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1.
Aggress Behav ; 50(1): e22120, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37942824

RESUMEN

Intimate partner aggression (IPA) is a costly and incompletely understood phenomenon. Negative urgency, the tendency to act impulsively in response to negative affect, is predictive of IPA perpetration. Mindfulness, by virtue of its emphasis on nonreactivity to negative affect, is an opposing force to urgent tendencies that may mitigate the negative urgency-IPA link. Yet, no research to date investigates the interactive effects of negative urgency and mindfulness on IPA perpetration. Two studies were conducted that measured and manipulated multiple facets of mindfulness alongside measures of negative urgency and tendencies of IPA perpetration (combined N = 508 undergraduate students in monogamous intimate relationships). Counter to our preregistered predictions, we found that negative urgency's association with greater IPA perpetration increased at higher levels of mindfulness. These findings suggest that mindfulness may not be a protective factor against IPA perpetration for individuals higher in negative urgency, but rather may serve as a risk factor.


Asunto(s)
Violencia de Pareja , Atención Plena , Humanos , Agresión , Relaciones Interpersonales , Conducta Sexual , Parejas Sexuales
2.
Artículo en Inglés | MEDLINE | ID: mdl-37526802

RESUMEN

As first generation (FG)/low income (LI) students enter the elite profession of medicine, schools make presumptions about how FGLI students allocate their time. However, their lives are markedly different compared to their peers. This study argues that while all forms of capital are necessary for success, time as a specific form keeps classism in place. Using constructivist grounded theory techniques, we interviewed 48 FGLI students to understand where, why and how they allocated their time, and the perceived impact it had on them. Using open coding and constant comparison, we developed an understanding of FGLI students' relationship to time and then contextualized it within larger conversations on how time is conceptualized in a capitalist system that demands time efficiency, and the activities where time is needed in medical school. When students discussed time, they invoked the concept of 'time famine;' having too much to do and not enough time. In attempting to meet medicine's expectations, they conceptualized time as something that was 'spent' or 'given/taken' as they traversed different marketplaces, using their time as a form of currency to make up for the social capital expected of them. This study shows that because medical education was designed around the social elite, a strata of individuals who have generational resources, time is a critical aspect separating FGLI students from their peers. This study undergirds the idea that time is a hidden organizational framework that helps to maintain classism, thus positioning FGLI students at a disadvantage.

3.
Photodermatol Photoimmunol Photomed ; 38(5): 478-488, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35073443

RESUMEN

Clothing is recognized by leading health agencies as a primary method to protect against the harmful effects of photodamage caused by ultraviolet (UV) radiation and visible light. The photoprotective capacity of clothing is commonly measured as the ultraviolet protective factor (UPF). While the technology driving photoprotective clothing has been well-established, there continues to be efforts to discover new materials to improve the UPF of clothing. Here, we show increased Google searches for photoprotective clothing over the last decade, suggesting a high level of public interest in photoprotective clothing. In addition, we investigate the frequency of UPF-graded photoprotective clothing sold by large retail stores featured in Fortune 1000. We review factors that alter the UPF of clothing and describe emerging textile technologies used to increase clothing's photoprotective capacity. Finally, we compare how photoprotective clothing is regulated among different countries, the importance of photoprotective clothing in occupational health, and research in visible light and clothing photoprotection.


Asunto(s)
Ropa de Protección , Rayos Ultravioleta , Humanos , Textiles , Rayos Ultravioleta/efectos adversos
4.
Hum Mutat ; 40(9): 1519-1529, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31342580

RESUMEN

The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α-N-acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to .61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population-scale analysis of disease epidemiology and rare variant association analysis.


