GFP dimer

Intramolecular Fluorescent Protein Association in a Class of Zinc FRET Sensors Leads to Increased Dynamic Range

Oct. 29, 2019

Genetically encoded Förster resonance energy transfer (FRET) sensors enable the visualization of ions, molecules, and processes in live cells. However, despite their widespread use, the molecular states that determine sensor performance are usually poorly understood, which limits efforts to improve them. We used dynamic light scattering (DLS) and time-resolved fluorescence...

Identification and characterization of molecules that inhibit Notch signaling.

Discovery of a ZIP7 inhibitor from a Notch pathway screen.

Oct. 29, 2019

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum...

Genetically encoded Zn2+ FRET sensor measurements in resting neurons.

Intracellular Zn2+ transients modulate global gene expression in dissociated rat hippocampal neurons

Oct. 29, 2019

Zinc (Zn2+) is an integral component of many proteins and has been shown to act in a regulatory capacity in different mammalian systems, including as a neurotransmitter in neurons throughout the brain. While Zn2+ plays an important role in modulating neuronal potentiation and synaptic plasticity, little is known about the...

Thiol-ene PEG hydrogels for adult mouse cardiac myocytes 3D encapsulation and culture

Three-dimensional encapsulation of adult mouse cardiomyocytes in hydrogels with tunable stiffness

Oct. 29, 2019

Numerous diseases, including those of the heart, are characterized by increased stiffness due to excessive deposition of extracellular matrix proteins. Cardiomyocytes continuously adapt their morphology and function to the mechanical changes of their microenvironment. Because traditional cell culture is conducted on substrates that are many orders of magnitude stiffer than...

Transcatheter aortic valve replacements alter circulating serum factors to mediate myofibroblast deactivation

Oct. 29, 2019

The transcatheter aortic valve replacement (TAVR) procedure has emerged as a minimally invasive treatment for patients with aortic valve stenosis (AVS). However, alterations in serum factor composition and biological activity after TAVR remain unknown. Here, we quantified the systemic inflammatory effects of the TAVR procedure and hypothesized that alterations in...

Structural location of HCM mutations

Myosin motor domains carrying mutations implicated in early or late onset hypertrophic cardiomyopathy have similar properties.

Oct. 29, 2019

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder characterized by left ventricular hypertrophy and cardiac hyper-contractility. Mutations in the β cardiac myosin heavy chain gene (β-MyHC) are a major cause of HCM, but the specific mechanistic changes to myosin function that lead to this disease remain incompletely understood. Predicting the...

The svtools pipeline

svtools: population-scale analysis of structural variation

Oct. 29, 2019

Large-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more...

Stochastic sampling leads to variation in observed overlap.

Bayes-optimal estimation of overlap between populations of fixed size

Oct. 23, 2019

Measuring the overlap between two populations is, in principle, straightforward. Upon fully sampling both populations, the number of shared objects—species, taxonomical units, or gene variants, depending on the context—can be directly counted. In practice, however, only a fraction of each population’s objects are likely to be sampled due to stochastic...

A layer (chapter) of a network of character co-occurences from David Foster Wallace’s novel Infinite Jest

webweb: a tool for creating, displaying, and sharing interactive network visualizations on the web

Oct. 23, 2019

webweb is a package for creating interactive and portable visualizations of complex networks in the web browser that can be easily shared. With webweb, users of MATLAB, pure Python, and Python’s networkX (Aric A. Hagberg & Pieter J. Swart, 2008) are able to write complex network data directly to a...

Schematics of the nuclear pore complex and model

Design principles of selective transport through biopolymer barriers

Oct. 23, 2019

In biological systems, polymeric materials block the movement of some macromolecules while allowing the selective passage of others. In some cases, binding enables selective transport, while in others the most inert particles appear to transit most rapidly. To study the general principles of filtering, we develop a model motivated by...

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