Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 71
Filtrar
1.
mBio ; : e0115724, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757970

RESUMEN

Coordinated membrane and cell wall synthesis is vital for maintaining cell integrity and facilitating cell division in bacteria. However, the molecular mechanisms that underpin such coordination are poorly understood. Here we uncover the pivotal roles of the staphylococcal proteins CozEa and CozEb, members of a conserved family of membrane proteins previously implicated in bacterial cell division, in the biosynthesis of lipoteichoic acids (LTA) and maintenance of membrane homeostasis in Staphylococcus aureus. We establish that there is a synthetic lethal relationship between CozE and UgtP, the enzyme synthesizing the LTA glycolipid anchor Glc2DAG. By contrast, in cells lacking LtaA, the flippase of Glc2DAG, the essentiality of CozE proteins was alleviated, suggesting that the function of CozE proteins is linked to the synthesis and flipping of the glycolipid anchor. CozE proteins were indeed found to modulate the flipping activity of LtaA in vitro. Furthermore, CozEb was shown to control LTA polymer length and stability. Together, these findings establish CozE proteins as novel players in membrane homeostasis and LTA biosynthesis in S. aureus.IMPORTANCELipoteichoic acids are major constituents of the cell wall of Gram-positive bacteria. These anionic polymers are important virulence factors and modulators of antibiotic susceptibility in the important pathogen Staphylococcus aureus. They are also critical for maintaining cell integrity and facilitating proper cell division. In this work, we discover that a family of membrane proteins named CozE is involved in the biosynthesis of lipoteichoic acids (LTAs) in S. aureus. CozE proteins have previously been shown to affect bacterial cell division, but we here show that these proteins affect LTA length and stability, as well as the flipping of glycolipids between membrane leaflets. This new mechanism of LTA control may thus have implications for the virulence and antibiotic susceptibility of S. aureus.

2.
Nat Struct Mol Biol ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671230

RESUMEN

Human syncytin-1 and suppressyn are cellular proteins of retroviral origin involved in cell-cell fusion events to establish the maternal-fetal interface in the placenta. In cell culture, they restrict infections from members of the largest interference group of vertebrate retroviruses, and are regarded as host immunity factors expressed during development. At the core of the syncytin-1 and suppressyn functions are poorly understood mechanisms to recognize a common cellular receptor, the membrane transporter ASCT2. Here, we present cryo-electron microscopy structures of human ASCT2 in complexes with the receptor-binding domains of syncytin-1 and suppressyn. Despite their evolutionary divergence, the two placental proteins occupy similar positions in ASCT2, and are stabilized by the formation of a hybrid ß-sheet or 'clamp' with the receptor. Structural predictions of the receptor-binding domains of extant retroviruses indicate overlapping binding interfaces and clamping sites with ASCT2, revealing a competition mechanism between the placental proteins and the retroviruses. Our work uncovers a common ASCT2 recognition mechanism by a large group of endogenous and disease-causing retroviruses, and provides high-resolution views on how placental human proteins exert morphological and immunological functions.

3.
Antioxidants (Basel) ; 13(3)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38539807

RESUMEN

Maqui berries contain a high percentage of anthocyanins with high antioxidant and anti-inflammatory capacity but that are unstable in the colonic site. Nanocarriers based on polysaccharides and/or proteins can protect against the degradation of anthocyanins. The aim of this study was the nanoencapsulation of maqui extract (ME) in chitosan-tripolyphosphate (CTPP-ME), chenopodin (CH-ME), and chenopodin-alginate (CHA-ME). A standardised ME was prepared and then encapsulated in the nanosystems. The physicochemical properties, encapsulation parameters, and the interactions of ME with the nanovehicles were characterised. The cyanidin-3-glucoside released and ORAC activity in phosphate buffer at pH 7.4 were evaluated. The content of ME was 8-9 mg of cyanidin-3-glucoside/g of extract. CTPP with ME at 3% obtained the highest encapsulation efficiency (EE = 91%), and no significant differences were observed in size (274-362 nm), PDI (0.5-0.7), and zeta potential (+34-+41 mV) when the concentration of ME changed from 1% to 5%. CH-ME was shown to be smaller (152 nm) than CTPP-ME, and CH-ME and CHA-ME showed lower EE (79% and 54%, respectively) than CTPP-ME. FT-IR revealed a stronger interaction of ME with CTPP-ME than with CH-ME. Both systems showed a significantly lower release than free ME, and the T50 value of CTPP-ME 3% (328 min) was higher than CH-ME (197 min). Both protected the ORAC activity of ME.