Asunto(s)
Acetilglucosaminidasa/metabolismo , Biología Computacional/métodos , Mutación Missense , Acetilglucosaminidasa/genética , Humanos , Modelos Genéticos , Análisis de Regresión
5.
Med Mycol ; 57(1): 23-29, 2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-29390156

RESUMEN

In Northern Ireland there are concerns about candidaemia, with rates higher than those reported in England and Wales. Our aim was to explore the epidemiology of candidaemia during a 10 year period and the clinical management upon suspicion of cases during a one year enhanced investigation in Northern Ireland.Candidaemia reports to the Public Health Agency were validated during 2002-2011 and used to examine incidence and antifungal sensitivity trends (during 2007-2011). A clinical proforma was used to collate information for all patients with candidaemia in 2011.The majority (96%) of isolates were captured through voluntary laboratory reporting. There was a year-on-year increase in candidaemia from 2002-2011, from 80 to 131 episodes (incidence rate ratio 1.09 95% CI 1.05-1.13). Rates were highest in males under 1 year and over 75 years. 83/98 (85%) of case notes were available from candidaemia patients during 2011. The most prevalent risk factors were patients on total parenteral nutrition (26 people, 31.3%), surgery in the two months prior to the candidaemia (25 people, 30.1%), significant steroid use in the previous 3 months (24 people, 28.9%) and active neoplastic disease (23 people, 27.7%),This study confirmed an increase in candidaemia rates over time, with the observed incidence in 2011 higher than England and Wales. We identified areas for improvement around the clinical management of candidaemia. We recommend raising the awareness of guidelines for fundoscopy, echocardiography and central venous catheter removal.


Asunto(s)
Antifúngicos/uso terapéutico , Candidemia/tratamiento farmacológico , Candidemia/epidemiología , Antifúngicos/farmacología , Candida/clasificación , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candidemia/prevención & control , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Pruebas de Sensibilidad Microbiana/estadística & datos numéricos , Pruebas de Sensibilidad Microbiana/tendencias , Irlanda del Norte/epidemiología , Estudios Retrospectivos , Factores de Riesgo
6.
Nat Methods ; 10(3): 221-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23353650

RESUMEN

Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.


Asunto(s)
Biología Computacional/métodos , Biología Molecular/métodos , Anotación de Secuencia Molecular , Proteínas/fisiología , Algoritmos , Animales , Bases de Datos de Proteínas , Exorribonucleasas/clasificación , Exorribonucleasas/genética , Exorribonucleasas/fisiología , Predicción , Humanos , Proteínas/química , Proteínas/clasificación , Proteínas/genética , Especificidad de la Especie
7.
Bioinformatics ; 30(17): i609-16, 2014 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-25161254

RESUMEN

MOTIVATION: The automated functional annotation of biological macromolecules is a problem of computational assignment of biological concepts or ontological terms to genes and gene products. A number of methods have been developed to computationally annotate genes using standardized nomenclature such as Gene Ontology (GO). However, questions remain about the possibility for development of accurate methods that can integrate disparate molecular data as well as about an unbiased evaluation of these methods. One important concern is that experimental annotations of proteins are incomplete. This raises questions as to whether and to what degree currently available data can be reliably used to train computational models and estimate their performance accuracy. RESULTS: We study the effect of incomplete experimental annotations on the reliability of performance evaluation in protein function prediction. Using the structured-output learning framework, we provide theoretical analyses and carry out simulations to characterize the effect of growing experimental annotations on the correctness and stability of performance estimates corresponding to different types of methods. We then analyze real biological data by simulating the prediction, evaluation and subsequent re-evaluation (after additional experimental annotations become available) of GO term predictions. Our results agree with previous observations that incomplete and accumulating experimental annotations have the potential to significantly impact accuracy assessments. We find that their influence reflects a complex interplay between the prediction algorithm, performance metric and underlying ontology. However, using the available experimental data and under realistic assumptions, our results also suggest that current large-scale evaluations are meaningful and almost surprisingly reliable. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Proteínas/fisiología , Algoritmos , Biología Computacional/métodos , Ontología de Genes , Anotación de Secuencia Molecular , Proteínas/genética , Alineación de Secuencia
8.
Pulm Pharmacol Ther ; 31: 55-62, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25681618

