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1.
Brief Bioinform ; 23(3)2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35229157

RESUMEN

SARS-CoV-2 is a novel positive-sense single-stranded RNA virus from the Coronaviridae family (genus Betacoronavirus), which has been established as causing the COVID-19 pandemic. The genome of SARS-CoV-2 is one of the largest among known RNA viruses, comprising of at least 26 known protein-coding loci. Studies thus far have outlined the coding capacity of the positive-sense strand of the SARS-CoV-2 genome, which can be used directly for protein translation. However, it has been recently shown that transcribed negative-sense viral RNA intermediates that arise during viral genome replication from positive-sense viruses can also code for proteins. No studies have yet explored the potential for negative-sense SARS-CoV-2 RNA intermediates to contain protein-coding loci. Thus, using sequence and structure-based bioinformatics methodologies, we have investigated the presence and validity of putative negative-sense ORFs (nsORFs) in the SARS-CoV-2 genome. Nine nsORFs were discovered to contain strong eukaryotic translation initiation signals and high codon adaptability scores, and several of the nsORFs were predicted to interact with RNA-binding proteins. Evolutionary conservation analyses indicated that some of the nsORFs are deeply conserved among related coronaviruses. Three-dimensional protein modeling revealed the presence of higher order folding among all putative SARS-CoV-2 nsORFs, and subsequent structural mimicry analyses suggest similarity of the nsORFs to DNA/RNA-binding proteins and proteins involved in immune signaling pathways. Altogether, these results suggest the potential existence of still undescribed SARS-CoV-2 proteins, which may play an important role in the viral lifecycle and COVID-19 pathogenesis.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/genética , Genoma Viral , Humanos , Pandemias , ARN Viral/química , ARN Viral/genética , Proteínas de Unión al ARN/genética , SARS-CoV-2/genética
2.
Biochem Biophys Res Commun ; 666: 61-67, 2023 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-37178506

RESUMEN

The RGD motif on the SARS-CoV-2 spike protein has been suggested to interact with RGD-binding integrins αVß3 and α5ß1 to enhance viral cell entry and alter downstream signaling cascades. The D405N mutation on the Omicron subvariant spike proteins, resulting in an RGN motif, has recently been shown to inhibit binding to integrin αVß3. Deamidation of asparagines in protein ligand RGN motifs has been demonstrated to generate RGD and RGisoD motifs that permit binding to RGD-binding integrins. Two asparagines, N481 and N501, on the Wild-type spike receptor-binding domain have been previously shown to have deamidation half-lives of 16.5 and 123 days, respectively, which may occur during the viral life cycle. Deamidation of Omicron subvariant N405 may recover the ability to interact with RGD-binding integrins. Thus, herein, all-atom molecular dynamics simulations of the Wild-type and Omicron subvariant spike protein receptor-binding domains were conducted to investigate the potential for asparagines, the Omicron subvariant N405 in particular, to assume the optimized geometry for deamidation to occur. In summary, the Omicron subvariant N405 was primarily found to be stabilized in a state unfavourable for deamidation after hydrogen bonding with downstream E406. Nevertheless, a small number of RGD or RGisoD motifs on the Omicron subvariant spike proteins may restore the ability to interact with RGD-binding integrins. The simulations also provided structural clarification regarding the deamidation rates of Wild-type N481 and N501 and highlighted the utility of tertiary structure dynamics information in predicting asparagine deamidation. Further work is needed to characterize the effects of deamidation on spike-integrin interactions.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/genética , Asparagina , Integrina alfaVbeta3
3.
Brief Bioinform ; 22(2): 769-780, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33416848

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly growing infectious disease, widely spread with high mortality rates. Since the release of the SARS-CoV-2 genome sequence in March 2020, there has been an international focus on developing target-based drug discovery, which also requires knowledge of the 3D structure of the proteome. Where there are no experimentally solved structures, our group has created 3D models with coverage of 97.5% and characterized them using state-of-the-art computational approaches. Models of protomers and oligomers, together with predictions of substrate and allosteric binding sites, protein-ligand docking, SARS-CoV-2 protein interactions with human proteins, impacts of mutations, and mapped solved experimental structures are freely available for download. These are implemented in SARS CoV-2 3D, a comprehensive and user-friendly database, available at https://sars3d.com/. This provides essential information for drug discovery, both to evaluate targets and design new potential therapeutics.