5.
Nature ; 618(7967): 1065-1071, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37198476

RESUMEN

Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture as the defining terminal event1-7. Plasma membrane rupture was long thought to be driven by osmotic pressure, but it has recently been shown to be in many cases an active process, mediated by the protein ninjurin-18 (NINJ1). Here we resolve the structure of NINJ1 and the mechanism by which it ruptures membranes. Super-resolution microscopy reveals that NINJ1 clusters into structurally diverse assemblies in the membranes of dying cells, in particular large, filamentous assemblies with branched morphology. A cryo-electron microscopy structure of NINJ1 filaments shows a tightly packed fence-like array of transmembrane α-helices. Filament directionality and stability is defined by two amphipathic α-helices that interlink adjacent filament subunits. The NINJ1 filament features a hydrophilic side and a hydrophobic side, and molecular dynamics simulations show that it can stably cap membrane edges. The function of the resulting supramolecular arrangement was validated by site-directed mutagenesis. Our data thus suggest that, during lytic cell death, the extracellular α-helices of NINJ1 insert into the plasma membrane to polymerize NINJ1 monomers into amphipathic filaments that rupture the plasma membrane. The membrane protein NINJ1 is therefore an interactive component of the eukaryotic cell membrane that functions as an in-built breaking point in response to activation of cell death.


Asunto(s)
Moléculas de Adhesión Celular Neuronal , Muerte Celular , Membrana Celular , Factores de Crecimiento Nervioso , Animales , Humanos , Ratones , Moléculas de Adhesión Celular Neuronal/química , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Moléculas de Adhesión Celular Neuronal/ultraestructura , Membrana Celular/metabolismo , Membrana Celular/patología , Membrana Celular/ultraestructura , Microscopía por Crioelectrón , Factores de Crecimiento Nervioso/química , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Factores de Crecimiento Nervioso/ultraestructura , Mutagénesis Sitio-Dirigida , Biopolímeros/química , Biopolímeros/genética , Biopolímeros/metabolismo
8.
Angew Chem Int Ed Engl ; 62(22): e202218694, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-36972170

RESUMEN

To overcome the thermodynamic and kinetic impediments of the Sabatier CO2 methanation reaction, the process must be operated under very high temperature and pressure conditions, to obtain an industrially viable conversion, rate, and selectivity. Herein, we report that these technologically relevant performance metrics have been achieved under much milder conditions using solar rather than thermal energy, where the methanation reaction is enabled by a novel nickel-boron nitride catalyst. In this regard, an in situ generated HOB⋅⋅⋅B surface frustrated Lewis's pair is considered responsible for the high Sabatier conversion 87.68 %, reaction rate 2.03 mol gNi -1 h-1 , and near 100 % selectivity, realized under ambient pressure conditions. This discovery bodes well for an opto-chemical engineering strategy aimed at the development and implementation of a sustainable 'Solar Sabatier' methanation process.

10.
Nat Commun ; 14(1): 1435, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36918553

RESUMEN

Operating the dry reforming reaction photocatalytically presents an opportunity to produce commodity chemicals from two greenhouse gases, carbon dioxide and methane, however, the top-performing photocatalysts presented in the academic literature invariably rely on the use of precious metals. In this work, we demonstrate enhanced photocatalytic dry reforming performance through surface basicity modulation of a Ni-CeO2 photocatalyst by selectively phosphating the surface of the CeO2 nanorod support. An optimum phosphate content is observed, which leads to little photoactivity loss and carbon deposition over a 50-hour reaction period. The enhanced activity is attributed to the Lewis basic properties of the PO43- groups which improve CO2 adsorption and facilitate the formation of small nickel metal clusters on the support surface, as well as the mechanical stability of CePO4. A hybrid photochemical-photothermal reaction mechanism is demonstrated by analyzing the wavelength-dependent photocatalytic activities. The activities, turnover numbers, quantum efficiencies, and energy efficiencies are shown to be on par with other dry-reforming photocatalysts that use noble metals, representing a step forward in understanding how to stabilize ignoble nickel-based dry reforming photocatalysts. The challenges associated with comparing the performance of photocatalysts reported in the academic literature are also commented on.

