Proximity Interactions Research Articles

A High-Density Human Mitochondrial Proximity Interaction Network

We used BioID, a proximity-dependent biotinylation assay, to interrogate 100 mitochondrial baits from all mitochondrial sub-compartments to create a high resolution human mitochondrial proximity interaction network. We identified 1465 proteins, producing 15626 unique high confidence proximity interactions. Of these, 528 proteins were previously annotated as mitochondrial, nearly half of the mitochondrial proteome defined by Mitocarta 2.0. Bait-bait analysis showed a clear separation of mitochondrial compartments, and correlation analysis among preys across all baits allowed us to identify functional clusters involved in diverse mitochondrial functions, and to assign uncharacterized proteins to specific modules. We demonstrate that this analysis can assign isoforms of the same mitochondrial protein to different mitochondrial sub-compartments, and show that some proteins may have multiple cellular locations. Outer membrane baits showed specific proximity interactions with cytosolic proteins and proteins in other organellar membranes, suggesting specialization of proteins responsible for contact site formation between mitochondria and individual organelles. This proximity network will be a valuable resource for exploring the biology of uncharacterized mitochondrial proteins, the interactions of mitochondria with other cellular organelles, and will provide a framework to interpret alterations in sub-mitochondrial environments associated with mitochondrial disease.

Description of Interface Between Semiconductor Electrostatic Qubit and Josephson Junction in Tight Binding Model

The interface between superconducting Josephson junction and semiconductor position-based qubit implemented in coupled semiconductor q-dots is described such that it can be the base for electrostatic interface between superconducting and semiconductor quantum computer. Modification of Andreev Bound State in Josephson junction by the presence of semiconductor qubit in its proximity and electrostatic interaction with superconducting qubit is spotted by the minimalist tight-binding model. The obtained analytical results allow in creating interface between semiconductor quantum computer and superconducting quantum computer. They open the perspective of construction of QISKIT like software that will describe both types of quantum computers as well as their interface. Key words: electrostatic entanglement, interface between semiconductor and superconducting quantum computer, tight-binding BdGe equations, analytical solutions, topological states of matter, hybrid quantum computer

Nuclear gene proximity and protein interactions shape transcript covariations in mammalian single cells

Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply a tailored experimental design that eliminates these confounders, and report thousands of intrinsically covarying gene pairs in mouse embryonic stem cells. These covariations form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariations and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariations. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex formation. Our results lend support to the concept of post-transcriptional RNA operons, but we further present evidence that nuclear proximity of genes may provide substantial functional regulation in mammalian single cells.

Human P2X7 Receptor Causes Cycle Arrest in RPMI-8226 Myeloma Cells to Alter the Interaction with Osteoblasts and Osteoclasts.

Multiple myeloma is a malignant expansion of plasma cells and aggressively affects bone health. We show that P2X7 receptor altered myeloma growth, which affects primary bone cells in vitro. Expression on six human myeloma cell lines confirmed the heterogeneity associated with P2X7 receptor. Pharmacology with 2′(3′)-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (BzATP) as agonist showed dose-dependent membranal pores on RPMI-8226 (p = 0.0027) and blockade with P2X7 receptor antagonists. Ca2+ influx with increasing doses of BzATP (p = 0.0040) was also inhibited with antagonists. Chronic P2X7 receptor activation reduced RPMI-8226 viability (p = 0.0208). No apoptosis or RPMI-8226 death was observed by annexin V/propidium iodide (PI) labeling and caspase-3 cleavage, respectively. However, bromodeoxyuridine (BrdU) labelling showed an accumulation of RPMI-8226 in the S phase of cell cycle progression (61.5%, p = 0.0114) with significant decline in G0/G1 (5.2%, p = 0.0086) and G2/M (23.5%, p = 0.0015) phases. As myeloma pathology depends on a positive and proximal interaction with bone, we show that P2X7 receptor on RPMI-8226 inhibited the myeloma-induced suppression on mineralization (p = 0.0286) and reversed the excessive osteoclastic resorption. Our results demonstrate a view of how myeloma cell growth is halted by P2X7 receptor and the consequences on myeloma–osteoblast and myeloma–osteoclast interaction in vitro.

Triadic interaction and gestural communication: Hierarchical and child-centered interactions of rural and urban Gujarati (Indian) caregivers and 9-month-old infants.

