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1.
JMIR Perioper Med ; 7: e56033, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141909

RESUMO

BACKGROUND: Digital technology and gamified apps can be useful in the health care context. Gamification uses technology to influence users' actions and motivations through experiences that resemble games. Patient adherence to the enhanced recovery after surgery (ERAS) program is crucial for achieving early recovery after surgery and continuous monitoring is essential for obtaining good results. OBJECTIVE: This study aimed to describe the development and validation of a mobile app for enhanced recovery after surgery (MobERAS), a gamified mobile health app for telemonitoring patients in the postoperative period based on the ERAS program, and to evaluate its functionality and usability and the experience of patients, health care professionals, and computer professionals with its use. METHODS: We developed MobERAS for postoperative telemonitoring, with active participation of patients in the process, and offering availability of real-time information for the health team. The app development process included idealization, interdisciplinary team formation, potential needs assessment, and product deployment. Usability tests were conducted throughout the development process with improvements, technical adjustments, and updates. After finalization, comprehensive verification tests were performed. The parameters evaluated are those that can influence the length of hospital stay, such as nausea, vomiting, pain scales, return to normal gastrointestinal function, and thromboembolic events. MobERAS was designed to be downloaded by users on their phones, tablets, or other mobile devices and to provide postoperative data. The app has a GPS that monitors the patient's walking time and distance and is connected to a virtual database that stores the collected data. RESULTS: Women undergoing medium and major gynecologic oncologic surgeries were included. We included 65 patients with an average age of 53.2 (SD 7.4, range 18-85) years. The time of use ranged from 23.4 to 70 hours (mean 45.1, SD 19.2 hours). Regarding adherence to the use of MobERAS, the mean fill rate was 56.3% (SD 12.1%, range 41.7%-100%), and ambulation data were obtained for 60 (92.3%) of the 65 patients. The researcher had access to the data filled out by the patients in real time. There was good acceptance of the use of MobERAS by the patients, with good evaluation of the app's usability. MobERAS was easy to use and considered attractive because of its gamified design. The app was rated as good or very good in all items by health care professionals (n=20) and professionals specializing in technological innovation (n=10). CONCLUSIONS: MobERAS is easy to use, safe, well accepted by patients, and well evaluated by experts. It can be of great use in clinical surgical practice and an important tool for greater engagement of patients and health care professionals with the ERAS program.

2.
Int J Mol Sci ; 25(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38612751

RESUMO

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.


Assuntos
Medicamentos Biossimilares , Neoplasias , Humanos , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Medicamentos Biossimilares/farmacologia , Medicamentos Biossimilares/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Cromatografia em Gel
4.
Medicina (B.Aires) ; Medicina (B.Aires);83(5): 799-803, dic. 2023. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1534885

RESUMO

Resumen Se considera infección mixta por Mycobacterium tuberculosis (Mtb) a la coexistencia en forma simul tánea y en un mismo paciente de 2 cepas diferentes de Mtb o 2 variantes distintas de la misma cepa. Cuando una de las variantes selecciona mutaciones de resistencia, se denomina heterorresistencia (HTR) monoclonal; en caso de que sean 2 cepas diferentes, una sensible y una resistente (o cepas con diferentes patrones de resistencia), se denomina HTR policlo nal. Se presentan 3 pacientes, HIV/sida, todos con reiterados problemas de adherencia al tratamiento, en los cuales a través de la secuenciación genómica completa de Mtb se diagnosticó HTR monoclonal con coexistencia de 2 variantes de la misma cepa aisladas de muestras de pulmón y ganglios linfáticos, con diferentes perfiles de resistencia en cada uno de los casos. Es importante pensar en la posibilidad de HTR, principalmente en pacientes con múltiples intentos terapéuticos previos y altas poblaciones bacilares, como en el sida avanzado, dado que esta situación compromete potencialmente los resultados del tratamiento al coexistir cepas o variantes de ce pas sensibles y resistentes.


