Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 144
Filtrar
1.
Phys Chem Chem Phys ; 26(17): 13412-13419, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38647047

RESUMEN

Anodic aluminum oxide (AAO) membranes were used as templates to control orientation of an ion-channel forming columnar mesophase obtained by self assembly of a wedge-shaped sulfonate molecule. Inside the AAO structure, the director vector of the mesophase is oriented parallel to the pore axis due to the confinement effect. The molecular arrangement induced by the spatial confinement within the pores is extended over several microns into the remnant film on the AAO surface. The homeotropic alignment of the channels promotes unidimensional ion conduction through the film plane, which is manifested by a considerable increase in conductivity relative to isotropic samples.

2.
Nature ; 628(8006): 171-179, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38509360

RESUMEN

The myriad microorganisms that live in close association with humans have diverse effects on physiology, yet the molecular bases for these impacts remain mostly unknown1-3. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the 'exoproteome'). Commensal microorganisms may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct exoproteome-microbiota interactions remain largely unexplored. Here we developed and validated a novel technology, BASEHIT, that enables proteome-scale assessment of human exoproteome-microbiome interactions. Using BASEHIT, we interrogated more than 1.7 million potential interactions between 519 human-associated bacterial strains from diverse phylogenies and tissues of origin and 3,324 human exoproteins. The resulting interactome revealed an extensive network of transkingdom connectivity consisting of thousands of previously undescribed host-microorganism interactions involving 383 strains and 651 host proteins. Specific binding patterns within this network implied underlying biological logic; for example, conspecific strains exhibited shared exoprotein-binding patterns, and individual tissue isolates uniquely bound tissue-specific exoproteins. Furthermore, we observed dozens of unique and often strain-specific interactions with potential roles in niche colonization, tissue remodelling and immunomodulation, and found that strains with differing host interaction profiles had divergent interactions with host cells in vitro and effects on the host immune system in vivo. Overall, these studies expose a previously unexplored landscape of molecular-level host-microbiota interactions that may underlie causal effects of indigenous microorganisms on human health and disease.


Asunto(s)
Bacterias , Interacciones Microbiota-Huesped , Microbiota , Filogenia , Proteoma , Simbiosis , Animales , Femenino , Humanos , Ratones , Bacterias/clasificación , Bacterias/inmunología , Bacterias/metabolismo , Bacterias/patogenicidad , Interacciones Microbiota-Huesped/inmunología , Interacciones Microbiota-Huesped/fisiología , Tropismo al Anfitrión , Microbiota/inmunología , Microbiota/fisiología , Especificidad de Órganos , Unión Proteica , Proteoma/inmunología , Proteoma/metabolismo , Reproducibilidad de los Resultados
3.
Artículo en Inglés | MEDLINE | ID: mdl-37956788

RESUMEN

Acid sphingomyelinase deficiency is a neurodegenerative lysosomal storage disorder caused by mutations in the sphingomyelin-degrading enzyme acid sphingomyelinase (ASM) gene. Upregulated neuroinflammation has been well-characterized in an ASM knockout mouse model of acid sphingomyelinase deficiency disease, but lipid mediator pathways involved in 'mediating' inflammation and inflammation-resolution have yet to be characterized. In this study, we 1) measured free (bioactive) and esterified (inactive) lipid mediators involved in inflammation and inflammation resolution in cerebellum and neuronal cultures of ASM knockout (ASMko) mice and wildtype (WT) controls, and 2) quantified the esterification of labeled pro-resolving free d11-14(15)-epoxyeicosatrienoic acid in cultured neurons from ASMko and WT mice. We found elevated concentrations of esterified pro-resolving lipid mediators and hydroxyeicosatrienoic acids typically destined for pro-resolving lipid mediator synthesis (e.g. lipoxins) in the cerebellum and neurons of ASMko mice compared to controls. Free d11-14(15)-epoxyeicosatrienoic acid esterification within neurons of ASMko mice was significantly elevated compared to WT. Our findings show evidence of increased inactivation of free pro-resolving lipid mediators through esterification in ASMko mice, suggesting impaired resolution as a new pathway underlying ASM deficiency pathogenesis.


