RESUMEN
The conserved multifunctional protein Gle1 regulates gene expression at multiple steps: nuclear mRNA export, translation initiation, and translation termination. A GLE1 mutation (FinMajor) is causally linked to human lethal congenital contracture syndrome-1 (LCCS1); however, the resulting perturbations on Gle1 molecular function were unknown. FinMajor results in a proline-phenylalanine-glutamine peptide insertion within the uncharacterized Gle1 coiled-coil domain. Here, we find that Gle1 self-associates both in vitro and in living cells via the coiled-coil domain. Electron microscopy reveals that high-molecular-mass Gle1 oligomers form ?26 nm diameter disk-shaped particles. With the Gle1-FinMajor protein, these particles are malformed. Moreover, functional assays document a specific requirement for proper Gle1 oligomerization during mRNA export, but not for Gle1's roles in translation. These results identify a mechanistic step in Gle1's mRNA export function at nuclear pore complexes and directly implicate altered export in LCCS1 disease pathology.
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Artrogriposis/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , ARN Mensajero/metabolismo , Transporte Activo de Núcleo Celular , Artrogriposis/genética , Artrogriposis/patología , Células HeLa , Humanos , Mutación , Poro Nuclear/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
PURPOSE: Arterial stiffness, expedited wave reflection, and autonomic dysfunction are risk factors for cardiovascular disease, which is the leading cause of death in women in the United States. Evaluation of the effects of resistance training on these factors has been inconclusive, and even less is known about the effects of high-intensity resistance training (HIRT). This study evaluated the effects of a 4-week HIRT intervention on central arterial stiffness, wave reflection, and heart rate variability in young healthy and active women. METHODS: 9 women were recruited and underwent a 4-week control period followed by the intervention. Measurements were recorded pre-control, post-control/pre-intervention, and post-intervention. RESULTS: There were no significant changes to central arterial stiffness, wave reflection, or heart rate variability. There was a significant increase in resting heart rate (bpm: 62 ± 7, 66 ± 10; p = 0.003) and a significant decrease in baroreceptor sensitivity (30 ± 7, 21 ± 7; p = 0.018) pre- to post-intervention. There was a significant decrease in total peripheral resistance pre- to post-intervention (1.076 ± 0.281, 0.916 ± 0.250; p = 0.002). Squat, bench press, and deadlift increased pre- to post-intervention (kg: 62 ± 11, 71 ± 9, p = 0.000; 37 ± 7, 40 ± 7, p = 0.002; 76 ± 19, 84 ± 19, p = 0.000). CONCLUSION: 4 weeks of HIRT can supplement a healthy lifestyle in women by increasing strength while decreasing peripheral resistance and preserving arterial pressures. Further evaluation is necessary to investigate the observed increase in resting heart rate and decrease in baroreceptor sensitivity and to determine long-term effects of this training.
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Entrenamiento de Fuerza , Rigidez Vascular , Presión Sanguínea/fisiología , Ejercicio Físico/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Análisis de la Onda del Pulso , Rigidez Vascular/fisiologíaRESUMEN
PURPOSE: To investigate the association between the heart rate (HR) at maximal fat oxidation (MFO) and the HR at the aerobic threshold (AerT) in adolescent boys and girls, and to identify sex differences in the intensity that elicits MFO (Fatmax) as a percentage of HR peak (HRpeak). METHODS: Fifty-eight healthy adolescents participated in this study (29 boys and 29 girls). Participants performed a cardiopulmonary exercise test on a cycle ergometer. MFO was calculated using a stoichiometric equation, and the AerT was identified using gas exchange parameters. RESULTS: A strong correlation between HR at Fatmax and HR at AerT was found in both boys and girls (r = .96 and .94, respectively). Fatmax as a percentage of HRpeak occurred at 61.0% (4.9%) of HRpeak and 66.8% (6.9%) of HRpeak in adolescent boys and girls (P = .001, F = 13.6), respectively. MFO was higher in boys compared with girls (324 [150] and 240 [95] mg/min, respectively), and no sex differences were observed in the relative contribution of fat to energy expenditure at Fatmax. CONCLUSIONS: HR at Fatmax and HR at AerT were highly correlated in adolescent boys and girls. Girls obtained Fatmax at a higher percentage of HRpeak than boys.
