Thomas Hollis
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View article: K294E change in the rotavirus factory forming protein NSP2 stabilizes a rare C-terminal conformation
K294E change in the rotavirus factory forming protein NSP2 stabilizes a rare C-terminal conformation Open
Rotaviruses (RVs) induce the formation of cytoplasmic viral factories, termed viroplasms, which are the sites of early particle assembly and viral RNA synthesis. The RV octameric nonstructural protein 2 (NSP2) plays critical, albeit incomp…
View article: Three Prime Repair Exonuclease 1 preferentially degrades the integration-incompetent HIV-1 DNA through favorable kinetics, thermodynamic, structural and conformational properties
Three Prime Repair Exonuclease 1 preferentially degrades the integration-incompetent HIV-1 DNA through favorable kinetics, thermodynamic, structural and conformational properties Open
HIV-1 integration into the human genome is dependent on 3’-processing of the reverse transcribed viral DNA. Recently, we reported that the cellular Three Prime Repair Exonuclease 1 (TREX1) enhances HIV-1 integration by degrading the unproc…
View article: Improving the Performance of Selective Solid-State Nanopore Sensing Using a Polyhistidine-Tagged Monovalent Streptavidin
Improving the Performance of Selective Solid-State Nanopore Sensing Using a Polyhistidine-Tagged Monovalent Streptavidin Open
Solid-state (SS-) nanopore sensing has gained tremendous attention in recent years, but it has been constrained by its intrinsic lack of selectivity. To address this, we previously established a novel SS-nanopore assay that produces transl…
View article: Protein oxidation increases SAMHD1 binding ssDNA via its regulatory site
Protein oxidation increases SAMHD1 binding ssDNA via its regulatory site Open
SAMHD1 dNTP hydrolase activity places it at the crossroad of several important biological pathways, such as viral restriction, cell cycle regulation, and innate immunity. Recently, a dNTPase independent function for SAMHD1 in homologous re…
View article: An FDA-Approved Antifungal, Ketoconazole, and Its Novel Derivative Suppress tGLI1-Mediated Breast Cancer Brain Metastasis by Inhibiting the DNA-Binding Activity of Brain Metastasis-Promoting Transcription Factor tGLI1
An FDA-Approved Antifungal, Ketoconazole, and Its Novel Derivative Suppress tGLI1-Mediated Breast Cancer Brain Metastasis by Inhibiting the DNA-Binding Activity of Brain Metastasis-Promoting Transcription Factor tGLI1 Open
The goal of this study is to identify pharmacological inhibitors that target a recently identified novel mediator of breast cancer brain metastasis (BCBM), truncated glioma-associated oncogene homolog 1 (tGLI1). Inhibitors of tGLI1 are not…
View article: A Monomeric Mycobacteriophage Immunity Repressor Utilizes Two Domains to Recognize an Asymmetric DNA Sequence
A Monomeric Mycobacteriophage Immunity Repressor Utilizes Two Domains to Recognize an Asymmetric DNA Sequence Open
Supporting source data consisting of simulation topologies and trajectories in pdb and xtc file formats, respectively.
View article: A Monomeric Mycobacteriophage Immunity Repressor Utilizes Two Domains to Recognize an Asymmetric DNA Sequence
A Monomeric Mycobacteriophage Immunity Repressor Utilizes Two Domains to Recognize an Asymmetric DNA Sequence Open
Supporting source data consisting of simulation topologies and trajectories in pdb and xtc file formats, respectively.
View article: SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression
SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression Open
SAMHD1 activity is regulated by a network of mechanisms including phosphorylation, oxidation, oligomerization, and others. Significant questions remain about the effects of phosphorylation on SAMHD1 function and activity. We investigated t…
View article: Human Three Prime Repair Exonuclease 1 Promotes HIV-1 Integration by Preferentially Degrading Unprocessed Viral DNA
Human Three Prime Repair Exonuclease 1 Promotes HIV-1 Integration by Preferentially Degrading Unprocessed Viral DNA Open
Productive HIV-1 infection is dependent on a number of cellular factors. Therefore, a clear understanding of how the virus exploits the cellular machinery will identify new targets for inhibiting HIV-1 infection.
