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2.
Cell Rep ; 43(3): 113816, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38393946

RESUMEN

Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis reveals that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon-stimulated genes in macrophages. Using genetic and biochemical assays, we discover that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define a role for an SR protein in activating transcription and reveal an RBP-chromatin network that orchestrates macrophage antiviral gene expression.


Asunto(s)
Interferón Tipo I , Humanos , Transcripción Genética , Regiones Promotoras Genéticas/genética , Macrófagos , Factores de Empalme de ARN , Empalme Alternativo/genética , Factores de Empalme Serina-Arginina/genética
3.
bioRxiv ; 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37503164

RESUMEN

Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis revealed that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon stimulated genes (ISGs) in macrophages. Using genetic and biochemical assays, we discovered that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define an unorthodox role for an SR protein in activating transcription and reveal an unappreciated RNA binding protein-chromatin network that orchestrates macrophage antiviral gene expression.

4.
Elife ; 112022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36409059

RESUMEN

To mount a protective response to infection while preventing hyperinflammation, gene expression in innate immune cells must be tightly regulated. Despite the importance of pre-mRNA splicing in shaping the proteome, its role in balancing immune outcomes remains understudied. Transcriptomic analysis of murine macrophage cell lines identified Serine/Arginine Rich Splicing factor 6 (SRSF6) as a gatekeeper of mitochondrial homeostasis. SRSF6-dependent orchestration of mitochondrial health is directed in large part by alternative splicing of the pro-apoptosis pore-forming protein BAX. Loss of SRSF6 promotes accumulation of BAX-κ, a variant that sensitizes macrophages to undergo cell death and triggers upregulation of interferon stimulated genes through cGAS sensing of cytosolic mitochondrial DNA. Upon pathogen sensing, macrophages regulate SRSF6 expression to control the liberation of immunogenic mtDNA and adjust the threshold for entry into programmed cell death. This work defines BAX alternative splicing by SRSF6 as a critical node not only in mitochondrial homeostasis but also in the macrophage's response to pathogens.


Asunto(s)
Empalme Alternativo , Inmunidad Innata , Mitocondrias , Proteína X Asociada a bcl-2 , Animales , Ratones , Proteína X Asociada a bcl-2/genética , ADN Mitocondrial , Factores de Empalme Serina-Arginina/metabolismo
5.
Artículo en Inglés | MEDLINE | ID: mdl-36011420

RESUMEN

Internalized weight bias is associated with body image disturbances and the development of disordered eating. The association between weight bias internalization and body dissatisfaction has proven difficult to disrupt. In order to develop more effective interventions, we must identify the behavioral targets which account for this robust association. The present study sought to examine whether body checking and body image avoidance mediate the relationship between weight bias internalization and body dissatisfaction. In total, 279 female undergraduates (Mage = 20.13, SD = 4.10) were administered a battery of survey measures. Results demonstrated that body checking partially mediates the relationship between weight bias internalization and body dissatisfaction, Z = 7.42, p < 0.001. Body image avoidance was also found to partially mediate the relationship between weight bias internalization and body dissatisfaction, Z = 70.03, p < 0.001. These findings suggest that body checking and body image avoidance may both partially account for the association between weight bias internalization and body dissatisfaction. These findings extend the existing literature on weight bias internalization by highlighting two behavioral targets for prevention and intervention efforts. Understanding these relationships has important implications for both reducing weight bias internalization and improving body dissatisfaction.


Asunto(s)
Insatisfacción Corporal , Trastornos de Alimentación y de la Ingestión de Alimentos , Prejuicio de Peso , Adulto , Imagen Corporal , Peso Corporal , Mecanismos de Defensa , Femenino , Humanos , Adulto Joven
6.
Cell ; 185(17): 3214-3231.e23, 2022 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-35907404

