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1.
Nature ; 548(7665): 78-81, 2017 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-28738409

RESUMEN

Metasedimentary rocks from Isua, West Greenland (over 3,700 million years old) contain 13C-depleted carbonaceous compounds, with isotopic ratios that are compatible with a biogenic origin. Metamorphic garnet crystals in these rocks contain trails of carbonaceous inclusions that are contiguous with carbon-rich sedimentary beds in the host rock, where carbon is fully graphitized. Previous studies have not been able to document other elements of life (mainly hydrogen, oxygen, nitrogen and phosphorus) structurally bound to this carbonaceous material. Here we study carbonaceous inclusions armoured within garnet porphyroblasts, by in situ infrared absorption on approximately 10-21 m3 domains within these inclusions. We show that the absorption spectra are consistent with carbon bonded to nitrogen and oxygen, and probably also to phosphate. The levels of C-H or O-H bonds were found to be low. These results are consistent with biogenic organic material isolated for billions of years and thermally matured at temperatures of around 500 °C. They therefore provide spatial characterization for potentially the oldest biogenic carbon relics in Earth's geological record. The preservation of Eoarchean organic residues within sedimentary material corroborates earlier claims for the biogenic origins of carbon in Isua metasediments.


Asunto(s)
Carbono/análisis , Sedimentos Geológicos/química , Vida , Minerales/química , Compuestos Orgánicos/análisis , Anhídridos/química , Carbono/química , Cristalización , Groenlandia , Microscopía de Fuerza Atómica , Minerales/análisis , Nitrilos/química , Compuestos Orgánicos/química , Fosfatos/química , Espectrofotometría Infrarroja , Factores de Tiempo
2.
Matern Child Health J ; 27(7): 1254-1263, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37029891

RESUMEN

INTRODUCTION: Pregnancy is a time of increased vulnerability to mental health disorders. Additionally, the COVID-19 pandemic has increased the incidence of depression and anxiety. Thus, we aimed to assess mental health and associated healthy behaviors of pregnant people in California during the pandemic in order to contextualize prenatal well-being during the first pandemic of the twenty-first century. METHODS: We conducted an online cross-sectional study of 433 pregnant people from June 6 through July 29, 2020. We explored 3 hypotheses: (1) mental health would be worse during the pandemic than in general pregnant samples to date; (2) first-time pregnant people would have worse mental health; and (3) healthy behaviors would be positively related to mental health. RESULTS: Many of our participants (22%) reported clinically significant depressive symptoms and 31% reported clinically significant anxiety symptoms. Multiparous pregnant people were more likely to express worries about their own health and wellbeing and the process of childbirth than were primiparous pregnant people. Additionally, as pregnancy advanced, sleep and nutrition worsened, while physical activity increased. Lastly, anxious-depressive symptomology was significantly predictive of participant sleep behaviors, nutrition, and physical activity during the past week. DISCUSSION: Pregnant people had worse mental health during the pandemic, and this was associated with worse health-promoting behaviors. Given that the COVID-19 pandemic and associated risks are likely to persist due to low vaccination rates and the emergence of variants with high infection rates, care that promotes mental and physical well-being for the pregnant population should be a public health priority.


Asunto(s)
COVID-19 , Pandemias , Femenino , Embarazo , Humanos , Estudios Transversales , COVID-19/epidemiología , Conductas Relacionadas con la Salud , California/epidemiología , Ansiedad/epidemiología , Depresión/epidemiología
3.
Eur Eat Disord Rev ; 31(6): 802-812, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37406031