Asunto(s)
Antivirales/farmacología , COVID-19/virología , Bases de Datos de Proteínas , Sistemas de Liberación de Medicamentos , Proteoma , SARS-CoV-2/efectos de los fármacos , Humanos , SARS-CoV-2/aislamiento & purificación
4.
J Med Virol ; 94(9): 4181-4192, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35575289

RESUMEN

Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directed kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. Further experimental work is needed to confirm the effect of mutations and posttranslational modifications on SARS-CoV-2 spike protein cleavage sites.


Asunto(s)
SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Glicosilación , Mutación , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética
5.
Int J Mol Sci ; 23(2)2022 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-35054954

RESUMEN

Z-DNA and Z-RNA are functionally important left-handed structures of nucleic acids, which play a significant role in several molecular and biological processes including DNA replication, gene expression regulation and viral nucleic acid sensing. Most proteins that have been proven to interact with Z-DNA/Z-RNA contain the so-called Zα domain, which is structurally well conserved. To date, only eight proteins with Zα domain have been described within a few organisms (including human, mouse, Danio rerio, Trypanosoma brucei and some viruses). Therefore, this paper aimed to search for new Z-DNA/Z-RNA binding proteins in the complete PDB structures database and from the AlphaFold2 protein models. A structure-based similarity search found 14 proteins with highly similar Zα domain structure in experimentally-defined proteins and 185 proteins with a putative Zα domain using the AlphaFold2 models. Structure-based alignment and molecular docking confirmed high functional conservation of amino acids involved in Z-DNA/Z-RNA, suggesting that Z-DNA/Z-RNA recognition may play an important role in a variety of cellular processes.


Asunto(s)
ADN de Forma Z/química , Proteínas de Unión al ADN/química , Modelos Moleculares , Dominios y Motivos de Interacción de Proteínas , Proteínas de Unión al ARN/química , ARN/química , Secuencia de Aminoácidos , Sitios de Unión , ADN de Forma Z/metabolismo , Proteínas de Unión al ADN/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Conformación de Ácido Nucleico , Unión Proteica , Conformación Proteica , ARN/metabolismo , Proteínas de Unión al ARN/metabolismo , Relación Estructura-Actividad
6.
J Med Internet Res ; 23(8): e30612, 2021 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-34182460

RESUMEN

BACKGROUND: COVID-19 preventive perceptions and behaviors, especially among US millennials, are an important means by which the pandemic can be slowed and negative health outcomes can be averted. OBJECTIVE: This manuscript aims to advance knowledge on COVID-19 preventive perceptions and behaviors and their main predictors, including digital health information-seeking behavior (HISB), political party identification, and COVID-19 testing status. METHODS: Two cross-sectional online surveys of US millennials were conducted from April 10 to 14, 2020 (N=274) (ie, Study 1), and from April 27 to May 7, 2020 (N=1037) (ie, Study 2). In the regression models, dependent variables included preventive behaviors (eg, wearing a face mask and social distancing) as well as four preventive perceptions: severity (ie, a person's conception of the seriousness of COVID-19), susceptibility (ie, a person's conception of the likelihood of being infected with COVID-19), self-efficacy (ie, a person's perception that he or she can wear a face mask and perform social distancing to prevent COVID-19 infection), and response efficacy (ie, a person's perception of whether wearing a face mask and social distancing can prevent COVID-19 infection). Key independent variables included digital HISB for self, digital HISB for another person, political party identification, and COVID-19 testing status. RESULTS: Millennials reported lower levels of perceived susceptibility than the other three preventive perceptions (ie, severity, self-efficacy, and response efficacy), as well as fairly high levels of preventive behaviors. Unlike HISB for another person, digital HISB for self was positively associated with preventive perceptions and behaviors. In Study 1, respondents with higher levels of digital HISB for self had significantly higher perceptions of severity (ß=.22, P<.001), self-efficacy (ß=.15, P=.02), and response efficacy (ß=.25, P<.001) as well as, at nearing significance, higher perceptions of susceptibility (ß=.11, P=.07). In Study 2, respondents with higher levels of digital HISB for self had significantly higher perceptions of severity (ß=.25, P<.001), susceptibility (ß=.14, P<.001), and preventive behaviors (ß=.24, P<.001). Preventive behaviors did not vary significantly according to political party identification, but preventive perceptions did. In Study 1, respondents who identified as being more Republican had significantly lower perceptions of self-efficacy (ß=-.14, P=.02) and response efficacy (ß=-.13, P=.03) and, at nearing significance, lower perceptions of severity (ß=-.10, P=.08) and susceptibility (ß=-.12, P=.06). In Study 2, respondents who identified as being more Republican had significantly lower perceptions of severity (ß=-.08, P=.009). There were mixed effects of COVID-19 testing status on preventive perceptions, with respondents who had tested positive for COVID-19 having significantly higher perceptions of susceptibility in Study 1 (ß=.17, P=.006) and significantly lower perceptions of severity in Study 2 (ß=-.012, P<.001). CONCLUSIONS: As the largest and most digitally savvy generation, US millennials saw COVID-19 as a severe threat, but one that they were less susceptible to. For millennials, digital HISB for self, but not for another person, was critical to the development of preventive perceptions and behaviors.