RESUMEN

Although mutations in mitochondrial-associated genes are linked to inflammation and susceptibility to infection, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) perturbs mitochondrial homeostasis and reprograms cell death pathways in macrophages. When the inflammasome is activated in Lrrk2G2019S macrophages, elevated mitochondrial ROS (mtROS) directs association of the pore-forming protein gasdermin D (GSDMD) to mitochondrial membranes. Mitochondrial GSDMD pore formation then releases mtROS, promoting a switch to RIPK1/RIPK3/MLKL-dependent necroptosis. Consistent with enhanced necroptosis, infection of Lrrk2G2019S mice with Mycobacterium tuberculosis elicits hyperinflammation and severe immunopathology. Our findings suggest a pivotal role for GSDMD as an executer of multiple cell death pathways and demonstrate that mitochondrial dysfunction can direct immune outcomes via cell death modality switching. This work provides insights into how LRRK2 mutations manifest or exacerbate human diseases and identifies GSDMD-dependent necroptosis as a potential target to limit Lrrk2G2019S-mediated immunopathology.


Asunto(s)
Mitocondrias , Necroptosis , Proteínas de Unión a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Animales , Humanos , Inflamasomas , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Macrófagos , Ratones , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo
7.
J Am Coll Health ; 70(8): 2476-2482, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33513070

RESUMEN

Objective: The current study aimed to compare endorsement of the muscular- and thin-ideals alone, as well as simultaneous endorsement of both as representative of the fit-ideal and examine potential negative correlates of each type of ideal internalization. Participants: Participants were 300 female undergraduate students. Methods: Participants completed measures of internalization of the thin- and muscular-ideals, body dissatisfaction, body checking, and body avoidance. Results: Analyses revealed that approximately 24.9% of participants endorsed scores in the upper quartile on thin-ideal internalization, and 27.4% of participants fell in the upper quartile of muscular-ideal internalization, while 10.3% endorsed high internalization of both ideals. Analyses revealed that individuals endorsing only the thin-ideal reported significantly higher levels of body dissatisfaction and body avoidance than those endorsing the fit-ideal. Conclusions: Overall, findings suggested that thin- and muscular-ideal internalization present different patterns of association depending on whether an individual endorses one or both of these body ideals.


Asunto(s)
Imagen Corporal , Trastornos de Alimentación y de la Ingestión de Alimentos , Femenino , Humanos , Estudiantes , Delgadez , Satisfacción Personal , Prevalencia , Universidades , Encuestas y Cuestionarios
8.
Eat Disord ; 30(2): 230-238, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34702149

RESUMEN

Little is known about patients' perceptions toward open and blind weighing for eating disorders. Upon admission to a partial hospitalization program, 35 child/adolescent patients, 55 adult patients, and 36 parents of child/adolescent patients completed questionnaires assessing attitudes toward open and blind weighing. Participants perceived blind weighing as more effective in the short term. No differences emerged on measures assessing preference, credibility, or long-term effectiveness. Relative to adults, parents preferred blind weighing, and child/adolescents perceived blind weighing as more credible. On a forced-choice question, a majority of adults, about half of children/adolescents, and a minority of parents preferred open weighing over blind weighing. There was a positive association between past treatment experience and current attitudes about weighing. Results suggest that individuals enter treatment with variable attitudes about weighing procedures for eating disorders, and may develop more favorable attitudes toward the practice they receive in treatment.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Adolescente , Adulto , Actitud , Niño , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Hospitalización , Humanos , Padres , Encuestas y Cuestionarios
9.
Front Immunol ; 12: 656885, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34305890

