Publications by authors named "G J Phillips"

2,289 Publications

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Repurposing CRISPR-Cas Systems as Genetic Tools for the Enterobacteriales.

EcoSal Plus 2021 Jun 14:eESP00062020. Epub 2021 Jun 14.

Department of Veterinary Microbiology, Iowa State University, Ames, Iowa, USA.

Over the last decade, the study of CRISPR-Cas systems has progressed from a newly discovered bacterial defense mechanism to a diverse suite of genetic tools that have been applied across all domains of life. While the initial applications of CRISPR-Cas technology fulfilled a need to more precisely edit eukaryotic genomes, creative "repurposing" of this adaptive immune system has led to new approaches for genetic analysis of microorganisms, including improved gene editing, conditional gene regulation, plasmid curing and manipulation, and other novel uses. The main objective of this review is to describe the development and current state-of-the-art use of CRISPR-Cas techniques specifically as it is applied to members of the . While many of the applications covered have been initially developed in Escherichia coli, we also highlight the potential, along with the limitations, of this technology for expanding the availability of genetic tools in less-well-characterized non-model species, including bacterial pathogens.
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http://dx.doi.org/10.1128/ecosalplus.ESP-0006-2020DOI Listing
June 2021

Associations with COVID-19 Symptoms, Prevention Interest, and Testing Among Sexual and Gender Minority Adults in a Diverse National Sample.

LGBT Health 2021 Jun 11. Epub 2021 Jun 11.

Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Sexual and gender minority (SGM) and racial/ethnic minority populations may differ in coronavirus disease 2019 (COVID-19) prevention, testing, and vaccine interest, although little research has explored these disparities. It is critical to understand the differential experiences within minoritized communities to ensure effective intervention and vaccine rollout. In a national online survey of U.S. adult SGM individuals, conducted between April and August 2020, 932 participants responded about COVID-19 testing, symptoms, interest in vaccination, and interest in at-home testing. Bivariate associations between these outcomes and demographic factors, including sexual orientation, gender identity, endorsing intersex traits, gender modality, race/ethnicity, and HIV status were calculated. Despite 24% of the sample reporting COVID-19 symptoms, testing was relatively low at 13.3%. Transgender and bisexual/pansexual individuals were more likely to be interested in a COVID-19 vaccine and an at-home test compared with cisgender and gay/lesbian respondents, respectively. Compared with cisgender individuals, transgender individuals were nearly twice as likely to report COVID-19 symptoms. Latinx individuals were less likely to be interested in a future COVID-19 vaccination and Black individuals were less likely to be interested in an at-home COVID-19 test compared with White participants. Both respondents who endorsed intersex traits and people with HIV were less likely to be interested in an at-home test compared with those who did not endorse having intersex traits and people without HIV, respectively. These results show critical disparities in COVID-19 symptomology and prevention interest within SGM populations that must be taken into account when designing or tailoring effective COVID-19 interventions.
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http://dx.doi.org/10.1089/lgbt.2021.0002DOI Listing
June 2021

Conformational Dynamics in the Interaction of SARS-CoV-2 Papain-like Protease with Human Interferon-Stimulated Gene 15 Protein.

J Phys Chem Lett 2021 Jun 10;12(23):5608-5615. Epub 2021 Jun 10.

Neutron Scattering Division, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, Tennessee 37831, United States.

Papain-like protease (PLpro) from SARS-CoV-2 plays essential roles in the replication cycle of the virus. In particular, it preferentially interacts with and cleaves human interferon-stimulated gene 15 (hISG15) to suppress the innate immune response of the host. We used small-angle X-ray and neutron scattering combined with computational techniques to study the mechanism of interaction of SARS-CoV-2 PLpro with hISG15. We showed that hISG15 undergoes a transition from an extended to a compact state after binding to PLpro, a conformation that has not been previously observed in complexes of SARS-CoV-2 PLpro with ISG15 from other species. Furthermore, computational analysis showed significant conformational flexibility in the ISG15 N-terminal domain, suggesting that it is weakly bound to PLpro and supports a binding mechanism that is dominated by the C-terminal ISG15 domain. This study fundamentally improves our understanding of the SARS-CoV-2 deISGylation complex that will help guide development of COVID-19 therapeutics targeting this complex.
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http://dx.doi.org/10.1021/acs.jpclett.1c00831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204754PMC
June 2021

Activity of trastuzumab emtansine (T-DM1) in 3D cell culture.

Breast Cancer Res Treat 2021 Jun 5. Epub 2021 Jun 5.

Roche Tissue Diagnostics, 1910 E Innovation Park Drive, Tucson, AZ, 85755, USA.

Background: Cell spheroids and aggregates generated from three-dimensional (3D) cell culture methods are similar to in vivo tumors in terms of tissue morphology, biology, and gene expression, unlike cells grown in 2D cell cultures. Breast cancer heterogeneity is one of the main drug resistant mechanisms and needs to be overcome in order to increase the efficacy of drug activity in its treatments.

Methods: We performed a unique 3D cell culture and drug efficacy study with trastuzumab emtansine (Kadcyla®, T-DM1) across five breast cancer cell lines (BT-474, SK-BR-3, MDA-MB-361, MDA-MB-175, and MCF-7) that were previously investigated in 2D cell culture. We performed HER2 IHC staining, cell viability experiments, Gene-protein-assay (GPA), and T-DM1 internalization studies.

Results: We obtained significantly different results including higher IC for some of the cell lines. Our GPA showed some significant heterogeneous HER2 gene and protein expression in 3D cultured spheroids or aggregates. The fluorescent images also showed that a longer incubation time is needed for T-DM1 to be internalized effectively into 3D cultured spheroids or aggregates.

Conclusion: Our study demonstrated that the difference of T-DM1 drug activity in 3D spheroids or aggregates might be due to tumor heterogeneity and less efficient internalization of T-DM1 that is not seen using 2D cell culture models. Drug studies using 3D cell culture are expected to provide biologically relevant models for determining drug activity in tumor tissue in future drug response and resistance research.
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http://dx.doi.org/10.1007/s10549-021-06272-xDOI Listing
June 2021

Network Canvas: Key decisions in the design of an interviewer assisted network data collection software suite.

Soc Networks 2021 Jul 24;66:114-124. Epub 2021 Feb 24.

University of Oxford, Oxford Internet Institute, Oxford, UK.

Self-reported social network analysis studies are often complex and burdensome, both during the interview process itself, and when conducting data management following the interview. Through funding obtained from the National Institute on Drug Abuse (NIDA/NIH), our team developed the Network Canvas suite of software - a set of complementary tools that are designed to simplify the collection and storage of complex social network data, with an emphasis on usability and accessibility across platforms and devices, and guided by the practical needs of researchers. The suite consists of three applications: Architect: an application for researchers to design and export interview protocols; Interviewer: a touch-optimized application for loading and administering interview protocols to study participants; and Server: an application for researchers to manage the interview deployment process and export their data for analysis. Together, they enable researchers with minimal technological expertise to access a complete research workflow, by building their own network interview protocols, deploying these protocols widely within a variety of contexts, and immediately attaining the resulting data from a secure central location. In this paper, we outline the critical decisions taken in developing this suite of tools for the network research community. We also describe the work which guides our decision-making, including prior experiences and key discovery events. We focus on key design choices, taken for theoretical, philosophical, and pragmatic reasons, and outline their strengths and limitations.
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http://dx.doi.org/10.1016/j.socnet.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153363PMC
July 2021