Asunto(s)
COVID-19/prevención & control , Conductas Relacionadas con la Salud , Internet , Percepción , Encuestas y Cuestionarios , Adulto , Prueba de COVID-19 , Estudios Transversales , Femenino , Humanos , Masculino , Máscaras , Distanciamiento Físico , Política , SARS-CoV-2
7.
J Med Internet Res ; 22(11): e21652, 2020 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-33252348

RESUMEN

BACKGROUND: Although binge drinking peaks at age 21 to 25 years, there is limited research on the effects of serious games in this population, as well as on the process by which playing serious games impacts alcohol-related outcomes. Designed with both health behavioral theory and game theory, One Shot is an online serious game that aims to prevent binge drinking. OBJECTIVE: This study utilized a conceptual model for serious video game processes. Using One Shot, the model assessed the following process stages: (1) Alcohol Use Disorders Identification Test-Concise (AUDIT-C); (2) in-game factors of game time and risky alcohol decisions; (3) game enjoyment; and (4) postgame outcomes of intention to drink less and drinking refusal self-efficacy. METHODS: In a one-group pretest-posttest quasi-experimental design, a sample (N=550) of young adults (age 21-25 years) who reported recent binge drinking played the One Shot game. Intention to drink less and drinking refusal self-efficacy were measured at pregame and postgame, with their effects lagged in statistical analysis. Participants were presented with various scenarios in the game that pertained to risky alcohol decisions, which, along with game time, were unobtrusively recorded by the server. A structural equation model (SEM) was used to test the conceptual model, with assessments made to determine if enjoyment mediated the effects of game time and risky alcohol decisions on the 2 postgame alcohol-related outcomes. RESULTS: A well-fitting SEM demonstrated support for the multistep model, with AUDIT-C predicting risky alcohol decisions (ß=.30). Risky alcohol decisions (ß=-.22) and game time (ß=.18) predicted enjoyment, which, in turn, predicted intention to drink less (ß=.21) and drinking refusal self-efficacy (ß=.16). Enjoyment significantly (P<.001) mediated the effects of game time and risky alcohol decision on intention to drink less and drinking refusal self-efficacy. CONCLUSIONS: The results support a conceptual model in which staggered individual and in-game factors influence alcohol-related outcomes. Enjoyment is important for participants' intentions to drink less and beliefs that they can refuse alcohol.


Asunto(s)
Consumo Excesivo de Bebidas Alcohólicas/prevención & control , Juegos de Video/psicología , Adulto , Emociones , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados no Aleatorios como Asunto , Placer , Adulto Joven
8.
J Cancer Educ ; 32(1): 183-189, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-26462478

RESUMEN

This paper evaluates the effectiveness of community health workers/promotores (CHWs) in promoting cancer preventive behaviors in the 2011-2013 Education to Promote Improved Cancer Outcomes (ÉPICO) project. The ÉPICO project utilized CHWs to disseminate cancer education to predominately Spanish-speaking Hispanics living in colonias in the Lower Rio Grande Valley of Texas. The CHWs received training to become Texas-certified CHW instructors and specialized training in message tailoring, and they delivered more than 5000 units of resident education on cancer prevention/detection, treatment, and survivorship for breast, cervical, and colorectal cancer. Using panel data to examine overtime changes in cancer knowledge among Lower Rio Grande Valley residents, the evaluation found significant changes from baseline to both times 1 and 2. Additional individual-level analysis indicated that the increase in resident cancer knowledge was predicted by residents' perceptions of CHW credibility and intention to change their lifestyles. Multilevel analysis also showed that the increase in cancer prevention knowledge among residents was predicted by attributes of the CHWs who taught them. In particular, CHWs with higher education levels had the most impact on residents' increased knowledge over time. Unexpectedly, CHWs with more years of experience were less effective teachers than their early-career counterparts.


