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1.
Death Stud ; 46(1): 189-199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32048548

RESUMO

Dying, death, and grief are universal human experiences that are impacted by cultural values and beliefs. We provide service providers a context from which to consider the importance of spirituality and religiosity in the grief process and the variances in grief practices that exist within the Black community. This knowledge can serve as a catalyst for developing culturally appropriate interventions for Black people aimed at helping them to more effectively cope with grief and further enabling them to thrive rather than merely survive a sociopolitical US climate that is laden with grief producing experiences.


Assuntos
Pesar , Espiritualidade , Adaptação Psicológica , Humanos , Religião
2.
Death Stud ; 46(4): 891-901, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32609079

RESUMO

To date, 110,000+ people in the United States have died from the COVID-19 pandemic. In this paper, the authors will discuss COVID-19 relative to Black people and their overrepresentation among those who are infected and died from the disease. Their dying, death, and grief experiences are explored through a cultural and spiritual lens. The physical distancing, social isolation, misinformation, and restrictive burials and cremations now elicited by this unprecedented pandemic have had diminished familial, cultural, emotional, and economic impacts on the Black community. Implications for public health and Black peoples' involvement in the political process are also addressed.


Assuntos
COVID-19 , Pesar , Humanos , Pandemias , Isolamento Social , Estados Unidos/epidemiologia
3.
Support Care Cancer ; 28(6): 2949-2957, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31768735

RESUMO

BACKGROUND: Head and neck radiotherapy (H&N RT) patients are at risk for malnutrition following treatment due to dysphagia and alterations in taste quality. This project studied feasibility of a food skills intervention strategy support food preparation, cooking confidence, and individualized dietary choices to support nutritional status in this patient population. METHODS: We piloted a monthly cooking class (called "Eat to Live") from November 2018 to January 2019. Every class included cooking and nutrition domains, organized around a specific meal of the day (i.e., breakfast, lunch, or dinner). Seven participants (4 patients, 3 caregivers) attended at least one class, with four participants (3 patients, 1 caregiver) completing all three classes. Pre- and post-study measures (self-administered questionnaires) assessed changes in cooking behavior, dietary choices, and taste sensation before and after the intervention. RESULTS: Healthful eating scores increased modestly from start to finish of the class (1.5 to 1.7 on a 3-point scale), with averaged patient preference scores for healthy foods increasing incrementally. This took place despite physical taste scores declining across the 3-month study. After completing the class, participants were more likely to select fresh fruits and vegetables, grains, lean cuts of meat, and dairy products. Patients also adopted positive behavioral modifications to their diets, such as eating out at restaurants less often and baking/grilling foods instead of frying. CONCLUSIONS: To our knowledge, this is the first published report on feasibility and patient acceptance of an evidence-based culinary medicine intervention in H&N RT patients. We observed objective improvements in dietary choices and cooking confidence in a small cohort of patient/caregiver dyads. This pilot work justifies follow-on development of a more comprehensive intervention optimized for patient convenience and longitudinal support.


Assuntos
Atitude Frente a Saúde , Culinária , Transtornos de Deglutição/dietoterapia , Transtornos de Deglutição/etiologia , Neoplasias de Cabeça e Pescoço/radioterapia , Educação de Pacientes como Assunto/métodos , Lesões por Radiação/dietoterapia , Adulto , Pesquisa Participativa Baseada na Comunidade , Culinária/métodos , Estudos de Viabilidade , Feminino , Frutas , Neoplasias de Cabeça e Pescoço/dietoterapia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Nutricional/métodos , Fenômenos Fisiológicos da Nutrição , Aceitação pelo Paciente de Cuidados de Saúde , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Lesões por Radiação/etiologia , Inquéritos e Questionários , Verduras
4.
Clin Gerontol ; 43(1): 76-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31671031