RESUMEN

Pathogen sensing via pattern recognition receptors triggers massive reprogramming of macrophage gene expression. While the signaling cascades and transcription factors that activate these responses are well-known, the role of post-transcriptional RNA processing in modulating innate immune gene expression remains understudied. Given their crucial role in regulating pre-mRNA splicing and other RNA processing steps, we hypothesized that members of the SR/hnRNP protein families regulate innate immune gene expression in distinct ways. We analyzed steady state gene expression and alternatively spliced isoform production in ten SR/hnRNP knockdown RAW 264.7 macrophage-like cell lines following infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (Salmonella). We identified thousands of transcripts whose abundance is increased or decreased by SR/hnRNP knockdown in macrophages. Notably, we observed that SR and hnRNP proteins influence expression of different genes in uninfected versus Salmonella-infected macrophages, suggesting functionalization of these proteins upon pathogen sensing. Likewise, we found that knockdown of SR/hnRNPs promoted differential isoform usage (DIU) for thousands of macrophage transcripts and that these alternative splicing changes were distinct in uninfected and Salmonella-infected macrophages. Finally, having observed a surprising degree of similarity between the differentially expressed genes (DEGs) and DIUs in hnRNP K and U knockdown macrophages, we found that hnRNP K and U knockdown macrophages are both more restrictive to Vesicular Stomatitis Virus (VSV), while hnRNP K knockdown macrophages are more permissive to Salmonella Typhimurium. Based on these findings, we conclude that many innate immune genes evolved to rely on one or more SR/hnRNPs to ensure the proper magnitude of their induction, supporting a model wherein pre-mRNA splicing is critical for regulating innate immune gene expression and controlling infection outcomes in macrophages ex vivo.


Asunto(s)
Empalme Alternativo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Inmunidad Innata/genética , Macrófagos/inmunología , Macrófagos/metabolismo , Transcriptoma , Animales , Biomarcadores , Biología Computacional/métodos , Ontología de Genes , Redes Reguladoras de Genes , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Masculino , Ratones , Modelos Biológicos , Células RAW 264.7 , Infecciones por Salmonella/genética , Infecciones por Salmonella/inmunología , Infecciones por Salmonella/microbiología , Salmonella typhimurium/inmunología
10.
J Clin Psychol Med Settings ; 28(2): 384-393, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32430737

RESUMEN

Literature regarding mental health and quality of life (QOL) in bariatric patients has reported high occurrence of psychological disturbance and suggested that patients may provide socially desirable responses during pre-surgical assessments in order to minimize the apparent presence of psychological disturbance. We sought to evaluate the associations between socially desirable responding and clinical outcomes of significance and to compare self-reported psychopathology with clinically evaluated diagnoses. Data were retrospectively analyzed for patients undergoing bariatric surgery at one academic medical center. Cross-sectional self-report measures were given to patients prior to surgery. Measures assessed psychopathology, disordered eating, quality of life, and social desirability. Statistical methods included descriptive statistics, correlations and building of univariate linear regression models. Patient psychopathology, disordered eating, and QOL self-report scores were all significantly related to social desirability. Rates of psychopathology were underreported using self-report measures when compared to clinical evaluations by a licensed psychologist. Socially desirable responding may have a significant effect on preoperative assessment of psychopathology and disordered eating of patients preparing for surgical weight loss.


Asunto(s)
Cirugía Bariátrica , Obesidad Mórbida , Estudios Transversales , Humanos , Obesidad Mórbida/cirugía , Calidad de Vida , Estudios Retrospectivos , Deseabilidad Social , Pérdida de Peso
11.
Eur Eat Disord Rev ; 28(6): 657-670, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32896966

RESUMEN

OBJECTIVE: The role of family and caregiver accommodation is a well-defined maintenance factor for anxiety disorders and OCD. Family accommodation for patients with eating disorders is beginning to be described and characterized, but gaps in the literature remain. The current project compares levels of accommodation in families of those with anorexia nervosa (AN) to those with avoidant/restrictive food intake disorder (ARFID). It additionally establishes whether accommodation changes over the course of treatment and the extent to which these changes are related to changes in eating disorder pathology. METHODS: A total of 39 adolescents with ARFID and 59 with AN presenting to a partial hospitalization program were included, with measures completed at intake and discharge. RESULTS: Caregivers of adolescents with AN and those with ARFID reported similar levels of accommodation, with the exception of the Reassurance Seeking subscale of the Accommodation and Enabling Scale for Eating Disorders (AESED). Additionally, accommodation decreased significantly from intake to discharge for both patient groups. Intake AESED scores were also significantly related to caregiver distress, and changes in AESED scores were related to decreases in relevant eating disorder psychopathology for both groups. CONCLUSIONS: The results of the current study highlight the importance of considering family accommodation for ARFID patients and point to the need for future research to capture changes in accommodation over the course of treatment in relation to the delivery of evidence-based interventions and subsequent changes in ED symptoms.


