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T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour1 that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation2,3. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes. Analyses of chromatin topology revealed multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific manner, thereby demonstrating widespread involvement of the noncoding genome. We show that the immunophenotypically described, high-risk entity of early T cell precursor ALL is superseded by a broader category of 'early T cell precursor-like' leukaemia. This category has a variable immunophenotype and diverse genomic alterations of a core set of genes that encode regulators of hematopoietic stem cell development. Using multivariable outcome models, we show that genetic subtypes, driver and concomitant genetic alterations independently predict treatment failure and survival. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.
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A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study2. We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P ≤ 2.18 × 10-11. Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension (SLC9A3R2), diabetes (MAP3K15, FAM234A) and asthma (SLC27A3). Six genes were associated with brain imaging phenotypes, including two involved in neural development (GBE1, PLD1). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene-trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale.
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Bancos de Muestras Biológicas , Bases de Datos Genéticas , Secuenciación del Exoma , Exoma/genética , África/etnología , Asia/etnología , Asma/genética , Diabetes Mellitus/genética , Europa (Continente)/etnología , Oftalmopatías/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Hipertensión/genética , Hepatopatías/genética , Masculino , Mutación , Neoplasias/genética , Carácter Cuantitativo Heredable , Reino UnidoRESUMEN
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world1. Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenic BRCA1 and BRCA2 variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
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Bases de Datos Genéticas , Secuenciación del Exoma , Exoma/genética , Mutación con Pérdida de Función/genética , Fenotipo , Anciano , Densidad Ósea/genética , Colágeno Tipo VI/genética , Demografía , Femenino , Genes BRCA1 , Genes BRCA2 , Genotipo , Humanos , Canales Iónicos/genética , Masculino , Persona de Mediana Edad , Neoplasias/genética , Penetrancia , Fragmentos de Péptidos/genética , Reino Unido , Várices/genética , Proteínas Activadoras de ras GTPasa/genéticaRESUMEN
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.
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COVID-19/diagnóstico , COVID-19/genética , Secuenciación del Exoma , Exoma/genética , Predisposición Genética a la Enfermedad , Hospitalización/estadística & datos numéricos , COVID-19/inmunología , COVID-19/terapia , Femenino , Humanos , Interferones/genética , Masculino , Pronóstico , SARS-CoV-2 , Tamaño de la MuestraRESUMEN
PURPOSE: To estimate incidence and evaluate demographic risk factors and visual acuity (VA) outcomes of open-globe injuries requiring surgical repair in the IRIS® Registry (Intelligent Research in Sight). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with open-globe injury repairs (OGRs) were identified by Current Procedural Terminology codes (65275, 65280, 65285, 65286, 65235, 65260, and 65265) from 2014 through 2018 in the IRIS Registry. METHODS: Logistic regression models adjusting for age, sex, race, ethnicity, United States region, concurrent and subsequent surgeries, and baseline VA. MAIN OUTCOME MEASURES: Outcomes included annual and 5-year incidence rates per 100 000 people and factors associated with OGR, VA better than 20/40, and VA of 20/200 or worse at final follow-up (3-12 months after OGR). RESULTS: Thirteen thousand seven hundred sixty-six OGRs were identified; 5-year cumulative incidence was 28.0 per 100 000 patients. Open-globe repair was associated with age 21 to 40 years compared with younger than 21 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.5-1.7]), male sex (OR, 2.8; 95% CI, 2.7-2.9), Black versus White race (OR, 1.3; 95% CI, 1.2-1.4), Hispanic versus non-Hispanic ethnicity (OR, 1.7; 95% CI, 