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Ejercicio Físico , Consumo de Oxígeno , Tejido Adiposo/metabolismo , Adolescente , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Oxidación-ReducciónRESUMEN
How the distinctive lipid composition of mammalian plasma membranes impacts membrane protein structure is largely unexplored, partly because of the dearth of isotropic model membrane systems that contain abundant sphingolipids and cholesterol. This gap is addressed by showing that sphingomyelin and cholesterol-rich (SCOR) lipid mixtures with phosphatidylcholine can be cosolubilized by n-dodecyl-ß-melibioside to form bicelles. Small-angle X-ray and neutron scattering, as well as cryo-electron microscopy, demonstrate that these assemblies are stable over a wide range of conditions and exhibit the bilayered-disc morphology of ideal bicelles even at low lipid-to-detergent mole ratios. SCOR bicelles are shown to be compatible with a wide array of experimental techniques, as applied to the transmembrane human amyloid precursor C99 protein in this medium. These studies reveal an equilibrium between low-order oligomer structures that differ significantly from previous experimental structures of C99, providing an example of how ordered membranes alter membrane protein structure.
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Colesterol/química , Proteínas de la Membrana/química , Esfingolípidos/química , Microscopía por Crioelectrón , HumanosRESUMEN
The aim of this study was to examine the cardiac autonomic nervous system differences following either continuous vs. discontinuous exercise in males and females. Forty-seven healthy male and female subjects (M=19, F=28; Age=36.95±13.79) underwent a baseline test for VO2peak and tilt table testing. They were assigned to a one-month control period before returning to repeat the testing and then begin one month of either continuous aerobic treadmill work for 30 min at 70% peak heart rate (N=23) or 3 bouts of 10 min at 70% of peak heart rate with two 10-min break periods in between (N=24). Following exercise, both groups demonstrated a significant improvement in VO2peak (p<0.001). Treatment differences were detected while tilted in continuous as a decreases in the percentage of instances within an hour that the normal sinus interval exceeds 50 ms (p=0.036) and in the high-frequency component (p=0.023). While supine, the discontinuous group saw reduction in heart rate (p=0.004), and an increase in high-frequency (p=0.018). These data suggest that for healthy people either continuous or discontinuous aerobic training is effective in improving measures of fitness; however discontinuous is better able to improve supine indices of vagal activity on heart rate variability.
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Frecuencia Cardíaca , Corazón/inervación , Acondicionamiento Físico Humano/métodos , Nervio Vago/fisiología , Adulto , Capacidad Cardiovascular , Prueba de Esfuerzo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Resistencia Física/fisiología , Pruebas de Mesa Inclinada , Adulto JovenRESUMEN
Kinesin-8s are plus-end-directed motors that negatively regulate microtubule (MT) length. Well-characterized members of this subfamily (Kip3, Kif18A) exhibit two important properties: (i) They are "ultraprocessive," a feature enabled by a second MT-binding site that tethers the motors to a MT track, and (ii) they dissociate infrequently from the plus end. Together, these characteristics combined with their plus-end motility cause Kip3 and Kif18A to enrich preferentially at the plus ends of long MTs, promoting MT catastrophes or pausing. Kif18B, an understudied human kinesin-8, also limits MT growth during mitosis. In contrast to Kif18A and Kip3, localization of Kif18B to plus ends relies on binding to the plus-end tracking protein EB1, making the relationship between its potential plus-end-directed motility and plus-end accumulation unclear. Using single-molecule assays, we show that Kif18B is only modestly processive and that the motor switches frequently between directed and diffusive modes of motility. Diffusion is promoted by the tail domain, which also contains a second MT-binding site that decreases the off rate of the motor from the MT lattice. In cells, Kif18B concentrates at the extreme tip of a subset of MTs, superseding EB1. Our data demonstrate that kinesin-8 motors use diverse design principles to target MT plus ends, which likely target them to the plus ends of distinct MT subpopulations in the mitotic spindle.