RESUMEN

Inhalation of agricultural occupational dusts from swine confinement facilities can result in lung inflammation. The innate immune response to organic barn dusts results in production of a number of pro-inflammatory factors in the lungs of barn workers such as cytokines, chemokines, and an influx of neutrophils. Many of these inflammatory factors are influenced by the chemokine CXCL8/IL-8 (KC or MIP-2 in mice). Previously, we have demonstrated that an endotoxin-independent component of swine barn dust extract (SBE) elevates lung chemokines in a protein kinase C (PKC)-dependent manner resulting in the significant formation of lung inflammatory cell infiltrates in a mouse model of SBE injury. In this study we test the ability of a CXCR1/CXCR2 antagonist, CXCL8(3-74)K11R/G31P (G31P) to block many of the features of lung-inflammation in response to challenge with SBE in an established mouse exposure system. Injection of G31P concurrent with SBE nasal instillation over a course of 3 weeks significantly reduced neutrophil accumulation in the lungs of barn dust exposed animals compared to those given SBE alone. There was a similar reduction in pro-inflammatory cytokines and chemokines IL-6, KC, and MIP-2 in SBE plus G31P-treated mice. In addition to excreted products, the receptors ICAM-1, CXCR1, and CXCR2, which all were elevated with SBE exposure, were also decreased with G31P treatment. SBE activation of PKCα and PKCε was reduced as well with G31P treatment. Thus, G31P was found to be highly effective at reducing several features of lung inflammation in mice exposed to barn dust extracts.


Asunto(s)
Quimiocinas CXC/antagonistas & inhibidores , Inflamación/fisiopatología , Interleucina-8/farmacología , Fragmentos de Péptidos/farmacología , Crianza de Animales Domésticos , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Polvo , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Ratones , Enfermedades Profesionales/fisiopatología , Proteína Quinasa C/metabolismo , Porcinos
9.
Am J Physiol Lung Cell Mol Physiol ; 306(6): L584-9, 2014 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-24487393

RESUMEN

The elderly are at much higher risk for developing pneumonia than younger individuals. Pneumonia is a leading cause of death and is the third most common reason for hospitalization in the elderly. One reason that elderly people may be more susceptible to pneumonia is a breakdown in the lung's first line of defense, mucociliary clearance. Cilia beat in a coordinated manner to propel out invading microorganisms and particles. Ciliary beat frequency (CBF) is known to slow with aging, however, little is known about the mechanism(s) involved. We compared the CBF in BALB/c and C57BL/6 mice aged 2, 12, and 24 mo and found that CBF diminishes with age. Cilia in the mice at age 12 and 24 mo retained their ability to be stimulated by the ß2 agonist procaterol. To help determine the mechanism of ciliary slowing, we measured protein kinase C alpha and epsilon (PKCα and PKCε) activity. There were no activity differences in PKCα between the mice aged 2, 12, or 24 mo. However, we demonstrated a significantly higher PKCε activity in the mice at 12 and 24 mo than the in the mice 2 mo of age. The increase in activity is likely due to a nearly threefold increase in PKCε protein in the lung during aging. To strengthen the connection between activation of PKCε and ciliary slowing, we treated tracheas of mice at 2 mo with the PKCε agonist 8-[2-(2-pentylcyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA). We noted a similar decrease in baseline CBF, and the cilia remained sensitive to stimulation with ß2 agonists. The mechanisms for the slowing of baseline CBF have not been previously determined. In this mouse model of aging we were able to show that decreases in CBF are related to an increase in PKCε activity.


Asunto(s)
Envejecimiento/fisiología , Pulmón/fisiopatología , Depuración Mucociliar/fisiología , Neumonía/enzimología , Proteína Quinasa C-epsilon/metabolismo , Agonistas de Receptores Adrenérgicos beta 2/farmacología , Factores de Edad , Animales , Caprilatos/farmacología , Cilios/enzimología , Cilios/fisiología , Células Epiteliales/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Animales , Procaterol/farmacología , Proteína Quinasa C-alfa/metabolismo
10.
Fungal Genet Biol ; 64: 11-24, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24412483

