52 results match your criteria: "R.D.Berlin Center for Cell Analysis and Modeling[Affiliation]"

Biochemical interactions at membranes are the starting points for cell signaling networks. But bimolecular reaction kinetics are difficult to experimentally measure on 2-dimensional membranes and are usually measured in volumetric assays. Membrane tethering produces confinement and steric effects that will significantly impact binding rates in ways that are not readily estimated from volumetric measurements.

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Cellular condensates often consist of 10s to 100s of distinct interacting molecular species. Because of the complexity of these interactions, predicting the point at which they will undergo phase separation is daunting. Using experiments and computation, we therefore studied a simple model system consisting of polySH3 and polyPRM designed for pentavalent heterotypic binding.

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bnglViz: online visualization of rule-based models.

Bioinformatics

June 2024

R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, CT 06030, United States.

Motivation: Rule-based modeling is a powerful method to describe and simulate interactions among multi-site molecules and multi-molecular species, accounting for the internal connectivity of molecules in chemical species. This modeling technique is implemented in BioNetGen software that is used by various tools and software frameworks, such as BioNetGen stand-alone software, NFSim simulation engine, Virtual Cell simulation and modeling framework, SmolDyn and PySB software tools. These tools exchange models using BioNetGen scripting language (BNGL).

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Cellular condensates often consist of 10s to 100s of distinct interacting molecular species. Because of the complexity of these interactions, predicting the point at which they will undergo phase separation into discrete compartments is daunting. Using experiments and computation, we therefore studied a simple model system consisting of 2 proteins, polySH3 and polyPRM, designed for pentavalent heterotypic binding.

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Optical mapping of cardiac electromechanics in beating in vivo hearts.

Biophys J

November 2023

Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:

Optical mapping has been widely used in the study of cardiac electrophysiology in motion-arrested, ex vivo heart preparations. Recent developments in motion artifact mitigation techniques have made it possible to optically map beating ex vivo hearts, enabling the study of cardiac electromechanics using optical mapping. However, the ex vivo setting imposes limitations on optical mapping such as altered metabolic states, oversimplified mechanical loads, and the absence of neurohormonal regulation.

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Optogenetics, utilising light-reactive proteins to manipulate tissue activity, are a relatively novel approach in the field of cardiac electrophysiology. We here provide an overview of light-activated transmembrane channels (optogenetic actuators) currently applied in strategies to modulate cardiac activity, as well as newly developed variants yet to be implemented in the heart. In addition, we touch upon genetically encoded indicators (optogenetic sensors) and fluorescent dyes to monitor tissue activity, including cardiac transmembrane potential and ion homeostasis.

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Unlabelled: The clinical success of combined androgen deprivation therapy (ADT) and radiotherapy (RT) in prostate cancer created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at a steady state and in response to ionizing radiation (IR).

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Summary: Low-affinity interactions among multivalent biomolecules may lead to the formation of molecular complexes that undergo phase transitions to become supply-limited large clusters. In stochastic simulations, such clusters display a wide range of sizes and compositions. We have developed a Python package, MolClustPy, which performs multiple stochastic simulation runs using NFsim (Network-Free stochastic simulator); MolClustPy characterizes and visualizes the distribution of cluster sizes, molecular composition, and bonds across molecular clusters.

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S Ummary: Low-affinity interactions among multivalent biomolecules may lead to the formation of molecular complexes that undergo phase transitions to become extra-large clusters. Characterizing the physical properties of these clusters is important in recent biophysical research. Due to weak interactions such clusters are highly stochastic, demonstrating a wide range of sizes and compositions.

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The maximum solubility product marks the threshold for condensation of multivalent biomolecules.

Biophys J

May 2023

R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, Connecticut. Electronic address:

Clustering of weakly interacting multivalent biomolecules underlies the formation of membraneless compartments known as condensates. As opposed to single-component (homotypic) systems, the concentration dependence of multicomponent (heterotypic) condensate formation is not well understood. We previously proposed the solubility product (SP), the product of monomer concentrations in the dilute phase, as a tool for understanding the concentration dependence of multicomponent systems.

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Article Synopsis
  • Subcorneal pustular dermatosis (SPD) and annular pustular psoriasis (APP) are rare skin conditions in children that are challenging to tell apart.
  • A 10-year-old boy had a long history of red, scaly, ring-shaped patches with pustules, initially diagnosed as SPD, but his treatment and biopsy results pointed to APP.
  • After starting treatment with adalimumab, the boy completely recovered, highlighting the similarities between SPD and APP and suggesting they might be variations of the same disease.
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Cancer cells feature a resting membrane potential (V) that is depolarized compared to normal cells, and express active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities to 'excitable' tissues, relatively little is known about cancer cell V dynamics. Here high-throughput, cellular-resolution V imaging reveals that V fluctuates dynamically in several breast cancer cell lines compared to non-cancerous MCF-10A cells.

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Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors.