11.
Rev. cuba. med. mil ; 52(1)mar. 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1521964

RESUMEN

Introducción: El análisis factorial exploratorio se usa comúnmente para evaluar la validez de la estructura interna en escalas de calidad de vida de la salud bucal. Empero, existen discusiones sobre usar indiscriminadamente el análisis de componentes principales para extraer los factores. Objetivo: Comparar los resultados de la validez basada en la estructura interna del Parental-Caregiver Perception Questionnaire - 8 ítems mediante análisis factorial exploratorio utilizando el análisis de componentes principales y otros métodos de extracción de factores. Métodos: Se realizó una revisión preliminar de la literatura para examinar el uso del análisis factorial exploratorio y sus métodos en la validación de escalas de calidad de vida relacionada con la salud bucal y se ejecutó un análisis factorial con datos de la validación del instrumento Parental-Caregiver Perception Questionnaire - versión 8, para comparar los valores de las comunalidades y las cargas factoriales de las soluciones extraídas. Resultados: La mayoría de los artículos que exploran la estructura factorial reportan el análisis de componentes principales como método de extracción y Varimax en la rotación. La información sobre los criterios para utilizar estos métodos fue insuficiente. En el análisis factorial se obtuvo que, las cargas factoriales, las comunidades y el número de factores extraídos fueron superiores con el método componentes principales. Conclusión: Usar el análisis de componentes principales como método de extracción de factores acarrea el riesgo de obtener una dimensionalidad sobreestimada en la evaluación de la validez basada en la estructura interna de las escalas de calidad de vida relacionada con la salud bucal.


Introduction: Exploratory factor analysis is commonly used to assess the validity of the internal structure in oral health quality of life scales. However, there are discussions about using principal component analysis indiscriminately to extract the factors. Objective: To compare the results of the internal structure-based validity of the Parental-Caregiver Perception Questionnaire - 8 items by exploratory factor analysis using principal component analysis and other factor estimation extraction methods. Methods: A literature review was conducted to examine the use of exploratory factor analysis and its methods in validating oral health-related quality of life scales, and a factor analysis was performed with validation data from the Parental-Caregiver Perception instrument. Questionnaire - version 8 to compare the values ​​of the communalities and the factor loads of the solutions extracted. Results: Most of the articles that explored the factorial structure reported the analysis of principal components as extraction method and Varimax in rotation. Information on the criteria for using these methods was insufficient. In the factorial analysis, it was obtained that the factorial loads, the communities and the number of extracted factors were higher with the principals component method. Conclusion: Using principal components analysis as a factor extraction method carries the risk of obtaining an overestimated dimensionality in the validity assessment based on the internal structure of oral health-related quality of life scales.

12.
Rev. Finlay ; 13(1)mar. 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1441017

RESUMEN

Fundamento: la reanimación cardiopulmocerebral es el conjunto de maniobras para asegurar la oxigenación de los órganos cuando la circulación de la sangre se detiene. La reanimación cardiopulmocerebral intrahospitalaria es una intervención que salva vidas. Objetivo: caracterizar la atención médica durante la reanimación cardiopulmocerebral en pacientes que presentan parada cardiaca dentro del Hospital General Universitario Dr. Gustavo Aldereguía Lima de Cienfuegos. Método se realizó un estudio descriptivo, transversal en las cinco unidades de cuidados intensivos de la Vicedirección de Urgencias, entre enero hasta junio del 2020. Se estudiaron 152 pacientes que realizaron un paro cardiorespiratorio. Se estudiaron las variables relacionadas con el paciente, los síntomas y signos previos al PCR presentados por los pacientes así como signos vitales. Resultados la media de edad fue de 62,66 años, en el 54,6 % predominó el sexo masculino. La hipertensión arterial fue la comorbilidad más frecuente con un 60,5 %. El 32,9 % tuvo un tiempo de estadía previo al evento de más de 72 horas. En orden de frecuencia los signos o síntomas previos al evento de PCR con más presencia fueron: bradicardia (32,2 %); pulsos débiles (15,1 %); inconciencia (12,5 %) y cianosis con 10,5 %. El servicio de mayor de ocurrencia fue la Unidad de Cuidados Intensivos Clínica. La asistolia constituyó el ritmo eléctrico inicial más común (57,9 %). En el 100 % de los casos se realizó manejo avanzado de la vía aérea con tubo endotraqueal. La desfibrilación estuvo indicada en 42 pacientes donde el 15,1 % de estos recibió la primera desfibrilación en menos de 5 minutos. La causa de la suspensión de la reanimación en 95 de los pacientes estudiados fue el fallecimiento. Conclusiones: la atención médica ante el paro cardiorrespiratorio debe seguir perfeccionándose, a través de la superación del personal sanitario y el desarrollo de acciones organizativas hacia el proceso de reanimación cardiopulmocerebral intrahospitalaria.


