Proteolethargy is a pathogenic mechanism in chronic disease.

The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species.

Impact of Rhg1 copy number variation on a soybean cyst nematode resistance transcriptional network.

Soybean yield loss due to soybean cyst nematode (SCN) infestation has a negative impact on the U.S. economy.

Risk Factors Associated With General and Abdominal Obesity Among South Asian Minorities in Hong Kong.

South Asians have become a sizable ethnic minority in Hong Kong with unique health and social needs often being overlooked. Elevated obesity risk among South Asians has been highlighted in high-income Western settings; however, relevant local evidence is scarce. This cross-sectional study aims to explore the obesity prevalence and related risk factors among South Asians in Hong Kong.

Low-Shot Unsupervised Visual Anomaly Detection via Sparse Feature Representation.

Visual anomaly detection is an essential component in modern industrial manufacturing. Existing studies using notions of pairwise similarity distance between a test feature and nominal features have achieved great breakthroughs. However, the absolute similarity distance lacks certain generalizations, making it challenging to extend the comparison beyond the available samples.

Whole genome sequence data of 516 F plants of tomato ().

The large-fruited fresh-market tomato cultivated in the U.S. represents a unique fruit market class of contemporary (modern) tomatoes for direct consumption.

Protein codes promote selective subcellular compartmentalization.

Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must efficiently assemble. Here, we demonstrate that proteins with shared functions share amino acid sequence codes that guide them to compartment destinations. A protein language model, ProtGPS, was developed that predicts with high performance the compartment localization of human proteins excluded from the training set.

Using machine learning and partial dependence to evaluate robustness of best linear unbiased prediction (BLUP) for phenotypic values.

Best linear unbiased prediction (BLUP) is widely used in plant research to address experimental variation. For phenotypic values, BLUP accuracy is largely dependent on properly controlled experimental repetition and how variable components are outlined in the model. Thus, determining BLUP robustness implies the need to evaluate contributions from each repetition.

Precise sensorimotor control impacts reproductive fitness of C. elegans in 3D environments.

The ability of animals to sense and navigate towards relevant cues in complex and elaborate habitats is paramount for their survival and reproductive success. The nematode Caenorhabditis elegans uses a simple and elegant sensorimotor program to track odors in its environments. Whether this allows the worm to effectively navigate a complex environment and increase its evolutionary success has not been tested yet.

Distinct chemical environments in biomolecular condensates.

Diverse mechanisms have been described for selective enrichment of biomolecules in membrane-bound organelles, but less is known about mechanisms by which molecules are selectively incorporated into biomolecular assemblies such as condensates that lack surrounding membranes. The chemical environments within condensates may differ from those outside these bodies, and if these differed among various types of condensate, then the different solvation environments would provide a mechanism for selective distribution among these intracellular bodies. Here we use small molecule probes to show that different condensates have distinct chemical solvating properties and that selective partitioning of probes in condensates can be predicted with deep learning approaches.

Transcription factors interact with RNA to regulate genes.

Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat.

Adaptive Safe Reinforcement Learning With Full-State Constraints and Constrained Adaptation for Autonomous Vehicles.

High-performance learning-based control for the typical safety-critical autonomous vehicles invariably requires that the full-state variables are constrained within the safety region even during the learning process. To solve this technically critical and challenging problem, this work proposes an adaptive safe reinforcement learning (RL) algorithm that invokes innovative safety-related RL methods with the consideration of constraining the full-state variables within the safety region with adaptation. These are developed toward assuring the attainment of the specified requirements on the full-state variables with two notable aspects.

Data-Driven Linear Quadratic Optimization for Controller Synthesis With Structural Constraints.

For various typical cases and situations where the formulation results in an optimal control problem, the linear quadratic regulator (LQR) approach and its variants continue to be highly attractive. In certain scenarios, it can happen that some prescribed structural constraints on the gain matrix would arise. Consequently then, the algebraic Riccati equation (ARE) is no longer applicable in a straightforward way to obtain the optimal solution.