RESUMEN

OBJECTIVE: In April 2022 the Calorie Labelling (Out of Home) Regulations came into effect in England where cafés, restaurants, and takeaways with over 250 employees were required to provide calorie labelling on menus. Concerns have been raised regarding the potential negative impact this could have on individuals with eating disorders (EDs), yet this has not been explored using qualitative methodology. METHOD: Eleven participants with a current or previously diagnosed restrictive ED were interviewed in September 2022. Interpretative Phenomenological Analysis (IPA) was used to explore their experience of the introduction of calories on menus. RESULTS: Using IPA we established six themes and seven subordinate themes. These included the introduction of calories on menus as an 'attack' on individuals with EDs; the prominent visual display of calories as an attentional pull; normalising of calories counting; the impact on behaviour; and associated strategies for managing. CONCLUSION: This contributes to research surrounding the implications for public health policies on individuals with EDs, especially their ability to reinforce and amplify disordered thoughts and behaviours, and the need for greater consideration of how to minimise impact and potential harm of large public health campaigns.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Etiquetado de Alimentos , Humanos , Etiquetado de Alimentos/métodos , Ingestión de Energía , Conducta Alimentaria , Restaurantes
4.
Matern Child Nutr ; 19(1): e13446, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36218286

RESUMEN

This study evaluated the collateral, or unanticipated, impacts of Smart Beginnings (SB), a two-site, tiered intervention designed to promote responsive parenting and school readiness, on breastfeeding intensity in a low-income sample. Impact analyses for the SB intervention were conducted using an intent-to-treat design leveraging a two-arm random assignment structure. Mothers assigned to the SB intervention group were more than three times more likely to give breastmilk as the only milk source at infant age 6 months than mothers assigned to the control group at one site, an effect not evident at the other study site. As development and growth are the two most salient domains of child health, understanding how interventions impact subsequent parenting practices across both domains is critical to address long-term economic and racial/ethnic disparities. Implications of the findings are discussed for improving the efficacy of interventions based on paediatric primary care.


Asunto(s)
Lactancia Materna , Madres , Lactante , Femenino , Niño , Humanos , Responsabilidad Parental , Desarrollo Infantil , Instituciones Académicas
5.
Hum Mutat ; 43(11): 1590-1608, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35510381

RESUMEN

While whole-genome and exome sequencing have transformed our collective understanding of genetics' role in disease pathogenesis, there are certain conditions and populations for whom DNA-level data fails to identify the underlying genetic etiology. Specifically, patients of non-White race and non-European ancestry are disproportionately affected by "variants of unknown/uncertain significance" (VUS), limiting the scope of precision medicine for minority patients and perpetuating health disparities. VUS often include deep intronic and splicing variants which are difficult to interpret from DNA data alone. RNA analysis can illuminate the consequences of VUS, thereby allowing for their reclassification as pathogenic versus benign. Here we review the critical role transcriptome analysis plays in clarifying VUS in both neoplastic and non-neoplastic diseases.


Asunto(s)
Predisposición Genética a la Enfermedad , Variación Genética , Perfilación de la Expresión Génica , Pruebas Genéticas , Humanos , Intrones , ARN
6.
J Biol Inorg Chem ; 27(6): 553-564, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35831671

RESUMEN

Myocilin is secreted from trabecular meshwork cells to an eponymous extracellular matrix that is critical for maintaining intraocular pressure. Missense mutations found in the myocilin olfactomedin domain (OLF) lead to intracellular myocilin misfolding and are causative for the heritable form of early-onset glaucoma. The OLF domain contains a unique internal, hetero-dinuclear calcium site. Here, we tested the hypothesis that calcium dysregulation causes wild-type (WT) myocilin misfolding reminiscent of that observed for disease variants. Using two cellular models expressing WT myocilin, we show that the Ca2+ ATPase channel blocker thapsigargin inhibits WT myocilin secretion. Intracellular WT myocilin is at least partly insoluble and aggregated in the endoplasmic reticulum (ER), and stains positively with an amyloid dye. By comparing the effect of thapsigargin on WT myocilin to that on a de novo secretion-competent Ca2+-free variant D478S, we discern that non-secretion of WT myocilin is due initially to calcium dysregulation, and is potentiated further by resultant ER stress. In E. coli, depletion of calcium leads to recombinant expression of misfolded isolated WT OLF but the D478S variant is still produced as a folded monomer. Treatment of cells expressing a double mutant composed of D478S and either disease variants P370L or Y437H with thapsigargin promotes its misfolding and aggregation, demonstrating the limits of D478S to correct secretion defects. Taken together, the heterodinuclear calcium site is a liability for proper folding of myocilin. Our study suggests a molecular mechanism by which WT myocilin misfolding may contribute broadly to glaucoma-associated ER stress. This study explores the effect of calcium depletion on myocilin olfactomedin domain folding.