Background: cardiopulmonary-cerebral resuscitation is the set of maneuvers to ensure oxygenation of organs when blood circulation stops. In-hospital cardiopulmonary-cerebral resuscitation is a life-saving intervention. Objective: to characterize medical care during cardiopulmonary-cerebral resuscitation in patients with cardiac arrest at the Dr. Gustavo Aldereguía Lima University General Hospital in Cienfuegos. Method: a descriptive, cross-sectional study was carried out in the five intensive care units of the Emergency Department, from January to June 2020. 152 patients who suffered cardiorespiratory arrest were studied. The variables related to the patient, the symptoms and signs presented by the patients prior to the PCR, as well as vital signs, were studied. Results: the average age was 62.66 years, in 54.6% the male sex predominated. Arterial hypertension was the most frequent comorbidity with 60.5%. 32.9% had a length of stay prior to the event of more than 72 hours. In order of frequency, the most prevalent signs or symptoms prior to the PCR event were: bradycardia (32.2%); weak pulses (15.1%); unconsciousness (12.5%) and cyanosis with 10.5%. The service with the highest occurrence was the Clinical Intensive Care Unit. Asystole was the most common initial electrical rhythm (57.9%). In 100% of the cases, advanced airway management was performed with an endotracheal tube. Defibrillation was indicated in 42 patients where 15.1% of these received the first defibrillation in less than 5 minutes. The cause of suspension of resuscitation in 95 of the patients studied was death. Conclusions: medical care in the face of cardiorespiratory arrest must continue to be improved, through the improvement of health personnel and the development of organizational actions towards the process of intrahospital cardiopulmonary-cerebral resuscitation.

13.
PLoS Biol ; 21(1): e3001990, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36716340

RESUMEN

Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation, and virulence. Competent bacteria produce so-called "fratricins" such as CbpD that kill noncompetent siblings by cleaving peptidoglycan (PGN). CbpD is a choline-binding protein (CBP) that binds to phosphorylcholine residues found on wall and lipoteichoic acids (WTA and LTA) that together with PGN are major constituents of the pneumococcal cell wall. Competent pneumococci are protected against fratricide by producing the immunity protein ComM. How competence and fratricide contribute to virulence is unknown. Here, using a genome-wide CRISPRi-seq screen, we show that genes involved in teichoic acid (TA) biosynthesis are essential during competence. We demonstrate that LytR is the major enzyme mediating the final step in WTA formation, and that, together with ComM, is essential for immunity against CbpD. Importantly, we show that key virulence factors PspA and PspC become more surface-exposed at midcell during competence, in a CbpD-dependent manner. Together, our work supports a model in which activation of competence is crucial for host adherence by increased surface exposure of its various CBPs.


Asunto(s)
Streptococcus pneumoniae , Factores de Virulencia , Humanos , Streptococcus pneumoniae/genética , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , N-Acetil Muramoil-L-Alanina Amidasa/química , N-Acetil Muramoil-L-Alanina Amidasa/genética , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo , Colina/metabolismo , Pared Celular/metabolismo , Proteínas Bacterianas/metabolismo
14.
Rev Cient Odontol (Lima) ; 10(4): e130, 2023.
Artículo en Español | MEDLINE | ID: mdl-38390611