Asunto(s)
Agentes Comunitarios de Salud/estadística & datos numéricos , Educación en Salud/métodos , Hispánicos o Latinos/estadística & datos numéricos , Tamizaje Masivo , Neoplasias/prevención & control , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/terapia , Encuestas y Cuestionarios , Texas
9.
J Health Commun ; 21(7): 755-64, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27232655

RESUMEN

The China Tobacco Control Media Campaign on Sina Weibo is novel in the context of smoking prevention and cessation in China and has not to date been evaluated. This study draws on health behavior theories and dialogic theory in public relations to analyze microblog campaign postings and their relationships with the outcome of online audience engagement. Microblog postings from May 2011 to January 2015 were content analyzed, showing that the most common persuasive content characteristic was perceived risk, followed by subjective norms and self-efficacy. Perceived risk and self-efficacy postings positively influenced online audience engagement, whereas subjective norm postings was a nonsignificant predictor. Postings were more likely to share information than aim to interact with audience members. However, both information sharing and audience interaction postings were positive predictors of online audience engagement. There was also evidence of main and interactive effects of message originality on online audience engagement. The current study has, to the best of our knowledge, broken new ground in 2 regards: (a) using health behavior theories as a basis for analyzing the content of an anti-smoking social media campaign and (b) examining the content of an anti-smoking media campaign of any type in China.


Asunto(s)
Promoción de la Salud/métodos , Prevención del Hábito de Fumar , Medios de Comunicación Sociales/estadística & datos numéricos , China , Humanos , Comunicación Persuasiva , Teoría Psicológica , Medición de Riesgo , Autoeficacia , Fumar/psicología , Normas Sociales
10.
J Health Commun ; 21(4): 415-23, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26855176

RESUMEN

Rapid population growth in Pakistan poses major risks, including those pertinent to public health. In the context of family planning in Pakistan, the current study evaluates the Touch condom media campaign and its effects on condom-related awareness, attitudes, behavioral intention, and behavior. This evaluation relies on 3 waves of panel survey data from men married to women ages 15-49 living in urban and rural areas in Pakistan (N = 1,012): Wave 1 was March 15 to April 7, 2009; Wave 2 was August 10 to August 24, 2009; and Wave 3 was May 1 to June 13, 2010. Analysis of variance provided evidence of improvements in 10 of 11 condom-related outcomes from Wave 1 to Wave 2 and Wave 3. In addition, there was no evidence of outcome decay 1 year after the conclusion of campaign advertising dissemination. To help compensate for violating the assumption of random assignment, propensity score modeling offered evidence of the beneficial effects of confirmed Touch ad recall on each of the 11 outcomes in at least 1 of 3 time-lagged scenarios. By using these different time-lagged scenarios (i.e., from Wave 1 to Wave 2, from Wave 1 to Wave 3, and from Wave 2 to Wave 3), propensity score modeling permitted insights into how the campaign had time-variant effects on the different types of condom-related outcomes, including carryover effects of the media campaign.


Asunto(s)
Publicidad , Condones/estadística & datos numéricos , Servicios de Planificación Familiar , Promoción de la Salud/métodos , Medios de Comunicación de Masas , Adolescente , Adulto , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Modelos Estadísticos , Pakistán , Evaluación de Programas y Proyectos de Salud , Puntaje de Propensión , Encuestas y Cuestionarios , Adulto Joven
11.
J Health Commun ; 21(7): 773-81, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27337154

RESUMEN

Although prior research has tested the nomological validity of media campaign exposure, including the related comparative validity of some measures, it has not well studied predictive validity or made extensions to other types of media campaign exposure. To help build on research in this area, the current study tested the nomological and predictive validity of 5 ad recall and recognition measures specific to the Touch condom media campaign in Pakistan. Between-effects regression of panel survey data confirmed the nomological validity of each of the 5 measures of Touch ad exposure. In addition, 2 sets of panel regression models (i.e., fixed-effects models and fixed-effects with lag models) confirmed the predictive validity of each of the 5 ad exposure measures. Results on comparative validity were quite similar for nomological and predictive validity, indicating that confirmed ad recall and recognition measures tend to have greater validity than unconfirmed measures.