Asunto(s)
Calcio , Glaucoma , Proteínas del Citoesqueleto , Escherichia coli/metabolismo , Proteínas del Ojo/química , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Glaucoma/genética , Glaucoma/metabolismo , Glicoproteínas , Humanos , Mutación , Tapsigargina/farmacología
7.
Appetite ; 168: 105755, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34648909

RESUMEN

Parental restriction of food intake has been associated with heightened eating disorder psychopathology in some longitudinal research. Yet, relatively little is known about the determinants of restrictive feeding practices. This cross-sectional study explored the association between parents' anti-fat attitudes and their use of restrictive feeding practices in a mixed British (41.10% England, 39.90% Scotland, 4.20% Other) and Irish (14.80%) sample. Parents and caregivers (N = 472; 94.10% female; 70.90% university level education) of children between the ages of 4-8 (48.20% female; 91.10% rated as "normal weight" by their parents) completed self-report questionnaires assessing their anti-fat attitudes (dislike, fear, and blame subscales), use of restrictive feeding practices (for weight control, health purposes, and covert restriction), and how influential their child's body-weight and -shape is for their perception of themselves as parents. Overall, our hypothesis that parental anti-fat attitudes would be significantly associated with restrictive feeding practices was supported. Anti-fat attitudes related to disliking higher body-weight people and blaming parents for their child's weight were significant predictors of all forms of restrictive feeding (all ps < .05). However, anti-fat attitudes related to fearing being a higher body-weight were not significant predictors of restrictive feeding for the purposes of health nor for covert restriction (ps > .05). Additionally, our hypothesis that the associations between anti-fat attitudes and restrictive feeding practices would be stronger for parents for whom their child's body-weight and -shape more strongly influenced how they judged themselves as parents was not supported (the interaction term was not significant in two out of three analyses). Future research is needed to investigate these associations across time and in samples of higher body-weight children.


Asunto(s)
Conducta Alimentaria , Padres , Actitud , Índice de Masa Corporal , Peso Corporal , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Sobrepeso , Responsabilidad Parental , Encuestas y Cuestionarios
8.
Qual Health Res ; 32(1): 31-47, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34558371

RESUMEN

What is breastfeeding "success"? In this article, we challenge the traditional biomedical definition, instead centering visions of success described by breastfeeding mothers themselves. Using semi-structured interviews, quantitative surveys, and written narratives of 38 first-time mothers in the United States, we describe five common pathways through the first-year postpartum, a taxonomic distinction far more complex than a success-failure dichotomy: sustained breastfeeding, exclusive pumping, combination feeding, rapid weaning, and grinding back to exclusivity. We also explore the myriad ways in which mothers define and experience breastfeeding success, and in the process uncover the ways that cultural narratives-especially intensive mothering-color those experiences. Finally, we discuss how these experiences are shaped by infant feeding pathway. In doing so, we discover nuance that has gone unexplored in the breastfeeding literature. These findings have implications for supporting, promoting, and protecting breastfeeding in the United States and other high-income countries.


Asunto(s)
Lactancia Materna , Madres , Femenino , Humanos , Lactante , Periodo Posparto , Investigación Cualitativa , Encuestas y Cuestionarios
9.
Ann Surg Oncol ; 28(6): 3312-3319, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33073342