Asunto(s)
Enfermedad de Niemann-Pick Tipo A , Enfermedades de Niemann-Pick , Animales , Ratones , Encéfalo/metabolismo , Esterificación , Inflamación/metabolismo , Ratones Noqueados , Neuronas/metabolismo , Enfermedad de Niemann-Pick Tipo A/genética , Enfermedad de Niemann-Pick Tipo A/metabolismo , Enfermedad de Niemann-Pick Tipo A/patología , Enfermedades de Niemann-Pick/metabolismo , Enfermedades de Niemann-Pick/patología , Esfingomielina Fosfodiesterasa/genética , Esfingomielina Fosfodiesterasa/metabolismo , Esfingomielinas/metabolismo
4.
Expert Rev Clin Pharmacol ; 17(2): 165-176, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38108102

RESUMEN

BACKGROUND: In psychedelic therapy, the importance of set and setting is a fundamental but under-researched assumption. The aim of this study is to correlate variables of set (psychedelic use motivation) and setting (psychedelic use location and type of companion) with psychopathology, wellbeing and personality variables. RESEARCH DESIGN AND METHODS: A sample of 1022 participants of the Spanish-speaking population was collected through an online survey. A novel instrument, the Psychedelic Use Scale (PUS), was developed to measure substance use variables of LSD, mescaline, psilocybin, DMT, 5-Meo-DMT, ketamine, Salvia divinorum, ibogaine and MDMA. Various personality, well-being and psychopathology instruments were implemented to measure outcome variables. RESULTS: Growth motivations, natural settings and presence of significant others predicted less psychopathology, greater wellbeing and meaningfulness of psychedelic experiences, whereas problematic motivations predicted greater psychopathology, lower wellbeing and did not predict meaningfulness of psychedelic experiences. CONCLUSIONS: Based on these results, we suggest experimental hypotheses for future clinical trials and longitudinal studies with potential clinical implications.


Asunto(s)
Alucinógenos , Salvia , Trastornos Relacionados con Sustancias , Humanos , Alucinógenos/farmacología , Alucinógenos/uso terapéutico , Psilocibina/farmacología , Psilocibina/uso terapéutico , Mescalina/uso terapéutico , Trastornos Relacionados con Sustancias/tratamiento farmacológico
5.
J Environ Manage ; 346: 118958, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37716167

RESUMEN

This paper presents an approach to integrate tire wear buildup and rainfall-runoff models to simulate tire wear buildup on road surfaces and its subsequent transport in stormwater runoff events. To do so, a buildup model is presented based on vehicle kilometers traveled, vehicle type, vehicle speed, and road roughness within a watershed. This buildup model was integrated into an EPA SWMM model that simulated the runoff of tire wear particles in twelve watersheds in the San Francisco, CA bay area. Results demonstrate that tire wear particle buildup within the watersheds ranged between 0.4 and 0.51 (kg/km2) per hour. Applied to the SWMM model, total event mean tire wear concentrations ranged between 0.5 and 67 µg/L. These concentrations were linearly correlated to depth-integrated samples collected at the outlet of each of the watersheds (R2 = 0.66). The proposed modeling approach can ultimately be applied to create solutions to an emerging stormwater contaminant.


Asunto(s)
Monitoreo del Ambiente , Monitoreo del Ambiente/métodos
6.
Cell ; 186(14): 3095-3110.e19, 2023 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-37321219

RESUMEN

The human body contains thousands of metabolites derived from mammalian cells, the microbiota, food, and medical drugs. Many bioactive metabolites act through the engagement of G-protein-coupled receptors (GPCRs); however, technological limitations constrain current explorations of metabolite-GPCR interactions. Here, we developed a highly multiplexed screening technology called PRESTO-Salsa that enables simultaneous assessment of nearly all conventional GPCRs (>300 receptors) in a single well of a 96-well plate. Using PRESTO-Salsa, we screened 1,041 human-associated metabolites against the GPCRome and uncovered previously unreported endogenous, exogenous, and microbial GPCR agonists. Next, we leveraged PRESTO-Salsa to generate an atlas of microbiome-GPCR interactions across 435 human microbiome strains from multiple body sites, revealing conserved patterns of cross-tissue GPCR engagement and activation of CD97/ADGRE5 by the Porphyromonas gingivalis protease gingipain K. These studies thus establish a highly multiplexed bioactivity screening technology and expose a diverse landscape of human, diet, drug, and microbiota metabolome-GPCRome interactions.