Asunto(s)
Anorexia Nerviosa/terapia , Trastorno de la Ingesta Alimentaria Evitativa/Restrictiva , Cuidadores/psicología , Psicopatología/métodos , Adolescente , Anorexia Nerviosa/psicología , Niño , Femenino , Humanos , Masculino , Distrés Psicológico , Estudios Retrospectivos
12.
J Immunol ; 205(1): 153-167, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32404352

RESUMEN

Tripartite motif-containing proteins (TRIMs) play a variety of recently described roles in innate immunity. Although many TRIMs regulate type I IFN expression following cytosolic nucleic acid sensing of viruses, their contribution to innate immune signaling and gene expression during bacterial infection remains largely unknown. Because Mycobacterium tuberculosis is an activator of cGAS-dependent cytosolic DNA sensing, we set out to investigate a role for TRIM proteins in regulating macrophage responses to M. tuberculosis In this study, we demonstrate that TRIM14, a noncanonical TRIM that lacks an E3 ubiquitin ligase RING domain, is a critical negative regulator of the type I IFN response in Mus musculus macrophages. We show that TRIM14 interacts with both cGAS and TBK1 and that macrophages lacking TRIM14 dramatically hyperinduce IFN stimulated gene (ISG) expression following M. tuberculosis infection, cytosolic nucleic acid transfection, and IFN-ß treatment. Consistent with a defect in resolution of the type I IFN response, Trim14 knockout macrophages have more phospho-Ser754 STAT3 relative to phospho-Ser727 and fail to upregulate the STAT3 target Socs3, which is required to turn off IFNAR signaling. These data support a model whereby TRIM14 acts as a scaffold between TBK1 and STAT3 to promote phosphorylation of STAT3 at Ser727 and resolve ISG expression. Remarkably, Trim14 knockout macrophages hyperinduce expression of antimicrobial genes like Nos2 and are significantly better than control cells at limiting M. tuberculosis replication. Collectively, these data reveal an unappreciated role for TRIM14 in resolving type I IFN responses and controlling M. tuberculosis infection.


Asunto(s)
Interferón Tipo I/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Mycobacterium tuberculosis/inmunología , Transducción de Señal/inmunología , Proteínas de Motivos Tripartitos/metabolismo , Tuberculosis/inmunología , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/inmunología , Técnicas de Inactivación de Genes , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/aislamiento & purificación , Macrófagos/inmunología , Macrófagos/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/aislamiento & purificación , Nucleotidiltransferasas/metabolismo , Fosforilación/inmunología , Cultivo Primario de Células , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/aislamiento & purificación , Proteínas Serina-Treonina Quinasas/metabolismo , Células RAW 264.7 , Receptor de Interferón alfa y beta/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Factor de Transcripción STAT3/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/aislamiento & purificación , Tuberculosis/microbiología
13.
Eat Weight Disord ; 25(3): 643-648, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30859464

RESUMEN

PURPOSE: Previous research has found that fear of fat, or the fear of gaining weight, is fairly common within both normative and clinical populations. Similarly, weight bias, or biased attitudes directed at obese individuals, has been found across multiple segments of society. A common link shared between fear of fat and weight bias is the inherent emphasis on anti-fat feelings. Previous research has demonstrated an anti-fat bias within media content. Therefore, the purpose of the current research is to examine exposure to appearance-focused media as a moderator of the relationship between fear of fat and weight bias. METHODS: One hundred and eighty-seven female participants (Mage = 21.05, MBMI = 22.60) were administered a battery of assessments, including the Goldfarb Fear of Fat Scale and the Universal Measure of Bias of Fat Scale. Participants were also asked to report their frequency of exposure to appearance-focused media (TV and magazines). RESULTS: Results of this study suggest that appearance-focused media partially moderated the relationship between fear of fat and weight bias. CONCLUSIONS: This suggests the messages portrayed by the media may be strengthening the relationship between fear of gaining weight and discrimination directed at obese individuals. Understanding this relationship has important implications for reducing weight stigma. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.