In this study 9-month-old infants in rural and urban Gujarat, India were compared in how frequently and in which way they engage in triadic interactions. It was assumed that urban caregivers would engage in a child-centered interaction style, frequently creating triadic interactions and following infants' signals. It was also expected that they would engage in more gestural communication in line with results on young infants often being involved in distal interactions. Rural caregivers were assumed to engage in a hierarchical interaction style in which the caregiver directs the interactions. It was expected that they would engage more in bodily ways of communicating as young infants in these communities often experience large amounts of proximal interactions. Infants were observed in everyday situations to assess their everyday engagement in triadic interactions and experience with gestures. Additionally, infants' mothers were asked to show their children something distant to assess how triadic attention is created. These interactions were video recorded and analyzed in terms of gestures and bodily behaviors. The results indicate that urban infants experience more triadic interactions and have caregivers who are more likely to follow their initiatives than rural infants. In the observations, urban caregivers also used gestures more frequently than rural caregivers. For rural infants the results are less clear with some indications that caregivers directed their attention more, particularly using their bodies. These differences were only apparent in the video-recorded situations. Implications for infants' further development are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

A discrete interface in matrix stiffness creates an oscillatory pattern of endothelial monolayer disruption.

Intimal stiffening upregulates endothelial cell contractility, disrupting barrier integrity; however, intimal stiffening is non-uniform. The impact of local changes in intimal stiffness on proximal and distal cell-cell interactions is unknown. To investigate the range at which matrix stiffness heterogeneities impact neighboring endothelial cells within a monolayer, we built a micropillar system with adjacent regions of stiff and compliant matrix. The stiffness interface results in an oscillatory pattern of neutrophil transendothelial migration, symmetrical about the interface and well-fit by a sinusoid function. 'Peaks' of the sinusoid were found to have increased cellular contractility and decreased barrier function relative to 'troughs' of the sinusoid. Pharmacological modulation of contractility was observed to break symmetry, altering the amplitude and wavelength of the sinusoid, indicating that contractility may regulate this effect. This work illuminates a novel biophysical phenomenon of the role of stiffness-mediated cell-matrix interactions on cell-cell interactions at a distance. Additionally, it provides insight into the range at which intimal matrix stiffness heterogeneities will impact endothelial barrier function and potentially contribute to atherogenesis.

A High-Density Human Mitochondrial Proximity Interaction Network

We used BioID, a proximity-dependent biotinylation assay with 100 mitochondrial baits from all mitochondrial sub-compartments, to create a high-resolution human mitochondrial proximity interaction network. We identified 1,465 proteins, producing 15,626 unique high-confidence proximity interactions. Of these, 528 proteins were previously annotated as mitochondrial, nearly half of the mitochondrial proteome defined by Mitocarta 2.0. Bait-bait analysis showed a clear separation of mitochondrial compartments, and correlation analysis among preys across all baits allowed us to identify functional clusters involved in diverse mitochondrial functions and to assign uncharacterized proteins to specific modules. We demonstrate that this analysis can assign isoforms of the same mitochondrial protein to different mitochondrial sub-compartments and show that some proteins may have multiple cellular locations. Outer membrane baits showed specific proximity interactions with cytosolic proteins and proteins in other organellar membranes, suggesting specialization of proteins responsible for contact site formation between mitochondria and individual organelles.

ARID1a Associates with Lymphoid-Restricted Transcription Factors and Has an Essential Role in T Cell Development.

Maturation of lymphoid cells is controlled by the action of stage and lineage-restricted transcription factors working in concert with the general transcription and chromatin remodeling machinery to regulate gene expression. To better understand this functional interplay, we used Biotin Identification in human embryonic kidney cells to identify proximity interaction partners for GATA3, TCF7 (TCF1), SPI1, HLF, IKZF1, PAX5, ID1, and ID2. The proximity interaction partners shared among the lineage-restricted transcription factors included ARID1a, a BRG1-associated factor complex component. CUT&RUN analysis revealed that ARID1a shared binding with TCF7 and GATA3 at a substantial number of putative regulatory elements in mouse T cell progenitors. In support of an important function for ARID1a in lymphocyte development, deletion of Arid1a in early lymphoid progenitors in mice resulted in a pronounced developmental arrest in early T cell development with a reduction of CD4+CD8+ cells and a 20-fold reduction in thymic cellularity. Exploring gene expression patterns in DN3 cells from Wt and Arid1a-deficient mice suggested that the developmental block resided in the DN3a to DN3b transition, indicating a deficiency in β-selection. Our work highlights the critical importance of functional interactions between stage and lineage-restricted factors and the basic transcription machinery during lymphocyte differentiation.

