Biology subjects

Williams, N. S.

Publications and source records attributed to Williams, N. S..

4 recordsLinked to original sources

bioRxiv2022

Crowdsourced EEG Experiments: A proof of concept for remote EEG acquisition using EmotivPRO Builder and EmotivLABS

Online research platforms have enabled mass data collection enabling representative samples for cognitive behavioural studies. However, the benefits of online data collection have not been available for cognitive neuroscience fields such as electroencephalography (EEG). In this study, we introduce an approach for remote EEG data collection. We demonstrate how an experiment can be built via the EmotivPRO Builder and deployed to the EmotivLABS website where it can be completed by participants who own EMOTIV EEG headsets. To demonstrate the data collection technique, we collected EEG while participants engaged in a resting state task where participants sat with their eyes open and then eyes closed for two minutes each. We observed a significant difference in alpha power between the two conditions thereby demonstrating the well-known alpha suppression effect. Thus, we demonstrate that EEG data collection, particularly for frequency domain analysis, can be successfully conducted online with remote users.

neuroscience↗

bioRxiv2021

Polymer microparticles prolong delivery of the 15-PGDH inhibitor SW033291

As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. While bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles - specifically {beta}-CD microparticles ({beta}-CD MPs) - to extend the delivery of 15-PGDH inhibitor, (+)SW033291, to over one week. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/456403v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@13aed1dorg.highwire.dtl.DTLVardef@1a541eaorg.highwire.dtl.DTLVardef@8a9fd5org.highwire.dtl.DTLVardef@1038a77_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin remodeling

Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. As the list of PARP1/2:HPF1 substrates continues to expand, there is a need for technologies to prepare mono- and poly-ADP-ribosylated proteins for biochemical interrogation. Here we investigate the unique peptide ADPr activities catalyzed by PARP1 in the absence and presence of HPF1. We then exploit these activities to develop a method that facilitates installation of ADP-ribose polymers onto full-length proteins with precise control over chain length and modification site. A series of semi-synthetic ADP-ribosylated histone proteins are prepared which demonstrate that ADPr at H2BS6 or H3S10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. Importantly, we found ALC1 selectively remodels activated substrates within heterogeneous nucleosome populations and that nucleosome serine ADPr is sufficient to stimulate ALC1 activity in nuclear extracts. Our study identifies a biochemical function for nucleosome serine ADPr and describes a method that is broadly applicable to explore the impact that site-specific serine mono- and poly-ADPr have on protein function.

biochemistry↗

bioRxiv2021

Cancer drug discovery as a low rank tensor completion problem

The heterogeneity of cancer necessitates developing a multitude of targeted therapies. We propose the view that cancer drug discovery is a low rank tensor completion problem. We implement this vision by using heterogeneous public data to construct a tensor of drug-target-disease associations. We show the validity of this approach computationally by simulations, and experimentally by testing drug candidates. Specifically, we show that a novel drug candidate, SU11652, controls melanoma tumor growth, including BRAFWT melanoma. Independently, we show that another molecule, TC-E 5008, controls tumor proliferation on ex vivo ER+ human breast cancer. Most importantly, we identify these chemicals with only a few computationally selected experiments as opposed to brute-force screens. The efficiency of our approach enables use of ex vivo human tumor assays as a primary screening tool. We provide a web server, the Cancer Vulnerability Explorer (accessible at https://cavu.biohpc.swmed.edu), to facilitate the use of our methodology.

cancer biology↗