Asunto(s)
Actitud , Imagen Corporal/psicología , Peso Corporal/fisiología , Miedo/psicología , Medios de Comunicación de Masas , Estigma Social , Adolescente , Índice de Masa Corporal , Femenino , Humanos , Estereotipo , Adulto Joven
14.
J Am Coll Health ; 68(5): 502-508, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-30908131

RESUMEN

Objective: To assess the effects of social media consumption on body dissatisfaction and negative affect using ecological momentary assessment, a method of assessment over time in the participants' naturalistic environment. Participants: Woman college students (N = 30) from a large public university participated in the study in Fall 2015. Methods: Participants were contacted via their smartphones five times per day for five days and asked to complete a battery of measures which assessed social media use, body dissatisfaction, and negative affect. Results: Results demonstrated that the number of social media sites visited was a significant predictor of body dissatisfaction while time spent using social media was not. The number of sites visited and time spent on social media were both significant predictors of general negative affect, sadness, and guilt. Conclusions: Results demonstrate the negative impact that social media use can have on body dissatisfaction and negative affect.


Asunto(s)
Afecto , Insatisfacción Corporal/psicología , Medios de Comunicación Sociales/estadística & datos numéricos , Estudiantes/psicología , Adolescente , Factores de Edad , Imagen Corporal , Índice de Masa Corporal , Evaluación Ecológica Momentánea , Femenino , Humanos , Factores Socioeconómicos , Universidades , Adulto Joven
15.
Qual Life Res ; 28(7): 1825-1833, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30783875

RESUMEN

PURPOSE: We examined the relative importance of body dissatisfaction (BD) and internalized weight bias (IWB) in accounting for variance in quality of life (QoL) impairment in an ethnically diverse sample of college students (n = 630) and potential moderation of these associations by sex. METHODS: Participants completed an online survey that included established measures of BD, IWB and QoL. Regression models were used to examine the relative contributions of BD and IWB in accounting for variance in physical and mental QoL impairment. RESULTS: BD and IWB were highly correlated with bivariate analysis in both women (r = .76) and men (r = .60). In multivariable analysis, IWB was found to be associated with both physical (b = - 1.33, 95% CI - 1.93, - 0.72) and mental (b = - 2.58, 95% CI - 3.45, - 1.72) QoL impairment, whilst BD was not associated with impairment in either physical (b = - 0.29, 95% CI - 0.68, 0.09) or mental (b = - 0.48, 95% CI - 1.03, 0.07) QoL. While levels of both BD and IWB were higher for women than for men, sex did not moderate the association between either BD or IWB and either physical or mental QoL. CONCLUSIONS: The findings support the view that IWB warrants greater attention in interventions seeking to reduce the adverse impact of BD in both women and men and both normal-weight and overweight individuals.


Asunto(s)
Imagen Corporal/psicología , Peso Corporal/fisiología , Calidad de Vida/psicología , Estudiantes/psicología , Adolescente , Adulto , Mecanismos de Defensa , Emociones , Etnicidad/psicología , Femenino , Humanos , Discapacidad Intelectual , Masculino , Factores Sexuales , Encuestas y Cuestionarios , Adulto Joven
16.
Psychiatr Clin North Am ; 42(1): 105-119, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30704632

RESUMEN

Personality variables have long been implicated in the onset and maintenance of eating disorders, as well as in symptom divergence between anorexia nervosa and bulimia nervosa. Clinical observations are broadly supported by the data, with restricting anorexia nervosa associated with higher levels of constraint and Persistence, and binge-purge behaviors linked to the tendency to take impulsive action when emotionally distressed. Considerable heterogeneity is found within diagnostic categories, however, suggesting that different personality structures may predispose individuals to develop disordered eating through alternative pathways.


