Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates

Liquid-liquid phase separation promotes the formation of membraneless condensates that mediate diverse cellular functions, including autophagy of misfolded proteins. However, how phase separation participates in autophagy of dysfunctional mitochondria (mitophagy) remains obscure. We previously discovered that nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) translocates from the nucleus to mitochondria to mediate celastrol-induced mitophagy through interaction with p62/SQSTM1. Here, we show that the ubiquitinated mitochondrial Nur77 forms membraneless condensates capable of sequestrating damaged mitochondria by interacting with the UBA domain of p62/SQSTM1. However, tethering clustered mitochondria to the autophagy machinery requires an additional interaction mediated by the N-terminal intrinsically disordered region (IDR) of Nur77 and the N-terminal PB1 domain of p62/SQSTM1, which confers Nur77-p62/SQSTM1 condensates with the magnitude and liquidity. Our results demonstrate how composite multivalent interaction between Nur77 and p62/SQSTM1 coordinates to sequester damaged mitochondria and to connect targeted cargo mitochondria for autophagy, providing mechanistic insight into mitophagy.

Pauli approximation for a vector particle with anomalous magnetic moment in an external Coulomb field

Herein, a spin 1 particle with anomalous magnetic moment in an external Coulomb field is studied. We start with the relativistic tensor system of the Proca type in Cartesian coordinates. In these equations the Γ parameter is present related to an additional characteristic of the particle. In the case of an external magnetic field, it is interpreted as an anomalous magnetic moment. In the presence of an external electric field, additional interaction terms are presented as well; moreover, the terms of the first and second orders in parameter Γ appear. The case of an external Coulomb field is considered in detail. In the nonrelativistic approximation a Pauli type equation is obtained. In the nonrelativistic equation the separation of the variables with the use of spherical vectors is realized. One separate 2-nd order differential equation is found, in which additional interaction terms are missing. Besides, we derive systems of two coupled 2-nd order equations wherein linear and quadratic in parameter Γ interaction terms are presented. Previously, another approach was developed for analyzing the vector particle with anomalous magnetic moment. It was based on the use of tetrad formalism and separation of the variables in the Duffin – Kemmer equation with the help of the Wigner function. The nonrelativistic approximation was performed directly in the system of radial equations. Besides, previously formal Frobenius type solutions for an arising 4-th order differential equation were constructed; however, physically interpretable energy spectra were not found. We have proved that the radial equations derived by different methods are the same up to a simple liner transformation over two radial functions. In this paper, we have obtained a simpler 4-th order equation, the construction of Frobenius solutions becomes technically easier, but physical energy spectra are not found either.

THE DEVELOPMENT OF ONLINE TUTORIAL MOODLE TO INCREASE THE EFFECTIVENESS OF LECTURES DURING PANDEMIC COVID-19

Efforts can be done to increase the effectiveness of conventional learning process by making additional interaction extension outside classroom. In this regard, information technology can be utilized. The use of information technology which has same function as the conventional inside classroom learning provided in online learning. This research aims at testing the validity and practicality of Moodle online tutorial. The research uses development design (R&D). The research results show that online tutorial Moodle is valid (95,37%) and practical (80,36%) hence can be used in the online class widely.

PPARγ S273 Phosphorylation Modifies the Dynamics of Coregulator Proteins Recruitment

The nuclear receptor PPARγ is essential to maintain whole-body glucose homeostasis and insulin sensitivity, acting as a master regulator of adipogenesis, lipid, and glucose metabolism. Its activation through natural or synthetic ligands induces the recruitment of coactivators, leading to transcription of target genes such as cytokines and hormones. More recently, post translational modifications, such as PPARγ phosphorylation at Ser273 by CDK5 in adipose tissue, have been linked to insulin resistance trough the dysregulation of expression of a specific subset of genes. Here, we investigate how this phosphorylation may disturb the interaction between PPARγ and some coregulator proteins as a new mechanism that may leads to insulin resistance. Through cellular and in vitro assays, we show that PPARγ phosphorylation inhibition increased the activation of the receptor, therefore the increased recruitment of PGC1-α and TIF2 coactivators, whilst decreases the interaction with SMRT and NCoR corepressors. Moreover, our results show a shift in the coregulators interaction domains preferences, suggesting additional interaction interfaces formed between the phosphorylated PPARγ and some coregulator proteins. Also, we observed that the CDK5 presence disturb the PPARγ-coregulator’s synergy, decreasing interaction with PGC1-α, TIF2, and NCoR, but increasing coupling of SMRT. Finally, we conclude that the insulin resistance provoked by PPARγ phosphorylation is linked to a differential coregulators recruitment, which may promote dysregulation in gene expression.