1.6-1.8), and South (OR, 1.4; 95% CI, 1.3-1.5) and West (OR, 1.3; 95% CI, 1.2-1.4) versus Midwest regions and associated inversely with Asian versus White race (OR, 0.6; 95% CI, 0.6-0.7). Visual acuity outcomes, analyzed in a subset of 2966 patients with VA data available, showed vision impairment (VA < 20/40) at final follow-up was associated with VA of 20/200 or worse at presentation (20/200 better than 20/40; OR, 11.1; 95% CI, 8.0-15.7), older age (e.g., > 80 years vs. < 21 years; OR, 5.8; 95% CI, 3.2-10.7), and Black versus White race (OR, 1.8; 95% CI, 1.3-2.6). Risk factors were similar for VA of 20/200 or worse after OGR. Among the 1063 patients undergoing OGR with VA of 20/200 or worse at presentation, VA did not improve to better than 20/200 at follow-up in 35% of patients (1063/2996). CONCLUSIONS: Our findings bring to light racial disparities in risk of OGR and poor visual outcomes that warrant further exploration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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Lesiones Oculares , Oftalmología , Humanos , Masculino , Estados Unidos/epidemiología , Adulto Joven , Adulto , Incidencia , Estudios Retrospectivos , Lesiones Oculares/epidemiología , Lesiones Oculares/cirugía , Factores de Riesgo , Sistema de RegistrosRESUMEN
BACKGROUND: The hand is highly visible and contributes to an individual's aesthetic image and perceived age. Current perspectives on hand aesthetics are primarily based on expert opinion rather than on lay population perspectives, which are less understood. Our study explores general population perceptions on the features that contribute most to an attractive hand. METHODS: Participants rated the attractiveness of 20 standardized hands as well as the appearance based on each characteristic: freckles, hair presence, skin tone, wrinkles, vein appearance, and soft tissue volume. The relative importance of each feature was assessed by comparison with overall attractiveness scores through multivariate analysis of variance. RESULTS: A total of 223 participants completed the survey. Soft tissue volume ( r = 0.73) was most strongly correlated with overall attractiveness, followed by wrinkles ( r = 0.71), skin tone consistency ( r = 0.69), veins ( r = 0.65), freckles ( r = 0.61), and hair ( r = 0.47). Female hands were perceived as more attractive, with a mean rating of 4.7 of 10, compared with 4.4 in males ( P < 0.001). Participants correctly identified the gender of 90.4% of male hands and 65.0% of female hands. Age was strongly inversely correlated with attractiveness ( r = -0.80). CONCLUSIONS: Soft tissue volume is the most important factor in lay perception of hand aesthetics. Female and younger hands were perceived as more attractive. Hand rejuvenation may be optimized by prioritizing soft tissue volume with filler or fat grafting, with secondary priority on resurfacing to address skin tone and wrinkling. An understanding of the factors most important to patients in aesthetic appearance is critical to achieving a pleasing result.
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Mano , Envejecimiento de la Piel , Humanos , Masculino , Femenino , Estética , Mano/cirugía , Piel , CabelloRESUMEN
Our understanding of molecules has stagnated at a single quantum system, with atoms as Newtonian particles and electrons as quantum particles. Here, however, we reveal that both atoms and electrons in a molecule are quantum particles, and their quantum-quantum interactions create a previously unknown, newfangled molecular property-supracence. Molecular supracence is a phenomenon in which the molecule transfers its potential energy from quantum atoms to photo-excited electrons so that the emitted photon has more energy than that of the absorbed one. Importantly, experiments reveal such quantum energy exchanges are independent of temperature. When quantum fluctuation results in absorbing low-energy photons, yet still emitting high-energy photons, supracence occurs. This report, therefore, reveals novel principles governing molecular supracence via experiments that were rationalized by full quantum (FQ) theory. This advancement in understanding predicts the super-spectral resolution of supracence, and molecular imaging confirms such innovative forecasts using closely emitting rhodamine 123 and rhodamine B in living cell imaging of mitochondria and endosomes.