Molecular intrinsic proximal interaction infer oxidative stress and apoptosis modulated in vivo biocompatibility of P.niruri contrived antibacterial iron oxide nanoparticles with zebrafish

Extensive use of magnetic iron oxide (magnetite) nanoparticles (IONP) has raised concerns about their biocompatibility. It has also stimulated the search for its green synthesis with greater biocompatibility. Addressing the issue, this study investigates the molecular nanotoxicity of IONP with embryonic and adult zebrafish, and reveal novel green fabrication of iron oxide nanoparticles (P-IONP) using medicinal plant extract of Phyllanthus niruri. The synthesized P-IONP was having a size of 42 ± 08 nm and a zeta potential of −38 ± 06 mV with hydrodynamic diameter of 109 ± 09 nm and 90emu/g magnetic saturation value. High antibacterial efficacy of P-IONP was found against E.coli. Comparative in vivo biocompatibility assessment with zebrafish confirmed higher biocompatibility of P-IONP compared to commercial C-IONP in the relevance of mortality rate, hatching rate, heart rate, and morphological abnormalities. LC50 of P-IONP and C-IONP was 202 μg/ml and 126 μg/ml, respectively. Molecular nano-biocompatibility analysis revealed the phenomenon as an effect of induced apoptosis lead by dysregulation of induced oxidative stress due to structural and functional influence of IONP to Sod1 and Tp53 proteins through intrinsic atomic interaction.

Multiplexed Proximity Biotinylation Coupled to Mass Spectrometry for Defining Integrin Adhesion Complexes.

BioID, a proximity biotinylation technique, offers a valuable approach to examine the interactions occurring within protein complexes that complements traditional protein biochemical methods. BioID has various advantages that are beneficial to the study of complexes, including an ability to detect insoluble and transient proteins. We have applied BioID to the study of integrin adhesion complexes (IACs), which are located at the junction between the plasma membrane and actin cytoskeleton. The use of multiple BioID baits enables a complex-wide, spatial annotation of IACs, which in turn facilitates the detection of novel proximal interactors and provides insights into IAC architecture. This article describes the labeling and affinity purification of IAC-proximal proteins and their analysis by label-free quantitative mass spectrometry. The article also outlines steps to identify high-confidence proximity interactors, and to interrogate the topology and functional relevance of proximity interaction networks through bioinformatic analyses. © 2020 The Authors. Basic Protocol 1: Proximity biotinylation of integrin adhesion complex components Basic Protocol 2: Mass spectrometry data processing by MaxQuant and detection of high-confidence proximal interactors Basic Protocol 3: Bioinformatic analysis and data visualization.

Distributed Rendezvous of Heterogeneous Robots with Motion-Based Power Level Estimation

This article introduces distributed rendezvous algorithms to make all heterogeneous robots (agents) rendezvous at a designated agent in environments with many obstacles. The proposed control laws are developed considering heterogeneous agents having distinct power level, sensing range, or communication range. It is assumed that each agent is initially distributed in a cluttered environment. An agent cannot utilize global positioning systems (GPS) to localize itself. Each agent can only sense neighboring agents and moves based on proximity interaction. This article presents distributed rendezvous algorithms so that heterogeneous agents rendezvous at a designated agent while maintaining (directed) network connectivity. The speed of each agent is set proportional to the remaining power level of the agent. This article then presents a method of estimating the power of each agent by measuring the movement of the agent. Then, we present a method of sharing power if an agent is lack of power. Under the proposed approach, we achieve distributed rendezvous as well as power recharging. It is proved that multiple heterogeneous agents rendezvous at the designated agent while maintaining (directed) network connectivity. Utilizing MATLAB simulations, the performance of the proposed distributed controls is verified in an environment with many obstacles.

Behavioral Link Analytics on Heterogeneous Human Interaction Networks

For designing and modeling Artificial Intelligence (AI) systems in the area of human-machine interaction, suitable approaches for user modeling are important in order to both capture user characteristics. Using multimodal data, this can be performed from various perspectives. Specifically, for modeling user interactions in human interaction networks, appropriate approaches for capturing those interactions, as well as to analyze them in order to extract meaningful patterns are important. Specifically, for modeling user behavior for the respective AI systems, we can make use of diverse heterogeneous data sources. This paper investigates face-to-face as well as socio-spatial interaction networks for modeling user interactions from three perspectives: We analyze preferences and perceptions of human social interactions in relation to the interactions observed using wearable sensors, i. e., face-to-face as well as socio-spatial interactions fo the respective actors. For that, we investigate the correspondence of according networks, in order to identify conformance, exceptions, and anomalies. The analysis is performed on a real-world dataset capturing networks of proximity interactions coupled with self-report questionnaires about preferences and perception of those interactions. The different networks, and according perspectives then provide different options for user modeling and integration into AI systems modeling such user behavior.