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Fenómenos Biofísicos , Cinesinas/metabolismo , Microtúbulos/metabolismo , Movimiento (Física) , Rastreo Celular , Difusión , Células HeLa , Humanos , Cinesinas/química , Cinética , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Unión Proteica , Multimerización de Proteína , Estructura Terciaria de Proteína , Grabación en VideoRESUMEN
Landram, MJ, Utter, AC, Baldari, C, Guidetti, L, McAnulty, SR, and Collier, SR. Differential effects of continuous versus discontinuous aerobic training on blood pressure and hemodynamics. J Strength Cond Res 32(1): 97-104, 2018-The purpose of this study was to compare the hemodynamic, arterial stiffness, and blood flow changes after 4 weeks of either continuous or discontinuous aerobic exercise in adults. Forty-seven subjects between the ages of 18 and 57 were recruited for 1 month of either continuous aerobic treadmill work for 30 minutes at 70% max heart rate or 3 bouts of 10 minutes of exercise at 70% of max heart rate with two 10 minutes break periods in between, totaling 30 minutes of aerobic work. After exercise, both continuous (CON) and discontinuous (DIS) groups demonstrated a significant improvement in maximal oxygen uptake (V[Combining Dot Above]O2max, CON 35.39 ± 1.99 to 38.19 ± 2.03; DIS 36.18 ± 1.82 to 39.33 ± 1.75), heart rate maximum (CON 183.5 ± 3.11 to 187.17 ± 3.06; DIS 179.06 ± 2.75 to 182 ± 2.61), decreases in systolic blood pressure (CON 119 ± 1.82 to 115.11 ± 1.50; DIS 117.44 ± 1.90 to 112.67 ± 1.66), diastolic blood pressure (CON 72.56 ± 1.65 to 70.56 ± 1.06; DIS 71.56 ± 1.59 to 69.56 ± 1.43), augmentation index (CON 17.17 ± 2.17 to 14.9 ± 1.92; DIS 19.71 ± 2.66 to 13.91 ± 2.46), central pulse wave velocity (CON 8.29 ± 0.32 to 6.92 ± 0.21; DIS 7.85 ± 0.30 to 6.83 ± 0.29), peripheral pulse wave velocity (CON 9.49 ± 0.35 to 7.72 ± 0.38; DIS 9.11 ± 0.37 to 7.58 ± 0.47), and significant increases in average forearm blood flow (CON 4.06 ± 0.12 to 4.34 ± 0.136; DIS 4.26 ± 0.18 to 4.53 ± 0.15), peak forearm blood flow (FBF) after reactive hyperemia (CON 28.45 ± 0.094 to 29.96 ± 0.45; DIS 29.29 ± 0.46 to 30.6 ± 0.38), area under the curve (AUC) of FBF (CON 28.65 ± 1.77 to 30.4 ± 1.08; DIS 30.52 ± 1.9 to 31.67 ± 1.44), and AUC peak FBF after reactive hyperemia (CON 222.3 ± 5.68 to 231.95 ± 4.42; DIS 230.81 ± 6.91 to 237.19 ± 5.39). These data suggest that for healthy people either 4 weeks of continuous or discontinuous aerobic training is effective in improving measures of fitness and vascular health.
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Presión Sanguínea/fisiología , Ejercicio Físico/fisiología , Hemodinámica/fisiología , Adolescente , Adulto , Factores de Edad , Prueba de Esfuerzo , Femenino , Antebrazo/irrigación sanguínea , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Rigidez Vascular , Adulto JovenRESUMEN
A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O2, and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing.