Asunto(s)
Publicidad/estadística & datos numéricos , Servicios de Planificación Familiar , Promoción de la Salud/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pakistán , Reproducibilidad de los Resultados , Adulto Joven
12.
Langmuir ; 31(22): 6114-21, 2015 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-26020573

RESUMEN

Thin films can integrate the versatility and great potential found in the emerging field of metal-organic frameworks directly into device architectures. For fabrication of smart interfaces containing surface-anchored metal-organic frameworks, it is important to understand how the foundational layers form to create the interface between the underlying substrate and porous framework. Herein, the formation and morphology of the first ten cycles of film deposition are investigated for the well-studied HKUST-1 system. Effects of processing variables, such as deposition temperature and substrate quality, are studied. Sequences of scanning probe microscopy images collected after cycles of alternating solution-phase deposition reveal the formation of a discontinuous surface with nucleating and growing crystallites consistent with a Volmer-Weber growth mechanism. Quantitative image analysis determines surface roughness and surface coverage as a function of deposition cycles, producing insight regarding growth and structure of foundational film layers. For carboxylic acid terminated self-assembled monolayers on gold, preferred crystal orientation is influenced by deposition temperature with crystal growth along [100] observed at 25 °C and [111] favored at 50 °C. This difference in crystal orientation results in reduced surface roughness and increased surface coverage at 50 °C. To properly fabricate and fully determine the potential of this material for industrial applications, fundamental understanding of film formation is crucial.

13.
J Health Commun ; 20(7): 799-806, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25962104

RESUMEN

The authors present the results of a media documentary, Weight of the Nation, disseminated in rural communities in the Brazos Valley region of east central Texas. Researchers relied on a community-based participatory research strategy to assure community participation in the implementation and evaluation of the media documentary in rural communities. To measure the short-term effects of the documentary, the research team used a mixed-methods approach of quantitative panel data from a pre/post survey, qualitative meeting notes, and observations from facilitated discussion groups. Results showed short-term increases in behavioral intention, as well as an increase in self and collective efficacy of participants to make healthy changes at individual and community levels to reduce obesity. The findings suggest that Weight of the Nation is a catalyst for increasing awareness about obesity and initiating changes in intention and efficacy perceptions.


Asunto(s)
Investigación Participativa Basada en la Comunidad , Promoción de la Salud/métodos , Difusión de la Información/métodos , Medios de Comunicación de Masas , Obesidad/prevención & control , Población Rural , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Texas , Adulto Joven
14.
J Health Commun ; 18(8): 913-30, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23767700

RESUMEN

Given that alcohol consumption and binge drinking among adolescents in the United States remain prevalent, this study assesses changes in the influence of peer norms-and their interactions with time, gender, and ethnicity-on alcohol consumption. Panel survey interviews of adolescents (N = 1,607) were completed in 9th grade and then again in 12th grade with students from Louisiana. Fixed effects multiple regression assessed the relations between the changes in 2 types of peer norms (i.e., descriptive norms and injunctive norms) and 2 alcohol consumption measures: 30-day alcohol prevalence and binge drinking. Increases in 30-day alcohol prevalence and binge drinking were associated with only descriptive norms. The effects of both types of peer norms intensified over time, and the effects of descriptive norms varied according to gender and ethnicity. Specifically, the influence of descriptive norms was greater on boys than on girls and on Caucasians than on African Americans. Communication interventions that target adolescents in the context of alcohol consumption should consider the temporal variability of peer normative influence and how it varies by gender and ethnicity.


Asunto(s)
Conducta del Adolescente/psicología , Consumo de Bebidas Alcohólicas/psicología , Comunicación en Salud/métodos , Relaciones Interpersonales , Grupo Paritario , Servicios de Salud Escolar/organización & administración , Percepción Social , Adolescente , Conducta del Adolescente/etnología , Negro o Afroamericano/psicología , Consumo de Bebidas Alcohólicas/etnología , Consumo de Bebidas Alcohólicas/prevención & control , Consumo Excesivo de Bebidas Alcohólicas/etnología , Consumo Excesivo de Bebidas Alcohólicas/prevención & control , Consumo Excesivo de Bebidas Alcohólicas/psicología , Femenino , Humanos , Louisiana/epidemiología , Masculino , Investigación Cualitativa , Distribución por Sexo , Factores de Tiempo , Población Blanca/psicología
15.
Biomolecules ; 13(12)2023 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-38136628