RESUMEN

INTRODUCTION: Current recommendations regarding the size of wide local excision (WLE) margins for Merkel cell carcinoma (MCC) are not well established. METHODS: WLE and pathologic margins were respectively reviewed from 79 patients with stage I or II MCC, who underwent WLE at Washington University in St Louis from 2005 to 2019. Outcomes included local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant recurrence-free survival (DRFS), disease-free survival (DFS), and disease-specific survival (DSS). RESULTS: Thirty-two percent of patients received adjuvant radiotherapy (aRT). At 1 year, DFS was 51.3%, 71.4%, and 87.8% for patients with WLE margins < 1 cm, 1-1.9 cm, and ≥ 2 cm, respectively (p = 0.02). At 3 years, the DSS was 57.7%, 82.6%, and 100% for patients with WLE margins < 1 cm, 1-1.9 cm, and ≥ 2 cm, respectively (p = 0.02). Multivariable Cox analysis demonstrated that every 1-cm increase in WLE margins was associated with improved RRFS [hazard ratio (HR) = 0.28, 95% confidence interval (CI): 0.11-0.75], DRFS (HR 0.30, CI 0.08-0.99), DFS (HR 0.42, CI 0.21-0.86), and DSS (HR 0.16, CI 0.04-0.61). WLE and pathologic margin size were moderately-to-strongly correlated (r = 0.66). Close or positive pathologic margins (< 3 mm) were associated with reduced DRFS (HR 6.83, CI 1.80-25.9), DFS (HR 2.98, CI 1.31-6.75), and DSS (HR 3.52, CI 1.14-10.9). CONCLUSION: Reduced WLE and pathologic margins were associated with higher risk of relapse and death from MCC. Larger WLE margins are important in populations with lower rates of adjuvant radiation.


Asunto(s)
Carcinoma de Células de Merkel , Neoplasias Cutáneas , Carcinoma de Células de Merkel/cirugía , Humanos , Márgenes de Escisión , Recurrencia Local de Neoplasia/cirugía , Recurrencia , Estudios Retrospectivos , Neoplasias Cutáneas/cirugía , Tasa de Supervivencia
10.
Exp Eye Res ; 211: 108729, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34400147

RESUMEN

Myocilin, a modular multidomain protein, is expressed broadly in the human body but is best known for its presence in the trabecular meshwork extracellular matrix, and myocilin misfolding is associated with glaucoma. Despite progress in comprehending the structure and misfolding of the myocilin olfactomedin domain, the structure and function of full-length myocilin, and contextual changes in glaucoma, remain unknown. Here we expressed and purified milligram-scale quantities of full-length myocilin from suspension mammalian cell culture (Expi293F), enabling molecular characterization in detail not previously accessible. We systematically characterized disulfide-dependent and -independent oligomerization as well as confirmed glycosylation and susceptibility to proteolysis. We identified oligomeric states with glycosylation sites that are inaccessible to enzymatic removal. Low-resolution single particle 2D class averaging from conventional transmission electron microscopy imaging confirms an extended arrangement of tetramers, truncated products consistent with dimers, and a higher-ordered state consistent with octamer. Taken together, our study reveals new myocilin misfolded states and layers of intrinsic heterogeneity, expands our knowledge of olfactomedin-family proteins and lays the foundation for a better molecular understanding of myocilin structure and its still enigmatic biological function.


Asunto(s)
Proteínas del Citoesqueleto/química , Proteínas del Ojo/química , Glicoproteínas/química , Malla Trabecular/metabolismo , Animales , Western Blotting , Línea Celular , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/ultraestructura , Proteínas del Ojo/metabolismo , Proteínas del Ojo/ultraestructura , Expresión Génica , Glicoproteínas/metabolismo , Glicoproteínas/ultraestructura , Glicosilación , Humanos , Microscopía Electrónica de Transmisión , Pliegue de Proteína , Dominios y Motivos de Interacción de Proteínas , Multimerización de Proteína , Procesamiento Proteico-Postraduccional , Proteómica , Transfección
11.
J Pediatr Psychol ; 46(7): 768-778, 2021 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-34270767

RESUMEN

OBJECTIVE: To test breastfeeding duration and responsive parenting as independent predictors of infant weight change from birth to 12 months, and to test the moderating effect of a tiered parenting intervention on relations between breastfeeding and responsive parenting in relation to infant weight change. METHODS: Mother-infant dyads (N = 403) were participants in the ongoing Smart Beginnings (SB) randomized controlled trial testing the impact of the tiered SB parenting model that incorporates two evidence-based interventions: Video Interaction Project (VIP) and Family Check-Up (FCU). The sample was low income and predominantly Black and Latinx. Responsive parenting variables (maternal sensitivity and intrusiveness) came from coded observations of mother-infant interactions when infants were 6 months. Continuous weight-for-age (WFA) z-score change and infant rapid weight gain (RWG) from 0 to 12 months were both assessed. RESULTS: Longer breastfeeding duration was significantly associated with less WFA z-score change. The relationship between breastfeeding duration and WFA z-score change was significant only for infants in the intervention group. Intrusive parenting behaviors were also associated with greater WFA z-score change after accounting for breastfeeding duration. CONCLUSIONS: This study is one of the first to test both breastfeeding and parenting in relation to infant weight gain in the first year. Findings may have implications for family-focused child obesity prevention programs.


