Publications by authors named "Jessica B Lee"

7 Publications

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Mapping the dynamic transfer functions of eukaryotic gene regulation.

Cell Syst 2021 11 31;12(11):1079-1093.e6. Epub 2021 Aug 31.

Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27606, USA. Electronic address:

Biological information can be encoded within the dynamics of signaling components, which has been implicated in a broad range of physiological processes including stress response, oncogenesis, and stem cell differentiation. To study the complexity of information transfer across the eukaryotic promoter, we screened 119 dynamic conditions-modulating the pulse frequency, amplitude, and pulse width of light-regulating the binding of an epigenome editor to a fluorescent reporter. This system revealed tunable gene expression and filtering behaviors and provided a quantification of the limit to the amount of information that can be reliably transferred across a single promoter as ∼1.7 bits. Using a library of over 100 orthogonal chromatin regulators, we further determined that chromatin state could be used to tune mutual information and expression levels, as well as completely alter the input-output transfer function of the promoter. This system unlocks the information-rich content of eukaryotic gene regulation.
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http://dx.doi.org/10.1016/j.cels.2021.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602734PMC
November 2021

Synthesis of -2-Substituted Cyclopropylamines from α-Chloroaldehydes.

Org Lett 2019 10 8;21(20):8409-8413. Epub 2019 Oct 8.

Davenport Research Laboratories, Department of Chemistry , University of Toronto , 80 St. George Street , Toronto , Ontario M5S 3H6 , Canada.

Cyclopropylamines are prevalent in pharmaceuticals and agrochemicals. Herein, we report the synthesis of -2-substituted cyclopropylamines in high diastereoselectivity from readily available α-chloroaldehydes. The reaction proceeds via trapping of an electrophilic zinc homoenolate with an amine followed by ring closure to generate the cyclopropylamine. We have also observed that cyclopropylamine /isomerization occurs in the presence of zinc halide salts and that this process can be turned off by the addition of a polar aprotic cosolvent.
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http://dx.doi.org/10.1021/acs.orglett.9b03172DOI Listing
October 2019

Chromatin Immunoprecipitation in Human and Yeast Cells.

Methods Mol Biol 2018 ;1767:257-269

Chemical and Biomolecular Engineering Department, North Carolina State University, Raleigh, NC, USA.

Chromatin immunoprecipitation (ChIP) is an invaluable method to characterize interactions between proteins and genomic DNA, such as the genomic localization of transcription factors and posttranslational modification of histones. DNA and proteins are reversibly and covalently crosslinked using formaldehyde. Then the cells are lysed to release the chromatin. The chromatin is fragmented into smaller sizes either by micrococcal nuclease (MNase) or sonication and then purified from other cellular components. The protein-DNA complexes are enriched by immunoprecipitation (IP) with antibodies that target the epitope of interest. The DNA is released from the proteins by heat and protease treatment, followed by degradation of contaminating RNAs with RNase. The resulting DNA is analyzed using various methods, including PCR, qPCR, or sequencing. This protocol outlines each of these steps for both yeast and human cells.
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http://dx.doi.org/10.1007/978-1-4939-7774-1_14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987192PMC
February 2019

Sequential Functionalizations of Carbohydrates Enabled by Boronic Esters as Switchable Protective/Activating Groups.

J Org Chem 2017 09 17;82(17):8777-8791. Epub 2017 Aug 17.

Department of Chemistry, University of Toronto , Toronto, Ontario M5S 3H6, Canada.

Processes for site-selective, sequential functionalizations of carbohydrate derivatives are described. In these processes, a tricoordinate boronic ester initially serves as a protective group for a sugar-derived 1,2- or 1,3-diol motif, permitting functionalization of free OH groups. In a second step, addition of a Lewis base generates a tetracoordinate adduct, which serves as an activating group, enabling functionalization of one of the boron-bound oxygen atoms by a second electrophile. By combining an initial acylation, alkylation, or glycosylation step with an amine-mediated glycosylation of the boronic ester, a variety of selectively protected di- and trisaccharide derivatives can be accessed in an operationally simple fashion without purification of intermediates. This Lewis base-triggered switching of behavior from "latent" to "active" nucleophile is a unique feature of boronic esters relative to other protective groups for diol moieties in carbohydrate chemistry.
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http://dx.doi.org/10.1021/acs.joc.7b01605DOI Listing
September 2017

Boronic esters as protective groups in carbohydrate chemistry: processes for acylation, silylation and alkylation of glycoside-derived boronates.