Abstract Mixed infection by Mycobacterium tuberculosis (Mtb) consists in the simultaneous coexistence in the same patient of two different strains of Mtb or 2 different variants of the same strain. When one of the variants selects for resistance mutations, it is called monoclonal heteroresistance (HTR); if there are 2 different strains, one sensitive and one resistant (or with different resis tance patterns), it is called polyclonal HTR. Three cases of HIV/AIDS patients are presented, all with repeated treatment adherence problems, in whom monoclonal HTR was diagnosed through Mtb complete genomic sequentiation with the coexistence of two variants of the same strain isolated from samples from lung and lymph nodes, with different resistance profiles in each case. It is important to consider the possibility of HTR, especially in patients with multiple previous therapeu tic attempts and high bacillary populations, such as in advanced AIDS, since this situation potentially com promises treatment results by coexisting sensitive and resistant variants of a strain (or strains).

5.
Int J Mol Sci ; 24(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37569408

RESUMO

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physicochemical conditions similar to those found in the tumoral environment. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium-free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared with the pertuzumab-HER2 complex.


Assuntos
Anticorpos Monoclonais , Receptor ErbB-2 , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Receptor ErbB-2/metabolismo , Trastuzumab
6.
J Mass Spectrom ; 58(1): e4900, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36688359

RESUMO

Sweet almond oil is a raw material with high-added value used in different products. Then, the aim of this study is to evaluate the quality and purity of 10 body oils based on sweet almond oils currently available in the Brazilian market. Fatty acid composition and triacylglycerol (TAG) profile were determined by gas chromatography with flame ionization detector (GC-FID) and atmospheric solids analysis probe mass spectrometry (ASAP-MS), respectively. The authenticity of samples was assessed using an analytical curve equation. Soybean oil was chosen as the adulterant because it is the cheapest vegetable oil commercialized in Brazil. Hierarchical clustering analysis (HCA) in conjunction with ASAP-MS classified product samples according to the type of vegetable oil (soybean and sweet almond oils). The addition of soybean oil (8.79% to 99.70%) was confirmed in samples. However, only two samples stated in their label the presence of soybean oil as an ingredient. These findings highlight the need for better oversight by regulatory bodies to ensure that consumers acquire high quality and authentic products based on equally high quality and purity of sweet almond oils.


Assuntos
Óleos de Plantas , Óleo de Soja , Óleo de Soja/análise , Brasil , Cromatografia Gasosa-Espectrometria de Massas , Óleos de Plantas/química , Espectrometria de Massas/métodos
7.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1439303

RESUMO

Introducción: La inactividad física en adolescentes es uno de los problemas actuales que ha cobrado relevancia, debido a que investigaciones proyectan hábitos de vida no saludables en la adultez. Es por ello, que instancias públicas y privadas buscan romper con esta mala práctica. Esto estimula a investigar sobre los actores que interactúan de forma continua con los adolescentes, de tal manera que los motive a entrar a un entorno que promueva la realización de actividades físicas. Objetivo: Evaluar la influencia de los modelos sociales que influyen en la realización de actividades físicas y en la salud de los estudiantes del nivel secundario en República Dominicana. Métodos: El estudio fue realizado en base a un enfoque cuantitativo descriptivo de corte transversal mediante encuesta, empleando el muestreo no probabilístico por conveniencia, debido a la disponibilidad mostrada por la población objeto de estudio al llenado del instrumento. La población estuvo integrada por 777 estudiantes, quienes brindaron las informaciones relativas al índice de actividad física y modelos sociales que influyen a su práctica. En la investigación se utilizó Cuestionario Internacional sobre el Estilo de Vida del Alumnado. Resultados: Los datos alcanzados muestran altos niveles de sedentarismo sobrepasando el 83 % en ambos sexos, con mayor presencia en las mujeres. En lo concerniente a los modelos sociales que tributan a la práctica de actividad física, se reafirman los padres y las amistades como los más influyentes. Conclusiones: Existen altos niveles de sedentarismo chicos y chicas adolescentes contrastado con la influencia positiva que reciben de padres y amigos para la realización de actividad física, lo cual puede ser utilizado con el objetivo de crear proyectos que incentiven la práctica de actividad físico-deportiva y contribuyan a la prevención de las enfermedades no transmisibles.