RESUMEN

Introduction: Hypersensitivity, altered dental appearance and fractures are common problems in molar incisor hypomineralization that generate functional and socio-emotional problems. Objective: to evaluate the effect of MIH on oral health-related quality of life in children and adolescents. Materials and methods: A systematic bibliographic search was carried out in electronic databases (Pubmed, Epistemonikos, Dentistry & Oral Sciences Source and Virtual Health Library). Observational studies in English or Spanish conducted between 2016-2022 that evaluated the quality of life of children and adolescents with molar incisor hypomineralization were identified. Most studies were of good methodological quality. Results: Of 96 identified studies, thirteen were included in the synthesis. The most frequent diagnostic criterion for hypomineralization of molar incisors was the index of the European Academy of Pediatric Dentistry and nine studies reported the severity of the disease. The most widely used scale to measure quality of life was the Child Perception Questionnaire (CPQ). According to the children's perception, the most affected dimensions were "Oral Symptoms" and "Emotional Well-Being", according to the parents they were "Oral Symptoms" and "Functional Limitations". Girls with molar incisor hypomineralization had worse oral health-related quality of life. Conclusions: The negative effect of molar incisor hypomineralization on children's oral health-related quality of life seems to vary between the perception of parents and children.

15.
Odontoestomatol ; 24(40)dic. 2022.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1431008

RESUMEN

Objetivo: Determinar el efecto de la severidad de la periodontitis en la calidad de vida relacionada con la salud bucal. Métodos: Estudio transversal que reclutó una muestra de 229 adultos con periodontitis leve, moderada y severa. La calidad de vida se midió con el Perfil de Impacto en la Salud Oral (OHIP-14). Resultados: Se encontró que los sujetos con periodontitis moderada tenían peor OHRQoL (40,2 %) en comparación con aquellos con periodontitis leve (31,8 %) y grave (28 %). Se encontraron diferencias estadísticamente significativas entre los grupos en cuanto a limitación funcional (p=0,004), dolor físico (p=0,004), incapacidad física (p=0,015), incapacidad psicológica (p=0,01) e incapacidad social (p= 0,004). Conclusiones: las dimensiones discapacidad psicológica y malestar psicológico se vieron afectadas de manera similar independientemente del estado periodontal. En sujetos con periodontitis severa hubo mayor afectación en limitación funcional e incapacidad física .


Objetivo: Determinar o efeito da gravidade da periodontite na qualidade de vida relacionada à saúde bucal. Métodos: Estudo transversal que recrutou uma amostra de 229 adultos com periodontite leve, moderada e grave. A qualidade de vida foi medida com o Oral Health Impact Profile (OHIP-14). Resultados: Indivíduos com periodontite moderada apresentaram pior QVRSO (40,2%) em comparação com aqueles com periodontite leve (31,8%) e grave (28%). Foram encontradas diferenças estatisticamente significativas entre os grupos quanto à limitação funcional (p=0,004), dor física (p=0,004), incapacidade física (p=0,015), incapacidade psicológica (p=0,01) e incapacidade social (p= 0,004). Conclusões: As dimensões deficiência psicológica e sofrimento psíquico foram afetadas de forma semelhante, independentemente do estado periodontal. Nos indivíduos com periodontite severa houve maior envolvimento na limitação funcional e incapacidade física.


Objective: To determine the effect of the severity of periodontitis on quality of life related to oral health. Methods: Cross-sectional study that recruited a sample of 229 adults with mild, moderate and severe periodontitis. Quality of life was measured with the Oral Health Impact Profile (OHIP-14). Results: Subjects with moderate periodontitis were found to have worse OHRQoL (40.2%) compared to those with mild (31.8%) and severe (28%) periodontitis. Statistically significant differences were found between the groups regarding functional limitation (p=0.004), physical pain (p=0.004), physical disability (p=0.015), psychological disability (p=0.01) and social disability (p= 0.004). Conclusions: the psychological disability and psychological distress dimensions were similarly affected regardless of periodontal status. In subjects with severe periodontitis there was greater involvement in functional limitation and physical disability.

