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1.
Sports Health ; : 19417381241273264, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233400

RESUMEN

BACKGROUND: Repetitive motion can alter joint angles and subsequently affect the control of the center of mass (CoM). While the CoM has been studied as a fatigue indicator in various sports, the control of the whole-body CoM during repetitive pitching in baseball pitchers has not been examined. This study aimed to investigate changes in lower-extremity joint angles and CoM control in collegiate baseball pitchers after repetitive pitching. HYPOTHESIS: Baseball pitchers would exhibit significant increase in lower-extremity flexion angles, CoM position, and CoM variability after repetitive pitching. STUDY DESIGN: Descriptive laboratory study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 23 pitchers from the Collegiate Baseball League were recruited. A motion analysis system was employed to assess lower-extremity joint angles and CoM position during the simulated game, while pitching accuracy and velocity were also recorded. RESULTS: The results revealed a significant forward and downward shift in CoM position (P < 0.05), along with increased CoM variability in all directions (P < 0.05) after the simulated game. Furthermore, there was a significant increase in flexion angles of the knee and hip (P < 0.05); however, pitching velocity and accuracy did not demonstrate significant changes. CONCLUSION: Repetitive pitching leads to kinematic changes that should be monitored to prevent sports injuries. CLINICAL RELEVANCE: Baseball pitchers have the ability to modify the control of their CoM and angles of their lower-extremity joints to sustain their pitching performance. It is crucial to monitor compensatory strategies closely to avoid shoulder and elbow injuries among these pitchers.

2.
Animals (Basel) ; 14(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39272377

RESUMEN

The Formosan pangolin (Manis pentadactyla pentadactyla) is an endemic animal of Taiwan. Due to their reduced population and behavior, very little is known about this enigmatic species. To unravel male pangolin reproduction, in the present study, we built a complete genomic database of the male Formosan pangolin reproductive tract and revealed highly expressing genes as well as critical signaling pathways and their associated biological processes in both the testis and the epididymis. Moreover, we evaluated the domestic cat (Felis catus) as a potential model species for male pangolin reproduction by comparing their testicular transcriptomes. We demonstrated a clear tissue-specific gene expression supporting the unique biological signature of each reproductive tissue and identified critical genes of the different reproductive organs. Pathway enrichment analysis revealed unique pathways in the testis as well as a clear epididymal transition. Furthermore, domestic cats, despite being the closest domestic species to pangolin, demonstrated their unfitness as a male reproduction model species as clear differences in spermatid differentiation and metabolism were observed. These results enable a better understanding of male pangolin reproduction characteristics and may inspire improvements in in Formosan pangolin conservation strategies.

3.
J Biomech ; 138: 111132, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35569428

RESUMEN

A repetitive sit-to-stand (STS) task is often used as a fatiguing protocol. Although post-fatigue reductions in muscle strength have been frequently used to indicate fatigue, little is known about changes in body movement during the fatiguing process. This study examined changes in variability of hip-knee and knee-ankle coordination during the STS fatiguing course in 15 young (age: 26.7 ± 5.8 years; 9 females, 6 males) and 15 older adults (age: 69.3 ± 5.7 years; 9 females, 6 males). Participants were asked to perform repetitive STS movements until exhaustion or for 30 min at a self-selected pace. Motion data from 3 consecutive STS cycles were extracted from every minute during the entire fatiguing course and time normalized to STS duration and dummy coded as five stages: 0-20, 20-40, 40-60, 60-80, and 80-100% of the course. Outcome variables were hip-knee and knee-ankle inter-joint coordination variabilities. A 2*5 mixed-effect ANOVA was used to examine changes in variability during different stages of the course in young and older adults. No Age × Time interactions were found in either hip-knee or knee-ankle coordination variability. The hip-knee coordinative variability significantly increased along the STS fatiguing course regardless of age, and the knee-ankle variability from standing to sitting was also higher at the ending, when compared to the beginning, of the fatiguing protocol. The impact of fatigue during repetitive STS protocol is not only limited to a force production decline but also manifested as increased coordinative variability, which could be considered as a fatigue indicator.