Asunto(s)
Lactancia Materna , Responsabilidad Parental , Niño , Conducta Alimentaria , Femenino , Humanos , Lactante , Recién Nacido , Relaciones Madre-Hijo , Madres
12.
BMC Pregnancy Childbirth ; 21(1): 477, 2021 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-34215218

RESUMEN

BACKGROUND: During public health emergencies, including the COVID-19 pandemic, access to adequate healthcare is crucial for providing for the health and wellbeing of families. Pregnant and postpartum people are a particularly vulnerable subgroup to consider when studying healthcare access. Not only are perinatal people likely at higher risk for illness, mortality, and morbidity from COVID-19 infection, they are also at higher risk for negative outcomes due to delayed or inadequate access to routine care. METHODS: We surveyed 820 pregnant people in California over two waves of the COVID-19 pandemic: (1) a 'non-surge' wave (June 2020, n = 433), and (2) during a 'surge' in cases (December 2020, n = 387) to describe current access to perinatal healthcare, as well as concerns and decision-making regarding childbirth, over time. We also examined whether existing structural vulnerabilities - including acute financial insecurity and racial/ethnic minoritization - are associated with access, concerns, and decision-making over these two waves. RESULTS: Pregnant Californians generally enjoyed more access to, and fewer concerns about, perinatal healthcare during the winter of 2020-2021, despite surging COVID-19 cases and hospitalizations, as compared to those surveyed during the COVID-19 'lull' in the summer of 2020. However, across 'surge' and 'non-surge' pandemic circumstances, marginalized pregnant people continued to fare worse - especially those facing acute financial difficulty, and racially minoritized individuals identifying as Black or Indigenous. CONCLUSIONS: It is important for clinicians, researchers, and policymakers to understand whether and how shifting community transmission and infection rates may impact access to perinatal healthcare. Targeting minoritized and financially insecure communities for increased upstream perinatal healthcare supports are promising avenues to blunt the negative impacts of the COVID-19 pandemic on pregnant people in California.


Asunto(s)
COVID-19 , Toma de Decisiones , Estatus Económico , Etnicidad , Accesibilidad a los Servicios de Salud , Atención Perinatal , Adolescente , Adulto , Entorno del Parto , COVID-19/epidemiología , California/epidemiología , Femenino , Humanos , Grupos Minoritarios , Parto , Embarazo , Atención Prenatal , SARS-CoV-2 , Encuestas y Cuestionarios , Adulto Joven
13.
J Biol Chem ; 294(34): 12717-12728, 2019 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-31270212

RESUMEN

Nonsynonymous gene mutations can be beneficial, neutral, or detrimental to the stability, structure, and biological function of the encoded protein, but the effects of these mutations are often not readily predictable. For example, the ß-propeller olfactomedin domain of myocilin (mOLF) exhibits a complex interrelationship among structure(s), stability, and aggregation. Numerous mutations within mOLF are linked to glaucoma; the resulting variants are less stable, aggregation-prone, and sequestered intracellularly, causing cytotoxicity. Here, we report the first stable mOLF variants carrying substitutions in the calcium-binding site that exhibit solution characteristics indistinguishable from those of glaucoma variants. Crystal structures of these stable variants at 1.8-2.0-Å resolution revealed features that we could not predict by molecular dynamics simulations, including loss of loop structure, helix unwinding, and a blade shift. Double mutants that combined a stabilizing substitution and a selected glaucoma-causing single-point mutant rescued in vitro folding and stability defects. In the context of full-length myocilin, secretion of stable single variants was indistinguishable from that of the WT protein, and the double mutants were secreted to varying extents. In summary, our finding that mOLF can tolerate particular substitutions that render the protein stable despite a conformational switch emphasizes the complexities in differentiating between benign and glaucoma-causing variants and provides new insight into the possible biological function of myocilin.