Cell Rep

February 2022

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Genetics, University of Alabama, Birmingham, AL 35233, USA. Electronic address:

Many lncRNAs have been discovered using transcriptomic data; however, it is unclear what fraction of lncRNAs is functional and what structural properties affect their phenotype. MUNC lncRNA (also known as eRNA) acts as an enhancer RNA for the Myod1 gene in cis and stimulates the expression of other promyogenic genes in trans by recruiting the cohesin complex. Here, experimental probing of the RNA structure revealed that MUNC contains multiple structural domains not detected by prediction algorithms in the absence of experimental information.

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Histone chaperones modulate the stability of histones beginning from histone synthesis, through incorporation into DNA, and during recycling during transcription and replication. Following histone removal from DNA, chaperones regulate histone storage and degradation. Here, we demonstrate that UBR7 is a histone H3.

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Fast Optical Investigation of Cardiac Electrophysiology by Parallel Detection in Multiwell Plates.

Front Physiol

September 2021

European Laboratory for Non-linear Spectroscopy, Sesto Fiorentino, Italy.

Current techniques for fast characterization of cardiac electrophysiology employ optical technologies to control and monitor action potential features of single cells or cellular monolayers placed in multiwell plates. High-speed investigation capacities are commonly achieved by serially analyzing well after well employing fully automated fluorescence microscopes. Here, we describe an alternative cost-effective optical approach (MULTIPLE) that exploits high-power LED arrays to globally illuminate a culture plate and an sCMOS sensor for parallel detection of the fluorescence coming from multiple wells.

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Background: Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurogenetic disorder caused by duplications of the maternal copy of this region. In addition to hypotonia, motor deficits, and language impairments, patients with Dup15q commonly meet the criteria for autism spectrum disorder and have a high prevalence of seizures. It is known from mouse models that synaptic impairments are a strong component of Dup15q pathophysiology; however, cellular phenotypes that relate to seizures are less clear.

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Mechanism of actin filament nucleation.

Biophys J

October 2021

Departments of Molecular Cellular and Developmental Biology, of Molecular Biophysics and Biochemistry, and of Cell Biology, Yale University, New Haven, Connecticut. Electronic address:

We used computational methods to analyze the mechanism of actin filament nucleation. We assumed a pathway where monomers form dimers, trimers, and tetramers that then elongate to form filaments but also considered other pathways. We aimed to identify the rate constants for these reactions that best fit experimental measurements of polymerization time courses.

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Biomolecular condensates are formed by liquid-liquid phase separation (LLPS) of multivalent molecules. LLPS from a single ("homotypic") constituent is governed by buffering: above a threshold, free monomer concentration is clamped, with all added molecules entering the condensed phase. However, both experiment and theory demonstrate that buffering fails for the concentration dependence of multicomponent ("heterotypic") LLPS.

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SBGN Bricks Ontology as a tool to describe recurring concepts in molecular networks.

Brief Bioinform

September 2021

European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Université de Lyon, 50 Avenue Tony Garnier, 69007 Lyon, France.

A comprehensible representation of a molecular network is key to communicating and understanding scientific results in systems biology. The Systems Biology Graphical Notation (SBGN) has emerged as the main standard to represent such networks graphically. It has been implemented by different software tools, and is now largely used to communicate maps in scientific publications.

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Microtubules (MTs) often form a polarized array with minus ends anchored at the centrosome and plus ends extended toward the cell margins. Plus ends display behavior known as dynamic instability-transitions between rapid shortening and slow growth. It is known that dynamic instability is regulated locally to ensure entry of MTs into nascent areas of the cytoplasm, but details of this regulation remain largely unknown.

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Arrhythmia susceptibility in a rat model of acute atrial dilation.

Prog Biophys Mol Biol

August 2020

European Laboratory for Non-Linear Spectroscopy, 50019, Sesto Fiorentino (FI), Italy; Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134, Florence, Italy. Electronic address:

Atrial fibrillation (AF) is the most common cardiac arrhythmia, associated with an increased risk of stroke and heart failure. Acute AF occurs in response to sudden increases of atrial hemodynamic load, leading to atrial stretch. The mechanisms of stretch-induced AF were investigated in large mammals with controversial results.

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Recent progress in optical voltage-sensor technology and applications to cardiac research: from single cells to whole hearts.

Prog Biophys Mol Biol

August 2020

R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, 400 Farmington Avenue, Farmington, CT, 06030, USA.

The first workshop on Novel Optics-based approaches for Cardiac Electrophysiology (NOtiCE) was held in Florence Italy in 2018. Here, we learned how optical approaches have shaped our basic understanding of cardiac electrophysiology and how new technologies and approaches are being developed and validated to advance the field. Several technologies are being developed that may one day allow for new clinical approaches for diagnosing cardiac disorders and possibly intervening to treat human patients.

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Minimally-invasive monitoring of electrophysiological neural activities in real-time-that enables quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET-presents a very challenging yet significant task for neuroimaging. In this paper, we present functional PA (fPA) imaging of chemoconvulsant rat seizure model with intact scalp using a fluorescence quenching-based cyanine voltage-sensitive dye (VSD) characterized by a lipid vesicle model mimicking different levels of membrane potential variation. The framework also involves use of a near-infrared VSD delivered through the blood-brain barrier (BBB), opened by pharmacological modulation of adenosine receptor signaling.

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