16.
Rev. cir. (Impr.) ; 74(5)oct. 2022.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1423757

RESUMEN

Introducción: Los schwannomas suelen ser tumores benignos con origen en el sistema neural que sostiene la célula de Schwann. La mayoría presentan síntomas abdominales inespecíficos. Dado su escasa frecuencia, 1-5% de todos los tumores retroperitoneales en la población mundial, se presenta el siguiente caso. Pueden tener múltiples localizaciones, como el páncreas, tracto gastrointestinal y espacio retroperitoneal. Son pocos los casos que se han reportado siendo apenas notificados menos de 150 casos a la actualidad. Caso Clínico: Paciente femenina de 33 años con dolor abdominal inespecífico. Niega antecedentes relevantes y no presenta hallazgos positivos al examen físico. Estudios complementarios con tomografía y resonancia magnética nuclear de abdomen contrastados mostraron una masa retroperitoneal quística de 5x4 cm de localización suprarrenal derecha, que desplazaba la cava retrohepatica y que realza con medio contraste intravenoso. Debido a que el dolor era incapacitante se realizó resección quirúrgica. No se consideró biopsia preoperatoria, ante el riesgo de ruptura y diseminación tumoral. Se realizó escisión transperitoneal con resección completa, técnicamente compleja por su localización. El reporte histopato-lógico fue Schwannoma, sin tejido supra-adrenal, sugiriendo lesión yuxta-adrenal.


Introduction: Schwannomas are usually benign tumors originating in the neural system that supports the Schwann cell. Most have nonspecific abdominal symptoms. Given its low frequency, 1-5% of all retroperitoneal tumors in the world population, the following case is presented. They can have multiple locations, such as the pancreas, gastrointestinal tract and retroperitoneal space. Few cases have been reported, with less than 150 cases reported to date. Clinical Case: 33-year-old female patient with nonspecific abdominal pain. She denies relevant history and has no positive findings on physical examination. Complementary studies with contrast-enhanced tomography and magnetic resonance imaging of the abdomen showed a 5x4 cm cystic retroperitoneal mass located in the right suprarenal region, displacing the retrohepatic vena cava and enhancing with intravenous contrast medium. Because the pain was incapacitating, surgical resection was performed. A preoperative biopsy was not considered, given the risk of rupture and tumor dissemination. Transperitoneal excision was performed with complete resection, technically complex due to its location. The histopathological report was Schwannoma, without supra-adrenal tissue, suggesting a juxta-adrenal lesion.

17.
Cureus ; 14(4): e24589, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35664390

RESUMEN

Colorectal invasion is an unusual late-stage presentation of metastatic primary mucinous ovarian cancer. In this article, we report a fatal case of a 65-year-old female who presented to our clinic with progressive weight loss, severe constipation, and postprandial early satiety. She underwent an esophagogastroduodenoscopy (EGD) and colonoscopy. Direct visualization during colonoscopy revealed acute inflammation with ulceration and highly atypical glands in the ileocecal valve. The initial biopsy was unremarkable, and a repeat biopsy was performed due to high suspicion of malignancy. The repeat biopsy revealed poorly differentiated, invasive colon adenocarcinoma with partial mucinous features. The patient was referred to the surgery service. While planning for surgical resection, they obtained a CT abdomen and pelvis, which revealed a large ovarian mass and peritoneal carcinomatosis. Immunohistochemistry for the tumor cells was positive for pancytokeratin and cytokeratin 7, partially positive (up to 20%) for cytokeratin 20 and CDX2, and negative for estrogen receptors, monoclonal carcinoembryonic antigen (CEA), and synaptophysin. This immunophenotypic pattern is strongly consistent with metastatic mucinous carcinoma of ovarian origin.

18.
Sci Adv ; 8(9): eabm1122, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35235350

RESUMEN

Phosphocholine molecules decorating bacterial cell wall teichoic acids and outer-membrane lipopolysaccharide have fundamental roles in adhesion to host cells, immune evasion, and persistence. Bacteria carrying the operon that performs phosphocholine decoration synthesize phosphocholine after uptake of the choline precursor by LicB, a conserved transporter among divergent species. Streptococcus pneumoniae is a prominent pathogen where phosphocholine decoration plays a fundamental role in virulence. Here, we present cryo-electron microscopy and crystal structures of S. pneumoniae LicB, revealing distinct conformational states and describing architectural and mechanistic elements essential to choline import. Together with in vitro and in vivo functional characterization, we found that LicB displays proton-coupled import activity and promiscuous selectivity involved in adaptation to choline deprivation conditions, and describe LicB inhibition by synthetic nanobodies (sybodies). Our results provide previously unknown insights into the molecular mechanism of a key transporter involved in bacterial pathogenesis and establish a basis for inhibition of the phosphocholine modification pathway across bacterial phyla.