Asunto(s)
Proteínas del Citoesqueleto/genética , Proteínas de la Matriz Extracelular/genética , Proteínas del Ojo/genética , Glaucoma/genética , Glicoproteínas/genética , Mutación , Proteínas del Citoesqueleto/química , Proteínas de la Matriz Extracelular/química , Proteínas del Ojo/química , Variación Genética/genética , Glicoproteínas/química , Células HEK293 , Humanos , Simulación de Dinámica Molecular
14.
EMBO J ; 35(14): 1537-49, 2016 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-27261198

RESUMEN

It is now known that proteins associated with neurodegenerative disease can spread throughout the brain in a prionlike manner. However, the mechanisms regulating the trans-synaptic spread propagation, including the neuronal release of these proteins, remain unknown. The interaction of neurodegenerative disease-associated proteins with the molecular chaperone Hsc70 is well known, and we hypothesized that much like disaggregation, refolding, degradation, and even normal function, Hsc70 may dictate the extracellular fate of these proteins. Here, we show that several proteins, including TDP-43, α-synuclein, and the microtubule-associated protein tau, can be driven out of the cell by an Hsc70 co-chaperone, DnaJC5. In fact, DnaJC5 overexpression induced tau release in cells, neurons, and brain tissue, but only when activity of the chaperone Hsc70 was intact and when tau was able to associate with this chaperone. Moreover, release of tau from neurons was reduced in mice lacking the DnaJC5 gene and when the complement of DnaJs in the cell was altered. These results demonstrate that the dynamics of DnaJ/Hsc70 complexes are critically involved in the release of neurodegenerative disease proteins.


Asunto(s)
Proteínas del Choque Térmico HSC70/metabolismo , Proteínas del Choque Térmico HSP40/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas tau/metabolismo , Línea Celular , Proteínas de Unión al ADN/metabolismo , Humanos , alfa-Sinucleína/metabolismo
15.
PLoS Biol ; 15(6): e2001336, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28654636

RESUMEN

The accumulation of amyloidogenic proteins is a pathological hallmark of neurodegenerative disorders. The aberrant accumulation of the microtubule associating protein tau (MAPT, tau) into toxic oligomers and amyloid deposits is a primary pathology in tauopathies, the most common of which is Alzheimer's disease (AD). Intrinsically disordered proteins, like tau, are enriched with proline residues that regulate both secondary structure and aggregation propensity. The orientation of proline residues is regulated by cis/trans peptidyl-prolyl isomerases (PPIases). Here we show that cyclophilin 40 (CyP40), a PPIase, dissolves tau amyloids in vitro. Additionally, CyP40 ameliorated silver-positive and oligomeric tau species in a mouse model of tau accumulation, preserving neuronal health and cognition. Nuclear magnetic resonance (NMR) revealed that CyP40 interacts with tau at sites rich in proline residues. CyP40 was also able to interact with and disaggregate other aggregating proteins that contain prolines. Moreover, CyP40 lacking PPIase activity prevented its capacity for disaggregation in vitro. Finally, we describe a unique structural property of CyP40 that may permit disaggregation to occur in an energy-independent manner. This study identifies a novel human protein disaggregase and, for the first time, demonstrates its capacity to dissolve intracellular amyloids.