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Actigrafía/instrumentación , Investigación Biomédica/instrumentación , Ejercicio Físico/fisiología , Monitores de Ejercicio/tendencias , Fisiología/instrumentación , Telemedicina/instrumentación , Actigrafía/métodos , Actigrafía/tendencias , Investigación Biomédica/métodos , Investigación Biomédica/tendencias , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Aplicaciones Móviles/tendencias , Fisiología/métodos , Fisiología/tendencias , Evaluación de la Tecnología Biomédica , Telemedicina/métodos , Telemedicina/tendenciasRESUMEN
Germ cells give rise to all cell lineages in the next-generation and are responsible for the continuity of life. In a variety of organisms, germ cells and stem cells contain large ribonucleoprotein granules. Although these particles were discovered more than 100 years ago, their assembly and functions are not well understood. Here we report that glycolytic enzymes are components of these granules in Drosophila germ cells and both their mRNAs and the enzymes themselves are enriched in germ cells. We show that these enzymes are specifically required for germ cell development and that they protect their genomes from transposable elements, providing the first link between metabolism and transposon silencing. We further demonstrate that in the granules, glycolytic enzymes associate with the evolutionarily conserved Tudor protein. Our biochemical and single-particle EM structural analyses of purified Tudor show a flexible molecule and suggest a mechanism for the recruitment of glycolytic enzymes to the granules. Our data indicate that germ cells, similarly to stem cells and tumor cells, might prefer to produce energy through the glycolytic pathway, thus linking a particular metabolism to pluripotency.
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Gránulos Citoplasmáticos/metabolismo , Elementos Transponibles de ADN/fisiología , Proteínas de Drosophila/metabolismo , Drosophila/enzimología , Células Germinativas/fisiología , Proteínas de Transporte de Membrana/metabolismo , Ribonucleoproteínas/metabolismo , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Drosophila/fisiología , Glucólisis , MicroARNs/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
Dehydration has been shown to hinder performance of sustained exercise in the heat. Consuming fluids before exercise can result in hyperhydration, delay the onset of dehydration during exercise and improve exercise performance. However, humans normally drink only in response to thirst, which does not result in hyperhydration. Thirst and voluntary fluid consumption have been shown to increase following oral ingestion or infusion of sodium into the bloodstream. We measured the effects of acute sodium ingestion on voluntary water consumption and retention during a 2-hr hydration period before exercise. Subjects then performed a 60-min submaximal dehydration ride (DR) followed immediately by a 200 kJ performance time trial (PTT) in a warm (30 °C) environment. Water consumption and retention during the hydration period was greater following sodium ingestion (1380 ± 580 mL consumed, 821 ± 367 ml retained) compared with placebo (815 ± 483 ml consumed, 244 ± 402 mL retained) and no treatment (782 ± 454 ml consumed, 148 ± 289 mL retained). Dehydration levels following the DR were significantly less after sodium ingestion (0.7 ± 0.6%) compared with placebo (1.3 ± 0.7%) and no treatment (1.6 ± 0.4%). Time to complete the PTT was significantly less following sodium consumption (773 ± 158 s) compared with placebo (851 ± 156 s) and no treatment (872 ± 190 s). These results suggest that voluntary hyperhydration can be induced by acute consumption of sodium and has a favorable effect on hydration status and performance during subsequent exercise in the heat.
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Rendimiento Atlético/fisiología , Deshidratación/prevención & control , Ingestión de Líquidos/efectos de los fármacos , Calor , Sodio en la Dieta/administración & dosificación , Fenómenos Fisiológicos en la Nutrición Deportiva/efectos de los fármacos , Adulto , Ciclismo/fisiología , Estudios Cruzados , Deshidratación/etiología , Método Doble Ciego , Prueba de Esfuerzo/métodos , Humanos , Masculino , Sed/fisiología , Factores de TiempoRESUMEN
Short sleep duration and poor quality of sleep have been associated with health risks including cardiovascular disease, diabetes, and obesity. Prior research has suggested that regular aerobic exercise improves the quality of sleep; however, less is known regarding resistance exercise (RE) and how RE may affect sleep architecture. The purpose of this study was to investigate the acute effects of timing of RE on sleep architecture and nocturnal blood pressure. College-aged subjects engaged in 5 laboratory visits. Visits 1 (C) and 2 provided a non-RE control day and established the 10-repetition maximum on each of 9 RE machines, respectively. During visits 3-5, the subjects reported at 0700 hours (7A), 1300 hours (1P), and 1900 hours (7P) in a randomized order to perform 30 minutes of RE. Ambulatory blood pressure and sleep-monitoring devices were worn during sleep after C, 7A, 1P, and 7P. Time to fall asleep was significantly different between RE conditions 7A and 1P and between 7A and 7P. All exercise conditions exhibited significantly fewer times woken than the non-RE control day, with 7P resulting in significantly less time awake after initially falling asleep as compared with C. Although timing of RE does not seem to statistically impact sleep stages or nocturnal blood pressure, these data indicate that engaging in RE at any time of the day may improve quality of sleep as compared with no RE. Resistance exercise may offer additional benefits regarding the ability to fall asleep and stay asleep to populations with osteoporosis, sarcopenia, anxiety, or depression.