Asunto(s)
Anorexia Nerviosa/fisiopatología , Bulimia Nerviosa/fisiopatología , Conducta Impulsiva/fisiología , Perfeccionismo , Trastornos de la Personalidad/fisiopatología , Humanos
17.
Hawaii J Med Public Health ; 77(8): 183-187, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30083430

RESUMEN

The purpose of this study was to identify community providers' perspectives on risk and protective factors for youth alcohol use in Hawai'i to inform future trainings of providers. A total of 104 providers within communities and prevention organizations in Hawai'i were asked to list risk and protective factors for underage drinking in each of the socioecological levels (individual, family, community, and society). The majority of participants were female (66.3%). Overall, 507 risk and protective factors were listed. There were significantly more risk factors identified (54.8%) than protective factors (45.2%). Participants identified significantly fewer society level risk and protective factors than all other levels. The top three overall themes identified by participants were resources (8.3%), peer influence (7.7%), and family function (6.9%). These results not only provide information about how providers conceptualize substance abuse, but may also indicate that it is necessary to continue training providers in how to identify society level factors influencing individuals' substance use. It is recommended that more research should be conducted with community providers in Hawai'i to understand the attitudes about prevention in the community. Such research may allow for improvements in prevention strategies by providing a larger picture of substance use in the community.


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Personal de Salud/psicología , Factores Protectores , Adolescente , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Femenino , Hawaii/epidemiología , Humanos , Masculino , Influencia de los Compañeros , Investigación Cualitativa , Factores de Riesgo , Apoyo Social
18.
Neurobiol Aging ; 70: 117-124, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30007160

RESUMEN

This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. The rate of mean change (95% confidence interval) in PEF6 z-score over 12 weeks was 0.270 (0.159, 0.380) for placebo, compared with 0.121 (0.011, 0.232) for guanfacine 0.1 mg (p = 0.06, compared to placebo) and 0.213 (0.101, 0.324) for 0.5 mg (p = 0.47). Neither dose of guanfacine improved the quality of life or global function relative to placebo. Among common adverse events, only dry mouth was significantly more frequent on guanfacine compared to placebo. Guanfacine failed to ameliorate prefrontal cognitive function in older individuals, who were cognitively normal for age.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Guanfacina/uso terapéutico , Corteza Prefrontal/fisiopatología , Factores de Edad , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/fisiopatología , Método Doble Ciego , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Calidad de Vida , Resultado del Tratamiento
19.
G3 (Bethesda) ; 7(8): 2439-2460, 2017 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-28667019

RESUMEN

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5' ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.


Asunto(s)
Cromosomas/genética , Drosophila/genética , Retroelementos/genética , Animales , Composición de Base/genética , Secuencia de Bases , Codón/genética , Femenino , Perfilación de la Expresión Génica , Genes de Insecto , Histonas/metabolismo , Procesamiento Proteico-Postraduccional/genética , Wolbachia/genética
20.
Eat Behav ; 23: 137-140, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27679970

RESUMEN

The present study aimed to further validate the Loss of Control Over Eating Scale (LOCES) for use with undergraduate men and women with and without eating disorder (ED) symptoms. A total of 261 participants completed the LOCES and the Eating Disorder Examination - Questionnaire (EDE-Q) and were identified as non-clinical or having probable ED symptomatology based on previously used EDE-Q cutoff scores. Results indicated that the LOCES and its subscales were significantly associated with and a significant predictor of global ED pathology and binge episode frequency. The LOCES behavioral subscale appeared to be a stronger predictor of episode frequency compared to other subscales. The ED pathology groups reported significantly higher LOCES scores compared to the non-ED pathology groups. Binary logistic regression analyses revealed that the LOCES was able to accurately distinguish between those with ED pathology and those without ED pathology in the majority of cases. Findings from the present study suggest that the LOCES is highly predictive of ED pathology, strongly associated with ED cognitions and behaviors, and an accurate index for global eating disorder pathology. Future directions for research are discussed.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Hiperfagia/psicología , Control Interno-Externo , Estudiantes/psicología , Encuestas y Cuestionarios , Adolescente , Adulto , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Estudiantes/estadística & datos numéricos , Adulto Joven
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