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  1. Malik, Harmit S. (Ed.)
    Bacteria that live inside the cells of insect hosts (endosymbionts) can alter the reproduction of their hosts, including the killing of male offspring (male killing, MK). MK has only been described in a few insects, but this may reflect challenges in detecting MK rather than its rarity. Here, we identify MK Wolbachia at a low frequency (around 4%) in natural populations of Drosophila pseudotakahashii . MK Wolbachia had a stable density and maternal transmission during laboratory culture, but the MK phenotype which manifested mainly at the larval stage was lost rapidly. MK Wolbachia occurred alongside a second Wolbachia strain expressing a different reproductive manipulation, cytoplasmic incompatibility (CI). A genomic analysis highlighted Wolbachia regions diverged between the 2 strains involving 17 genes, and homologs of the wmk and cif genes implicated in MK and CI were identified in the Wolbachia assembly. Doubly infected males induced CI with uninfected females but not females singly infected with CI-causing Wolbachia . A rapidly spreading dominant nuclear suppressor genetic element affecting MK was identified through backcrossing and subsequent analysis with ddRAD SNPs of the D . pseudotakahashii genome. These findings highlight the complexity of nuclear and microbial components affecting MK endosymbiont detection and dynamics inmore »populations and the challenges of making connections between endosymbionts and the host phenotypes affected by them.« less
    Free, publicly-accessible full text available March 22, 2024
  2. Abstract

    Wood stiffness (modulus of elasticity, MOE) is an important property for conifer wood, with the variability in MOE largely being a function of both the specific gravity (SG) (wood density) and the angle of the microfibrils within the S2 layer of longitudinal tracheids. Rapid analysis techniques can be used together to quantify MOE; while SG can be determined with relative ease, this is not the case for microfibril angle, requiring expensive X-ray diffraction equipment. An alternative to microfibril angle is to measure longitudinal acoustic velocity. The objective of this study was to measure and then model the within tree variation in dynamic MOE (MOEdyn) by developing the methodology to measure ultrasonic velocity (USV) in radial samples from pith to bark using ultrasonic frequencies (>20 kHz). A total of 419 pith-to-bark radial strips, collected from multiple height levels in 92 loblolly pine (Pinus taeda) trees, were processed to obtain matching SG (2mm longitudinal) and USV (8.2-mm longitudinal) samples. Ring-by-ring SG was measured using X-ray densitometry and time-of-flight USV was measured at a 10-mm radial resolution from pith to bark. A subset of samples was sent to SilviScan to determine microfibril angle using X-ray diffraction. The relationship between microfibril angle andmore »USV was strong (R2 = 0.91, RMSE = 2.6°). Nonlinear mixed-effects models were then developed to predict radial variation in SG, USV and MOEdyn. Fixed effects for the models, which included cambial age and height of disk within tree, had pseudo R2 values of 0.67 for SG (RMSE = 0.051), 0.71 for USV (RMSE = 316 m/s) and 0.69 for MOEdyn (RMSE = 1.9 GPa). When combined with SG measurements from X-ray densitometry, USV measurements from pith to bark are a powerful tool for assessing variability in wood stiffness.

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  3. Abstract

    Hearing loss is the leading sensory deficit, affecting ~ 5% of the population. It exhibits remarkable heterogeneity across 223 genes with 6328 pathogenic missense variants, making deafness-specific expertise a prerequisite for ascribing phenotypic consequences to genetic variants. Deafness-implicated variants are curated in the Deafness Variation Database (DVD) after classification by a genetic hearing loss expert panel and thorough informatics pipeline. However, seventy percent of the 128,167 missense variants in the DVD are “variants of uncertain significance” (VUS) due to insufficient evidence for classification. Here, we use the deep learning protein prediction algorithm, AlphaFold2, to curate structures for all DVD genes. We refine these structures with global optimization and the AMOEBA force field and use DDGun3D to predict folding free energy differences (∆∆GFold) for all DVD missense variants. We find that 5772 VUSs have a large, destabilizing ∆∆GFoldthat is consistent with pathogenic variants. When also filtered for CADD scores (> 25.7), we determine 3456 VUSs are likely pathogenic at a probability of 99.0%. Of the 224 genes in the DVD, 166 genes (74%) exhibit one or more missense variants predicted to cause a pathogenic change in protein folding stability. The VUSs prioritized here affect 119 patients (~ 3% of cases) sequenced by the OtoSCOPEmore »targeted panel. Approximately half of these patients previously received an inconclusive report, and reclassification of these VUSs as pathogenic provides a new genetic diagnosis for six patients.