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Presión Sanguínea , Ejercicio Físico/fisiología , Sueño/fisiología , Monitoreo Ambulatorio de la Presión Arterial , Humanos , Polisomnografía , Entrenamiento de Fuerza , Factores de Tiempo , Adulto JovenRESUMEN
The spliceosome is a dynamic macromolecular machine composed of five small nuclear ribonucleoparticles (snRNPs), the NineTeen Complex (NTC), and other proteins that catalyze the removal of introns mature to form the mature message. The NTC, named after its founding member Saccharomyces cerevisiae Prp19, is a conserved spliceosome subcomplex composed of at least nine proteins. During spliceosome assembly, the transition to an active spliceosome correlates with stable binding of the NTC, although the mechanism of NTC function is not understood. Schizosaccharomyces pombe Cdc5, a core subunit of the NTC, is an essential protein required for pre-mRNA splicing. The highly conserved Cdc5 N-terminus contains two canonical Myb (myeloblastosis) repeats (R1 and R2) and a third domain (D3) that was previously classified as a Myb-like repeat. Although the N-terminus of Cdc5 is required for its function, how R1, R2, and D3 each contribute to functionality is unclear. Using a combination of yeast genetics, structural approaches, and RNA binding assays, we show that R1, R2, and D3 are all required for the function of Cdc5 in cells. We also show that the N-terminus of Cdc5 binds RNA in vitro. Structural and functional analyses of Cdc5-D3 show that, while this domain does not adopt a Myb fold, Cdc5-D3 preferentially binds double-stranded RNA. Our data suggest that the Cdc5 N-terminus interacts with RNA structures proposed to be near the catalytic core of the spliceosome.
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Proteínas de Ciclo Celular/química , Modelos Moleculares , Empalme del ARN , ARN Bicatenario/metabolismo , ARN Nuclear Pequeño/metabolismo , Proteínas de Unión al ARN/química , Proteínas de Schizosaccharomyces pombe/química , Empalmosomas/química , Sitios de Unión , Dominio Catalítico , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Eliminación de Gen , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Resonancia Magnética Nuclear Biomolecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Conformación Proteica , Pliegue de Proteína , Dominios y Motivos de Interacción de Proteínas , Estabilidad Proteica , ARN de Hongos/química , ARN de Hongos/metabolismo , ARN Nuclear Pequeño/química , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Empalmosomas/genética , Empalmosomas/metabolismo , VolumetríaRESUMEN
The spliceosome is a dynamic macromolecular machine that catalyzes the removal of introns from pre-mRNA, yielding mature message. Schizosaccharomyces pombe Cwf10 (homolog of Saccharomyces cerevisiae Snu114 and human U5-116K), an integral member of the U5 snRNP, is a GTPase that has multiple roles within the splicing cycle. Cwf10/Snu114 family members are highly homologous to eukaryotic translation elongation factor EF2, and they contain a conserved N-terminal extension (NTE) to the EF2-like portion, predicted to be an intrinsically unfolded domain. Using S. pombe as a model system, we show that the NTE is not essential, but cells lacking this domain are defective in pre-mRNA splicing. Genetic interactions between cwf10-ΔNTE and other pre-mRNA splicing mutants are consistent with a role for the NTE in spliceosome activation and second-step catalysis. Characterization of Cwf10-NTE by various biophysical techniques shows that in solution the NTE contains regions of both structure and disorder. The first 23 highly conserved amino acids of the NTE are essential for its role in splicing but when overexpressed are not sufficient to restore pre-mRNA splicing to wild-type levels in cwf10-ΔNTE cells. When the entire NTE is overexpressed in the cwf10-ΔNTE background, it can complement the truncated Cwf10 protein in trans, and it immunoprecipitates a complex similar in composition to the late-stage U5.U2/U6 spliceosome. These data show that the structurally flexible NTE is capable of independently incorporating into the spliceosome and improving splicing function, possibly indicating a role for the NTE in stabilizing conformational rearrangements during a splice cycle.
