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Cover page of The focal adhesion protein Testin modulates KCNE2 potassium channel β subunit activity.

The focal adhesion protein Testin modulates KCNE2 potassium channel β subunit activity.

(2021)

Coronary Artery Disease (CAD) typically kills more people globally each year than any other single cause of death. A better understanding of genetic predisposition to CAD and the underlying mechanisms will help to identify those most at risk and contribute to improved therapeutic approaches. KCNE2 is a functionally versatile, ubiquitously expressed potassium channel β subunit associated with CAD and cardiac arrhythmia susceptibility in humans and mice. Here, to identify novel KCNE2 interaction partners, we employed yeast two-hybrid screening of adult and fetal human heart libraries using the KCNE2 intracellular C-terminal domain as bait. Testin (encoded by TES), an endothelial cell-expressed, CAD-associated, focal adhesion protein, was identified as a high-confidence interaction partner for KCNE2. We confirmed physical association between KCNE2 and Testin in vitro by co-immunoprecipitation. Whole-cell patch clamp electrophysiology revealed that KCNE2 negative-shifts the voltage dependence and increases the rate of activation of the endothelial cell and cardiomyocyte-expressed Kv channel α subunit, Kv1.5 in CHO cells, whereas Testin did not alter Kv1.5 function. However, Testin nullified KCNE2 effects on Kv1.5 voltage dependence and gating kinetics. In contrast, Testin did not prevent KCNE2 regulation of KCNQ1 gating. The data identify a novel role for Testin as a tertiary ion channel regulatory protein. Future studies will address the potential role for KCNE2-Testin interactions in arterial and myocyte physiology and CAD.

Cover page of Statistical Learning in Wasserstein Space

Statistical Learning in Wasserstein Space

(2021)

We seek a generalization of regression and principle component analysis (PCA) in a metric space where data points are distributions metrized by the Wasserstein metric. We recast these analyses as multimarginal optimal transport problems. The particular formulation allows efficient computation, ensures existence of optimal solutions, and admits a probabilistic interpretation over the space of paths (line segments). Application of the theory to the interpolation of empirical distributions, images, power spectra, as well as assessing uncertainty in experimental designs, is envisioned.

Cover page of Finite-time blowup and ill-posedness in Sobolev spaces of the inviscid primitive equations with rotation

Finite-time blowup and ill-posedness in Sobolev spaces of the inviscid primitive equations with rotation

(2021)

Large scale dynamics of the oceans and the atmosphere are governed by the primitive equations (PEs). It is well-known that the three-dimensional viscous PEs is globally well-posed in Sobolev spaces. On the other hand, the inviscid PEs without rotation is known to be ill-posed in Sobolev spaces, and its smooth solutions can form singularity in finite time. In this paper, we extend the above results in the presence of rotation. We construct finite-time blowup solutions to the inviscid PEs with rotation, and establish that the inviscid PEs with rotation is ill-posed in Sobolev spaces in the sense that its perturbation around a certain steady state background flow is both linearly and nonlinearly ill-posed in Sobolev spaces. Its linear instability is of the Kelvin-Helmholtz type similar to the one appears in the context of vortex sheets problem. This implies that the inviscid PEs is also linearly ill-posed in Gevrey class of order s>1, and suggests that a suitable space for the well-posedness is Gevrey class of order s=1, which is exactly the space of analytic functions.

Cover page of A Parallel Process Model of Integration and Multidimensional Prosocial Behaviors in Recent Immigrant U.S. Latinx Adolescents.

A Parallel Process Model of Integration and Multidimensional Prosocial Behaviors in Recent Immigrant U.S. Latinx Adolescents.