RESUMO

Objectives: To assess the preliminary effectiveness of Meaning-Centered Men's Groups (MCMG), a 12-session existentially-oriented, community-based, psychological group intervention designed to enhance psychological resiliency and prevent the onset or exacerbation of suicide ideation among men who are concerned about or struggling with the transition to retirement.Methods: We recruited 30 men (n= 10 per group), 55 years and older (M= 63.7, SD= 4.1) from community settings to participate in a course of MCMG to be delivered in a community center. Participants completed eligibility, pre-, mid-, and post-group assessments of suicide ideation and psychological risk and resiliency factors.Results: Participants experienced significant increases in attitudinal sources of meaning in life, psychological well-being, life satisfaction, retirement satisfaction, and general health, and decreases in depression, hopelessness, loneliness, and suicide ideation.Conclusions: Preliminary findings suggest that MCMG is a novel men's mental health intervention that may help to enhance psychological well-being and potentially reduce the severity or prevent the onset of symptoms of depression, hopelessness, and suicide ideation.Clinical Implications: Upstream psychological interventions may serve an important role in mental health promotion and suicide prevention with potentially vulnerable individuals facing challenging life transitions.


Assuntos
Resiliência Psicológica , Aposentadoria/psicologia , Grupos de Autoajuda , Ideação Suicida , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação Pessoal , Fatores de Risco , Autoimagem
6.
J Relig Health ; 57(3): 1095-1107, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29417396

RESUMO

This article explores the role the Black Church could play in facilitating spiritually sensitive, culturally relevant and gender-specific services to address the mental health and well-being of Black males. The help-seeking behaviors of Black men are examined as the authors offer two theories: the body, mind, spirit, environment, social, transcendent, and health, illness, men, and masculinities that may assist the Black Church in functioning as an effective support networks for healthy Black male mental health. Next, the authors discuss implications for practice, research, and education, and lastly, eight recommendations for Black Church leadership, social workers, and mental health professionals are also discussed.


Assuntos
Negro ou Afro-Americano/psicologia , Cristianismo , Comportamento de Busca de Ajuda , Masculinidade , Saúde Mental/etnologia , Religião e Psicologia , Clero , Humanos , Masculino , Estados Unidos
7.
Alcohol Clin Exp Res ; 41(3): 626-636, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28055132

RESUMO

BACKGROUND: The Monkey Alcohol Tissue Research Resource (MATRR) is a repository and analytics platform for detailed data derived from well-documented nonhuman primate (NHP) alcohol self-administration studies. This macaque model has demonstrated categorical drinking norms reflective of human drinking populations, resulting in consumption pattern classifications of very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD) individuals. Here, we expand on previous findings that suggest ethanol drinking patterns during initial drinking to intoxication can reliably predict future drinking category assignment. METHODS: The classification strategy uses a machine-learning approach to examine an extensive set of daily drinking attributes during 90 sessions of induction across 7 cohorts of 5 to 8 monkeys for a total of 50 animals. A Random Forest classifier is employed to accurately predict categorical drinking after 12 months of self-administration. RESULTS: Predictive outcome accuracy is approximately 78% when classes are aggregated into 2 groups, "LD and BD" and "HD and VHD." A subsequent 2-step classification model distinguishes individual LD and BD categories with 90% accuracy and between HD and VHD categories with 95% accuracy. Average 4-category classification accuracy is 74%, and provides putative distinguishing behavioral characteristics between groupings. CONCLUSIONS: We demonstrate that data derived from the induction phase of this ethanol self-administration protocol have significant predictive power for future ethanol consumption patterns. Importantly, numerous predictive factors are longitudinal, measuring the change of drinking patterns through 3 stages of induction. Factors during induction that predict future heavy drinkers include being younger at the time of first intoxication and developing a shorter latency to first ethanol drink. Overall, this analysis identifies predictive characteristics in future very heavy drinkers that optimize intoxication, such as having increasingly fewer bouts with more drinks. This analysis also identifies characteristic avoidance of intoxicating topographies in future low drinkers, such as increasing number of bouts and waiting longer before the first ethanol drink.