Asunto(s)
Movimiento , Fatiga Muscular , Adulto , Anciano , Fenómenos Biomecánicos , Fatiga , Femenino , Humanos , Articulación de la Rodilla/fisiología , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Fatiga Muscular/fisiología , Adulto Joven
4.
Gait Posture ; 95: 129-134, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35487020

RESUMEN

BACKGROUND: Fatigue is a commonly mentioned symptom in older adults, and walking under the influence of fatigue frequently occurs in daily activities. Studies have reported individual effects from fatigue or cognitive demand on gait performance. However, the information on how fatigue and cognitive demand interact to affect gait balance control is still lacking. RESEARCH QUESTION: How does fatigue affect walking balance control in young and older adults with and without performing a concurrent cognitive task? METHODS: We collected and analyzed motion data from 17 young and 17 older adults, who performed over-ground walking with and without a concurrent working memory test, before and after been fatigued by performing repetitive sit-to-stand movements. Three-way ANOVAs were used for statistical analysis with Age (young and older adults), Fatigue (pre- and post-fatigue), and Task (single-task and dual-task) as factors. RESULTS: From pre- to post-fatigue, an increased gait velocity was observed during dual-task walking regardless of age (p = .02). Only young adults demonstrated a significant increase in mediolateral center of mass displacement (M-L CoM) at post-fatigue (p = .019). Accuracies of the working memory test were not affected by Age, Task, or Fatigue. SIGNIFICANCE: Our findings revealed that gait balance control, as measured by the M-L CoM, deteriorated post-fatigue in young adults. Older adults maintained their mediolateral body sway from pre-fatigue to post-fatigue. Fatigue effects were not further exacerbated during dual-task walking, and similar cognitive performance was maintained as performance fatigability increased.


Asunto(s)
Marcha , Caminata , Anciano , Cognición , Fatiga , Humanos , Equilibrio Postural , Adulto Joven
5.
PLoS One ; 17(3): e0265525, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35298532

RESUMEN

Several studies have investigated factors influencing baseball pitching velocity. However, some measurements require expensive equipment, and some tests need familiarity to perform well. In this study, we adopted field tests executed using affordable equipment in a tryout event for a professional baseball team in Taiwan, 2019. We use half day to test 64 players, and the result of measurement are used to develop a model for predicting pitching velocity of amateur adult pitchers (age: 23.9 ±â€…2.8 years; height: 180.3 ±â€…5.9 cm; weight: 81.4 ±â€…10.9 kg). The measurements and tests in tryout settings should be easy to implement, take short time, do not need high skill levels, and correlate to the pitching velocity. The outcome measures included maximum external shoulder rotation, maximum internal shoulder rotation, countermovement jump (CMJ) height, 20-kg loaded CMJ height, 30-m sprint time, height, age, and weight tests. Multiple regression indicated a moderate correlation between these tests and pitching velocity (adjusted R2 = 0.230, p = 0.0003). Among the measures, the ratio of loaded CMJ to CMJ, ratio of first 10-m sprint time to 30-m sprint time, and height were significant contributors to pitching velocity. Overall, these measures explained 23% of the variance in the predicted pitching velocity. These field tests can be adopted in tryout events to predict a prospect's potential and to identify underestimated players. Coaches can obtain an expectation of a pitcher's performance by comparing his pitching velocity with the predicted value derived from the statistical model presented herein, and the room of growth by comparing his current strength to average strength growth after being drafted and trained with professional coaches.


Asunto(s)
Béisbol , Articulación del Hombro , Adulto , Fenómenos Biomecánicos , Humanos , Masculino , Rotación , Hombro , Adulto Joven
6.
Prog Cardiovasc Dis ; 73: 61-66, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33453285

RESUMEN

Sedentary behavior (SB) and physical activity (PA) are important risk factors of cardiovascular disease morbidity and mortality. In addition to increasing the amount of moderate-to-vigorous PA (MVPA), the current PA guidelines recommend that adults should reduce SB, or any waking activity performed while sitting, reclining, or lying, with low energy expenditure. While mounting evidence has emphasized the benefits of increasing MVPA, little has focused on the effect of SB on health. Therefore, this review discusses the pathophysiological effects of SB and the potential physiological benefits of reducing/breaking up SB at the levels below the current guidelines for PA. Such knowledge is important, given that the majority of the United States population performs insufficient or no MVPA and is at high risk of being negatively impacted by SB. Interventions targeting sedentary time, such as breaking up SB by standing and moving, may be safe, feasible, and applicable to execute daily for a wide range of the population. This review also discusses the importance of monitoring SB in the era of the coronavirus disease 2019 (COVID-19) pandemic and the clinical implications of sitting less and moving more.