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Electrones , FotonesRESUMEN
The neuropathology of hippocampal seizure foci in human temporal lobe epilepsy (TLE) and several animal models of epilepsy reveal extensive neuronal loss along with astrocyte and microglial activation. Studies of these models have advanced hypotheses that propose both pathological changes are essential for seizure generation. However, some seizure foci in human TLE show an extreme loss of neurons in all hippocampal fields, giving weight to hypotheses that favor neuroglia as major players. The epileptic (EL) mouse is a seizure model in which there is no observable neuron loss but associated proliferation of microglia and astrocytes and provides a good model to study the role of activated neuroglia in the presence of an apparently normal population of neurons. While many studies have been carried out on the EL mouse, there is a paucity of studies on the molecular changes in the EL mouse hippocampus, which may provide insight on the role of neuroglia in epileptogenesis. In this paper we have applied high throughput gene expression analysis to identify the molecular changes in the hippocampus that may explain the pathological processes. We have observed several classes of genes whose expression levels are changed. It is hypothesized that the upregulation of heat shock proteins (HSP70, HSP72, FOSL2 (HSP40), and their molecular chaperones BAG3 and DNAJB5 along with the down regulated gene MALAT1 may contribute to the neuroprotection observed. The increased expression of BDNF along with immediate early gene expression (FosB, JunB, ERG4, NR4A1, NR4A2, FBXO3) and the down regulation of GABRD, DBP and MALAT1 it is hypothesized may contribute to the hyperexcitability of the hippocampal neurons in this model. Activated astrocytes and microglia may also contribute to excitability pathomechanisms. Activated astrocytes in the ELS mouse are deficient in glutamine synthetase and thus reduce the clearance of extracellular glutamate. Activated microglia which may be associated with C1Q and MHC class I molecules we propose may mediate a process of selective removal of defective GABAergic synapses through a process akin to trogocytosis that may reduce neuronal inhibition and favor hyperexcitability.
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Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Neuroglía/metabolismo , Neuronas/metabolismo , Transcriptoma , Animales , Ratones , Ratones MutantesRESUMEN
BACKGROUND: Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. METHODS: We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples. RESULTS: A splice variant (rs72613567:TA) in HSD17B13, encoding the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13, was associated with reduced levels of ALT (P=4.2×10-12) and AST (P=6.2×10-10). Among DiscovEHR study participants, this variant was associated with a reduced risk of alcoholic liver disease (by 42% [95% confidence interval {CI}, 20 to 58] among heterozygotes and by 53% [95% CI, 3 to 77] among homozygotes), nonalcoholic liver disease (by 17% [95% CI, 8 to 25] among heterozygotes and by 30% [95% CI, 13 to 43] among homozygotes), alcoholic cirrhosis (by 42% [95% CI, 14 to 61] among heterozygotes and by 73% [95% CI, 15 to 91] among homozygotes), and nonalcoholic cirrhosis (by 26% [95% CI, 7 to 40] among heterozygotes and by 49% [95% CI, 15 to 69] among homozygotes). Associations were confirmed in two independent cohorts. The rs72613567:TA variant was associated with a reduced risk of nonalcoholic steatohepatitis, but not steatosis, in human liver samples. The rs72613567:TA variant mitigated liver injury associated with the risk-increasing PNPLA3 p.I148M allele and resulted in an unstable and truncated protein with reduced enzymatic activity. CONCLUSIONS: A loss-of-function variant in HSD17B13 was associated with a reduced risk of chronic liver disease and of progression from steatosis to steatohepatitis. (Funded by Regeneron Pharmaceuticals and others.).
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17-Hidroxiesteroide Deshidrogenasas/genética , Hígado Graso/genética , Predisposición Genética a la Enfermedad , Hepatopatías/genética , Mutación con Pérdida de Función , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Enfermedad Crónica , Progresión de la Enfermedad , Femenino , Variación Genética , Genotipo , Humanos , Modelos Lineales , Hígado/patología , Hepatopatías/patología , Masculino , Análisis de Secuencia de ARN , Secuenciación del ExomaRESUMEN
ABSTRACT: Studies show that medical school curriculums do not prepare graduates to manage the most common musculoskeletal (MSK) injuries they will encounter in the outpatient setting. The authors proposed a new multiple-choice assessment to identify individual and program deficiencies for curriculum improvement. A multiple-choice MSK assessment tool was administered to learners at various stages of training. Students took the examination after completing their core clerkship year; residents took the examination near the beginning of their respective academic year. Outcome measures included average examination score, percent correct for each question, and overall examination reliability. Average examinees scores were 75.6% with higher scores based on training years. No statistical differences were found between MD/DO, male/female, or military/civilian examinees. The tool was found to be a statistically valid method of determining cognitive knowledge in basic MSK topics, identifying individual deficiencies, and highlighting gaps in training programs' MSK curriculums.