Assuntos
Intoxicação Alcoólica/classificação , Intoxicação Alcoólica/psicologia , Etanol/administração & dosagem , Aprendizado de Máquina , Motivação/efeitos dos fármacos , Intoxicação Alcoólica/etiologia , Animais , Etanol/efeitos adversos , Feminino , Previsões , Haplorrinos , Macaca mulatta , Masculino , Motivação/fisiologia , Autoadministração
8.
Rapid Commun Mass Spectrom ; 31(9): 762-770, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28231608

RESUMO

RATIONALE: The lipid peroxidation product malondialdehyde forms M1 dG adducts with guanine bases in genomic DNA. The analysis of these adducts is important as a biomarker of lipid peroxidation, oxidative stress and inflammation which may be linked to disease risk or exposure to a range of chemicals. METHODS: Genomic DNA samples were subjected to acid hydrolysis to release the adducts in the base form (M1 G) alongside the other purines. A liquid chromatography/mass spectrometry method was optimised for the quantitation of the M1 G adducts in genomic DNA samples using product ion and multiple reaction monitoring (MRM) scans. RESULTS: Product ion scans revealed four product ions from the precursor ion; m/z 188 â†’ 160, 133, 106 and 79. The two smallest ions have not been observed previously and optimisation of the method revealed that these gave better sensitivity (LOQ m/z 79: 162 adducts per 107 nucleotides; m/z 106: 147 adducts per 107 nucleotides) than the other two ions. An MRM method gave similar sensitivity but the two smallest product ions gave better accuracy (94-95%). Genomic DNA treated with malondialdehyde showed a linear dose-response relationship. CONCLUSIONS: A fast reliable sample preparation method was used to release adducts in the base form rather than the nucleoside. The methods were optimised to selectively analyse the adducts in the presence of other DNA bases without the need for further sample clean-up. Analysis of genomic DNA gave results consistent with previous work and was applied to new samples. Thus, the method is suitable for the analysis of M1 (d)G adducts in biological samples. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Cromatografia Líquida/métodos , Adutos de DNA/química , Guanina/análise , Malondialdeído/análise , Espectrometria de Massas em Tandem/métodos , Animais , Bovinos , DNA/química , Adutos de DNA/análise , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
9.
J Gerontol Nurs ; 43(5): 12-17, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28448676

RESUMO

Early-onset dementia (EOD) occurs before age 65. The current study examined the lived experience from the point of view of four adults younger than 65 with dementia, particularly how they perceive their personhood. Using interpretative phenomenological analysis as the research approach, findings revealed that the EOD experience can be incorporated into six themes: (a) A Personal Journey, (b) Navigating the System, (c) The Stigma of Dementia, (d) Connecting to the World, (e) A Story Worth Telling, and (f) I'm Still Here. Participants' stories, as presented via these six thematic threads, reveal that individuals with EOD can have a strong sense of personhood. Findings are discussed and situated within the current EOD body of knowledge, and new knowledge is presented. Implications for practice and recommendations for future research are discussed. [Journal of Gerontological Nursing, 43 (5), 12-17.].


Assuntos
Doença de Alzheimer/enfermagem , Doença de Alzheimer/psicologia , Relações Enfermeiro-Paciente , Recursos Humanos de Enfermagem Hospitalar/psicologia , Pessoalidade , Adulto , Idade de Início , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Anal Chem ; 88(15): 7436-46, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27362284

RESUMO

Covalent binding of endo- or exogenous chemicals to DNA results in the formation of DNA adducts which are reflective of exposure of the human body to DNA-damaging molecules and their metabolic pathways. The study of DNA adduct types and levels in human tissue therefore offers an interesting tool in several fields of research, including toxicology and cancer epidemiology. Over the years, a range of techniques and methods have been developed to study the formation of endo- and exogenous DNA adducts. However, for the simultaneous detection, identification and quantification of both known and unknown DNA adducts, mass spectrometry (MS) is deemed to be the most promising technique. In this perspective, we focus on the analysis of multiple DNA adducts within a sample with the emphasis on untargeted analysis. The advantageous use of MS methodologies for DNA adductome mapping is discussed comprehensively with relevant field examples. In addition, several aspects of study design, sample pretreatment, and analysis are addressed as these factors significantly affect the reliability of DNA adductomics studies.