Asunto(s)
COVID-19 , Acelerometría , Adulto , COVID-19/epidemiología , COVID-19/prevención & control , Metabolismo Energético , Ejercicio Físico/fisiología , Humanos , Factores de Riesgo , Conducta Sedentaria
7.
Micromachines (Basel) ; 12(5)2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33919456

RESUMEN

Circulating tumor cell (CTC) test is currently used as a biomarker in cancer treatment. Unfortunately, the poor reproducibility and limited sensitivity with the CTC detection have limited its potential impact on clinical application. A reliable automated CTC detection system is therefore needed. We have designed an automated microfluidic chip-based CTC detection system and hypothesize this novel system can reliably detect CTC from clinical specimens. SKOV3 ovarian cancer cell line was used first to test the reliability of our system. Ten healthy volunteers, 5 patients with benign ovarian tumors, and 8 patients with epithelial ovarian cancer (EOC) were recruited to validate the CTC capturing efficacy in the peripheral blood. The capture rates for spiking test in SKOV3 cells were 48.3% and 89.6% by using anti-EpCAM antibody alone and a combination of anti-EpCAM antibody and anti-N-cadherin antibody, respectively. The system was sensitive to detection of low cell count and showed a linear relationship with the cell counts in our test range. The sensitivity and specificity were 62.5% and 100% when CTC was used as a biomarker for EOC. Our results demonstrated that this automatic CTC platform has a high capture rate and is feasible for detection of CTCs in EOC.

8.
Nat Commun ; 12(1): 1193, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608558

RESUMEN

Deep learning for digital pathology is hindered by the extremely high spatial resolution of whole-slide images (WSIs). Most studies have employed patch-based methods, which often require detailed annotation of image patches. This typically involves laborious free-hand contouring on WSIs. To alleviate the burden of such contouring and obtain benefits from scaling up training with numerous WSIs, we develop a method for training neural networks on entire WSIs using only slide-level diagnoses. Our method leverages the unified memory mechanism to overcome the memory constraint of compute accelerators. Experiments conducted on a data set of 9662 lung cancer WSIs reveal that the proposed method achieves areas under the receiver operating characteristic curve of 0.9594 and 0.9414 for adenocarcinoma and squamous cell carcinoma classification on the testing set, respectively. Furthermore, the method demonstrates higher classification performance than multiple-instance learning as well as strong localization results for small lesions through class activation mapping.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Adenocarcinoma/patología , Algoritmos , Carcinoma de Células Escamosas , Humanos , Redes Neurales de la Computación , Curva ROC
9.
Sci Rep ; 10(1): 22199, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33335192

RESUMEN

Peptides provide a framework for generating functional biopolymers. In this study, the pH-dependent structural changes in the 21-29 fragment peptide of ß2-microglobulin (ß2m21-29) during self-aggregation, i.e., the formation of an amyloid fibril, were discussed. The ß-sheet structures formed during parallel stacking under basic conditions (pH ≥ 7.7) adopted an anti-parallel stacking configuration under acidic conditions (pH ≤ 7.6). The parallel and anti-parallel ß-sheets existed separately at the intermediate pH (pH = 7.6-7.7). These results were attributed to the rigidity of the ß-sheets in the fibrils, which prevented the stable hydrogen bonding interactions between the parallel and anti-parallel ß-sheet moieties. This observed pH dependence was ascribed to two phenomena: (i) the pH-dependent collapse of the ß2m21-29 fibrils, which consisted of 16 ± 3 anti-parallel ß-sheets containing a total of 2000 ß-strands during the deprotonation of the NH3+ group (pKa = 8.0) of the ß-strands that occurred within 0.7 ± 0.2 strands of each other and (ii) the subsequent formation of the parallel ß-sheets. We propose a framework for a functional biopolymer that could alternate between the two ß-sheet structures in response to pH changes.