Asunto(s)
Microbiota , Receptores Acoplados a Proteínas G , Animales , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Metaboloma , Mamíferos/metabolismo
7.
Toxics ; 11(2)2023 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-36851023

RESUMEN

Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.

8.
ACS Biomater Sci Eng ; 9(2): 1020-1029, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36720461

RESUMEN

We present the design, fabrication, and characterization of an implantable neural interface based on anisotropic magnetoresistive (AMR) magnetic-field sensors that combine reduced size and high performance at body temperature. The sensors are based on La0.67Sr0.33MnO3 (LSMO) as a ferromagnetic material, whose epitaxial growth has been suitably engineered to get uniaxial anisotropy and large AMR output together with low noise even at low frequencies. The performance of LSMO sensors of different film thickness and at different temperatures close to 37 °C has to be explored to find an optimum sensitivity of ∼400%/T (with typical detectivity values of 2 nT·Hz-1/2 at a frequency of 1 Hz and 0.3 nT·Hz-1/2 at 1 kHz), fitted for the detection of low magnetic signals coming from neural activity. Biocompatibility tests of devices consisting of submillimeter-size LSMO sensors coated by a thin poly(dimethyl siloxane) polymeric layer, both in vitro and in vivo, support their high suitability as implantable detectors of low-frequency biological magnetic signals emerging from heterogeneous electrically active tissues.


Asunto(s)
Campos Magnéticos , Prótesis e Implantes , Anisotropía , Polímeros
9.
J Alzheimers Dis ; 91(1): 471-481, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36442199

RESUMEN

BACKGROUND: This longitudinal study addressed whether mindfulness practice prevents psychological and behavioral symptoms, especially mood disorders, in Alzheimer's disease (AD). OBJECTIVE: To assess the incidence of depression in the course of AD and to determine which non-pharmacological treatment (NPT) is most effective in preventing psychopathological symptoms. METHODS: We conducted a longitudinal, non-inferiority and equivalence randomized clinical trial, repeated-measures design, with a control group and three experimental treatments: mindfulness, cognitive stimulation, and relaxation. Each experimental group performed three weekly sessions for two years. The pharmacological treatment of all participants was donepezil (10 mg). Participants were patients with probable AD without diagnosed depression from the public neurology services of the Canary Health Service, Spain. Psychological evaluation was performed using the Geriatric Depression Scale (GDS), Hamilton Depression Rating Scale (HDRS), and Neuropsychiatric Inventory (NPI-Q). The statistical analysis included only patients who attended at least 75% of the sessions. A nonparametric, repeated-measures analysis was performed with Kruskal-Wallis H test and between-group differences with Mann-Whitney U test with Bonferroni correction (p < 0.008). Effect size was calculated with partial eta-squared. RESULTS: The results showed significant differences with large effect sizes (η2p>0.14) between mindfulness and the rest of the experimental groups as well as the control in the GDS, HDRS, and NPI-Q scales. CONCLUSION: Compared to the other experimental groups, only mindfulness prevented the onset of depression and other psychopathologies in early-stage AD. Based on its effectiveness in maintaining cognitive functions and preventing psychopathology, we recommend mindfulness as the first-choice NPT for mild to moderate AD.


Asunto(s)
Enfermedad de Alzheimer , Atención Plena , Humanos , Anciano , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/psicología , Depresión/terapia , Estudios Longitudinales , Donepezilo
10.
Micromachines (Basel) ; 13(12)2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36557505