Assuntos
Adutos de DNA/análise , Espectrometria de Massas/métodos , Mutagênicos , Adutos de DNA/química , Humanos , Mutagênicos/metabolismo
11.
J Infect Dis ; 212(7): 1032-41, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25791116

RESUMO

BACKGROUND: Dengue viruses (DENVs) infect >300 million people annually, causing 96 million cases of dengue disease and 22 000 deaths [1]. A safe vaccine that protects against DENV disease is a global health priority [2]. METHODS: We enrolled 72 flavivirus-naive healthy adults in a phase 1 double-blinded, randomized, placebo-controlled dose-escalation trial (low and high dose) of a live attenuated recombinant tetravalent dengue vaccine candidate (TDV) given in 2 doses 90 days apart. Volunteers were followed for safety, vaccine component viremia, and development of neutralizing antibodies to the 4 DENV serotypes. RESULTS: The majority of adverse events were mild, with no vaccine-related serious adverse events. Vaccinees reported injection site pain (52% vs 17%) and erythema (73% vs 25%) more frequently than placebo recipients. Low levels of TDV-serotype 2 (TDV-2), TDV-3, and TDV-4 viremia were observed after the first but not second administration of vaccine. Overall seroconversion rates and geometric mean neutralization titers after 2 doses were 84.2% and 54.1, respectively, for DENV serotype 1 (DENV-1); 92.1% and 292.8, respectively, for DENV-2; 86.8% and 32.3, respectively, for DENV-3; and 71.1% and 15.0, respectively, for DENV-4. More than 90.0% of high-dose recipients had trivalent or broader responses. CONCLUSIONS: TDV was generally well tolerated, induced trivalent or broader neutralizing antibodies to DENV in most flavivirus-naive vaccinees, and is undergoing further development. CLINICAL TRIALS REGISTRATION: NCT01110551.


Assuntos
Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Vacinação , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Dengue/imunologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança , Vacinas Atenuadas/imunologia , Viremia , Adulto Jovem
12.
Rapid Commun Mass Spectrom ; 27(21): 2493-503, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24097406

RESUMO

RATIONALE: The consumption of red meat is known to enhance the endogenous formation of N-nitroso compounds (NOCs), which are potent carcinogens. DNA damage related to NOCs, and hence red meat, has been detected in colorectal cells and in blood. We proposed to extend previous studies to a non-invasive approach for the detection of O(6)-carboxymethylguanine (O(6)CMG) and O(6)-carboxymethyl-2'-deoxyguanosine (O(6)CMdG) in urine in relation to red meat intake using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The presence of the adduct in urine samples either as the free base or as 2'-deoxynucleoside could help in determining the repair mechanism involved when such lesions are produced. A non-invasive assessment of DNA adducts could also allow for large-scale analyses in the population and cancer prevention dietary strategies. METHODS: An LC/MS/MS method for the quantitation of O(6)CMG and O(6)CMdG was developed. Urine samples collected from healthy volunteers on red meat and vegetarian diets were analysed either by direct injection or after purification by solid-phase extraction (SPE). A separate LC/MS/MS method for O(6)-methylguanine (O(6)MeG) and O(6)-methyl-2'-deoxyguanosine (O(6)MedG), which are possible hydrolysis products forming during the sample pre-treatment, was also developed. RESULTS: The developed LC/MS/MS method allowed the simultaneous measurement of O(6)CMG and O(6)CMdG. The limits of detection (LODs) were 0.38 ng/mL for O(6)CMG and 0.18 ng/mL for O(6)CMdG. The direct injection analysis of the clinical samples showed low sensitivity due to high background signal that was improved by SPE purification. However, the concentrations of the adducts in clinical samples were still found to be below the LOD. CONCLUSIONS: Novel, reproducible, and accurate LC/MS/MS methods were developed for the determination of the urinary content of O(6)CMG and O(6)CMdG, and of the possible formation of O(6)MeG and O(6)MedG by decarboxylation. Clinical samples from volunteers on different diets were analysed. Further studies are required to discover a link between the presence of these biomarkers in urine and red meat consumption.