10.
Clin Biomech (Bristol, Avon) ; 80: 105145, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32836079

RESUMEN

BACKGROUND: Concussion may result in acutely impaired dynamic balance control that can persist up to two months post injury. Such impairment has been detected using sophisticated whole body center of mass kinematic metrics derived from camera-based motion analysis under a dual-task paradigm. However, wearable sensor kinematics for describing gait imbalance is lacking. METHODS: This study employed a longitudinal design. Gait balance control of acutely concussed and healthy matched control participants was assessed at five post-injury time points (within 72 h of injury, at one week, two weeks, one month, and two months). Tri-axial accelerations and angular velocities were collected with a dual-task gait protocol using an inertial measurement unit placed over the fifth lumbar vertebra. FINDINGS: Eight consistent gait event specific peak accelerations and six peak angular velocities measured by the inertial measurement unit were examined. Peak yaw and roll angular velocities at heel strike and peak roll angular velocities during early single-support, distinguished healthy from concussed participants across the two month post-injury period, while peak vertical acceleration at the end of terminal stance peak medial-lateral acceleration to the right during loading response showed promise. INTERPRETATION: Utilization of peak accelerations and angular velocities collected from a single inertial measurement unit placed over the fifth lumbar vertebra in a divided attention paradigm may offer a clinically feasible method for detecting subtle changes in gait balance control in concussed individuals.


Asunto(s)
Conmoción Encefálica/fisiopatología , Análisis de la Marcha/métodos , Equilibrio Postural , Aceleración , Adulto , Fenómenos Biomecánicos , Conmoción Encefálica/diagnóstico , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Monitoreo Fisiológico
11.
J Phys Chem B ; 123(50): 10663-10671, 2019 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-31765151

RESUMEN

The acyclic form of monosaccharides exists in a structural equilibrium, with aldose having the aldehyde group and ketose the ketone group (ketose-aldose equilibrium). A basic catalyst facilitates their transformation, which affects the chemical properties of the monosaccharide. In this study, we investigated the ketose-aldose transformation of 1,3-dihydroxyacetone (1,3-DHA), one of the simplest systems of the ketose-aldose equilibrium. We examined the effects of piperidine as the basic catalyst and used IR electroabsorption spectroscopy to study the responses to an external electric field. We analyzed the changes in IR absorption by considering the changes in the molecular orientation and number of molecules in response to the external electric field. The results of the analysis revealed the permanent dipole moment µP, an angle η between µP and µT (the transition moment of the molecular vibration), and the equilibrium constants. The ketose-aldose transformation of 1,3-DHA can be explained in terms of the equilibrium of three states. In the presence of piperidine, a five-state equilibrium was concluded. On the basis of the experimental data, we propose plausible models of dihydroxyacetone, E-enediols, Z-enediol, or glyceraldehyde for each state. The results of our structural analysis of these tautomers provide a detailed understanding of the ketose-aldose transformation of acyclic saccharides and the effects of the basic catalyst.

12.
ACS Appl Mater Interfaces ; 11(6): 6384-6388, 2019 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-30652856

RESUMEN

Lateral heterojunctions in two-dimensional (2D) materials have demonstrated potential for high-performance sensors because of the unique electrostatic conditions at the interface. The increased complexity of producing such structures, however, has prevented their widespread use. We here demonstrate the simple and scalable fabrication of heterojunctions by a one-step synthesis process that yields photodetectors with superior device performance. Catalytic conversion of a solid precursor at optimized conditions was found to produce lateral nanostructured junctions between graphene domains and 3 nm thin amorphous carbon films. Carrier transport in these heterojunctions was found to proceed by minimizing the path through the amorphous carbon barriers, which results in a self-selective Schottky emission process with high uniformity and low emission barriers. We demonstrate the potential of thus produced heterojunctions by realizing a photodetector that combines an ultrahigh detectivity of 1013 Jones with microsecond response time, which represents the highest performance of 2D material heterojunction devices. These attractive features are retained even for millimeter-scale devices, and the demonstrated ability to produce transparent, patterned, and flexible sensors extends lateral heterojunction sensors toward wearable and large-scale electronics.