Genetic architecture of fresh-market tomato yield.

Background: The fresh-market tomato (Solanum lycopersicum) is bred for direct consumption and is selected for a high yield of large fruits. To understand the genetic variations (distinct types of DNA sequence polymorphism) that influence the yield, we collected the phenotypic variations in the yields of total fruit, extra-large-sized fruit, small-sized fruit, or red-colored fruit from 68 core inbred contemporary U.S.

The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance.

Insulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced.

A mutant allele of the gene at the tomato locus reduces plant height with high quality fruit.

Reduced plant height due to shortened stems is beneficial for improving crop yield potential, better resilience to biotic/abiotic stresses, and rapid crop producer adoption of the agronomic and management practices. Breeding tomato plants with a reduced height, however, poses a particular challenge because this trait is often associated with a significant fruit size (weight) reduction. The tomato locus controls plant height.

Local and Remote Forcing of Interannual Sea-Level Variability at Nantucket Island.

The relative contributions of local and remote wind stress and air-sea buoyancy forcing to sea-level variations along the East Coast of the United States are not well quantified, hindering the understanding of sea-level predictability there. Here, we use an adjoint sensitivity analysis together with an Estimating the Circulation and Climate of the Ocean (ECCO) ocean state estimate to establish the causality of interannual variations in Nantucket dynamic sea level. Wind forcing explains 67% of the Nantucket interannual sea-level variance, while wind and buoyancy forcing together explain 97% of the variance.

Barrier Lyapunov Function-Based Safe Reinforcement Learning for Autonomous Vehicles With Optimized Backstepping.

Guaranteed safety and performance under various circumstances remain technically critical and practically challenging for the wide deployment of autonomous vehicles. Safety-critical systems in general, require safe performance even during the reinforcement learning (RL) period. To address this issue, a Barrier Lyapunov Function-based safe RL (BLF-SRL) algorithm is proposed here for the formulated nonlinear system in strict-feedback form.

Genetic variation associated with condensate dysregulation in disease.

A multitude of cellular processes involve biomolecular condensates, which has led to the suggestion that diverse pathogenic mutations may dysregulate condensates. Although proof-of-concept studies have identified specific mutations that cause condensate dysregulation, the full scope of the pathological genetic variation that affects condensates is not yet known. Here, we comprehensively map pathogenic mutations to condensate-promoting protein features in putative condensate-forming proteins and find over 36,000 pathogenic mutations that plausibly contribute to condensate dysregulation in over 1,200 Mendelian diseases and 550 cancers.

Synthesis and biological evaluation of niclosamide PROTACs.

Roughly 268,000 new cases of prostate cancer and 34,000 deaths from prostate cancer are projected by the American Cancer Society to occur in the United States in 2022. Androgen receptor is a key protein in the proliferation and survival of prostate cancer cells and has been revealed to be overexpressed in 30% to 50% of castration-resistant prostate cancer patients. One promising approach to reducing the level of this protein is Proteolysis Targeting Chimeras (PROTACs) that is an emerging drug discovery technology.

postQTL: a QTL mapping R workflow to improve the accuracy of true positive loci identification.

Objective: The determination of the location of quantitative trait loci (QTL) (i.e., QTL mapping) is essential for identifying new genes.

Local Learning Enabled Iterative Linear Quadratic Regulator for Constrained Trajectory Planning.

Trajectory planning is one of the indispensable and critical components in robotics and autonomous systems. As an efficient indirect method to deal with the nonlinear system dynamics in trajectory planning tasks over the unconstrained state and control space, the iterative linear quadratic regulator (iLQR) has demonstrated noteworthy outcomes. In this article, a local-learning-enabled constrained iLQR algorithm is herein presented for trajectory planning based on hybrid dynamic optimization and machine learning.