Introduction : Physical inactivity in adolescents is one of the current problems that has gained relevance, due to the fact that research projects unhealthy lifestyle habits in adulthood in this age group. For this reason, public and private instances seek to break this bad practice. The aforementioned, stimulates research on the actors that interact continuously with adolescents, in such a way that motivates them to enter an environment that promotes physical activities. Objective: To evaluate the impact of social models that influence the performance of physical activities and the health of secondary school students in the Dominican Republic. Methods: The present study was carried out based on a cross-sectional, descriptive quantitative approach by means of a survey, using non-probabilistic sampling by convenience, due to the availability shown by the population under study when filling out the instrument. The population consisted of 777 students, who provided information on the rate of physical activity and social models that influence its practice. The International Student Lifestyle Questionnaire was used in the research. Results: The data obtained show high levels of sedentary lifestyles, exceeding 83% in both sexes, with a greater presence in women. Regarding the social models that contribute to the practice of physical activity, parents and friends are reaffirmed as the most influential. Conclusions: There are high levels of sedentary adolescent boys and girls contrasted with the positive influence they receive from parents and friends for the practice of physical activity, which can be used with the aim of creating projects that encourage the practice of physical-sports activities and contribute to the prevention of non-communicable diseases.

8.
Nat Struct Mol Biol ; 29(12): 1228-1238, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36482249

RESUMO

DEAD-box ATPases are ubiquitous enzymes essential in all aspects of RNA biology. However, the limited in vitro catalytic activities described for these enzymes are at odds with their complex cellular roles, most notably in driving large-scale RNA remodeling steps during the assembly of ribonucleoproteins (RNPs). We describe cryo-EM structures of 60S ribosomal biogenesis intermediates that reveal how context-specific RNA unwinding by the DEAD-box ATPase Spb4 results in extensive, sequence-specific remodeling of rRNA secondary structure. Multiple cis and trans interactions stabilize Spb4 in a post-catalytic, high-energy intermediate that drives the organization of the three-way junction at the base of rRNA domain IV. This mechanism explains how limited strand separation by DEAD-box ATPases is leveraged to provide non-equilibrium directionality and ensure efficient and accurate RNP assembly.


Assuntos
RNA Helicases DEAD-box , Proteínas de Saccharomyces cerevisiae , RNA Helicases DEAD-box/metabolismo , Ribonucleoproteínas/química , RNA Ribossômico , RNA , Adenosina Trifosfatases , Proteínas de Saccharomyces cerevisiae/metabolismo
9.
Front Genet ; 13: 960263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263432

RESUMO

The acetylation status of histones located in both oncogenes and tumor suppressor genes modulate cancer hallmarks. In lung cancer, changes in the acetylation status are associated with increased cell proliferation, tumor growth, migration, invasion, and metastasis. Histone deacetylases (HDACs) are a group of enzymes that take part in the elimination of acetyl groups from histones. Thus, HDACs regulate the acetylation status of histones. Although several therapies are available to treat lung cancer, many of these fail because of the development of tumor resistance. One mechanism of tumor resistance is the aberrant expression of HDACs. Specific anti-cancer therapies modulate HDACs expression, resulting in chromatin remodeling and epigenetic modification of the expression of a variety of genes. Thus, HDACs are promising therapeutic targets to improve the response to anti-cancer treatments. Besides, natural compounds such as phytochemicals have potent antioxidant and chemopreventive activities. Some of these compounds modulate the deregulated activity of HDACs (e.g. curcumin, apigenin, EGCG, resveratrol, and quercetin). These phytochemicals have been shown to inhibit some of the cancer hallmarks through HDAC modulation. The present review discusses the epigenetic mechanisms by which HDACs contribute to carcinogenesis and resistance of lung cancer cells to anticancer therapies.