13.
J Food Drug Anal ; 26(3): 1171-1179, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29976409

RESUMEN

This study developed a sensitive method involving capillary electrophoresis (CE) coupled with ultraviolet absorption for the simultaneous separation of chiral phenothiazine drugs at nanomolar concentration levels. The method consists of hydroxypropyl-γ-cyclodextrin (Hp-γ-CD) as a chiral selector and poly (diallyldimethylammonium chloride) (PDDAC)-based CE. Five pairs of d,l-phenothiazines were baseline separated using a background electrolyte containing 0.9% PDDAC, 5 mM Hp-γ-CD, and 100 mM tris(hydroxymethyl)aminomethane (Tris)-formate (pH 3.0). The five pairs were successfully stacked on the basis of the difference in viscosity between the PDDAC-containing background electrolyte and the sample solution, with almost no loss of resolution. The combination of a solid-phase extraction and PDDAC-mediated CE can efficiently improve the sensitivity of the phenothiazine enantiomers. Under optimal conditions, calibration graphs displayed the linear range between 6 and 1500 nM, with relative standard deviation values lower than 3.5% (n = 5). Detection limit ranged from 2.1 to 6.3 nM for target analytes, and 607- to 1555-fold enhancement was achieved. The practicality of using the proposed method to determine five pairs of d,l-phenothiazines in urine is also validated, in which recoveries between recoveries of all phenothiazines from urine ranged from 89% to 101%.


Asunto(s)
Electroforesis Capilar/métodos , Fenotiazinas/química , Fenotiazinas/aislamiento & purificación , Extracción en Fase Sólida/métodos , Límite de Detección , Polímeros/química , Extracción en Fase Sólida/instrumentación , Estereoisomerismo , gamma-Ciclodextrinas/química
14.
Gait Posture ; 62: 422-425, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29653403

RESUMEN

Texting during walking has become a very common daily activity and could alter gait performance, especially during locomotion when additional visual attention is demanded, such as obstacle crossing. The purpose of this study was to examine biomechanical changes in obstructed gait characteristics while engaging in a phone texting activity. Gait analyses were performed on ten young healthy adults under the following two tasks: 1) walking and crossing an obstacle set at a 10% of the subject's height and 2) walking and crossing an obstacle while responding to a text message. Whole body motion data were collected with a 10-camera motion capture system. Our data demonstrated that a conservative gait pattern was adopted while performing texting when approaching and crossing over the obstacle, which was indicated by slower walking speeds and greater toe-obstacle clearances. This gait pattern was, however, accompanied by a greater body sway in the frontal plane during crossing, which could be an indication of perturbed gait balance control. Increased visual-attentional demand from a concurrent phone texting could negatively impact young pedestrians' safety during obstacle crossing.


Asunto(s)
Marcha/fisiología , Comportamiento Multifuncional/fisiología , Equilibrio Postural/fisiología , Envío de Mensajes de Texto , Adulto , Atención , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Caminata/fisiología , Caminata/psicología , Adulto Joven
15.
J Chem Phys ; 147(15): 152718, 2017 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-29055297

RESUMEN

The calculation of minimum energy or minimum free energy paths is an important step in the quantitative and qualitative studies of chemical and physical processes. The computations of these coordinates present a significant challenge and have attracted considerable theoretical and computational interest. Here we present a new local-global approach to study reaction coordinates, based on a gradual optimization of an action. Like other global algorithms, it provides a path between known reactants and products, but it uses a local algorithm to extend the current path in small steps. The local-global approach does not require an initial guess to the path, a major challenge for global pathway finders. Finally, it provides an exact answer (the steepest descent path) at the end of the calculations. Numerical examples are provided for the Mueller potential and for a conformational transition in a solvated ring system.