Assuntos
Desoxiguanosina/análogos & derivados , Guanina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Cromatografia Líquida/métodos , Neoplasias Colorretais/urina , Estudos Cross-Over , Dano ao DNA , Desoxiguanosina/urina , Dieta , Dieta Vegetariana , Guanina/urina , Humanos , Limite de Detecção , Carne/análise
13.
Alcohol ; 113: 41-48, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37516372

RESUMO

The Non-Human Primate (NHP) model for the study of Alcohol Use Disorders (AUD) as developed in our laboratories is critical to our understanding of the pathophysiology of voluntary, chronic, ethanol consumption. Previous work in this model established categories of ethanol consumption that parallel reported categories of human consumption across a spectrum spanning low drinking, binge drinking, heavy drinking, and very heavy drinking, albeit at generally higher daily intakes across categories than documented in people. Original categories assigned to ethanol consumption patterns were established using a limited cohort of rhesus macaques. This study revisits the validity of categorical drinking using an additional 28 monkeys. In addition to finding categorical representations consistent with the original 2014 report, our findings demonstrate that drinking categories remain stable across the observed 12 months of nearly consistent access to ethanol (22 h/day), termed "open access". Animals occupying the two ends of the spectrum, "low" and "very heavy" drinkers, exhibit the largest stability. The findings also indicate a slight escalatory drift over time, with very heavy drinking animals experiencing fatigue near the end of open access.


Assuntos
Alcoolismo , Humanos , Animais , Consumo de Bebidas Alcoólicas , Macaca mulatta , Etanol , Autoadministração
14.
J Gerontol Nurs ; 38(10): 28-36, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22998092

RESUMO

The purpose of this hermeneutic photography study was to explore how older adults lived hope in their day-to-day lives. A purposive sample of 12 older adults 65 and older was asked to photograph how they experienced and lived hope in their everyday lives. Participants were asked to select four to five photographs that best reflected their "lived hope," and these photographs were used as prompts for subsequent interviews. Data were analyzed using thematic analysis of the interviews and photographs, which revealed that these study participants lived a philosophy of hope in which hope provided a kind of landscape through which these older adults lived and made sense of their life experiences. Implications for helping nurses foster and make hope more visible for their older clients are suggested.


Assuntos
Envelhecimento/psicologia , Fotografação , Idoso , Feminino , Humanos
15.
J Appl Gerontol ; 41(8): 1851-1859, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35543172

RESUMO

This study explores coping strategies and barriers to dementia care experienced by African American dementia caregivers in Kentucky. Utilizing a convergent mixed-method design integrating focus group and survey data on African American dementia caregivers recruited through churches in Kentucky (N = 28), we elucidate three coping strategies: love-based coping, religion-based coping, and family support. Results from survey data supported these themes, with over 90% of participants reporting that they provide care to give back to family members and for religious reasons. However, over half of the caregivers' reported strain due to three barriers identified by focus group data: time constraints, low support, and the high cost of formal care. This exploratory study highlights the importance of intervention tactics for African American dementia caregivers that focus not only on individual and family support but also community-based outreach and support.


Assuntos
Cuidadores , Demência , Adaptação Psicológica , Negro ou Afro-Americano , Demência/terapia , Família , Humanos , Kentucky
16.
Math Biosci ; 345: 108778, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35033503

RESUMO

We present a blood ethanol concentration compartment model which utilizes an animal's ethanol intake, food intake, and weight to predict the animal's blood ethanol concentration at any given time. By incorporating the food digestion process into the model we can predict blood ethanol concentration levels over time for a variety of drinking and eating scenarios. The model is calibrated and validated using data from cohorts of male monkeys, and is able to capture blood ethanol concentration kinetics of the monkeys from a variety of drinking behavior classifications.


Assuntos
Consumo de Bebidas Alcoólicas , Concentração Alcoólica no Sangue , Animais , Etanol , Alimentos , Masculino
17.
Biol Lett ; 7(2): 253-6, 2011 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-21047849

RESUMO

Parthenogenesis in vertebrates is considered an evolutionary novelty. In snakes, all of which exhibit genetic sex determination with ZZ : ZW sex chromosomes, this rare form of asexual reproduction has failed to yield viable female WW offspring. Only through complex experimental manipulations have WW females been produced, and only in fish and amphibians. Through microsatellite DNA fingerprinting, we provide the first evidence of facultative parthenogenesis in a Boa constrictor, identifying multiple, viable, non-experimentally induced females for the first time in any vertebrate lineage. Although the elevated homozygosity of the offspring in relation to the mother suggests that the mechanism responsible may be terminal fusion automixis, no males were produced, potentially indicating maternal sex chromosome hemizygosity (WO). These findings provide the first evidence of parthenogenesis in the family Boidae (Boas), and suggest that WW females may be more common within basal reptilian lineages than previously assumed.