10.
Rev. am. med. respir ; 22(2): 180-185, jun. 2022. graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1441126

RESUMO

La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.


The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practi cal pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.

11.
Rev. am. med. respir ; 22(2): 264-270, jun. 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1441141

RESUMO

ABSTRACT The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practical pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.


RESUMEN La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.

13.
Bol. malariol. salud ambient ; 62(4): 623-630, 2022.
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1411907

RESUMO

La calidad de los alimentos que consumimos se ha convertido en uno de los principales problemas de salud pública a nivel mundial, ya que son la puerta de entrada de patógenos y vectores para la trasmisión de diversas enfermedades. Se estimó que el 17,9% de las enfermedades trasmitidas por el consumo de alimentos, está relacionada con aves de corral, y el 19% de estas enfermedades, están asociadas a la contaminación por Salmonella entérica. La Salmonelosis es una enfermedad invasiva que afecta en gran medida a las poblaciones altamente vulnerables (niños, ancianos e inmunocomprometidos), causando la necesidad de hospitalización y en ocasiones la muerte. A nivel mundial se estima que anualmente hay más de 94 millones de personas afectadas por gastroenteritis causada por el consumo de aves contaminadas con Salmonella, así como más de 155.000 fallecidos. Sin embargo, los orígenes de esta cepa: Salmonella entérica y otras de mayor alcance patógeno están influenciadas muy de cerca por el control de dos cepas con poca acción en la población humana: la S. polloroum y la S. gallinarum. La casi desaparición de estos dos serovares impulsó la colonización de cepas más resistente a los antibióticos y más perjudiciales para los seres humanos(AU)


The quality of the food we consume has become one of the main public health problems worldwide, since it is the gateway for pathogens and vectors for the transmission of various diseases. It was estimated that 17.9% of diseases transmitted by food consumption are related to poultry, and 19% of these diseases are associated with contamination by Salmonella enterica. Salmonellosis is an invasive disease that greatly affects highly vulnerable populations (children, the elderly and immunocompromised), causing the need for hospitalization and sometimes death. Worldwide, it is estimated that annually there are more than 94 million people affected by gastroenteritis caused by the intake of poultry contaminated with Salmonella, as well as more than 155,000 deaths. However, the origins of this strain: Salmonella enterica and others with a greater pathogenic scope are closely influenced by the control of two strains with little action in the human population: S. polloroum and S. gallinarum. The near disappearance of these two serovars prompted the colonization of strains more resistant to antibiotics and more harmful to humans(AU)


Assuntos
Aves Domésticas , Salmonella , Qualidade dos Alimentos , Infecções por Salmonella , Saúde Pública , Poluição Ambiental , Gastroenterite
14.
Bol. malariol. salud ambient ; 62(3): 369-375, 2022.
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1395360

RESUMO

La Organización mundial de la Salud, ha señalado que 92% de la población mundial vive en lugares donde los niveles de calidad del aire se han reducido por debajo de los límites fijados, estimando que a nivel mundial aproximadamente 90% de las personas respiran aire contaminado y que la población de las ciudades pasa entre el 80 y el 90% de su tiempo en recintos cerrados, en un ambiente contaminado en mayor o menor grado; puesto que los niveles de contaminación pueden llegar a ser de 10 a 100 veces más elevados en espacios interiores respecto a los exteriores. La deficiencia en la calidad del aire interior puede dar origen a la manifestación de síntomas respiratorios relacionados como rinitis alérgica y asma, entre otras patologías y se estima que, a nivel global, millones de personas sufren de ambas enfermedades, reduciendo la calidad de vida de la población. Los ácaros constituyen los sensibilizantes respiratorios más extendidos en lugares de trabajo y están presentes en casi todos los hábitats, inclusive en el ambiente aéreo, movilizados por el viento o aerosoles, siendo la principal fuente de alérgenos interiores asociados a rinitis y asma. La presente revisión describe las características de los ácaros como fuente de contaminación ambiental y su posible utilidad como futuros bioindicadores de calidad del aire interior en sistemas de ventilación de edificios industriales con el fin de reducir la exposición y sensibilización de los trabajadores a sus alérgenos(AU)