RESUMEN

Glycine receptors (GlyRs) are glycine-gated inhibitory pentameric ligand-gated ion channels composed of α or α + ß subunits. A number of structures of these proteins have been reported, but to date, these have only revealed details of the extracellular and transmembrane domains, with the intracellular domain (ICD) remaining uncharacterised due to its high flexibility. The ICD is a region that can modulate function in addition to being critical for receptor localisation and clustering via proteins such as gephyrin. Here, we use modelling and molecular dynamics (MD) to reveal details of the ICDs of both homomeric and heteromeric GlyR. At their N and C ends, both the α and ß subunit ICDs have short helices, which are major sites of stabilising interactions; there is a large flexible loop between them capable of forming transient secondary structures. The α subunit can affect the ß subunit ICD structure, which is more flexible in a 4α2:1ß than in a 4α1:1ß GlyR. We also explore the effects of gephyrin binding by creating GlyR models bound to the gephyrin E domain; MD simulations suggest these are more stable than the unbound forms, and again there are α subunit-dependent differences, despite the fact the gephyrin binds to the ß subunit. The bound models also suggest that gephyrin causes compaction of the ICD. Overall, the data expand our knowledge of this important receptor protein and in particular clarify features of the underexplored ICD.


Asunto(s)
Simulación de Dinámica Molecular , Receptores de Glicina , Receptores de Glicina/metabolismo , Proteínas Portadoras/metabolismo , Glicina
16.
J Health Commun ; 17(5): 601-23, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22272557

RESUMEN

This study aims to assess communication processes involving a thematic condom advertising campaign in Pakistan in 2009. To evaluate the social marketing campaign for Touch condoms, the authors conducted a nationally representative survey of 1,606 men married to women aged 15-49 years. About 15% of urban married men were aware of Touch advertising. After controlling for a range of other variables including daily television viewership, confirmed awareness of Touch advertising was associated with a higher level of belief in the effectiveness of condoms, reduced embarrassment in negotiating condom use, reduced embarrassment in purchasing condoms, increased discussion of family planning, and increased use of condoms and other contraceptive methods. The findings have implications for the further development and dissemination of contraceptive advertising in Pakistan, as well as the broader construction of scientific knowledge on how advertising can influence contraceptive and other critical health behaviors in other contexts.


Asunto(s)
Publicidad , Condones/estadística & datos numéricos , Promoción de la Salud/métodos , Mercadeo Social , Población Urbana , Adulto , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Estado Civil , Persona de Mediana Edad , Pakistán , Evaluación de Programas y Proyectos de Salud , Población Urbana/estadística & datos numéricos , Adulto Joven
17.
Front Immunol ; 13: 801915, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35211117

RESUMEN

Due to the fast global spreading of the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), prevention and treatment options are direly needed in order to control infection-related morbidity, mortality, and economic losses. Although drug and inactivated and attenuated virus vaccine development can require significant amounts of time and resources, DNA and RNA vaccines offer a quick, simple, and cheap treatment alternative, even when produced on a large scale. The spike protein, which has been shown as the most antigenic SARS-CoV-2 protein, has been widely selected as the target of choice for DNA/RNA vaccines. Vaccination campaigns have reported high vaccination rates and protection, but numerous unintended effects, ranging from muscle pain to death, have led to concerns about the safety of RNA/DNA vaccines. In parallel to these studies, several open reading frames (ORFs) have been found to be overlapping SARS-CoV-2 accessory genes, two of which, ORF2b and ORF-Sh, overlap the spike protein sequence. Thus, the presence of these, and potentially other ORFs on SARS-CoV-2 DNA/RNA vaccines, could lead to the translation of undesired proteins during vaccination. Herein, we discuss the translation of overlapping genes in connection with DNA/RNA vaccines. Two mRNA vaccine spike protein sequences, which have been made publicly-available, were compared to the wild-type sequence in order to uncover possible differences in putative overlapping ORFs. Notably, the Moderna mRNA-1273 vaccine sequence is predicted to contain no frameshifted ORFs on the positive sense strand, which highlights the utility of codon optimization in DNA/RNA vaccine design to remove undesired overlapping ORFs. Since little information is available on ORF2b or ORF-Sh, we use structural bioinformatics techniques to investigate the structure-function relationship of these proteins. The presence of putative ORFs on DNA/RNA vaccine candidates implies that overlapping genes may contribute to the translation of smaller peptides, potentially leading to unintended clinical outcomes, and that the protein-coding potential of DNA/RNA vaccines should be rigorously examined prior to administration.