Asunto(s)
Lipopolisacáridos , Ácidos Teicoicos , Colina/metabolismo , Microscopía por Crioelectrón , Lipopolisacáridos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Fosforilcolina/metabolismo , Streptococcus pneumoniae/metabolismo , Ácidos Teicoicos/metabolismo
19.
Nat Commun ; 13(1): 1022, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-35197476

RESUMEN

Transport of lipids across membranes is fundamental for diverse biological pathways in cells. Multiple ion-coupled transporters take part in lipid translocation, but their mechanisms remain largely unknown. Major facilitator superfamily (MFS) lipid transporters play central roles in cell wall synthesis, brain development and function, lipids recycling, and cell signaling. Recent structures of MFS lipid transporters revealed overlapping architectural features pointing towards a common mechanism. Here we used cysteine disulfide trapping, molecular dynamics simulations, mutagenesis analysis, and transport assays in vitro and in vivo, to investigate the mechanism of LtaA, a proton-dependent MFS lipid transporter essential for lipoteichoic acid synthesis in the pathogen Staphylococcus aureus. We reveal that LtaA displays asymmetric lateral openings with distinct functional relevance and that cycling through outward- and inward-facing conformations is essential for transport activity. We demonstrate that while the entire amphipathic central cavity of LtaA contributes to lipid binding, its hydrophilic pocket dictates substrate specificity. We propose that LtaA catalyzes lipid translocation by a 'trap-and-flip' mechanism that might be shared among MFS lipid transporters.


Asunto(s)
Proteínas de Transporte de Membrana , Protones , Transporte Biológico , Lípidos , Proteínas de Transporte de Membrana/metabolismo , Simulación de Dinámica Molecular , Conformación Proteica
20.
Arch. méd. Camaguey ; 26: e8420, 2022. tab
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1403302

RESUMEN

RESUMEN Introducción: La adherencia terapéutica constituye uno de los principales problemas de las intervenciones en salud. Una de las poblaciones en las que se evidencian dificultades en la adherencia al tratamiento es en los pacientes quemados. Objetivo: Determinar la validez y confiabilidad de dos instrumentos para la evaluación de la adherencia al tratamiento y sus dimensiones influyentes en pacientes quemados hospitalizados. Métodos: Desde el enfoque cuantitativo se realizó un estudio transversal, en el periodo comprendido de enero de 2017 a diciembre de 2019. Se establecieron como variables de la investigación la adherencia al tratamiento y los factores influyentes en la adherencia al tratamiento. Se utilizó el criterio de expertos, la prueba piloto y por último se aplicaron los dos cuestionarios a 90 pacientes quemados. Resultados: Ambos instrumentos demostraron tener validez de contenido. La fiabilidad test-retest del instrumento para evaluar la adherencia terapéutica fue considerable y significativa, mientras que la consistencia interna fue aceptable. En el instrumento que evalúa las dimensiones influyentes en la adherencia terapéutica la fiabilidad fue muy fuerte y la consistencia buena. Conclusiones: Los dos instrumentos elaborados para la evaluación de la adherencia terapéutica en pacientes quemados hospitalizados, presentaron validez de contenido y confiabilidad.


ABSTRACT Introduction: Therapeutic adherence constitutesone of tema in problems of health interventions. One of the populations in which difficulties in adherence to treatment are evidence disburn patients. Objective: To determine the validity and reliability of two instruments for the evaluation of adherence to treatment and the irinfluential dimensions in hospitalized burn patients. Methods: From the quantitative approach, a cross-sectional study was conducted, in the period from January 2017 to December 2019. Adherence to treatment and influencing adherence to treat ment were established as research variables. Expert judgment wasused, the pilot test and finally the two question naireswere applied to 90 burn patients. Results: Both instruments proved to have content validity. The test-retestreliability of the instrument to evaluate therapeuticad herence was considerable and significant, whilethe internal consistency was acceptable. Reliability was very strong and consistency good in the instrument that evaluates the influencing dimensions in therapeutic adherence. Conclusions: The two instruments developed forthe evaluation of therapeutic adherence in hospitalized burn patients present content validity and reliability.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...