RESUMEN

The polyol mannitol is one of the main compatible solutes in Neosartorya fischeri and accumulates in conidia and ascospores. Here, it is shown that biosynthesis of mannitol in N. fischeri mainly depends on mannitol 1-phosphate dehydrogenase (MpdA). Reporter studies and qPCR analysis demonstrated that mpdA is moderately expressed in vegetative hyphae and conidiophores, while it is highly expressed during development of ascospores. Deletion of mpdA reduced mannitol in whole cultures as much as 85% of the wild type, while trehalose levels had increased more than 4-fold. Decreased mannitol accumulation had no effect on mycelial growth irrespective of heat- or oxidative stress. Notably, conidia of the ΔmpdA strain had higher mannitol and lower trehalose levels. They were more sensitive to heat stress. The most distinct phenotype of mpdA deletion was the absence of full development of ascospores. Formation of cleistothecia, and asci was not affected. The ascus cell wall, however, did not dissolve and asci contained incompletely formed or aborted ascospores. Addition of the Mpd inhibitor nitrophenide to the wild type strain also resulted in disturbed ascospore formation. Taken together, these results show that mannitol has a role in sexual development of N. fischeri and in stress resistance of conidia.


Asunto(s)
Manitol/metabolismo , Neosartorya/fisiología , Esporas Fúngicas/fisiología , Estrés Fisiológico , Secuencia de Aminoácidos , Calor , Datos de Secuencia Molecular , Estrés Oxidativo , Deshidrogenasas del Alcohol de Azúcar/metabolismo
11.
Bioinformatics ; 29(13): i53-61, 2013 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-23813009

RESUMEN

MOTIVATION: The development of effective methods for the prediction of ontological annotations is an important goal in computational biology, with protein function prediction and disease gene prioritization gaining wide recognition. Although various algorithms have been proposed for these tasks, evaluating their performance is difficult owing to problems caused both by the structure of biomedical ontologies and biased or incomplete experimental annotations of genes and gene products. RESULTS: We propose an information-theoretic framework to evaluate the performance of computational protein function prediction. We use a Bayesian network, structured according to the underlying ontology, to model the prior probability of a protein's function. We then define two concepts, misinformation and remaining uncertainty, that can be seen as information-theoretic analogs of precision and recall. Finally, we propose a single statistic, referred to as semantic distance, that can be used to rank classification models. We evaluate our approach by analyzing the performance of three protein function predictors of Gene Ontology terms and provide evidence that it addresses several weaknesses of currently used metrics. We believe this framework provides useful insights into the performance of protein function prediction tools. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Ontología de Genes , Anotación de Secuencia Molecular , Proteínas/fisiología , Algoritmos , Teorema de Bayes , Interpretación Estadística de Datos , Genes , Humanos , Proteínas/química , Proteínas/genética
12.
Oper Dent ; 49(3): 290-299, 2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38632850

RESUMEN

PURPOSE: This study's purpose was to evaluate the effect of simulated in vitro hydrostatic pulpal pressure (HPP) on microleakage. METHODS AND MATERIALS: Extracted third molars (n=12) were sectioned 5 mm below the cementoenamel junction, pulp tissue removed, and the sectioned crowns mounted on a Plexiglas plate penetrated by an 18-gauge stainless steel tube. The mounted specimen mesial surface received a 2×4×6 mm Class V preparation followed by restoration with a strongly acidic, one-step dental adhesive and a flowable microfilled resin, following all manufacturers' instructions. Restorations were finished to contour, and tubing was attached to a 20-cm elevated, 0.2% rhodamine G reservoir to the specimen steel tube for 48 hours. Specimens then received a nail polish coating to within 1 mm of the restoration margins and were placed in 2% methylene blue (MB) dye for 24 hours, followed by rinsing, embedding in epoxy resin, and sectioning into 1 mm slices using a diamond saw. Controls were intact molars (n=12) processed as above but without HPP. Specimen slices were evaluated using laser confocal microscopy with images exported to ImageJ software with microleakage assessed as the MB linear penetration as a percentage of the total interfacial wall length. Mean values were evaluated with the Kruskal Wallis/Dunn test at a 95% confidence level. RESULTS: The control specimens demonstrated significantly greater (p<0.0001) MB penetration than experimental specimens with simulated HPP. Under this study's conditions, simulated HPP significantly decreased MB dye penetration. CONCLUSION: Studies accomplished without simulated HPP may overestimate microleakage results.