Org Biomol Chem 2016 Dec;15(1):132-143

Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.

Procedures for selective installation of acyl, silyl ether and para-methoxybenzyl (PMB) ether groups to glycoside substrates have been developed, employing phenylboronic esters as protected intermediates. The sequence of boronic ester formation, functionalization and deprotection can be accomplished with only a single purification step, and the boronic acid component can be recovered and reused after deprotection. Key advances include the identification of reaction conditions for installation of PMB groups in the presence of boronic esters, and the use of the 'phase switching' protocol developed by Hall and co-workers as an efficient method for boronic ester cleavage. The relatively mild conditions for boronate deprotection are tolerant of several functional groups, including esters, silyl ethers, ketals and thioglycosides.
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http://dx.doi.org/10.1039/c6ob02278bDOI Listing
December 2016

Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors.

Immun Ageing 2011 Aug 16;8. Epub 2011 Aug 16.

Department of Pathology, Johns Hopkins University, 733 N Broadway BRB 632, Baltimore, MD, 21205, USA.

Background: While influenza vaccination results in protective antibodies against primary infections, clearance of infection is primarily mediated through CD8+ T cells. Studying the CD8+ T cell response to influenza epitopes is crucial in understanding the disease associated morbidity and mortality especially in at risk populations such as the elderly. We compared the CD8+ T cell response to immunodominant and subdominant influenza epitopes in HLA-A2+ control, adult donors, aged 21-42, and in geriatric donors, aged 65 and older.

Results: We used a novel artificial Antigen Presenting Cell (aAPC) based stimulation assay to reveal responses that could not be detected by enzyme-linked immunosorbent spot (ELISpot). 14 younger control donors and 12 geriatric donors were enrolled in this study. The mean number of influenza-specific subdominant epitopes per control donor detected by ELISpot was only 1.4 while the mean detected by aAPC assay was 3.3 (p = 0.0096). Using the aAPC assay, 92% of the control donors responded to at least one subdominant epitopes, while 71% of control donors responded to more than one subdominant influenza-specific response. 66% of geriatric donors lacked a subdominant influenza-specific response and 33% of geriatric donors responded to only 1 subdominant epitope. The difference in subdominant response between age groups is statistically significant (p = 0.0003).

Conclusion: Geriatric donors lacked the broad, multi-specific response to subdominant epitopes seen in the control donors. Thus, we conclude that aging leads to a decrease in the subdominant influenza-specific CTL responses which may contribute to the increased morbidity and mortality in older individuals.
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http://dx.doi.org/10.1186/1742-4933-8-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179433PMC
August 2011

Reliability and normative data for the comprehensive assessment of prospective memory (CAPM).

Neuropsychol Rehabil 2007 Dec;17(6):707-22

Division of Occupational Therapy, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia.

The Comprehensive Assessment of Prospective Memory (CAPM) is a questionnaire designed to evaluate frequency of prospective memory (PM) failures in people with brain injury. The aims of this study were to investigate the psychometric properties of the CAPM, including test-retest reliability and internal consistency, and to establish normative data by comparing CAPM scores between groups on the basis of sex, age, and education. Data were collected on 95 people aged 15-60 years living in the community, with no history of brain injury, using the CAPM. The results showed that the test-retest reliability and internal consistency for the CAPM were within acceptable ranges, indicating that the CAPM provides a stable and homogenous measure of an individual's self-report of PM failures. Normative data are presented in two age groups based on the significant difference found between the age groups 15-30 years and 31-60 years. These established norms can be used to describe perceived or observed behaviours indicative of PM failure in patients with brain injury by comparing CAPM ratings from significant others with the norms. The CAPM questionnaire provides researchers or clinicians with a stable and reliable assessment option that specifically focuses on PM for individuals with brain injury.
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http://dx.doi.org/10.1080/09602010600923926DOI Listing
December 2007
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