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GTP Fosfohidrolasas/metabolismo , Ribonucleoproteína Nuclear Pequeña U5/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimología , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Sitios de Unión , GTP Fosfohidrolasas/genética , Datos de Secuencia Molecular , Mutación , Unión Proteica , Estructura Terciaria de Proteína , Empalme del ARN , Ribonucleoproteína Nuclear Pequeña U5/química , Ribonucleoproteína Nuclear Pequeña U5/genética , Schizosaccharomyces/química , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/genética , Empalmosomas/metabolismoRESUMEN
Both aerobic (AT) and resistance training (RT) are recommended as nonpharmacological treatments to prevent hypertension. However, there is a paucity of literature investigating the effects of combined exercise modes (RT combined with AT) in elderly hypertensive women. Thus, our aim was to compare the postexercise hypotension (PEH) response to both protocol models and to assess the correlation between the degree of PEH after acute and chronic training. Furthermore, we also compared several biochemical variables for each training group. Sixty hypertensive older women were randomly assigned into nonexercised control (no systematic exercise training throughout the study), eccentric RT (ERT), and traditional RT (TRT). The training programs consisted of 16 weeks of RT combined with AT. Blood pressure (BP), biochemical profiles, and 1 repetition maximum (1RM) were evaluated. There was a significant increase in high-density lipoprotein (HDL) after both training regimens pre- to posttraining (combined ERT +5% and TRT +7%; p = 0.001 for both). There was a decrease in systolic BP (SBP) (combined ERT -19% and TRT -21%; p = 0.001 for both) and diastolic BP (DBP) (-13% for both; p = 0.001 for both). There was an increase in bench press 1RM (combined ERT +54% and TRT +35%; p = 0.001 for both) and leg press 1RM (combined ERT +52% and TRT +33%; p = 0.001 for both). The magnitude of decrease in SBP after acute exercise was moderately correlated with the drop in SBP after chronic training for the ERT combined with AT group (r = 0.64). Both combined training protocols are effective in promoting benefits in health-related factors (HDL, SBP, DBP, and 1RM). Considering the lower cardiovascular stress experienced during combined ERT, this type of training seems to be the most suitable for elders, deconditioned individuals, and hypertensives.
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Hipertensión/terapia , Acondicionamiento Físico Humano/métodos , Acondicionamiento Físico Humano/fisiología , Hipotensión Posejercicio/fisiopatología , Entrenamiento de Fuerza/métodos , Anciano , Presión Sanguínea , Femenino , Humanos , Hipertensión/fisiopatología , Lipoproteínas HDL/sangre , Persona de Mediana Edad , Fuerza Muscular , Músculo Esquelético/fisiologíaRESUMEN
In fission yeast (Schizosaccharomyces pombe), the E3 ubiquitin ligase Dma1 delays cytokinesis if chromosomes are not properly attached to the mitotic spindle. Dma1 contains a C-terminal RING domain, and we have found that the Dma1 RING domain forms a stable homodimer. Although the RING domain is required for dimerization, residues in the C-terminal tail are also required to help form or stabilize the dimeric structure because mutation of specific residues in this region disrupts Dma1 dimerization. Further analyses showed that Dma1 dimerization is required for proper localization at spindle pole bodies and the cell division site, E3 ligase activity, and mitotic checkpoint function. Thus, Dma1 forms an obligate dimer via its RING domain, which is essential for efficient transfer of ubiquitin to its substrate(s). This study further supports the mechanistic paradigm that many RING E3 ligases function as RING dimers.