RESUMEN

The number of individuals with upper or lower extremities dysfunction (ULED) has considerably increased in the past few decades, resulting in a high economic burden for their families and society. Individuals with ULEDs require assistive robots to fulfill all their activities of daily living (ADLs). However, a theory for the optimal design of assistive robots that reduces energy consumption while increasing the workspace is unavailable. Thus, this research presents an algorithm for the optimal link length selection of an assistive robot mounted on a wheelchair to minimize the torque demands of each joint while increasing the workspace coverage. For this purpose, this research developed a workspace to satisfy a list of 18 ADLs. Then, three torque indices from the literature were considered as performance measures to minimize; the three torque measures are the quadratic average torque (QAT), the weighted root square mean (WRMS), and the absolute sum of torques (AST). The proposed algorithm evaluates any of the three torque measures within the workspace, given the robot dimensions. This proposed algorithm acts as an objective function, which is optimized using a genetic algorithm for each torque measure. The results show that all tree torque measures are suitable criteria for assistance robot optimization. However, each torque measures yield different optimal results; in the case of the QAT optimization, it produces the least workspace with the minimum overall torques of all the joints. Contrarily, the WRMS and AST optimization yield similar results generating the maximum workspace coverage but with a greater overall torque of all joints. Thus, the selection between the three methods depends on the designer's criteria. Based on the results, the presented methodology is a reliable tool for the optimal dimensioning of assistive robots.

11.
J Ethnobiol Ethnomed ; 18(1): 69, 2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36461060

RESUMEN

BACKGROUND: We summarize comparative ethnoornithological data for ten Mexican Indigenous communities, an initial step towards a comprehensive archive of the avian diversity conserved within Mexico's Indigenous territories. We do so by counting highlighted species listed for bird conservation status on widely recognized "red lists" and their cultural value to build biocultural policies in Mexico for their conservation. METHODS: Indigenous bird names for each study site were determined to allow calculation of the "Scientific Species Recognition Ratio" (SSRR) for high cultural value birds obtained across communities. This demonstrated patterns of cultural prominence. A matrix of 1275 bird versus seven biocultural values was analysed using a correspondence analysis (InfoStat/L-v2020) to illustrate patterns of concordance between bird conservation status and cultural values. RESULTS: This paper contributes to quantitative and qualitative data on the role of ethnoornithology and ethnobiology in biocultural conservation. The areas studied provide refugia for almost 70% of the Mexican avifauna within a fraction of 1% of the national territory, that is 769 bird species recorded for all communities. The global correspondence of regions of biological and linguistic megadiversity is well established, while linguistic diversity is widely accepted as a good proxy for general cultural diversity. Our correspondence analysis explained 81.55% of the variation, indicating a strong relation between cultural importance and bird conservation status. We propose three main categories to establish a bioculturally informed public policy in Mexico for the conservation of what we described as high, medium, and bioculturally prominent bird species all include cultural value in any material or symbolic aspect. High are those species appearing on any threatened list, but also considered in any endemic status, while medium include threatened listed species. The last category included species not necessarily listed on any threat list, but with a wide range of social and cultural uses. We suggest that the concept might be extended to other species of biocultural importance. CONCLUSIONS: We argue that bird conservation policies should be biocultural, that is they should recognize birds of cultural value on a par with bird species "of special interest" because they are most critical for biodiversity conservation. The desire of local people to protect their traditional community lands and livelihoods can be an effective biodiversity conservation strategy, which should be recognized in national biocultural policies.


Asunto(s)
Aves , Políticas , Humanos , Animales , México , Biodiversidad , Especies en Peligro de Extinción
12.
Rev. cuba. reumatol ; 24(4)dic. 2022.
Artículo en Español | LILACS, CUMED | ID: biblio-1530171

RESUMEN

Los hábitos y estilos de vida en los adultos mayores constituyen un elemento fundamental para prevenir enfermedades o lograr el control de las ya existentes. Constituyen una prioridad para los directivos de salud con la finalidad de lograr el envejecimiento activo como premisa distintiva del proceso del envejecimiento en la población; sin embargo, son variados los factores que pueden influir en este proceso. El objetivo de esta investigación fue realizar una revisión bibliográfica para identificar elementos actualizados relacionados con los hábitos de vida saludables en adultos mayores. Se revisó la información publicada en los últimos 5 años referente al problema de investigación. La revisión incluyó bases de datos regionales (Scielo, Lilac, Redalyc y Latindex) y de alto impacto (PubMed, Ice Web, Web of Science y Scopus). Se identificó un total de 67 documentos, de los cuales 43 brindaron información relevante para la realización del estudio. Se concluye que tener una adecuada visión de los estilos de vida saludables es una prioridad en el manejo de las acciones de salud a implementar en los adultos mayores. Es necesario fomentar actitudes en este grupo poblacional que permitan adaptar hábitos y estilos de vida saludables en la población, lo que constituye la única alternativa viable para mejorar el estado de salud, prevenir la discapacidad y mejorar la calidad de vida relacionada con la salud(AU)