View article: Protein—Not Just a Food Group!
Protein—Not Just a Food Group! Open
Eating protein is important to help us grow strong and stay healthy. However, protein is more than just a food group! Proteins are the workers inside of our busy cells. These proteins have some amazing jobs to do, and thousands of proteins…
View article: TREX1 as a Novel Immunotherapeutic Target
TREX1 as a Novel Immunotherapeutic Target Open
Mutations in the TREX1 3’ → 5’ exonuclease are associated with a spectrum of autoimmune disease phenotypes in humans and mice. Failure to degrade DNA activates the cGAS-STING DNA-sensing pathway signaling a type-I interferon (IFN) response…
View article: Cationic Antimicrobial Peptides Promote Microbial Mutagenesis and Pathoadaptation in Chronic Infections
Cationic Antimicrobial Peptides Promote Microbial Mutagenesis and Pathoadaptation in Chronic Infections Open
Acquisition of adaptive mutations is essential for microbial persistence during chronic infections. This is particularly evident during chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients. Thus far, mutagenesis …
View article: Structural mechanism for regulation of DNA binding of BpsR, a Bordetella regulator of biofilm formation, by 6-hydroxynicotinic acid
Structural mechanism for regulation of DNA binding of BpsR, a Bordetella regulator of biofilm formation, by 6-hydroxynicotinic acid Open
Bordetella bacteria are respiratory pathogens of humans, birds, and livestock. Bordetella pertussis the causative agent of whopping cough remains a significant health issue. The transcriptional regulator, BpsR, represses a number of Bordet…
View article: Catch Me If You Can
Catch Me If You Can Open
As advances in signature recognition have reached a new plateau of performance at around 2% error rate, it is interesting to investigate alternative approaches. The approach detailed in this paper looks at using Variational Auto-Encoders (…
View article: A Comparison of LSTMs and Attention Mechanisms for Forecasting Financial Time Series
A Comparison of LSTMs and Attention Mechanisms for Forecasting Financial Time Series Open
While LSTMs show increasingly promising results for forecasting Financial Time Series (FTS), this paper seeks to assess if attention mechanisms can further improve performance. The hypothesis is that attention can help prevent long-term de…
View article: SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity
SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity Open
SAMHD1 is a deoxynucleotide triphosphate (dNTP) hydrolase that plays an important role in the homeostatic balance of cellular dNTPs. Its emerging role as an effector of innate immunity is affirmed by mutations in the SAMHD1 gene that cause…
View article: The Transcriptional Regulator BpsR Controls the Growth of Bordetella bronchiseptica by Repressing Genes Involved in Nicotinic Acid Degradation
The Transcriptional Regulator BpsR Controls the Growth of Bordetella bronchiseptica by Repressing Genes Involved in Nicotinic Acid Degradation Open
Many of the pathogenic species of the genus Bordetella have an absolute requirement for nicotinic acid (NA) for laboratory growth. These Gram-negative bacteria also harbor a gene cluster homologous to the nic cluster of Pseudomonas putida …
View article: Solid-State Nanopore Analysis of Diverse DNA Base Modifications Using a Modular Enzymatic Labeling Process
Solid-State Nanopore Analysis of Diverse DNA Base Modifications Using a Modular Enzymatic Labeling Process Open
Many regulated epigenetic elements and base lesions found in genomic DNA can both directly impact gene expression and play a role in disease processes. However, due to their noncanonical nature, they are challenging to assess with conventi…
View article: The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch
The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch Open
Here we report that SAMHD1 is a major target for redox regulation of nucleotide metabolism and cell cycle control. SAMHD1 is a triphosphate hydrolase, whose function involves regulation of deoxynucleotide triphosphate pools. We demonstrate…
View article: Autoimmunity: Why the Body Attacks Itself
Autoimmunity: Why the Body Attacks Itself Open
The human body is made up of 37 trillion cells and billions of these die every single day. The body has special cells, called macrophages, which consume dying cells to prevent them from building up in your body. Macrophages are also able t…