textFor years scholars have realized that Demogorgon owes his existence to a misreading of demiurgus in a commentary on Statius’ Thebaid and that Boccaccio’s Genealogy of the Pagan Gods was the most important text for establishing Demogorgon as the ancestor of the gods for the Renaissance. But the extent of scepticism about Demogorgon in Milton’s day is not widely known. In an early example of the polemical imitation that characterizes much of his mature poetry, Milton indicates his own scepticism in Prolusion I by extensively correcting Boccaccio’s account of Demogorgon and his progeny. Unlike his frighteningly powerful namesake in Boiardo, Ariosto, and Spenser, the Demogorgon of Paradise Lost is simply one member of the court of Chaos. The multivalent periphrasis—‘the dreaded name | Of Demogorgon’—suggests that Boccaccio’s ancestor of the gods is nothing more than a name
S1 represents multisensory contexts and somatotopic locations within and outside the bounds of the cortical homunculus
No full textRecent literature suggests that tactile events are represented in the primary somatosensory cortex (S1) beyond its long-established topography; in addition, the extent to which S1 is modulated by vision remains unclear. To better characterize S1, human electrophysiological data were recorded during touches to the forearm or finger. Conditions included visually observed physical touches, physical touches without vision, and visual touches without physical contact. Two major findings emerge from this dataset. First, vision strongly modulates S1 area 1, but only if there is a physical element to the touch, suggesting that passive touch observation is insufficient to elicit neural responses. Second, despite recording in a putative arm area of S1, neural activity represents both arm and finger stimuli during physical touches. Arm touches are encoded more strongly and specifically, supporting the idea that S1 encodes tactile events primarily through its topographic organization but also more generally, encompassing other areas of the body
NO at low concentration can enhance the formation of highly oxygenated biogenic molecules in the atmosphere
No full textThe interaction between nitrogen monoxide (NO) and organic peroxy radicals (RO2) greatly impacts the formation of highly oxygenated organic molecules (HOM), the key precursors of secondary organic aerosols. It has been thought that HOM production can be significantly suppressed by NO even at low concentrations. Here, we perform dedicated experiments focusing on HOM formation from monoterpenes at low NO concentrations (0 – 82 pptv). We demonstrate that such low NO can enhance HOM production by modulating the RO₂ loss and favoring the formation of alkoxy radicals that can continue to autoxidize through isomerization. These insights suggest that HOM yields from typical boreal forest emissions can vary between 2.5%-6.5%, and HOM formation will not be completely inhibited even at high NO concentrations. Our findings challenge the notion that NO monotonically reduces HOM yields by extending the knowledge of RO₂-NO interactions to the low-NO regime. This represents a major advance towards an accurate assessment of HOM budgets, especially in low-NO environments, which prevails in the pre-industrial atmosphere, pristine areas, and the upper boundary layer
Daily SARS-CoV-2 Nasal Antigen Tests Miss Infected and Presumably Infectious People Due to Viral Load Differences among Specimen Types
No full textIn a recent household transmission study of SARS-CoV-2, we found extreme differences in SARS-CoV-2 viral loads among paired saliva, anterior nares swab (ANS), and oropharyngeal swab specimens collected from the same time point. We hypothesized these differences may hinder low-analytical-sensitivity assays (including antigen rapid diagnostic tests [Ag-RDTs]) by using a single specimen type (e.g., ANS) from reliably detecting infected and infectious individuals. We evaluated daily at-home ANS Ag-RDTs (Quidel QuickVue) in a cross-sectional analysis of 228 individuals and a longitudinal analysis (throughout infection) of 17 individuals enrolled early in the course of infection. Ag-RDT results were compared to reverse transcription-quantitative PCR (RT-qPCR) results and high, presumably infectious viral loads (in each, or any, specimen type). The ANS Ag-RDT correctly detected only 44% of time points from infected individuals on cross-sectional analysis, and this population had an inferred limit of detection of 7.6 × 10⁶ copies/mL. From the longitudinal cohort, daily Ag-RDT clinical sensitivity was very low (<3%) during the early, preinfectious period of the infection. Further, the Ag-RDT detected ≤63% of presumably infectious time points. The poor observed clinical sensitivity of the Ag-RDT was similar to what was predicted based on quantitative ANS viral loads and the inferred limit of detection of the ANS Ag-RDT being evaluated, indicating high-quality self-sampling. Nasal Ag-RDTs, even when used daily, can miss individuals infected with the Omicron variant and even those presumably infectious. Evaluations of Ag-RDTs for detection of infected or infectious individuals should be compared with a composite (multispecimen) infection status to correctly assess performance.