Asunto(s)
Genes Sobrepuestos , Genes Virales , Vacunas de ADN/genética , Vacunas de ARNm/genética , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/genética , Codón , Humanos , Conformación de Ácido Nucleico , Sistemas de Lectura Abierta , Biosíntesis de Proteínas , Dominios Proteicos , ARN Mensajero , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas de ADN/efectos adversos , Vacunas de ARNm/efectos adversos
18.
Public Health Rep ; 126(3): 400-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21553669

RESUMEN

OBJECTIVES: Post-disaster trends in alcohol consumption and cigarette smoking, as well as their predictors, were identified. Methods. Data from cross-sectional and panel surveys of African American adults in New Orleans, Louisiana, were used from before (2004: n = 1,867; 2005: n = 879) and after (2006a: n = 500; 2006b: n = 500) Hurricane Katrina. RESULTS: Alcohol consumption increased significantly from pre- to post-Hurricane Katrina, while cigarette smoking remained constant. In 2006, posttraumatic stress disorder (PTSD) was associated with cigarette smoking, whereas "news attention" and "provided social support" were inversely associated with cigarette smoking. "News attention" was also inversely associated with cigarette smoking frequency, while "neighborliness" was associated with alcohol consumption. In addition, the effects of PTSD on alcohol consumption were moderated by "neighborliness." CONCLUSIONS: In the wake of Hurricane Katrina, there were complex predictive processes of addictive behaviors involving PTSD, news information, and social capital-related measures.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Negro o Afroamericano/estadística & datos numéricos , Tormentas Ciclónicas , Fumar/epidemiología , Adulto , Negro o Afroamericano/psicología , Femenino , Humanos , Louisiana/epidemiología , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Valor Predictivo de las Pruebas , Factores de Riesgo , Trastornos por Estrés Postraumático/epidemiología
19.
Comput Human Behav ; 123: 106876, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36311469

RESUMEN

Increasingly, people are turning to digital and social media to address health threats. While research has commonly investigated the psychosocial antecedents of digital health information seeking behavior (digital HISB) and social media use (SMU), there has been limited research on the independent effects of emotions and no research on the interactive effects of emotions. In the context of the coronavirus COVID-19 pandemic, this study investigates the affective, personal relevance, and socio-demographic antecedents of digital HISB and SMU, using data from an online survey of U.S. Millennials (N = 1037) in April-May 2020. Linear regression results show the effects of socio-demographic and personal relevance factors. For the independent effects of emotions, fear and sadness were associated with digital HISB; fear, joy, and disgust were associated with high-informational SMU; and joy and disgust were associated with low-informational SMU. Three interactive effects of discrete negative emotions suggest that an increase in one emotion can amplify the effect of another emotion on a measure of digital and social media use. In the fourth interaction of two negative emotions with strong biological regulatory processes, there is evidence that an increase in one emotion can diminish the effect of another emotion. Implications for theory and practice are discussed.

20.
Front Public Health ; 9: 689616, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34568252

RESUMEN

This study tested whether a cancer education intervention affected promotores' self-efficacy to deliver an intervention to Hispanics and which psychosocial determinants of promotores influenced the number of Hispanic residents reached by promotores in the subsequent education intervention. A quasi-experimental, pre/post-design with a treatment group (no control) assessed differences for promotores (n = 136) before and after exposure to the cancer education intervention. The design also included a cross-sectional evaluation of the number of residents promotores reached with the educational intervention. After being trained, the promotores delivered the intervention to Hispanic residents (n = 1,469). Paired t-tests demonstrated increases in promotores' self-efficacy from pre- to post-intervention. Regression models assessed associations between the numbers of residents reached and select psychosocial determinants of promotores. Age and promotores' years of experience influenced their delivery of a cervical cancer education intervention to Hispanics, but not their delivery of breast or colorectal cancer education interventions. This is the first study to examine which psychosocial determinants influence promotores delivery of cancer education interventions. The outcomes potentially have implications for CHW interventions and training by examining this potential connection between CHWs' psychosocial determinants and intervention outcomes.


Asunto(s)
Agentes Comunitarios de Salud , Neoplasias del Cuello Uterino , Estudios Transversales , Femenino , Educación en Salud , Hispánicos o Latinos , Humanos
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