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Proteínas de Ciclo Celular/química , Puntos de Control de la Fase M del Ciclo Celular , Multimerización de Proteína , Proteínas de Schizosaccharomyces pombe/química , Schizosaccharomyces/enzimología , Ubiquitina-Proteína Ligasas/química , Secuencia de Aminoácidos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Secuencia Conservada , Mitosis , Datos de Secuencia Molecular , Estructura Cuaternaria de Proteína , Transporte de Proteínas , Dominios RING Finger , Schizosaccharomyces/fisiología , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Homología de Secuencia de Aminoácido , Huso Acromático/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: Long chain omega-3 fatty acids from fish oils (O3) are known to have beneficial effects on a number of vascular risk factors in at-risk populations. The effects of a highly bioavailable emulsified preparation on an overweight young adult population are less well known. METHODS: Young adults, age 18-30, with body mass indices (BMIs) greater than 23 (average = 28.1) were administered 1.7 g of O3 per day (N = 30) or safflower oil placebo (N = 27) in an emulsified preparation (Coromega, Inc.) for 4 weeks in a double-blind randomized design. Blood was drawn and anthropometric measurements taken before and after dosing. Hemodynamic measures (central pulse wave velocity, augmentation index, and aortic systolic blood pressure), inflammatory cytokines (IL-6, IL-8, IL-10, and tumor necrosis factor-α), red blood cell and plasma phospholipid fatty acid profiles, fasting serum lipids, glucose, and C-reactive protein were measured. RESULTS: Red cell and plasma phospholipid eicosapentaenoic acid and docosahexaenoic acid concentrations increased over the four weeks of dosing in the O3 group. Dosing with O3 did not affect central pulse wave velocity, augmentation index, or aortic systolic blood pressure. None of the five American Heart Association metabolic syndrome components improved over the dosing period. None of the inflammatory cytokines, C-reactive protein, or lipids (total or LDL cholesterol) improved over the dosing period. CONCLUSIONS: No salutary effects of O3 were observed in hemodynamic, metabolic syndrome criteria or inflammatory markers as a result of this relatively short period of administration in this relatively overweight, but healthy young adult cohort.
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Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Aceites de Pescado/administración & dosificación , Inflamación/sangre , Síndrome Metabólico/sangre , Adolescente , Adulto , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Colesterol/sangre , Ácidos Docosahexaenoicos/sangre , Método Doble Ciego , Ácido Eicosapentaenoico/sangre , Ayuno , Femenino , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Masculino , Fosfolípidos/sangre , Aceite de Cártamo/administración & dosificación , Resultado del Tratamiento , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
AIM: To compare the effects of 4 and 8 weeks of play-based, supervised exercise during summer break versus an unsupervised break on cardiovascular function in adolescent children. METHODS: Twenty-two subjects were divided into a 4-week exercise group (age 10.1 ± 1.3 years), an 8-week exercise group (age 9.4 ± 1.7 years) or a control group (age 10.0 ± 1.3 years). The activity groups participated in a supervised summer camp for 6 h/day, 5 days/week including a discontinuous play-based physical activity program and a healthy lifestyle, while the control group were told to keep their regular summer break routines. Anthropometrics, pulse wave velocity, augmentation index, blood pressure and peak oxygen consumption were evaluated before and after the intervention. RESULTS: Normalized augmentation index (75 beats/min) significantly decreased after 4 and 8 weeks in the active groups (p = 0.04) while pulse wave velocity showed no significant changes in all groups. Mean arterial pressure decreased (p = 0.003) and peak oxygen consumption increased (p = 0.001) significantly in the 8 week group. CONCLUSION: These data suggest that 8 weeks of supervised play-based activity yield several cardio-beneficial results in adolescents, which may act as a clinical prophylaxis throughout their lifetime.