Assuntos
Boidae/fisiologia , Partenogênese , Animais , Boidae/genética , Impressões Digitais de DNA , Feminino , Masculino , Repetições de Microssatélites , Processos de Determinação Sexual
18.
J Afr Am Stud (New Brunsw) ; 25(3): 383-401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34230821

RESUMO

This article examines the history of racism in the American presidency and the implications that it has had for Black residents of this country. The paper begins with a discussion of President Trump's racist rhetoric towards Blacks but notes that a history of racism is woven into the US presidency. We employ critical race theory as a theoretical framework to demonstrate why institutional racism has always been pervasive in the American presidency. Using a case study analysis, the authors conduct a comparative study of the history of racism of American presidents with the presidency of former president Donald J. Trump. The authors conclude that for most of the nation's history, racism and indifference to African Americans permeated the US presidency. It has only been since the advent of the second half of the twentieth century, for the most part, that there have been meaningful efforts by US presidents to address the concerns of African Americans.

19.
Biomolecules ; 11(8)2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34439870

RESUMO

Chalcones belong to the flavonoid class of phenolic compounds. They form one of the largest groups of bioactive natural products. The potential anticancer, anti-inflammatory, antimicrobial, antioxidant, and antiparasitic properties of naturally occurring chalcones, and their unique chemical structural features inspired the synthesis of numerous chalcone derivatives. In fact, structural features of chalcones are easy to construct from simple aromatic compounds, and it is convenient to perform structural modifications to generate functionalized chalcone derivatives. Many of these synthetic analogs were shown to possess similar bioactivities as their natural counterparts, but often with an enhanced potency and reduced toxicity. This review article aims to demonstrate how bioinspired synthesis of chalcone derivatives can potentially introduce a new chemical space for exploitation for new drug discovery, justifying the title of this article. However, the focus remains on critical appraisal of synthesized chalcones and their derivatives for their bioactivities, linking to their interactions at the biomolecular level where appropriate, and revealing their possible mechanisms of action.


Assuntos
Antibacterianos , Anti-Inflamatórios , Antineoplásicos , Antioxidantes , Produtos Biológicos , Chalconas , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular , Chalconas/química , Chalconas/farmacologia , Descoberta de Drogas , Humanos , Relação Estrutura-Atividade
20.
J Virol ; 83(18): 9502-11, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19570857

RESUMO

The Ty1 retrotransposon of Saccharomyces cerevisiae is comprised of structural and enzymatic proteins that are functionally similar to those of retroviruses. Despite overall sequence divergence, certain motifs are highly conserved. We have examined the Ty1 integrase (IN) zinc binding domain by mutating the definitive histidine and cysteine residues and thirteen residues in the intervening (X(32)) sequence between IN-H22 and IN-C55. Mutation of the zinc-coordinating histidine or cysteine residues reduced transposition by more than 4,000-fold and led to IN and reverse transcriptase (RT) instability as well as inefficient proteolytic processing. Alanine substitution of the hydrophobic residues I28, L32, I37 and V45 in the X(32) region reduced transposition 85- to 688-fold. Three of these residues, L32, I37, and V45, are highly conserved among retroviruses, although their effects on integration or viral infectivity have not been characterized. In contrast to the HHCC mutants, all the X(32) mutants exhibited stable IN and RT, and protein processing and cDNA production were unaffected. However, glutathione S-transferase pulldowns and intragenic complementation analysis of selected transposition-defective X(32) mutants revealed decreased IN-IN interactions. Furthermore, virus-like particles with in-L32A and in-V45A mutations did not exhibit substantial levels of concerted integration products in vitro. Our results suggest that the histidine/cysteine residues are important for steps in transposition prior to integration, while the hydrophobic residues function in IN multimerization.


Assuntos
Motivos de Aminoácidos , Integrases/fisiologia , Retroelementos , Sítios de Ligação , Sequência Conservada , Cisteína , Histidina , Integrases/química , Integrases/genética , Mutação , Multimerização Proteica , Retroviridae , Saccharomyces cerevisiae , Integração Viral , Zinco/metabolismo
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