Asunto(s)
Amiloide/metabolismo , Ciclofilinas/metabolismo , Enfermedades Neurodegenerativas/metabolismo , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Amiloide/genética , Amiloide/ultraestructura , Animales , Western Blotting , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/fisiopatología , Peptidil-Prolil Isomerasa F , Ciclofilinas/genética , Ciclosporina/farmacología , Modelos Animales de Enfermedad , Femenino , Células HEK293 , Humanos , Masculino , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Enfermedades Neurodegenerativas/genética , Agregado de Proteínas/efectos de los fármacos , Agregación Patológica de Proteínas , Tauopatías/genética , Tauopatías/metabolismo , alfa-Sinucleína/genética , Proteínas tau/genética
16.
Appetite ; 155: 104797, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32652100

RESUMEN

The main objective of this systematic review was to provide a comprehensive overview of the psychometric properties of all available Orthorexia Nervosa (ON) assessment tools, in order to evaluate their scope of application for research and practice. Ten databases were searched for studies quantitatively assessing ON. The psychometric properties were evaluated according to specified quality criteria, focusing on the reliability, structural validity and construct validity of the scales. A meta-analytic approach was used to summarize eligible Cronbach's alpha coefficients between studies. Sixty-eight unique studies fulfilled the inclusion criteria for this systematic review. Ten discrete ON scales were identified. Half of the included studies exclusively utilized a version of the ORTO-15. The evaluation of all available ON measures raise issues regarding ON's dimensionality and conceptualization. Most of the identified scales require further validation. Based on the reported psychometric properties it is advised to re-evaluate existing tools and to focus on establishing consensus regarding the conceptualization of ON to establish a measure with sound psychometric properties.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Formación de Concepto , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Generalización Psicológica , Humanos , Psicometría , Reproducibilidad de los Resultados
17.
Matern Child Nutr ; 15(1): e12655, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30216665

RESUMEN

Patterns of breastfeeding over time are not currently well understood. Limited qualitative and quantitative evidence suggests that there may be latent subgroups of mothers in the United States following very different trajectories of breast milk provision for their infants. This study used a quantitative modelling method (group-based trajectory modelling) to identify and describe these subgroups. Using data from the Infant Feeding Practices Study II (n = 3,023), the authors identified four distinct trajectories of breastfeeding intensity, each of which included a substantial subset of the total sample. A model with four groups fit the data well by objective and conceptual standards. Bivariate associations were analysed, and significant difference between trajectory group membership was found on an array of maternal and family determinants, including maternal demographics, hospital experience, and psychosocial resources, as well as on postweaning perceptions. These associations were used to create group profiles for each subgroup. Controlling for sociodemographic covariates, we also found that trajectory membership was significantly associated with several health outcomes for the target child 6 years later, including certain infections, picky eating, and health care utilization; trajectory group membership was also associated with maternal breastfeeding of subsequent children and maternal body mass index (BMI) at Year 6. Child BMI z-score and maternal breast cancer diagnosis were not significantly different across trajectory groups after accounting for confounding covariates, nor was time missed from school for the target child. Though exploratory, the initial identification and description of these four subgroups suggest future directions using breastfeeding trajectory methods, with potential implications for measurement, intervention development, and targeting.


Asunto(s)
Lactancia Materna/estadística & datos numéricos , Modelos Estadísticos , Adolescente , Adulto , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Leche Humana , Madres/estadística & datos numéricos , Estados Unidos/epidemiología , Adulto Joven
18.
Diabetologia ; 61(8): 1849-1855, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29858650

RESUMEN

AIMS/HYPOTHESIS: Cre-loxP systems are frequently used in mouse genetics as research tools for studying tissue-specific functions of numerous genes/proteins. However, the expression of Cre recombinase in a tissue-specific manner often produces undesirable changes in mouse biology that can confound data interpretation when using these tools to generate tissue-specific gene knockout mice. Our objective was to characterise the actions of Cre recombinase in skeletal muscle, and we anticipated that skeletal muscle-specific Cre recombinase expression driven by the human α-skeletal actin (HSA) promoter would influence glucose homeostasis. METHODS: Eight-week-old HSA-Cre expressing mice and their wild-type littermates were fed a low- or high-fat diet for 12 weeks. Glucose homeostasis (glucose/insulin tolerance testing) and whole-body energy metabolism (indirect calorimetry) were assessed. We also measured circulating insulin levels and the muscle expression of key regulators of energy metabolism. RESULTS: Whereas tamoxifen-treated HSA-Cre mice fed a low-fat diet exhibited no alterations in glucose homeostasis, we observed marked improvements in glucose tolerance in tamoxifen-treated, but not corn-oil-treated, HSA-Cre mice fed a high-fat diet vs their wild-type littermates. Moreover, Cre dissociation from heat shock protein 90 and translocation to the nucleus was only seen following tamoxifen treatment. These improvements in glucose tolerance were not due to improvements in insulin sensitivity/signalling or enhanced energy metabolism, but appeared to stem from increases in circulating insulin. CONCLUSIONS/INTERPRETATION: The intrinsic glycaemia phenotype in the HSA-Cre mouse necessitates the use of HSA-Cre controls, treated with tamoxifen, when using Cre-loxP models to investigate skeletal muscle-specific gene/protein function and glucose homeostasis.


