Structure-guided discovery of anti-CRISPR and anti-phage defense proteins.

Bacteria use a variety of defense systems to protect themselves from phage infection. In turn, phages have evolved diverse counter-defense measures to overcome host defenses. Here, we use protein structural similarity and gene co-occurrence analyses to screen >66 million viral protein sequences and >330,000 metagenome-assembled genomes for the identification of anti-phage and counter-defense systems. We predict structures for ~300,000 proteins and perform large-scale, pairwise comparison to known anti-CRISPR (Acr) and anti-phage proteins to identify structural homologs that otherwise may not be uncovered using primary sequence search. This way, we identify a Bacteroidota phage Acr protein that inhibits Cas12a, and an Akkermansia muciniphila anti-phage defense protein, termed BxaP. Gene bxaP is found in loci encoding Bacteriophage Exclusion (BREX) and restriction-modification defense systems, but confers immunity independently. Our work highlights the advantage of combining protein structural features and gene co-localization information in studying host-phage interactions.

Toward snowpack runoff decision support.

Rain-on-snow (ROS) events are commonly linked to large historic floods in the United States. Projected increases in the frequency and magnitude of ROS multiply existing uncertainties and risks in operational decision making. Here, we introduce a framework for quality-controlling hourly snow water content, snow depth, precipitation, and temperature data to guide the development of an empirically based snowpack runoff decision support framework at the Central Sierra Snow Laboratory for water years 2006-2019. This framework considers the potential for terrestrial water input from the snowpack through decision tree classification of rain-on-snow and warm day melt events to aid in pattern recognition of prominent weather and antecedent snowpack conditions capable of producing snowpack runoff. Our work demonstrates how (1) present weather and (2) antecedent snowpack risk can be "learned" from hourly data to support eventual development of basin-specific snowpack runoff decision support systems aimed at providing real-time guidance for water resource management.

The Effectiveness of Multi-Label Classification and Multi-Output Regression in Social Trait Recognition.

First impressions make up an integral part of our interactions with other humans by providing an instantaneous judgment of the trustworthiness, dominance and attractiveness of an individual prior to engaging in any other form of interaction. Unfortunately, this can lead to unintentional bias in situations that have serious consequences, whether it be in judicial proceedings, career advancement, or politics. The ability to automatically recognize social traits presents a number of highly useful applications: from minimizing bias in social interactions to providing insight into how our own facial attributes are interpreted by others. However, while first impressions are well-studied in the field of psychology, automated methods for predicting social traits are largely non-existent. In this work, we demonstrate the feasibility of two automated approaches-multi-label classification (MLC) and multi-output regression (MOR)-for first impression recognition from faces. We demonstrate that both approaches are able to predict social traits with better than chance accuracy, but there is still significant room for improvement. We evaluate ethical concerns and detail application areas for future work in this direction.

Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic.

Killifish are euryhaline teleosts that adapt to rapid changes in the salinity of the seawater. It is generally accepted that acclimation to seawater is mediated by cortisol activation of the glucocorticoid receptor (GR), which stimulates CFTR mRNA expression and CFTR-mediated Cl- secretion by the gill. Because there is no direct evidence in killifish that the GR stimulates CFTR gene expression, quantitative PCR studies were conducted to test the hypothesis that cortisol activation of GR upregulates CFTR mRNA expression and that this response is required for acclimation to seawater. Inhibition of the GR by RU-486 prevented killifish from acclimating to increased salinity and blocked the increase in CFTR mRNA. In contrast, inhibition of the mineralocorticoid receptor by spironolactone had no effect on acclimation to seawater. Thus acclimation to increased salinity in killifish requires signaling via the GR and includes an increase in CFTR gene expression. Because arsenic, a toxic metalloid that naturally occurs in the aquatic environment, has been shown to disrupt GR transcriptional regulation in avian and mammalian systems, studies were also conducted to determine whether arsenic disrupts cortisol-mediated activation of CFTR gene expression in this in vivo fish model and thereby blocks the ability of killifish to acclimate to increased salinity. Arsenic prevented acclimation to seawater and decreased CFTR protein abundance. However, arsenic did not disrupt the GR-induced increase in CFTR mRNA. Thus arsenic blocks acclimation to seawater in killifish by a mechanism that does not disrupt GR-mediated induction of CFTR gene expression.