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Fenómenos Fisiológicos Cardiovasculares , Ejercicio Físico/fisiología , Juego e Implementos de Juego , Adolescente , Enfermedades Cardiovasculares/epidemiología , Niño , Femenino , Humanos , Masculino , Factores de Riesgo , Estaciones del AñoRESUMEN
The purpose of this study was to characterize the magnitude of acute weight gain (AWG) and dehydration in mixed martial arts (MMA) fighters before competition. Urinary measures of hydration status and body mass were determined approximately 24 hours before and then again approximately 2 hours before competition in 40 MMA fighters (mean ± SE, age: 25.2 ± 0.65 years, height: 1.77 ± 0.01 m, body mass: 75.8 ± 1.5 kg). The AWG was defined as the amount of body weight the fighters gained in the approximately 22-hour period between the official weigh-in and the actual competition. On average, the MMA fighters gained 3.40 ± 2.2 kg or 4.4% of their body weight in the approximately 22-hour period before competition. Urine specific gravity significantly decreased (p < 0.001) from 1.028 ± 0.001 to 1.020 ± 0.001 during the approximately 22-hour rehydration period. Results demonstrated that 39% of the MMA fighters presented with a Usg of >1.021 immediately before competition indicating significant or serious dehydration. The MMA fighters undergo significant dehydration and fluctuations in body mass (4.4% avg.) in the 24-hour period before competition. Urinary measures of hydration status indicate that a significant proportion of MMA fighters are not successfully rehydrating before competition and subsequently are competing in a dehydrated state. Weight management guidelines to prevent acute dehydration in MMA fighters are warranted to prevent unnecessary adverse health events secondary to dehydration.
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Conducta Competitiva , Deshidratación , Conducta de Ingestión de Líquido , Artes Marciales , Aumento de Peso , Adulto , Composición Corporal , Índice de Masa Corporal , Deshidratación/orina , Femenino , Humanos , Masculino , North Carolina , South Carolina , Pérdida de PesoRESUMEN
Ambulatory sleep and blood pressure monitoring are gaining popularity as these can be completed in an individual's home. Little is known regarding the reliability of data and the time it takes to acclimate to the equipment. This study aimed to determine how many nights of wearing the monitoring equipment were required to restore sleep architecture and blood pressure data to baseline. It was hypothesized familiarization would be demonstrated by night 3. Ten male and 10 female subjects completed three nights of sleep and blood pressure recordings. At visit 1, the subjects were familiarized with the equipment and instructed to wear the Sleep Profiler{trade mark, serif} and SunTech Medical Oscar2 ambulatory blood pressure cuff simultaneously for three consecutive nights, then subjects returned the equipment. The percent of time spent in rapid eye-movement (REM) sleep was statistically different on night 3 when compared to night 1. Wake-after-sleep onset and sleep latency were not statistically different between nights 1, 2, and 3. Systolic, diastolic, and pulse pressure were all significantly lower on night 3 compared to night 1. Cortical and autonomic arousals were statistically different on night 3. Ambulatory sleep and blood pressure monitoring need at least 3 nights for familiarization. The percent of time spent in REM sleep was statistically different on night 3 when compared to night 1. Systolic blood pressure, diastolic blood pressure, and pulse pressure were all significantly lower on night 3 compared to night 1. Cortical and autonomic arousals were statistically different on nights 3 and 2, respectively compared to night 1. Based on these findings, ambulatory sleep and blood pressure monitoring takes three nights before the data are reliable and the person is familiarized with the mode of measurement. Therefore, it is recommended to use at least three nights of data collection when using the Sleep Profiler and Oscar2 ambulatory blood pressure cuff in order for results to be valid and reliable.
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Monitoreo Ambulatorio de la Presión Arterial , Sueño , Humanos , Masculino , Femenino , Presión Sanguínea/fisiología , Reproducibilidad de los Resultados , Sueño/fisiología , Sueño REM/fisiologíaRESUMEN
Objective Heightened nocturnal blood pressure (BP) may be attributed to the disruption of sleep, a condition worsened by alcohol ingestion. This study investigated the effects of acute alcohol ingestion on hemodynamics and sleep architecture in a young, healthy cohort of male. METHODS: Subjects (n = 17) underwent acute alcohol ingestion reaching a breath alcohol content of 0.08. Each subject endured a battery of hemodynamic tests and had their sleep architecture and nocturnal blood pressure monitored pre- and post-ingestion. Results: Systolic blood pressure (SBP) increased both 30 minutes and 12 hours after alcohol. Ambulatory nocturnal SBP significantly increased after alcohol compared to baseline measures. Minutes of total, rapid eye movement, and light sleep all increased after alcohol ingestion, while a decrease was observed for sleep latency. Conclusions: An acute bout of heavy alcohol consumption may attenuate nocturnal BP dipping that, in turn, may hasten the progression of hypertension-related cardiovascular disease.