Habits and lifestyles in older adults are a fundamental element to prevent diseases or achieve control of existing ones. They constitute a priority for health managers in pursuit of active aging as a distinctive premise of the aging process in the population; however, there are many factors that can influence this process. The objective of this research was to carry out a bibliographic review to identify updated elements related to healthy lifestyles in older adults. Information published in the last 5 years regarding the research problem was reviewed. The review included regional databases (Scielo, Lilac, Redalyc, and Latindex) and high-impact databases (PubMed, Ice Web, Web of Science, and Scopus). A total of 67 documents were identified, of which 43 provided relevant information for the study. It is concluded having an adequate vision of healthy EVs constitutes a priority in the management of health actions to be implemented in older adults. It is necessary to promote skills in this population group that allow the adaptation of healthy habits and lifestyles in the population; which constitutes the only viable alternative to improve health status, prevent disability and improve health-related quality of life(AU)


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Anciano , Prevención de Enfermedades , Promoción de la Salud , Estilo de Vida
13.
Science ; 378(6618): eabm3233, 2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36302024

RESUMEN

Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous gut microbes remains to be defined. We established a pipeline to systematically evaluate the genotoxicity of an extensive collection of gut commensals from inflammatory bowel disease patients. We identified isolates from divergent phylogenies whose metabolites caused DNA damage and discovered a distinctive family of genotoxins-termed the indolimines-produced by the CRC-associated species Morganella morganii. A non-indolimine-producing M. morganii mutant lacked genotoxicity and failed to exacerbate colon tumorigenesis in mice. These studies reveal the existence of a previously unexplored universe of genotoxic small molecules from the microbiome that may affect host biology in homeostasis and disease.


Asunto(s)
Neoplasias Colorrectales , Daño del ADN , Microbioma Gastrointestinal , Indoles , Enfermedades Inflamatorias del Intestino , Morganella morganii , Mutágenos , Animales , Ratones , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/microbiología , Enfermedades Inflamatorias del Intestino/microbiología , Morganella morganii/genética , Morganella morganii/aislamiento & purificación , Morganella morganii/metabolismo , Indoles/metabolismo , Carcinogénesis/genética , Humanos , Mutágenos/metabolismo , Células HeLa
14.
Data Brief ; 42: 108138, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35496485

RESUMEN

Groundwater with high fluoride concentrations has been recognized as one of the serious concerns worldwide. Besides, the fluoride released into the groundwater by slow dissolution of fluoride-containing rocks, various industries also contribute to fluoride pollution [1]. Excess intake of fluoride leads to various health problems such as dental and skeletal fluorosis, cancer, infertility, brain damage, thyroid diseases, etc. [2]. On the other hand, bromide is naturally present in surface and groundwater sources. However, during the chlorination process, bromide can be oxidized to HOBr, which can react with natural organic matter in water to form brominated organic disinfection byproducts, which are very harmful to human health [3]. Among various methods for water treatment, the adsorption process has been widely used and seems to be an efficient and attractive method for the removal of many contaminants in water, such as anions, in terms of cost, simplicity of design, and operation [4], [5]. In the past years, xerogels and carbon xerogels, a new type of adsorbents, which are synthesized by the sol-gel polycondensation of resorcinol and formaldehyde, have gained attention due to their moldable texture and chemical properties [6]. Moreover, melamine addition in resorcinol and formaldehyde xerogels adds basic groups on its surface, favouring Lewis acid-base interactions between xerogels and other components by adsorption [7]. In this data article, the synthesis of three resorcinol-formaldehyde (R/F) xerogels with an increasing amount of melamine (M) was carried out by colloidal polymerization (molar ratios of M/R = 0.5, M/R = 1.0, and M/R = 2.0). Additionally, samples of M/R = 0.5 xerogel were carbonized at 400, 450, and 550 °C under an inert atmosphere to increase their specific area. Organic and carbon xerogels obtained were characterized by FTIR, TGA, SEM, Physisorption of N2, and the pH at the point of zero charge (pHPZC). All organic xerogels were also tested as adsorbents on the removal of fluoride and bromide ions from aqueous phase. The Freundlich, Langmuir, and Radke-Prausnitz isotherm models were applied to interpret the experimental data from adsorption equilibrium. Additionally, the data of the mass of the xerogel needed to remove fluoride and bromide from groundwater and fulfill the maximum concentration levels are also included.