Asunto(s)
Resinas Compuestas , Filtración Dental , Pulpa Dental , Presión Hidrostática , Humanos , Pulpa Dental/fisiología , Resinas Compuestas/química , Resinas Compuestas/uso terapéutico , Microscopía Confocal , Restauración Dental Permanente/métodos , Preparación de la Cavidad Dental/métodos , Tercer Molar , Cementos de Resina/química
13.
Curr Issues Personal Psychol ; 12(1): 11-19, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756194

RESUMEN

BACKGROUND: Personality traits are known factors that may influence levels of physical activity and other healthy lifestyle measures and behaviors that ultimately lead to health problems later in life. Participants And Procedure: The aim of this study was to examine the association between personality traits (HEXACO) and levels of physical activity and resting heart rate (RHR) - measured using Fitbits, BMI, and a self-reported whole-person healthy lifestyle score for N = 2580 college students. Data were collected and analyzed for students enrolled in a University Success type course from August 2017 to May 2021. The relationships between HEXACO personality traits and various physical activity and healthy lifestyle behaviors were analyzed by building several multiple regression models using R version 4.0.2. Results: In general, students who are extraverted were more physically active and students who are more open to experience had a higher RHR, even when controlling for gender. Females and males however had different profiles as to how personality influenced physical activity and other health-related measures. Male extraverts with high negative emotionality scores tend to be more physically active, whereas females tend to be more physically active when they were high in extroversion and conscientiousness, and low in openness to experience. BMI values were higher for female participants with high honesty-humility and low agreeableness and conscientiousness scores. Females also had a lower RHR for high honesty-humility and emotionality and low conscientiousness scores. CONCLUSIONS: Personality can influence levels of physical activity, RHR, and BMI. This is especially true of women. Being aware of one's personality and the relationship of personality traits to levels of physical activity and other measures of leading a healthy lifestyle can be beneficial in determining strategies to improve long-term health outcomes.

14.
Stud Mycol ; 74(1): 71-85, 2013 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-23449730

RESUMEN

The impact of natamycin on Aspergillus niger was analysed during the first 8 h of germination of conidia. Polarisation, germ tube formation, and mitosis were inhibited in the presence of 3 and 10 µM of the anti-fungal compound, while at 10 µM also isotropic growth was affected. Natamycin did not have an effect on the decrease of microviscosity during germination and the concomitant reduction in mannitol and trehalose levels. However, it did abolish the increase of intracellular levels of glycerol and glucose during the 8 h period of germination.Natamycin hardly affected the changes that occur in the RNA profile during the first 2 h of germination. During this time period, genes related to transcription, protein synthesis, energy and cell cycle and DNA processing were particularly up-regulated. Differential expression of 280 and 2586 genes was observed when 8 h old germlings were compared with conidia that had been exposed to 3 µM and 10 µM natamycin, respectively. For instance, genes involved in ergosterol biosynthesis were down-regulated. On the other hand, genes involved in endocytosis and the metabolism of compatible solutes, and genes encoding protective proteins were up-regulated in natamycin treated conidia.

15.
Mediators Inflamm ; 2013: 592892, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24307761

RESUMEN

The airway epithelium is exposed to alcohol during drinking through direct exhalation of volatized ethanol from the bronchial circulation. Alcohol exposure leads to a rapid increase in the cilia beat frequency (CBF) of bronchial epithelial cells followed by a chronic desensitization of cilia stimulatory responses. This effect is governed in part by the nitric oxide regulation of cyclic guanosine and adenosine monophosphate-dependent protein kinases (PKG and PKA) and is not fully understood. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is implicated in the pathogenesis of several pulmonary disorders. We hypothesized that the inhibition of nitric oxide synthase by ADMA blocks alcohol-stimulated increases in CBF. To test this hypothesis, ciliated primary bovine bronchial epithelial cells (BBEC) were preincubated with ADMA (100 µM) and stimulated with 100 mM ethanol. CBF was measured and PKA assayed. By 1 hr, ethanol activated PKA, resulting in elevated CBF. Both alcohol-induced PKA activation and CBF were inhibited in the presence of ADMA. ADMA alone had no effect on PKA activity or CBF. Using a mouse model overexpressing the ADMA-degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH), we examined PKA and CBF in precision-cut mouse lung slices. Alcohol-stimulated increases in lung slice PKA and CBF were temporally enhanced in the DDAH mice versus control mice.