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  4. Abstract Recent advances in brain clearing and imaging have made it possible to image entire mammalian brains at sub-micron resolution. These images offer the potential to assemble brain-wide atlases of neuron morphology, but manual neuron reconstruction remains a bottleneck. Several automatic reconstruction algorithms exist, but most focus on single neuron images. In this paper, we present a probabilistic reconstruction method, ViterBrain, which combines a hidden Markov state process that encodes neuron geometry with a random field appearance model of neuron fluorescence. ViterBrain utilizes dynamic programming to compute the global maximizer of what we call the most probable neuron path. We applied our algorithm to imperfect image segmentations, and showed that it can follow axons in the presence of noise or nearby neurons. We also provide an interactive framework where users can trace neurons by fixing start and endpoints. ViterBrain is available in our open-source Python package .
    Free, publicly-accessible full text available December 1, 2023
  5. Free, publicly-accessible full text available December 1, 2023
  6. Free, publicly-accessible full text available January 1, 2024
  7. Abstract Landfalling tropical cyclones (LTCs) are the most devastating disaster to affect the U.S., while the demonstration of skillful subseasonal (between 10 days and one season) prediction of LTCs is less promising. Understanding the mechanisms governing the subseasonal variation of TC activity is fundamental to improving its forecast, which is of critical interest to decision-makers and the insurance industry. This work reveals three localized atmospheric circulation modes with significant 10–30 days subseasonal variations: Piedmont Oscillation (PO), Great America Dipole (GAD), and the Subtropical High ridge (SHR) modes. These modes strongly modulate precipitation, TC genesis, intensity, track, and landfall near the U.S. coast. Compared to their strong negative phases, the U.S. East Coast has 19 times more LTCs during the strong positive phases of PO, and the Gulf Coast experiences 4–12 times more frequent LTCs during the positive phases of GAD and SHR. Results from the GFDL SPEAR model show a skillful prediction of 13, 9, and 22 days for these three modes, respectively. Our findings are expected to benefit the prediction of LTCs on weather timescale and also suggest opportunities exist for subseasonal predictions of LTCs and their associated heavy rainfalls.
    Free, publicly-accessible full text available December 1, 2023
  8. Abstract

    Hybridization is a common process that has broadly impacted the evolution of multicellular eukaryotes; however, how ecological factors influence this process remains poorly understood. Here, we report the findings of a 3-year recapture study of the Bryant’s woodrat (Neotoma bryanti) and desert woodrat (Neotoma lepida), two species that hybridize within a creosote bush (Larrea tridentata) shrubland in Whitewater, CA, USA. We used a genotype-by-sequencing approach to characterize the ancestry distribution of individuals across this hybrid zone coupled with Cormack–Jolly–Seber modeling to describe demography. We identified a high frequency of hybridization at this site with ~40% of individuals possessing admixed ancestry, which is the result of multigenerational backcrossing and advanced hybrid-hybrid crossing. F1, F2, and advanced generation hybrids had apparent survival rates similar to parental N. bryanti, while parental and backcross N. lepida had lower apparent survival rates and were far less abundant. Compared to bimodal hybrid zones where hybrids are often rare and selected against, we find that hybrids at Whitewater are common and have comparable survival to the dominant parental species, N. bryanti. The frequency of hybridization at Whitewater is therefore likely limited by the abundance of the less common parental species, N. lepida, rather than selection againstmore »hybrids.

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  9. Abstract

    Language is not only used to transmit neutral information; we often seek to persuade by arguing in favor of a particular view. Persuasion raises a number of challenges for classical accounts of belief updating, as information cannot be taken at face value. How should listeners account for a speaker’s “hidden agenda” when incorporating new information? Here, we extend recent probabilistic models of recursive social reasoning to allow for persuasive goals and show that our model provides a pragmatic account for why weakly favorable arguments may backfire, a phenomenon known as the weak evidence effect. Critically, this model predicts a systematic relationship between belief updates and expectations about the information source: weak evidence should only backfire when speakers are expected to act under persuasive goals and prefer the strongest evidence. We introduce a simple experimental paradigm called the Stick Contest to measure the extent to which the weak evidence effect depends on speaker expectations, and show that a pragmatic listener model accounts for the empirical data better than alternative models. Our findings suggest further avenues for rational models of social reasoning to illuminate classical decision-making phenomena.

  10. Supramolecular interactions are well recognized and many of them have been extensively studied in chemistry. The formation of supramolecular complexes that rely on weak force interactions are less well studied in bilayer membranes. Herein, a supported bilayer membrane is used to probe the penetration of a complex between tetracycline and a macrocyclic polyether. In a number of bacterial systems, the presence of the macrocycle has been found to significantly enhance the potency of the antimicrobial in vitro . The crown·tetracycline complex has been characterized in solution, neutron reflectometry has probed complex penetration, and the phenomena have been modeled by computational methods.
    Free, publicly-accessible full text available November 3, 2023