(2021)

With a growing population of Latinx youth immigrating to the United States, it is important to understand how Latinx youth adapt to mainstream U.S. culture. Given that the majority of research examining social development among recent immigrant adolescents has focused on negative adjustment outcomes, research examining positive social behaviors is needed to avoid deficit approaches to their development, gain a holistic understanding of youth development, and improve interventions with this population.This study examined the associations among trajectories in cultural integration and multiple prosocial behaviors among recent immigrant U.S. Latinx adolescents in Miami, Florida and Los Angeles, California. Adolescents (N =302; 53.3% males; M age = 14.51 years) completed measures of integration and prosocial behaviors across six time points. Latent growth curve models indicated that integration significantly increased, though this growth tapered off over time. The growth in prosocial behaviors depended on the specific form of helping assessed. While the growth in altruistic and compliant prosocial behaviors was stagnant, there was an increase in anonymous prosocial behaviors and a decrease in public and dire prosocial behaviors. Emotional behaviors did not linearly change, though slightly tapered off by the final time points. Parallel process latent growth curve model results indicated positive correlations between the slopes of cultural integration and most forms of prosocial behaviors. These findings highlight the positive role of cultural integration as an acculturative process for U.S. Latinx youth and the multidimensionality of prosocial behaviors.

Cover page of Sex-dependent long-term effects of prepubescent stress on the posterior parietal cortex.

Sex-dependent long-term effects of prepubescent stress on the posterior parietal cortex.

(2021)

Adolescence is a time of intense cortical development and a period of heightened sensitivity to insult. To determine how sex affects the short- and long-term outcomes of early-adolescent stress exposure, we subjected prepubescent (postnatal day 30) male and female mice to repeated multiple concurrent stressors (RMS). In the posterior parietal cortex (PPC), RMS caused the elimination of excitatory synapses in deeper layers while inhibitory synapse density was predominantly diminished in superficial layers. These short-term effects coincided with reduced visuo-spatial working memory and were similar in both sexes. The loss of excitatory synapses and impaired working memory persisted in males past a 30-day recovery period. In contrast, we observed a remarkable recovery of excitatory transmission and behavioral performance in females. Inhibitory synapse density recovered in both sexes. We have also observed a late onset anxiety phenotype in RMS exposed females that was absent in males. Overall, our results indicate that there are marked sex differences in the long-term effects of prepubescent stress on cortical synapses and behavior.

Cover page of A predictable home environment may protect child mental health during the COVID-19 pandemic.

A predictable home environment may protect child mental health during the COVID-19 pandemic.

(2021)

Objective

Information about the adverse effects of the COVID-19 pandemic on adolescent and adult mental health is growing, yet the impacts on preschool children are only emerging. Importantly, environmental factors that augment or protect from the multidimensional and stressful influences of the pandemic on emotional development of young children are poorly understood.

Methods

Depressive symptoms in 169 preschool children (mean age 4.1 years) were assessed with the Preschool Feelings Checklist during a state-wide stay-at-home order in Southern California. Mothers (46% Latinx) also reported on externalizing behaviors with the Strengths & Difficulties Questionnaire. To assess the role of environmental factors in child mental health we examined household income, food insecurity, parental essential worker status and loss of parental job, as well as preservation of the structure of children's daily experiences with the Family Routines Inventory.

Results

Sixty-one percent of families' incomes were below the living wage and 50% had at least one parent who was an essential worker. Overall, preschoolers' depressive and externalizing symptoms were elevated compared to pre-COVID norms. Practice of family routines robustly predicted better child mental health, and this protective effect persisted after covarying income, dual-parent status and food insecurity as well as maternal depression and stress.

Conclusion

The stress of the COVID-19 pandemic is exacting a significant toll on the mental health of preschool children. Importantly, maintaining a structured, predicable home environment by adherence to family routines appears to mitigate these adverse effects, providing empiric basis for public health recommendations.