Importance:
We reveal three findings from a longitudinal study of daily nasal antigen rapid diagnostic test (Ag-RDT) evaluated against SARS-CoV-2 viral load quantification in three specimen types (saliva, nasal swab, and throat swab) in participants enrolled at the incidence of infection. First, the evaluated Ag-RDT showed low (44%) clinical sensitivity for detecting infected persons at all infection stages. Second, the Ag-RDT poorly detected (≤63%) time points that participants had high and presumably infectious viral loads in at least one specimen type. This poor clinical sensitivity to detect infectious individuals is inconsistent with the commonly held view that daily Ag-RDTs have near-perfect detection of infectious individuals. Third, use of a combination nasal-throat specimen type was inferred by viral loads to significantly improve Ag-RDT performance to detect infectious individuals
Identification of Biochemical Pathways Responsible for Distinct Phenotypes Using Gene Ontology Causal Activity Models
No full textGene inactivation can affect the process(es) in which that gene acts and causally downstream ones, yielding diverse mutant phenotypes. Identifying the genetic pathways resulting in a given phenotype helps us understand how individual genes interact in a functional network. Computable representations of biological pathways include detailed process descriptions in the Reactome Knowledgebase, and causal activity flows between molecular functions in Gene Ontology-Causal Activity Models (GO-CAMs). A computational process has been developed to convert Reactome pathways to GO-CAMs. Laboratory mice are widely used models of normal and pathological human processes. We have converted human Reactome GO-CAMs to orthologous mouse GO-CAMs, as a resource to transfer pathway knowledge between humans and model organisms. These mouse GO-CAMs allowed us to define sets of genes that function in a connected and well-defined way. To test whether individual genes from well-defined pathways result in similar and distinguishable phenotypes, we used the genes in our pathway models to cross-query mouse phenotype annotations in the Mouse Genome Database (MGD). Using GO-CAM representations of two related but distinct pathways, gluconeogenesis and glycolysis, we can identify causal paths in gene networks that give rise to discrete phenotypic outcomes for perturbations of glycolysis and gluconeogenesis. The accurate and detailed descriptions of gene interactions recovered in this analysis of well-studied processes suggest that this strategy can be applied to less well-understood processes in less well-studied model systems to predict phenotypic outcomes of novel gene variants and to identify potential gene targets in altered processes.SummaryGenes act in interconnected biological pathways, so single mutations can yield diverse phenotypes. To use the large body of mouse functional gene annotations, we converted human Gene Ontology-Causal Activity Models (GO-CAMs) of glucose metabolism to orthologous mouse GO-CAMs. We then queried phenotypes for mouse genes in these GO-CAMs and identified gene networks associated with discrete phenotypic outcomes due to perturbations of glycolysis and gluconeogenesis. This strategy can be extended to less well-understood processes and model systems to predict phenotypic outcomes
Semantic Representation of Neural Circuit Knowledge in Caenorhabditis elegans
No full textIn modern biology, new knowledge is generated quickly, making it challenging for researchers to efficiently acquire and synthesise new information from the large volume of primary publications. To address this problem, computational approaches that generate machine-readable representations of scientific findings in the form of knowledge graphs have been developed. These representations can integrate different types of experimental data from multiple papers and biological knowledge bases in a unifying data model, providing a complementary method to manual review for interacting with published knowledge. The Gene Ontology Consortium (GOC) has created a semantic modelling framework that extends individual functional gene annotations to structured descriptions of causal networks representing biological processes (Gene Ontology Causal Activity Modelling, or GO-CAM). In this study, we explored whether the GO-CAM framework could represent knowledge of the causal relationships between environmental inputs, neural circuits and behavior in the model nematode C. elegans (C. elegans Neural Circuit Causal Activity Modelling (CeN-CAM)). We found that, given extensions to several relevant ontologies, a wide variety of author statements from the literature about the neural circuit basis of egg-laying and carbon dioxide (CO2) avoidance behaviors could be faithfully represented with CeN-CAM. Through this process, we were able to generate generic data models for several categories of experimental results. We also generated representations of multisensory integration and sensory adaptation, and we discuss how semantic modelling may be used to functionally annotate the C. elegans connectome. Thus, Gene Ontology-based semantic modelling has the potential to support various machine-readable representations of neurobiological knowledge