Asunto(s)
Arginina/análogos & derivados , Cilios/patología , Células Epiteliales/efectos de los fármacos , Etanol/farmacología , Óxido Nítrico/metabolismo , Amidohidrolasas/química , Animales , Arginina/farmacología , Bronquios/citología , Bronquios/patología , Bovinos , Supervivencia Celular , Células Cultivadas , Cilios/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Células Epiteliales/citología , Pulmón/patología , Enfermedades Pulmonares/fisiopatología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Factores de Tiempo , Tráquea/patología
16.
Genome Biol ; 24(1): 172, 2023 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-37480112

RESUMEN

BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by mutations in the arylsulfatase A gene (ARSA) and categorized into three subtypes according to age of onset. The functional effect of most ARSA mutants remains unknown; better understanding of the genotype-phenotype relationship is required to support newborn screening (NBS) and guide treatment. RESULTS: We collected a patient data set from the literature that relates disease severity to ARSA genotype in 489 individuals with MLD. Patient-based data were used to develop a phenotype matrix that predicts MLD phenotype given ARSA alleles in a patient's genotype with 76% accuracy. We then employed a high-throughput enzyme activity assay using mass spectrometry to explore the function of ARSA variants from the curated patient data set and the Genome Aggregation Database (gnomAD). We observed evidence that 36% of variants of unknown significance (VUS) in ARSA may be pathogenic. By classifying functional effects for 251 VUS from gnomAD, we reduced the incidence of genotypes of unknown significance (GUS) by over 98.5% in the overall population. CONCLUSIONS: These results provide an additional tool for clinicians to anticipate the disease course in MLD patients, identifying individuals at high risk of severe disease to support treatment access. Our results suggest that more than 1 in 3 VUS in ARSA may be pathogenic. We show that combining genetic and biochemical information increases diagnostic yield. Our strategy may apply to other recessive diseases, providing a tool to address the challenge of interpreting VUS within genotype-phenotype relationships and NBS.


Asunto(s)
Leucodistrofia Metacromática , Humanos , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/genética , Fenotipo , Genotipo , Alelos , Gravedad del Paciente
17.
Appl Environ Microbiol ; 78(19): 6930-7, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22843536

RESUMEN

Indoor mold represents an important environmental concern, but a fundamental knowledge of fungal growth stages is needed to limit indoor fungal proliferation on finishing materials used in buildings. The present study focused on the succession of germination stages of the common indoor fungus Penicillium rubens on a gypsum substrate. This substrate is used as a model system representing porous materials that are widely used in indoor environments. Imaging with cryo-scanning electron microscopy showed that the formation of an extracellular matrix (ECM) is a phase of the isotropic growth of P. rubens that is uniquely related to germinating conidia. Furthermore, the ECM is observed only when a dry-state inoculation of the surface is applied, i.e., applying conidia directly from a 7-day-old colony, mimicking airborne contamination of the surface. When inoculation is done by spraying an aqueous conidial suspension, no ECM is observed. Moreover, it is concluded that the formation of an ECM requires active processes in the fungal cell. The porosity of the substrate proved that the ECM substance has high-viscosity characteristics. The present results stress that studies of indoor fungal growth should consider the method of inoculation, knowing that the common aqueous suspension may obscure specific stages in the initial phases of germination.


Asunto(s)
Sulfato de Calcio/metabolismo , Microbiología Ambiental , Matriz Extracelular/metabolismo , Penicillium/crecimiento & desarrollo , Penicillium/metabolismo , Microscopía por Crioelectrón , Microscopía Electrónica de Rastreo , Esporas Fúngicas/crecimiento & desarrollo
18.
PLoS Comput Biol ; 7(6): e1002073, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21695233

RESUMEN

A common assumption in comparative genomics is that orthologous genes share greater functional similarity than do paralogous genes (the "ortholog conjecture"). Many methods used to computationally predict protein function are based on this assumption, even though it is largely untested. Here we present the first large-scale test of the ortholog conjecture using comparative functional genomic data from human and mouse. We use the experimentally derived functions of more than 8,900 genes, as well as an independent microarray dataset, to directly assess our ability to predict function using both orthologs and paralogs. Both datasets show that paralogs are often a much better predictor of function than are orthologs, even at lower sequence identities. Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species. We also find that paralogous pairs residing on the same chromosome are more functionally similar than those on different chromosomes, perhaps due to higher levels of interlocus gene conversion between these pairs. In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence. We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.