Cover page of Mechanical performance of 3D printed interpenetrating phase composites with spinodal topologies

Mechanical performance of 3D printed interpenetrating phase composites with spinodal topologies

(2021)

The mechanical response of interpenetrating phase composites (IPCs) with stochastic spinodal topologies is investigated experimentally and numerically. Model polymeric systems are fabricated by Polyjet multi-material printing, with the reinforcing phase taking the topology of a spinodal shell, and the remaining volume filled by a softer matrix. We show that spinodal shell IPCs have comparable compressive strength and stiffness to IPCs with two well-established periodic reinforcements, the Schwarz P triply periodic minimal surface (TPMS) and the octet truss-lattice, while exhibiting far less catastrophic failure and greater damage resistance, particularly at high volume fraction of reinforcing phase. The combination of high stiffness and strength and a long flat plateau after yielding makes spinodal shell IPCs a promising candidate for energy absorption and impact protection applications, where the lack of material softening upon large compressive strains can prevent sudden collapse. Importantly, in contrast with all IPCs with periodic reinforcements, spinodal shell IPCs are amenable to scalable manufacturing via self-assembly techniques.

Enhancer redundancy in development and disease.

(2021)

Shadow enhancers are seemingly redundant transcriptional cis-regulatory elements that regulate the same gene and drive overlapping expression patterns. Recent studies have shown that shadow enhancers are remarkably abundant and control most developmental gene expression in both invertebrates and vertebrates, including mammals. Shadow enhancers might provide an important mechanism for buffering gene expression against mutations in non-coding regulatory regions of genes implicated in human disease. Technological advances in genome editing and live imaging have shed light on how shadow enhancers establish precise gene expression patterns and confer phenotypic robustness. Shadow enhancers can interact in complex ways and may also help to drive the formation of transcriptional hubs within the nucleus. Despite their apparent redundancy, the prevalence and evolutionary conservation of shadow enhancers underscore their key role in emerging metazoan gene regulatory networks.

Cover page of A sub-modular receding horizon solution for mobile multi-agent persistent monitoring

A sub-modular receding horizon solution for mobile multi-agent persistent monitoring

(2021)

We study the problem of persistent monitoring of a finite number of inter-connected geographical nodes by a group of heterogeneous mobile agents. We assign to each geographical node a concave and increasing reward function that resets to zero after an agent's visit. Then, we design the optimal dispatch policy of which nodes to visit at what time and by what agent by finding a policy set that maximizes a utility that is defined as the total reward collected at visit times. We show that this optimization problem is NP-hard and its computational complexity increases exponentially with the number of the agents and the length of the mission horizon. By showing that the utility function is a monotone increasing and submodular set function of agents' policy, we proceed to propose a suboptimal dispatch policy design with a known optimality gap. To reduce the time complexity of constructing the feasible search set and also to induce robustness to changes in the operational factors, we perform our suboptimal policy design in a receding horizon fashion. Then, to compensate for the shortsightedness of the receding horizon approach for reward distribution beyond the feasible policies of the agents over the receding horizon, we add a new term to our utility, which provides a measure of nodal importance beyond the receding horizon's sight. This term gives the policy design an intuition to steer the agents towards the nodes with higher rewards on the patrolling graph. Finally, we discuss how our proposed algorithm can be implemented in a decentralized manner. A simulation study demonstrates our results.

Cover page of Carbon Cycle Implications of Soil Microbial Interactions

Carbon Cycle Implications of Soil Microbial Interactions

(2021)

The soil environment contains the largest pool of carbon on Earth, with controls on soil carbon residency and flux being an emergent property of microbial metabolism. Despite the fact that microbial interactions have metabolic implications, the contribution of interactions are often overlooked regarding the carbon cycle. Here, we hypothesize that microbial interactions are intrinsically coupled to carbon cycling through eco-evolutionary principles. Interactions drive phenotypic responses that result in allocation pattern shifts and changes in carbon use efficiency. These changes promote alterations in resource availability and community structure, thereby creating selective pressures that contribute to diffuse evolutionary mechanisms. The outcomes then feed back into microbial metabolic operations with consequences for carbon turnover, continuing a feedback loop of microbial interactions, evolutionary processes, and the carbon cycle.