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Prácticas Clínicas , Competencia Clínica , Curriculum , Evaluación Educacional , Internado y Residencia , Sistema Musculoesquelético/lesiones , Medicina Familiar y Comunitaria/educación , Femenino , Humanos , Masculino , Estados UnidosRESUMEN
Congenital diaphragmatic hernia (CDH) has been reported twice in individuals with a clinical diagnosis of Fraser syndrome, a genetic disorder that can be caused by recessive mutations affecting FREM2 and FRAS1. In the extracellular matrix, FREM2 and FRAS1 form a self-stabilizing complex with FREM1, a protein whose deficiency causes sac CDH in humans and mice. By sequencing FREM2 and FRAS1 in a CDH cohort, and searching online databases, we identified five individuals who carried recessive or double heterozygous, putatively deleterious variants in these genes which may represent susceptibility alleles. Three of these alleles were significantly enriched in our CDH cohort compared with ethnically matched controls. We subsequently demonstrated that 8% of Frem2ne/ne and 1% of Fras1Q1263*/Q1263* mice develop the same type of anterior sac CDH seen in FREM1-deficient mice. We went on to show that development of sac hernias in FREM1-deficient mice is preceded by failure of anterior mesothelial fold progression resulting in the persistence of an amuscular, poorly vascularized anterior diaphragm that is abnormally adherent to the underlying liver. Herniation occurs in the perinatal period when the expanding liver protrudes through this amuscular region of the anterior diaphragm that is juxtaposed to areas of muscular diaphragm. Based on these data, we conclude that deficiency of FREM2, and possibly FRAS1, are associated with an increased risk of developing CDH and that loss of the FREM1/FREM2/FRAS1 complex, or its function, leads to anterior sac CDH development through its effects on mesothelial fold progression.
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Proteínas de la Matriz Extracelular/genética , Hernias Diafragmáticas Congénitas/genética , Receptores de Interleucina/genética , Animales , Niño , Preescolar , Epitelio/patología , Proteínas de la Matriz Extracelular/deficiencia , Femenino , Hernias Diafragmáticas Congénitas/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Ratones , Ratones Noqueados , Mutación , EmbarazoRESUMEN
BACKGROUND: With the American College of Obstetricians and Gynecologists reaffirming its 2007 opposition to labiaplasty in 2019, the procedure continues to be controversial. Particular emphasis on pornography as a major influencer on women seeking labiaplasty contributes to its controversy and distracts from other motivations. Few articles have established pornography's influence relative to functional and appearance-related symptoms. OBJECTIVES: The objective of this study was to investigate the relative influence of pornography on women's decision to seek labiaplasty relative to other factors compared with a control cohort. METHODS: In this prospective study, 124 consecutive patients consulting about labiaplasty and a control cohort of 50 women were questioned about 11 labia-related symptoms and the possible influence of pornography. RESULTS: The mean age was 34.2 and 38.9 years in the labiaplasty and control cohorts, respectively. Women in the labiaplasty cohort had on average 2.8 of the 6 queried physical symptoms and 3.2 of the 5 queried appearance-related symptoms compared with control patients who reported an average of 0.3 of the 6 queried physical symptoms and 0.2 of the 5 queried appearance-related symptoms (P < 0.001). Less than one-half (47% of the labiaplasty and 42% of the control cohort) never viewed pornography. Pornography was not an influential factor to seek labiaplasty in 42% of the labiaplasty cohort and 54% of the control cohort. A minority (11% in the labiaplasty cohort and 4% in the control cohort) said that pornography influenced them to seek labiaplasty. There were no statistically significant differences between these 2 groups. CONCLUSION: Pornography influences some women to seek labiaplasty, but relative to other motivating factors its role is minor.
