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1.
Am J Bioeth ; 21(3): 56-74, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33345745

RESUMO

The COVID-19 pandemic has taken a substantial human, social and economic toll globally, but its impact on Black/African Americans, Latinx, and American Indian/Alaska Native communities in the U.S. is unconscionable. As the U.S. continues to combat the current COVID-19 cycle and prepares for future pandemics, it will be critical to learn from and rectify past and contemporary wrongs. Drawing on experiences in genomic research and intersecting areas in medical ethics, health disparities, and human rights, this article considers three key COVID-19-related issues: research to identify remedies; testing, contact tracing and surveillance; and lingering health needs and disability. It provides a pathway for the future: community engagement to develop culturally-sensitive responses to the myriad genomic/bioethical dilemmas that arise, and the establishment of a Truth and Reconciliation Commission to transition the country from its contemporary state of segregation in healthcare and health outcomes into an equitable and prosperous society for all.


Assuntos
COVID-19 , Racismo , Negro ou Afro-Americano , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
2.
Photochem Photobiol ; 93(1): 343-354, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27935052

RESUMO

Reduced anionic flavin adenine dinucleotide (FADH- ) is the critical cofactor in DNA photolyase (PL) for the repair of cyclobutane pyrimidine dimers (CPD) in UV-damaged DNA. The initial step involves photoinduced electron transfer from *FADH- to the CPD. The adenine (Ade) moiety is nearly stacked with the flavin ring, an unusual conformation compared to other FAD-dependent proteins. The role of this proximity has not been unequivocally elucidated. Some studies suggest that Ade is a radical intermediate, but others conclude that Ade modulates the electron transfer rate constant (kET ) through superexchange. No study has succeeded in removing or modifying this Ade to test these hypotheses. Here, FAD analogs containing either an ethano- or etheno-bridged Ade between the AN1 and AN6 atoms (e-FAD and ε-FAD, respectively) were used to reconstitute apo-PL, giving e-PL and ε-PL respectively. The reconstitution yield of e-PL was very poor, suggesting that the hydrophobicity of the ethano group prevented its uptake, while ε-PL showed 50% reconstitution yield. The substrate binding constants for ε-PL and rPL were identical. ε-PL showed a 15% higher steady-state repair yield compared to FAD-reconstituted photolyase (rPL). The acceleration of repair in ε-PL is discussed in terms of an ε-Ade radical intermediate vs superexchange mechanism.


Assuntos
Adenina/metabolismo , Reparo do DNA , Desoxirribodipirimidina Fotoliase/metabolismo , Flavina-Adenina Dinucleotídeo/metabolismo , Dímeros de Pirimidina/metabolismo , Raios Ultravioleta , Adenina/química , Dimerização , Elétrons , Interações Hidrofóbicas e Hidrofílicas , Conformação Proteica , Especificidade por Substrato
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