The World Health Organization has pointed out that 92% of the world's population lives in places where air quality levels have fallen below the limits set, estimating that approximately 90% of people worldwide they breathe polluted air and that the population of cities spends between 80 and 90% of their time indoors, in an environment that is polluted to a greater or lesser degree; since pollution levels can be 10 to 100 times higher indoors than outdoors. The deficiency in indoor air quality can give rise to the manifestation of related respiratory symptoms such as allergic rhinitis and asthma, among other pathologies, and it is estimated that, globally, millions of people suffer from both diseases, reducing the quality of life of the population. mites are the most widespread respiratory sensitizers in the workplace and are present in almost all habitats, including in the air environment, moved by the wind or aerosols, being the main source of indoor allergens associated with rhinitis and asthma. This review describes the characteristics of mites as a source of environmental contamination and their possible use as future bioindicators of indoor air quality in ventilation systems of industrial buildings in order to reduce the exposure and sensitization of workers to their allergens(AU)


Assuntos
Saúde Ambiental , Biomarcadores Ambientais , Poluentes Atmosféricos , Poluição do Ar , Ácaros , Doenças Respiratórias , Poluição do Ar em Ambientes Fechados , Local de Trabalho , Edifícios
15.
J Chem Inf Model ; 61(12): 6066-6078, 2021 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-34874722

RESUMO

The AS-48 bacteriocin is a potent antimicrobial polypeptide with enhanced stability due to its circular sequence of peptidic bonds. The mechanism of biological action is still not well understood in spite of both the elucidation of the molecular structure some years ago and several experiments performed that yielded valuable information about the AS-48 bacterial membrane poration activity. In this work, we present a computational study at an atomistic scale to analyze the membrane disruption mechanism. The process is based on the two-stage model: (1) peptide binding to the bilayer surface and (2) membrane poration due to the surface tension exerted by the peptide. Indeed, the induced membrane tension mechanism is able to explain stable formation of pores leading to membrane disruption. The atomistic detail obtained from the simulations allows one to envisage the contribution of the different amino acids during the poration process. Clustering of cationic residues and hydrophobic interactions between peptide and lipids seem to be essential ingredients in the process. GLU amino acids have shown to enhance the membrane disrupting ability of the bacteriocin. TRP24-TRP24 interactions make also an important contribution in the initial stages of the poration mechanism. The detailed atomistic information obtained from the simulations can serve to better understand bacteriocin structural characteristics to design more potent antimicrobial therapies.


Assuntos
Anti-Infecciosos , Bacteriocinas , Aminoácidos , Peptídeos Catiônicos Antimicrobianos/química , Bacteriocinas/farmacologia , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular
16.
J Mol Biol ; 432(23): 6028-6041, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33058875

RESUMO

Linker of nucleoskeleton and cytoskeleton (LINC) complexes are molecular tethers that span the nuclear envelope (NE) and physically connect the nucleus to the cytoskeleton. They transmit mechanical force across the NE in processes such as nuclear anchorage, nuclear migration, and homologous chromosome pairing during meiosis. LINC complexes are composed of KASH proteins traversing the outer nuclear membrane, and SUN proteins crossing the inner nuclear membrane. Humans have several SUN- and KASH-containing proteins, yet what governs their proper engagement is poorly understood. To investigate this question, we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5. In comparison to the published structures of SUN2-KASH1/2 we observe alternative binding modes for these KASH peptides. While the core interactions between SUN and the C-terminal residues of the KASH peptide are similar in all five complexes, the extended KASH-peptide adopts at least two different conformations. The much-improved resolution allows for a more detailed analysis of other elements critical for KASH interaction, including the KASH-lid and the cation loop, and a possible self-locked state for unbound SUN. In summary, we observe distinct differences between the examined SUN-KASH complexes. These differences may have an important role in regulating the SUN-KASH network.