Perturbation Theory of Transformed Quantum Fields

We consider a scalar quantum field ϕ with arbitrary polynomial self-interaction in perturbation theory. If the field variable ϕ is repaced by a global diffeomorphism ϕ(x) = ρ(x) + a1ρ2(x) + …, this field ρ obtains infinitely many additional interaction vertices. We propose a systematic way to compute connected amplitudes for theories involving vertices which are able to cancel adjacent edges. Assuming tadpole graphs vanish, we show that the S-matrix of ρ coincides with the one of ϕ without using path-integral arguments. This result holds even if the underlying field has a propagator of higher than quadratic order in the momentum. The diffeomorphism can be tuned to cancel all contributions of an underlying ϕt-type self interaction at one fixed external offshell momentum, rendering ρ a free theory at this momentum. Finally, we mention one way to extend the diffeomorphism to a non-diffeomorphism transformation involving derivatives without spoiling the combinatoric structure of the global diffeomorphism.

The Many Faces of Stress: Three Factors that Predict Physical Illness in Young Adults

Three studies examined how various forms of stress uniquely contribute to physical illness. We compared negative affect and perceived stress in Study 1, neuroticism and perceived stress in Study 2, and negative affect, neuroticism, and perceived stress in Study 3. We also controlled for health-related covariates (i.e., exercise, nutrition, substance use, and BMI). In all three studies ( ns = 271, 577, and 300), participants completed online surveys for course credit. The results of Study 1 demonstrated that both negative affect and perceived stress predicted physical illness. In Study 2, neuroticism and perceived stress each predicted illness symptoms, and an additional interaction between neuroticism and perceived stress, were found. In Study 3, where all three stress factors were included, only negative affect predicted illness symptoms. Taken together, these results suggest that negative affect uniquely explains most of the variance in physical illness symptoms while controlling for other forms of stress.

Binary interaction along the RGB: The Barium Star perspective

Barium (Ba) stars form via mass-transfer in binary systems, and can subsequently interact with their white dwarf companion in a second stage of binary interaction. We used observations of main-sequence Ba systems as input for our evolutionary models, and try to reproduce the orbits of the Ba giants. We show that to explain short and sometimes eccentric orbits, additional interaction mechanisms are needed along the RGB.

A Brand-level Ranking System with the Customized Attention-GRU Model

In e-commerce websites like Taobao, brand is playing a more important role in influencing users' decision of click/purchase, partly because users are now attaching more importance to the quality of products and brand is an indicator of quality. However, existing ranking systems are not specifically designed to satisfy this kind of demand. Some design tricks may partially alleviate this problem, but still cannot provide satisfactory results or may create additional interaction cost. In this paper, we design the first brand-level ranking system to address this problem. The key challenge of this system is how to sufficiently exploit users' rich behavior in e-commerce websites to rank the brands. In our solution, we firstly conduct the feature engineering specifically tailored for the personalized brand ranking problem and then rank the brands by an adapted Attention-GRU model containing three important modifications. Note that our proposed modifications can also apply to many other machine learning models on various tasks. We conduct a series of experiments to evaluate the effectiveness of our proposed ranking model and test the response to the brand-level ranking system from real users on a large-scale e-commerce platform, i.e. Taobao.

Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A

Protein phosphatase 2A (PP2A) is a highly abundant heterotrimeric Ser/Thr phosphatase involved in the regulation of a variety of signaling pathways. The PP2A phosphatase activator (PTPA) is an ATP-dependent activation chaperone, which plays a key role in the biogenesis of active PP2A. The C-terminal tail of the catalytic subunit of PP2A is highly conserved and can undergo a number of posttranslational modifications that serve to regulate the function of PP2A. Here we have studied structurally the interaction of PTPA with the conserved C-terminal tail of the catalytic subunit carrying different posttranslational modifications. We have identified an additional interaction site for the invariant C-terminal tail of the catalytic subunit on PTPA, which can be modulated via posttranslational modifications. We show that phosphorylation of Tyr307PP2A-C or carboxymethylation of Leu309PP2A-C abrogates or diminishes binding of the C-terminal tail, whereas phosphorylation of Thr304PP2A-C is of no consequence. We suggest that the invariant C-terminal residues of the catalytic subunit can act as affinity enhancer for different PP2A interaction partners, including PTPA, and a different ‘code’ of posttranslational modifications can favour interactions to one subunit over others.