2,403 research outputs found
Spatial and Temporal Sensing Limits of Microtubule Polarization in Neuronal Growth Cones by Intracellular Gradients and Forces
Neuronal growth cones are the most sensitive amongst eukaryotic cells in
responding to directional chemical cues. Although a dynamic microtubule
cytoskeleton has been shown to be essential for growth cone turning, the
precise nature of coupling of the spatial cue with microtubule polarization is
less understood. Here we present a computational model of microtubule
polarization in a turning neuronal growth cone (GC). We explore the limits of
directional cues in modifying the spatial polarization of microtubules by
testing the role of microtubule dynamics, gradients of regulators and
retrograde forces along filopodia. We analyze the steady state and transition
behavior of microtubules on being presented with a directional stimulus. The
model makes novel predictions about the minimal angular spread of the chemical
signal at the growth cone and the fastest polarization times. A regulatory
reaction-diffusion network based on the cyclic
phosphorylation-dephosphorylation of a regulator predicts that the receptor
signal magnitude can generate the maximal polarization of microtubules and not
feedback loops or amplifications in the network. Using both the
phenomenological and network models we have demonstrated some of the physical
limits within which the MT polarization system works in turning neuron.Comment: 7 figures and supplementary materia
SInC: An accurate and fast error-model based simulator for SNPs, Indels and CNVs coupled with a read generator for short-read sequence data
We report SInC (SNV, Indel and CNV) simulator and read generator, an
open-source tool capable of simulating biological variants taking into account
a platform-specific error model. SInC is capable of simulating and generating
single- and paired-end reads with user-defined insert size with high efficiency
compared to the other existing tools. SInC, due to its multi-threaded
capability during read generation, has a low time footprint. SInC is currently
optimised to work in limited infrastructure setup and can efficiently exploit
the commonly used quad-core desktop architecture to simulate short sequence
reads with deep coverage for large genomes. Sinc can be downloaded from
https://sourceforge.net/projects/sincsimulator/
Factoring Shape, Pose, and Layout from the 2D Image of a 3D Scene
The goal of this paper is to take a single 2D image of a scene and recover
the 3D structure in terms of a small set of factors: a layout representing the
enclosing surfaces as well as a set of objects represented in terms of shape
and pose. We propose a convolutional neural network-based approach to predict
this representation and benchmark it on a large dataset of indoor scenes. Our
experiments evaluate a number of practical design questions, demonstrate that
we can infer this representation, and quantitatively and qualitatively
demonstrate its merits compared to alternate representations.Comment: Project url with code: https://shubhtuls.github.io/factored3
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The signature motif of the Saccharomyces cerevisiae Pif1 DNA helicase is essential in vivo for mitochondrial and nuclear functions and in vitro for ATPase activity
Pif1 family DNA helicases are conserved from bacteria to humans and have critical and diverse functions in vivo that promote genome integrity. Pif1 family helicases share a 23 amino acid region, called the Pif1 signature motif (SM) that is unique to this family. To determine the importance of the SM, we did mutational and functional analysis of the SM from the Saccharomyces cerevisiae Pif1 (ScPif1). The mutations deleted portions of the SM, made one or multiple single amino acid changes in the SM, replaced the SM with its counterpart from a bacterial Pif1 family helicase and substituted an α-helical domain from another helicase for the part of the SM that forms an α helix. Mutants were tested for maintenance of mitochondrial DNA, inhibition of telomerase at telomeres and double strand breaks, and promotion of Okazaki fragment maturation. Although certain single amino acid changes in the SM can be tolerated, the presence and sequence of the ScPif1 SM were essential for all tested in vivo functions. Consistent with the in vivo analyses, in vitro studies showed that the presence and sequence of the ScPif1 SM were critical for ATPase activity but not substrate binding
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