Asunto(s)
Hibridación Genómica Comparativa , Evolución Molecular , Genes , Animales , Dosificación de Gen , Perfilación de la Expresión Génica , Humanos , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas/genética
19.
Can Med Educ J ; 13(1): 96-98, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35291450

RESUMEN

The Education Innovation Institute (EII) of Medical College of Georgia, Augusta University, hosted a conference on Twitter about Professional Identity Formation (PIF), #MCGConf2021PIF, on February 25, 2021. The conference featured five presentations by 15 authors from Canada and the U.S. A Twitter conference is a versatile, affordable, and accessible digital option for medical education groups interested in diversifying conference offerings and reaching a broader audience. It was low-cost, organized in six months, and garnered over 9,000 Twitter impressions. Small networks and interest groups can organize Twitter conferences for their constituencies and larger conference organizations can host online mini-conferences to supplement in-person events.


Le 25 février 2021, l'Educational Innovation Institute (EII) du Medical College of Georgia de l'Université Augusta a tenu une conférence sur la construction de l'identité professionnelle sur le réseau social Twitter (#MCGConf2021PIF). Cinq communications y ont été présentées par 15 chercheurs du Canada et des États-Unis. Elle a été organisée en six mois, à coût modeste, et elle a recueilli plus de 9000 impressions sur Twitter. La conférence Twitter s'avère être une option numérique polyvalente, abordable et accessible pour les membres du milieu de l'éducation médicale désireux de diversifier leur offre de symposiums et de toucher un public plus large. Twitter offre aux petits réseaux et groupes d'intérêt la possibilité de convier leurs membres à des conférences restreintes et aux organisateurs de conférences plus importantes la possibilité de tenir des mini-conférences en ligne pour compléter leurs activités en personne.

20.
J Natl Med Assoc ; 114(4): 456-464, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35728993

RESUMEN

OBJECTIVE: Professional identity formation (PIF) is considered a fundamental process in the development of healthcare providers. In medical education, the PIF literature has historically centered on medicine's socialization practices involving white male physicians. However, recently researchers have begun to reveal how larger socio-historical contexts influence PIF in minoritized physicians. To better understand what influences Black/African American physicians' PIF, this study compares their PIF experiences to a group of minoritized physician assistants (PAs). In comparing Black physicians' experiences to another provider, this study explored what PIF experiences may be attributed to participants' minoritized status and what might be attributed to the culture of medicine. METHODS: In this cross-case analysis, 45 minoritized PA students and practicing PAs were recruited from several Southeastern universities. The PA participants included 23 Black/African Americans, 12 Latinx, 4 Indigenous/Native, and 6 of mixed races/ethnicities. Interview data were then compared to previously collected data from 41 Black/African American medical trainees and physicians. Using constant comparative method, similarities and differences in PIF were explored. RESULTS: Similarities between the two groups included the importance of participants' racial/ethnic identity to patient care, experiences on-going microaggressions from patients and peers, and a desire to engage in racial uplift. However, one marked difference was found, namely that PAs felt they could bring their entire selves to the profession, whereas physicians described feeling splintered early in their training. CONCLUSIONS: Several possibilities that might explain why Black physicians and minoritized PAs have this one marked difference in their PIF experience, including identity threat, internalization of different discourses, and length of training for physicians. While this study was not designed to answer this question, it is clear that there is something in the culture of medicine and the training of physicians that signals to Black physicians that they cannot bring their whole selves to the profession.


Asunto(s)
Educación Médica , Medicina , Médicos , Humanos , Masculino , Identificación Social , Socialización
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