Assuntos
Proteínas de Ciclo Celular/ultraestrutura , Proteínas de Membrana/ultraestrutura , Proteínas dos Microfilamentos/ultraestrutura , Complexos Multiproteicos/ultraestrutura , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Nucléolo Celular/genética , Nucléolo Celular/ultraestrutura , Pareamento Cromossômico/genética , Cristalografia por Raios X , Citoesqueleto/genética , Citoesqueleto/ultraestrutura , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Meiose/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/genética , Complexos Multiproteicos/química , Complexos Multiproteicos/genética , Membrana Nuclear/genética , Membrana Nuclear/ultraestrutura , Matriz Nuclear/genética , Matriz Nuclear/ultraestrutura , Peptídeos/química , Peptídeos/genética , Conformação Proteica
17.
Physiol Mol Biol Plants ; 26(8): 1635-1648, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32801492

RESUMO

Soil waterlogging is a common problem in some agricultural areas, including regions under soybean (Glycine max) cultivation. In waterlogged soils, soil O2 depletion occurs due to aerobic microorganisms and plants, affecting the metabolic and physiological processes of plants after suffering anoxia in their root tissue. Another harmful factor in this situation is the exponential increase in the availability of iron (Fe) in the soil, which may result in absorption of excess Fe. The present study sought to evaluate the response mechanisms in soybean leaves 'Agroeste 3680' by physiological and biochemical analyses associating them with the development of pods in non-waterlogged and waterlogged soil, combined with one moderate and two toxic levels of Fe. Gas exchange was strongly affected by soil waterlogging. Excess Fe without soil waterlogging reduced photosynthetic pigments, and potentiated this reduction when associated with soil waterlogging. Starch and ureide accumulation in the first newly expanded trifoliate leaves proved to be response mechanisms induced by soil waterlogging and excess Fe, since plants cultivated under soil non-waterlogged soil at 25 mg dm-3 Fe showed lower contents when compared to stressed plants. Thus, starch and ureide accumulation could be considered efficient biomarkers of phytotoxicity caused by soil waterlogging and excess Fe in soybean plants. The reproductive development was abruptly interrupted by the imposition of stresses, leading to a loss of pod dry biomass, which was largely due to the substantial decrease in the net photosynthetic rate, as expressed by area (A), the blockage of carbohydrate transport to sink tissues and an increase of malondialdehyde (MDA). The negative effect on reproductive development was more pronounced under waterlogged soil.

18.
Dent. press endod ; 10(2): 60-66, maio-ago.2020. Tab, Ilus
Artigo em Inglês | LILACS | ID: biblio-1344589

RESUMO

Objetivo: O objetivo deste estudo foi avaliar a resistência à fadiga cíclica e torcional dos sistemas reciprocantes WFile 25.07 (WF, TDKaFile, Cidade do México, México) e X1 Blue File 25.06 (X1 BF, MK Life, Porto Alegre, Bra- sil) à temperatura corporal. Material e Métodos: Foram utilizados 40 instrumentos reciprocantes WFile 25.07 (WF 25.07) e X1 BF 25.06 (n=20, cada grupo). O teste de fadiga cíclica foi realizada à temperatura corporal (36±1°C). Os instrumentos foram ativados com movimento reciprocante em um canal artificial de aço inoxidável com ângulo de 60o e 5mm de raio de curvatura (n=10). O teste torcional avaliou o torque e o ângulo de rotação necessários para a fratura dos instrumentos (n=10) nos 3mm iniciais da parte ativa do instrumento, de acordo com a norma ISO 3630-1. Os fragmentos fraturados foram avaliados em microscopia eletrônica de varredura (MEV). Os dados obtidos foram submetidos aos testes estatísticos de Kolmogorov-Smirnov e t de Student, sendo utilizado o nível de significância de 5%. Resultado: O X1BF25.06 apresentou maior tempo e número de ciclos para a fratura do que o WF 25.07 (p<0,05). O teste de torção demonstrou que o WF 25.07 apresentou maior torque do que o X1 BF 25.06 (p<0,05). Em relação ao ângulo de rotação, o X1 BF 25.06 apresentou maiores valores do que o WF 25.07 (p<0,05). Conclusão: O X1 BF apresentou maior resistência à fadiga cíclica e maior ângulo para a fratura do que o WF 25.07. Entretanto, o WF 25.07 apresentou maior torque para a fratura do que o X1 BF 25.06 (AU).