15.
Front Med (Lausanne) ; 9: 808191, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35463025

RESUMEN

Hepatitis C virus-induced liver damage, chronic liver damage due to alcohol, and non-alcoholic liver disease-induced cellular alterations promote fibrosis, cirrhosis, and/or hepatocellular carcinoma. The recommended therapeutic option for advanced liver damage is liver transplantation. Extracellular matrix scaffolds have been evaluated as an alternative for tissue restoration. Studies on the biocompatibility and rejection of synthetic and natural scaffolds as an alternative to organ transplantation have been evaluated. Our group has recently described the xenoimplant of collagen matrix scaffold (CMS) in a rat model. However, no complete macroscopic and histological description of the liver parenchyma at the initial (day 3), intermediate (day 14), and advanced (day 21) stages has been obtained. In this study, we described and compared liver tissue from the CMS zone (CZ, CMS, and liver parenchyma), liver tissue from the normal zone (liver parenchyma close to the CMS), and basal tissue (resected tissue from the CMS implantation site). Our data strongly suggest that the collagen matrix xenoimplant is a good niche for hepatocytes, with no rejection, and does not affect liver function tests. The liver can regenerate after damage, but this capacity is inhibited in a chronic injury. At present, the use of CMS after liver damage has not been reported. This biomaterial could be a novel alternative in the field of regenerative medicine for liver diseases.

16.
Cell Rep Methods ; 2(2)2022 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-35360706

RESUMEN

Autoantibodies that recognize extracellular proteins (the exoproteome) exert potent biological effects but are challenging to detect. Here, we developed rapid extracellular antigen profiling (REAP), a high-throughput technique for the comprehensive discovery of exoproteome-targeting autoantibodies. Patient samples are applied to a genetically barcoded yeast surface display library containing 2,688 human extracellular proteins. Antibody-coated yeast are isolated, and sequencing of barcodes is used to identify displayed antigens. To benchmark REAP's performance, we screened 77 patients with autoimmune polyglandular syndrome type 1 (APS-1). REAP sensitively and specifically detected both known and previously unidentified autoantibodies in APS-1. We further screened 106 patients with systemic lupus erythematosus (SLE) and identified numerous autoantibodies, several of which were associated with disease severity or specific clinical manifestations and exerted functional effects on cell signaling ex vivo. These findings demonstrate the utility of REAP to atlas the expansive landscape of exoproteome-targeting autoantibodies and their impacts on patient health outcomes.


Asunto(s)
Lupus Eritematoso Sistémico , Poliendocrinopatías Autoinmunes , Humanos , Autoanticuerpos , Saccharomyces cerevisiae , Lupus Eritematoso Sistémico/genética , Autoantígenos , Gravedad del Paciente , Poliendocrinopatías Autoinmunes/complicaciones
17.
Rev Esp Cardiol (Engl Ed) ; 75(7): 559-567, 2022 Jul.
Artículo en Inglés, Español | MEDLINE | ID: mdl-34479845

RESUMEN

INTRODUCTION AND OBJECTIVES: Multiparametric scores have been designed for better risk stratification in Brugada syndrome (BrS). We aimed to validate 3 multiparametric approaches (the Delise score, Sieira score and the Shanghai BrS Score) in a cohort with Brugada syndrome and electrophysiological study (EPS). METHODS: We included patients diagnosed with BrS and previous EPS between 1998 and 2019 in 23 hospitals. C-statistic analysis and Cox proportional hazard regression models were used. RESULTS: A total of 831 patients were included (mean age, 42.8±13.1; 623 [75%] men; 386 [46.5%] had a type 1 electrocardiogram (ECG) pattern, 677 [81.5%] were asymptomatic, and 319 [38.4%] had an implantable cardioverter-defibrillator). During a follow-up of 10.2±4.7 years, 47 (5.7%) experienced a cardiovascular event. In the global cohort, a type 1 ECG and syncope were predictive of arrhythmic events. All risk scores were significantly associated with events. The discriminatory abilities of the 3 scores were modest (particularly when these scores were evaluated in asymptomatic patients). Evaluation of the Delise and Sieira scores with different numbers of extra stimuli (1 or 2 vs 3) did not substantially improve the event prediction c-index. CONCLUSIONS: In BrS, classic risk factors such as ECG pattern and previous syncope predict arrhythmic events. The predictive capabilities of the EPS are affected by the number of extra stimuli required to induce ventricular arrhythmias. Scores combining clinical risk factors with EPS help to identify the populations at highest risk, although their predictive abilities remain modest in the general BrS population and in asymptomatic patients.


