Biology subjects

You, W.

Publications and source records attributed to You, W..

4 recordsLinked to original sources

bioRxiv2018

MTHFD1 is a genetic interactor of BRD4 and links folate metabolism to transcriptional regulation

The histone acetyl-reader BRD4 is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for genetic and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1. We show that a fraction of MTHFD1 resides in the nucleus, where it is recruited to distinct genomic loci by direct interaction with BRD4. Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression, and pharmacologic inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo. Our finding that MTHFD1 and other metabolic enzymes are chromatin-associated suggests a direct role for nuclear metabolism in the control of gene expression.

cancer biology↗

bioRxiv2017

Study on Linear Combination of Long Memory Processes Corrupted by Additive Noises for fMRI Time Series Analysis

Estimating the long memory parameter of the fMRI time series enables us to understand the fractal behavior of neural activity of the brain through fMRI time series. However, the existence of white noise and physiological noise compounds which also have fractal properties prevent us from making the estimation precise. As basic strategies to overcome noises, we address how to estimate the long memory parameter in the presence of additive noises, and how to estimate the long memory parameters of linearly combined long memory processes.

biophysics↗

bioRxiv2017

Inter-slice motion correction using spatiotemporal interpolation for functional magnetic resonance imaging of the moving fetus

Fetal motion continues to be one of the major artifacts in in-utero functional MRI; interestingly few methods have been developed to address fetal motion correction. In this study, we propose a robust method for motion correction in fetal fMRI by which both inter-slice and inter-volume motion artifacts are jointly corrected. To accomplish this, an original volume is temporally split into odd and even slices, and then voxel intensities are spatially and temporally interpolated in the process of image registration. Our experimental data demonstrate that our method was more effective in correcting fetal motion artifact compared to traditional motion correction methods.

bioengineering↗

bioRxiv2017

Evaluating the accuracy of the umbrella sampling plots with different dissociation paths, conformational changes, and structure preparation

The kinetics of ligand dissociation has been found to be crucial for a good drug candidate. Therefore, examining the underlying free energy profile of the dissociation that governs the kinetics becomes important. Umbrella sampling (US), a widely used free energy calculation method, has long been used to explore the dissociation process of ligand-receptor systems. The potential of mean force (PMF) computed from US seems to always produce binding affinity and energy barriers that more or less agree with experiments. However, such PMFs are influenced by many practical aspects, like the method used to generate the initial dissociation pathway, collective variables (CVs) that used to describe the reaction coordinate (RC), and how intensive the sampling is in the conformational space restrained by the CVs. These critical factors were rarely studied. Here we applied US to study the dissociation processes of {beta}-cyclodextrin ({beta}-CD) and p38 complex systems. For {beta}-CD, we used three different {beta}-CD conformations to generate the dissociation path manually. For p38, we generated the dissociation pathway using accelerated molecular dynamics (AMD) followed by conformational relaxing with short conventional molecular dynamics (MD), steered molecular dynamics (SMD) and manual pulling. We found that even for small {beta}-CD complexes, different {beta}-CD conformations will alter the height of the PMF and different dissociation directions result in appearance/disappearance of local minima. SMD poorly samples the residue sidechain movement, leading to overestimated height of PMF. On the other hand, the AMD pathway relaxed by short conventional MD sampled more accurate structures, resulting in reasonable PMF.

biophysics↗