Introduction: The aim of this study was to evaluate the cyclic and torsional fatigue resistance of reciprocating single-file systems W File 25.07 (WF, TDKaFile, Mexico City, Mexico) and X1 Blue File 25.06 (X1 BF, MK Life, Porto Alegre, Brazil) at body temperature. Materials and Methods: Forty reciprocating instruments of the W File 25.07 (WF 25.07) and X1 BF 25.06 (n=20) were used. Cyclic fatigue tests were performed at body temperature (36° ± 1°C). The instruments were reciprocated until fracture occurred in an artificial stainless steel canal with a 600 angle and a 5-mm radius of curvature (n=10). The torsional test evaluated the torque and angle of rotation at failure of new instruments (n=10) in the portion 3 mm from the tip according to ISO 3630-1. The fractured surface of each fragment was observed by using scanning electron microscopy (SEM). Data were analyzed using one-way ANOVA and Tukey tests, and the level of significance was set at 5%. Results: X1 BF 25.06 had significantly higher time and NCF to failure than WF 25.07 (P<0.05). The torsional test showed that WF 25.07 had significantly greater torsional strength (p<0.05). In relation to angular rotation, the X1 BF 25.06 showed higher angular rotation values to failure than WF 25.07 (p<0.05). Conclusion: The X1 BF 25.06 had the highest cyclic fatigue resistance and highest angular rotation values to fracture in comparison with WF 25.07. However, WF 25.07 showed higher torsional resistance to fracture than X1 BF 25.06 (AU).


Assuntos
Instrumentos Odontológicos , Endodontia , Torção Mecânica , Titânio , Fadiga , Níquel
20.
Int J Mol Sci ; 20(5)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30832287

RESUMO

The combination of hydrodynamic and electrophoretic experiments and computer simulations is a powerful approach to study the interaction between proteins. In this work, we present hydrodynamic and electrophoretic experiments in an aqueous solution along with molecular dynamics and hydrodynamic modeling to monitor and compute biophysical properties of the interactions between the extracellular domain of the HER2 protein (eHER2) and the monoclonal antibody trastuzumab (TZM). The importance of this system relies on the fact that the overexpression of HER2 protein is related with the poor prognosis breast cancers (HER2++ positives), while the TZM is a monoclonal antibody for the treatment of this cancer. We have found and characterized two different complexes between the TZM and eHER2 proteins (1:1 and 1:2 TZM:eHER2 complexes). The conformational features of these complexes regulate their hydrodynamic and electrostatic properties. Thus, the results indicate a high degree of molecular flexibility in the systems that ultimately leads to higher values of the intrinsic viscosity, as well as lower values of diffusion coefficient than those expected for simple globular proteins. A highly asymmetric charge distribution is detected for the monovalent complex (1:1 complex), which has strong implications in correlations between the experimental electrophoretic mobility and the modeled net charge. In order to understand the dynamics of these systems and the role of the specific domains involved, it is essential to find biophysical correlations between dynamics, macroscopic transport and electrostatic properties. The results should be of general interest for researchers working in this area.


Assuntos
Antineoplásicos Imunológicos/química , Simulação de Acoplamento Molecular , Receptor ErbB-2/química , Trastuzumab/química , Antineoplásicos Imunológicos/farmacologia , Sítios de Ligação , Humanos , Hidrodinâmica , Ligação Proteica , Receptor ErbB-2/metabolismo , Eletricidade Estática , Trastuzumab/farmacologia
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