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Literatura Erótica , Vulva , Adulto , Femenino , Humanos , Motivación , Estudios Prospectivos , Vulva/cirugíaRESUMEN
Monitoring multiple molecular probes simultaneously establishes their correlations and reveals the holistic mechanism. Current fluorescence imaging, however, is limited to about four colors because of typically circa 100-nm spectral width. Herein, we show that molecular supracence imparts superior spectral resolution, resolving eight colors in 300-nm width, about 37.5-nm per color. A recently discovered light-molecule interacting phenomenon, supracence only measures molecular emission above its excitation energy due to entanglement between atomic quantum system and electronic quantum system. As such, supracence takes advantage of sharp spectral edge of a single pathway and excitation specificity to produce narrow bands, whereas fluorescence has to deal with multiple pathways spilling out low-energy long tail, that causes poor resolution. Thus, supracence enables myriad innovative molecular spectroscopy and microscopic imaging with profound impact broadly.
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Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into multiple lineages including osteoblastic lineage. Osteogenic differentiation of MSCs is a cascade that recapitulates most, if not all, of the molecular events occurring during embryonic skeletal development, which is regulated by numerous signaling pathways including bone morphogenetic proteins (BMPs). Through a comprehensive analysis of the osteogenic activity, we previously demonstrated that BMP9 is the most potent BMP for inducing bone formation from MSCs both in vitro and in vivo. However, as one of the least studied BMPs, the essential mediators of BMP9-induced osteogenic signaling remain elusive. Here we show that BMP9-induced osteogenic signaling in MSCs requires intact Notch signaling. While the expression of Notch receptors and ligands are readily detectable in MSCs, Notch inhibitor and dominant-negative Notch1 effectively inhibit BMP9-induced osteogenic differentiation in vitro and ectopic bone formation in vivo. Genetic disruption of Notch pathway severely impairs BMP9-induced osteogenic differentiation and ectopic bone formation from MSCs. Furthermore, while BMP9-induced expression of early-responsive genes is not affected by defective Notch signaling, BMP9 upregulates the expression of Notch receptors and ligands at the intermediate stage of osteogenic differentiation. Taken together, these results demonstrate that Notch signaling may play an essential role in coordinating BMP9-induced osteogenic differentiation of MSCs.
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Factores de Diferenciación de Crecimiento/fisiología , Células Madre Mesenquimatosas/fisiología , Osteogénesis , Receptores Notch/metabolismo , Diferenciación Celular , Factor 2 de Diferenciación de Crecimiento , Células HEK293 , Humanos , Transducción de Señal , Regulación hacia ArribaRESUMEN
Giant vesicles composed of phospholipids and amphiphilic block copolymers are useful for biomimetic drug delivery, for biophysical experiments, and for creating synthetic cells. Here, we report that large numbers of giant unilamellar vesicles (GUVs) can be formed on a broad range of fabrics composed of entangled cylindrical fibers. We show that fabrics woven from fibers of silk, wool, rayon, nylon, polyester, and fiberglass promote the formation of GUVs and giant polymer vesicles (polymersomes) in aqueous solutions. The result extends significantly previous reports on the formation of GUVs on cellulose paper and cotton fabric. Giant vesicles formed on all the fabrics from lipids with various headgroup charges, chains lengths, and chain saturations. Giant vesicles could be formed from multicomponent lipid mixtures, from extracts of plasma membranes, and from amphiphilic diblock and triblock copolymers, in both low ionic strength and high ionic strength solutions. Intriguingly, statistical characterization using a model lipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine, revealed that the majority of the fabrics yielded similar average counts of vesicles. Additionally, the vesicle populations obtained from the different fabrics had similar distributions of sizes. Fabrics are ubiquitous in society in consumer, technical, and biomedical applications. The discovery herein that biomimetic GUVs grow on fabrics opens promising new avenues in vesicle-based smart materials design.