Mechanics at the interfaces of 2D materials: Challenges and opportunities

At the interfaces of 2D materials, the solid-state condensed matter physics is closely intertwined with the mechanics in terms of adhesion/separation and friction as well as deformation of 2D materials. With atomically thin 2D layers in atomically close proximity, the chemical, physical, and mechanical interactions simultaneously evolve and influence each other, leading to a wide range of topological structures and properties across nano- and micro-scales. Can the study on the mechanics of interfaces help to understand the physics and chemistry at the interfaces of 2D materials or vice versa? This Opinion aims to highlight the recent mechanics research on such material interfaces, where a multiscale, multidisciplinary effort is most effective moving forward with plenty of challenges and opportunities.

Combinatorial Inhibition of Cell Surface Receptors Using Dual Aptamer-Functionalized Nanoconstructs for Cancer Treatment.

Membrane receptors overexpressed in diseased states are considered novel therapeutic targets. However, the single targeting approach faces several fundamental issues, such as poor efficacy, resistance, and toxicity. Here, we report a dual-targeting strategy to enhance anti-cancer efficacy via synergistic proximity interactions between therapeutics and two receptor proteins. Importantly, we report the first finding of an interaction between c-Met and nucleolin and demonstrate the therapeutic value of targeting the interaction between them. Bispecific nanocarriers densely grafted with anti-c-Met and -nucleolin aptamer increased the local concentration of aptamers at the target sites, in addition to inducing target receptor clustering. It was also demonstrated that the simultaneous targeting of c-Met and nucleolin inhibited the cellular functions of the receptors and increased anti-cancer efficacy by altering the cell cycle. Our findings pave the way for the development of an effective combinatorial treatment based on nanoconstruct-mediated interaction between receptors.

Version française de la Relationship Specific Experience in Close Relationships scale (RS-ECR)

A good daily social functioning depends on the fact that the individuals can find and maintain proximity, contacts, and real interactions with others, that is, the individuals can be provided with a sense of both physical and psychological security. This is adult attachment (e.g., Hazan & Diamond, 2000). Mizrahi et al. (2016) published a study whose aim was to explore the links between sexuality and specific attachment strategies within young couples. To this end, the authors adapted the brief version proposed by Mikulincer and Florian (2000) of the Experience in Close Relationships Scale (Brennan, Clark, & Shaver, 1998) – the Relationship Specific Experience in Close Relationships scale – in order to reflect the way the individuals are attached to their actual romantic partner. No such a tool exists for French native speakers. The present study is thus an attempt to propose a French version of this brief scale addressed to couple relationships. The participants were the partners of 115 heterosexual couples (n=230) whose couple duration varied from 1 to 54 years (M=15.83, ET=13.85). They filled out a translated version of Mizrahi et al. (2016)’s Relationship Specific Experience in Close Relationships Scale which is a self-report questionnaire including 16 items. These items are designed in such a way that half enable to evaluate anxious attachment strategies and half enable to evaluate avoidant attachment strategies vis-à-vis the partner. The factorial structure (two factors: anxious attachment strategy and avoidant attachment strategy) as well as the Cronbach's alphas are generally satisfying for the items of this version and are similar to those observed by Mizrahi et al. (2016). The same thing is true for the scores of women and men. Nevertheless, the results also show the weakness of several items or mixed saturations. These limitations are discussed. Generally, the use of this French version to rate the attachment strategies of romantic partners is discussed in terms of its relevance for the evaluation of the consequences of specific attachment strategies on diverse couples’ issues such as their dyadic adjustment, intimacy, or dyadic coping.

Seeing and Viewing Through a Postdigital Pandemic: Shifting from Physical Proximity to Scopic Mediation

This paper addresses a particular area of concern regarding our habits that pertains to embodied experience and education through the Covid-19 pandemic: the shift from comfort to discomfort regarding face-to-face social interaction within the same physical space. To explore this transition, I use the related concepts of seeing and viewing from Isaac Asimov’s novel, The Naked Sun (1957), which are useful tools for investigating a probable collateral effect of rapid social distancing for the sake of avoiding contagion and includes replacing physically proximate interaction and procedures with a scopic mediation. Seeing and viewing provide concepts for understanding how values change in the midst of fears concerning contagion through physical contact that are mollified through the use of technology analogous to video conferencing. Postdigital education and the concepts of we-think, we-learn, and we-act provide critical tools for helping us understand this transition of perspective regarding educational and social practices in the midst of a pandemic.

Genome-Wide Identification and Analysis of Enhancer-Regulated microRNAs Across 31 Human Cancers.