Asunto(s)
Síndrome de Brugada , Desfibriladores Implantables , Adulto , Síndrome de Brugada/complicaciones , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , China , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables/efectos adversos , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Síncope/etiología
18.
Opt Express ; 29(21): 34135-34149, 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34809211

RESUMEN

Roll-to-roll nanoimprint lithography (R2R-NIL) is an enabling technology for the low-cost mass production of high-quality micro- and nano-sized optical elements. Particularly, the fabrication of Fresnel lenses using R2R-NIL is a promising approach to produce optical arrays for micro-concentrator photovoltaic modules. This work investigates the application of a continuous R2R imprinting process based on ultraviolet curing of transparent photopolymer resins (UV-NIL) to fabricate high-efficiency and low-cost Fresnel lenses. The morphological attributes and the related optical performance of the lenses fabricated using roll-to-roll UV-NIL on flexible PET sheets yielded optical efficiency values up to ∼ 69% at a concentration ratio of 178X, whereas a value of ∼ 77% was obtained for the UV-NIL batch processed on a flat rigid substrate. Further improvement of the optical efficiency has been achieved by adding moth-eye inspired antireflective (AR) features on the side opposite to the Fresnel motifs via a double-sided R2R UV-NIL process. The process developed paves the way for cost-effective mass production of high-efficiency Fresnel lenses for micro-concentrator photovoltaics.

19.
Nanomaterials (Basel) ; 11(10)2021 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-34685096

RESUMEN

A combination of in situ nanocalorimetry with simultaneous nanofocus 2D Wide-Angle X-ray Scattering (WAXS) was used to study polymorphic behaviour and structure formation in a single micro-drop of isotactic polypropylene (iPP) with defined thermal history. We were able to generate, detect, and characterize a number of different iPP morphologies using our custom-built ultrafast chip-based nanocalorimetry instrument designed for use with the European Synchrotron Radiation Facility (ESRF) high intensity nanofocus X-ray beamline facility. The detected iPP morphologies included monoclinic alpha-phase crystals, mesophase, and mixed morphologies with different mesophase/crystalline compositional ratios. Monoclinic crystals formed from the mesophase became unstable at heating rates above 40 K s-1 and showed melting temperatures as low as ~30 K below those measured for iPP crystals formed by slow cooling. We also studied the real-time melt crystallization of nanogram-sized iPP samples. Our analysis revealed a mesophase nucleation time of around 1 s and the co-existence of mesophase and growing disordered crystals at high supercooling ≤328 K. The further increase of the iPP crystallization temperature to 338 K changed nucleation from homogeneous to heterogeneous. No mesophase was detected above 348 K. Low supercooling (≥378 K) led to the continuous growth of the alpha-phase crystals. In conclusion, we have, for the first time, measured the mesophase nucleation time of supercooled iPP melted under isothermal crystallization conditions using a dedicated experimental setup designed to allow simultaneous ultrafast chip-based nanocalorimetry and nanofocus X-ray diffraction analyses. We also provided experimental evidence that upon heating, the mesophase converts directly into thermodynamically stable monoclinic alpha-phase crystals via perfection and reorganization and not via partial melting. The complex phase behaviour of iPP and its dependence on both crystallization temperature and time is presented here using a time-temperature-transformation (TTT) diagram.

20.
JACC Case Rep ; 3(2): 202-205, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34317503

RESUMEN

We report a man with congenitally corrected transposition of the great arteries and moderate anteroseptal ischemia; and cardiac computed tomography showed a single coronary artery with origin from the right aortic sinus. The perfusion of the morphological right ventricle by a single right coronary artery may be a cause of ischemia. (Level of Difficulty: Beginner.).

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...