Asunto(s)
Actinas/genética , Glucosa/metabolismo , Integrasas/metabolismo , Músculo Esquelético/enzimología , Regiones Promotoras Genéticas , Animales , Composición Corporal , Metabolismo de los Hidratos de Carbono , Medios de Cultivo Condicionados/química , Dieta Alta en Grasa , Metabolismo Energético , Prueba de Tolerancia a la Glucosa , Homeostasis , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Ratones , Ratones Endogámicos C57BL , Fenotipo , Triglicéridos/química
19.
Hum Mol Genet ; 24(14): 3971-81, 2015 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-25882706

RESUMEN

The pathological accumulation of abnormally hyperphosphorylated and aggregated tau, a neuronal microtubule (MT)-associated protein that functions to maintain MT stability, is implicated in a number of hereditary and sporadic neurodegenerative diseases including frontotemporal dementia and Alzheimer's disease. Targeting tau for the treatment of these diseases is an area of intense interest and toward that end, modulation of cellular molecular chaperones is a potential therapeutic target. In particular, the constitutive Hsp70 isoform, Hsc70, seems highly interconnected with tau, preserving tau protein levels and synergizing with it to assemble MTs. But the relationship between tau and Hsc70, as well as the impact of this interaction in neurons and its therapeutic implications remain unknown. Using a human dominant negative Hsc70 that resembles isoform selective inhibition of this important chaperone, we found for the first time that Hsc70 activity is required to stimulate MT assembly in cells and brain. However, surprisingly, active Hsc70 also requires active tau to regulate MT assembly in vivo, suggesting that tau acts in some ways as a co-chaperone for Hsc70 to coordinate MT assembly. This was despite tau binding to Hsc70 as substrate, as determined biochemically. Moreover, we show that while chronic Hsc70 inhibition damaged MT dynamics, intermittent treatment with a small molecule Hsp70 inhibitor lowered tau in brain tissue without disrupting MT integrity. Thus, in tauopathies, where MT injury would be detrimental to neurons, the unique relationship of tau with the Hsc70 machinery can be exploited to deplete tau levels without damaging MT networks.


Asunto(s)
Proteínas del Choque Térmico HSC70/metabolismo , Microtúbulos/metabolismo , Proteínas tau/metabolismo , Animales , Encéfalo/metabolismo , Regulación de la Expresión Génica , Células HEK293 , Proteínas del Choque Térmico HSC70/genética , Humanos , Espectroscopía de Resonancia Magnética , Ratones Noqueados , Neuronas/metabolismo , Oocitos , Fosforilación , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Tauopatías/genética , Tauopatías/terapia , Xenopus , Proteínas tau/genética
20.
Child Dev ; 88(2): 459-465, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28160274

RESUMEN

This special section of Child Development brings together experts in developmental science and intervention research to incorporate current evidence on resilience for vulnerable populations and give concrete suggestions for action and research. This commentary synthesizes the contributions of the articles, noting themes such as simultaneous attention to multiple risk, protective, and promotive processes; integrating new principles from clinical and therapeutic interventions; and adapting intervention approaches for new populations. It then describes additional directions for interventions to maximize resilience, including approaches that address social psychological processes, issues related to demographic and other forms of diversity, policy-related individual behaviors, and sequenced interventions across the life span. It also gives suggestions for integrating implementation science on expansion and scale with behavioral intervention science.


Asunto(s)
Desarrollo Infantil , Psicoterapia/métodos , Poblaciones Vulnerables/psicología , Niño , Humanos
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