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner, and dysregulation of target genes could lead to various diseases, such as cancer. Recent studies have shown that enhancers can regulate microRNAs (miRNAs) and participate in their biological synthesis. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer–miRNA interactions and 1,280 distal enhancer–miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited a significant cancer type-specific feature trend at the tissue level rather than at the single-cell level, and there was a noteworthy positive correlation between the expression of the miRNA and the number of enhancers regulating the same miRNA in most cancers. Furthermore, we found that there was a high correlation between the formation of enhancer–miRNA pairs and the expression of enhancer RNAs (eRNAs) whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, guanine–cytosine (GC) content, and histone modification signatures. Notably, GC content, H3K4me1, and H3K36me3 were present differently between distal and proximal regulation, suggesting that they might participate in chromosome looping of enhancer–miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391–1186507 ∼ miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on the enhancer affected the expression of the TNFRSF18 gene as a tumor suppressor.

Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation.

Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry, and topological organization of proteins within IACs are not fully understood. To address this gap, we used multiplexed proximity biotinylation (BioID) to generate an in situ, proximity-dependent adhesome in mouse pancreatic fibroblasts. Integration of the interactomes of 16 IAC-associated baits revealed a network of 147 proteins with 361 proximity interactions. Candidates with underappreciated roles in adhesion were identified, in addition to established IAC components. Bioinformatic analysis revealed five clusters of IAC baits that link to common groups of prey, and which therefore may represent functional modules. The five clusters, and their spatial associations, are consistent with current models of IAC interaction networks and stratification. This study provides a resource to examine proximal relationships within IACs at a global level.

Analytical solutions for N interacting electron system confined in graph of coupled electrostatic semiconductor and superconducting quantum dots in tight-binding model

Analytical solutions for a tight-binding model are presented for position-based charge qubits and N-interacting qubits realized by quasi-one-dimensional network of coupled quantum dots (QD) expressed by connected or disconnected graphs of any topology in two and three dimensions where one electron is present at each separated graph. Electron(s) quantum dynamical state is described under various electromagnetic circumstances with omission spin degree-of-freedom. The action of Hadamard and phase-rotating gates is given by analytical formulas derived and formulated for any case of a physical field evolution preserving the occupancy of a two-energetic-level system. The interface between a superconducting Josephson junction and semiconductor position-based qubit implemented in coupled semiconductor QDs is described, which can be the base for electrostatic interface between superconducting and semiconductor quantum computer. Modification of Andreev Bound State in Josephson junction by the presence of semiconductor qubit in its proximity and electrostatic interaction with superconducting qubit is supported by the minimalistic tight-binding model that also can indicate topological phase transition. The obtained results can be generalized for a case of electrostatic interaction of the semiconductor qubit with the different types of Josephson junctions. The operation of phase rotating gate implemented in semiconductor position-based qubit with use of electrical and magnetic field is presented with use of analytical approach.

Dyadic affiliative preferences in a stable group of domestic pigs

Social preferences in pigs have received little attention despite the welfare implication of providing an adequate social environment for farm animals. We investigated the extent to which domestic pigs show affiliative preferences in three behavioural contexts—rest, exploration, social nosing—and whether these preferences were influenced by sex, relatedness and social dominance. We recorded the frequency at which pigs were associated in close spatial proximity during rest (≤30 cm) and exploration (≤1 m), and engaged in social nosing interactions (snout- snout and snout-body contacts) from age 23–29 weeks. The group consisted of 24 pigs from three mixed-sex litters of the same age, housed in an indoor pen and having free access to a large pasture area. To test for dyadic social preferences, we calculated associations in close proximity and social nosing interaction rates, classified them by strength and tested their significance with permutation methods. We then used the Multiple Regression Quadratic Assignment Procedure to test whether individual traits (sex, litter, dominance) and other social interactions (agonistic interactions, active lying down) explained the preferred partners. Preferences were overall relatively weak but found across all behavioural contexts—of all observed pairs, 44 % were preferred pairs when resting, 20 % when exploring, and 30 % when social nosing (snout-body contact). Snout-body contacts were weakly and negatively correlated with sex and dominance, whereas close proximity associations during rest and social nosing interactions were positively correlated with active lying down behaviour. Our results indicate that domestic pigs can develop preferred social relationships, and that such social preferences are weakly driven by individual attributes (sex and dominance) but influenced by the behavioural context. By shedding light on underexplored aspects of the social structure of pigs, our study strengthens the importance of accounting for the multiple drivers of social relationships to provide an adequate environment that improves management and welfare of pigs.