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Internado y Residencia , Cirugía Bucal , Cirugía Bucal/educación , Humanos , Estados Unidos , Selección de PersonalRESUMEN
The currently understood principles about light-molecule interactions are limited, and thus scientific scope beyond current theories is rarely harvested. Herein we demonstrate supracence phenomena, in which the emitted photons have more energy than the absorbed photons. The extra energy comes from couplings of the absorbed and emitted photon to molecular phonons, whose potentials are constantly exchanging with molecular quantum energy and the environment. Thus, supracence is a linear optical process rather than a nonlinear optical process, such as second harmonic generation. Because supracence results in cooled molecular phonons and thus cooled molecules, behavior opposite to that of hot fluorescing emitters is expected. This report reveals certain supracence principles while contrasting fluorescence with supracence in high-resolution imaging.
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Self-assembled micrometer-scale vesicles composed of lamellar phase forming amphiphiles are useful as chemical microreactors, as minimal artificial cells, as protocell mimics for studies of the origins of life, and as vehicles for the targeted delivery of drugs. Given their varied uses, discovery of a universal mechanism that is simple, rapid, and that produces vesicles from a large variety of amphiphiles with different chemical and physical properties at high yield is extremely desirable. Here we show that cellulose, in the form of cellulose paper, facilitates the assembly of membranous vesicles 5-20 µm in diameter from scientifically and technologically important amphiphiles of diverse chemical structures and functionality such as fatty acids (fatty acid vesicles), amphiphilic diblock copolymers, and amphiphilic triblock copolymers (polymersomes). Assembly of vesicles occurred within 90 min of placing the amphiphile-coated cellulose paper into aqueous solutions. Varying thermal and chemical conditions, however, are required for the high-yield assembly of vesicles from the different amphiphiles. The vesicles, when attached to cellulose fibers, have membranes that remain unsealed. This topological characteristic of the vesicles grown on paper allowed the scalable separation of the process of growth from the process of loading cargo (temporally decoupled growth and loading). We demonstrate a temporally decoupled process to rapidly produce large quantities of protein-loaded polymersomes on the benchtop by using high temperatures to accelerate the growth of the polymersomes and subsequently milder temperatures during diffusive loading of the protein cargo.
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Celulosa/química , Albúmina Sérica Bovina/química , Tensoactivos/química , Animales , Bovinos , PapelRESUMEN
BACKGROUND: Scientific publications are the cornerstone of scholarly activities. The importance of appropriately assigned authorship cannot be overstated. Hence, we felt it prudent to examine the perception of plastic surgery trainees regarding authorship. We hypothesized that plastic surgery trainees would not be in compliance with International Committee of Medical Journal Editors guidelines when determining what constitutes an authorship justifying contribution. METHODS: An online survey describing 4 distinct scenarios was distributed to plastic surgery trainees at 2 academic institutions using the Qualtrics research software (Provo, UT). Additional parameters queried included level of training and number of publications. Linear regression models were used to test correlation between responses and level of training and number of publications. RESULTS: Thirty-three of 48 trainees responded (response rate, 68.8%). All respondents had previously authored publications, with the majority (54.5%) having at least 10 publications. Although none of the scenarios presented justified authorship based on international guidelines, 33.3% of respondents believed that authorship was warranted in at least 3 of the 4 presented scenarios. Linear regression comparing for demographic variables to number of perceived authorship scenarios found a mild-moderate positive correlation with level of training (R = 0.34, P = 0.05) and number of publications (R = 0.32, P = 0.07). CONCLUSIONS: Plastic surgery trainees do not seem to be familiar with guidelines regarding authorship justifying contributions. It is important to raise awareness regarding criteria that warrant authorship and to educate our residents and fellows in matters of appropriate scholarly conduct because nothing short of the credibility of our scientific endeavors is otherwise in question.