16.
J Biomech ; 59: 23-28, 2017 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-28549601

RESUMEN

Examining whole-body center of mass (COM) motion is one of method being used to quantify dynamic balance and energy during gait. One common method for estimating the COM position is to apply an anthropometric model to a marker set and calculate the weighted sum from known segmental COM positions. Several anthropometric models are available to perform such a calculation. However, to date there has been no study of how the anthropometric model affects whole-body COM calculations during gait. This information is pertinent to researchers because the choice of anthropometric model may influence gait research findings and currently the trend is to consistently use a single model. In this study we analyzed a single stride of gait data from 103 young adult participants. We compared the whole-body COM motion calculated from 4 different anthropometric models (Plagenhoef et al., 1983; Winter, 1990; de Leva, 1996; Pavol et al., 2002). We found that anterior-posterior motion calculations are relatively unaffected by the anthropometric model. However, medial-lateral and vertical motions are significantly affected by the use of different anthropometric models. Our findings suggest that the researcher carefully choose an anthropometric model to fit their study populations when interested in medial-lateral or vertical motions of the COM. Our data can provide researchers a priori information on the model determination depending on the particular variable and how conservative they may want to be with COM comparisons between groups.


Asunto(s)
Marcha/fisiología , Modelos Biológicos , Equilibrio Postural/fisiología , Adolescente , Adulto , Antropometría , Femenino , Humanos , Masculino , Movimiento/fisiología , Adulto Joven
17.
Protein Sci ; 25(1): 135-46, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26073558

RESUMEN

Switches form a special class of proteins that dramatically change their three-dimensional structures upon a small perturbation. One possible perturbation that we explore is that of a single point mutation. Building on the pioneering experimental work of Alexander et al. (Alexander et al. PNAS, 2007; 104,11963-11968) that determines switch sequences between α and α+ß folds we conduct a comprehensive sequence sampling by a Markov Chain with multiple fitness criteria to identify new switches given the experimental folds. We screen for switch sequences using a combination of contact potential, secondary structure prediction, and finally molecular dynamics simulations. Statistical properties of switch sequences are discussed and illustrated to be most sensitive to mutation at the N- and C- termini of the switch protein. Based on this analysis, a particularly stable putative switch pair is identified and proposed for further experimental analysis.


Asunto(s)
Simulación de Dinámica Molecular , Proteínas/química , Secuencia de Aminoácidos , Cadenas de Markov , Pliegue de Proteína , Estructura Secundaria de Proteína
18.
Opt Express ; 23(3): A149-56, 2015 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-25836243

RESUMEN

A precise correlated color temperature (CCT) tuning method for light-emitting diodes (LEDs) has been developed and is demonstrated in this article. By combining LEDs and a liquid crystal (LC) cell, a light source with continuous CCT variation along a straight track on the chromaticity diagram is achieved. Moreover, the manner of CCT variation can be modulated by choosing appropriate LEDs and phosphors to yield a variation going from 3800 K to 6100 K with the track near the black-body locus. By adapting various developed LC technologies for diverse demands, the performance and applications of LEDs can be greatly improved.

19.
Phys Chem Chem Phys ; 16(14): 6407-21, 2014 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-24473276

RESUMEN

Protein switches are made of highly similar sequences that fold to dramatically different structures. A structural switching system with 31 sequence variants for α and α+ß folds has been illustrated experimentally by He et al., Structure, 2012, 20, 283 and is investigated computationally in the present study. Methods to assign a sequence to one of the two folds are reported and analyzed. A fast and accurate protocol to identify the correct fold of the 31 sequences is based on enriching modeled structures using short molecular dynamics (MD) trajectories and scoring these structures with coarse-grained energy functions. We examine five coarse-grained energy functions and illustrate that the Hinds-Levitt potential works the best for this task. We show that enrichment by MD significantly enhances prediction accuracy. Finally, we find that melting temperature correlates well with the energy difference between the two folds (correlation coefficient ∼-0.7). The correlation reduces dramatically (∼0.4) if the absolute energy of the correct fold is considered. Moreover, prediction of melting temperature is sensitive to the structural templates. We emphasize in our analyses the use of native structures as templates since these folds are more readily available from structural biology experiments.


Asunto(s)
Proteínas/química , Termodinámica , Secuencia de Aminoácidos , Simulación de Dinámica Molecular , Estructura Terciaria de Proteína , Proteínas/metabolismo , Temperatura de Transición
20.
Obesity (Silver Spring) ; 15(10): 2407-15, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17925466

RESUMEN

OBJECTIVE: Very limited information regarding the cardiac molecular mechanism in obesity is available. The purpose of this study was to evaluate the cardiac Fas receptor-dependent (type I) apoptotic pathway in obese Zucker rats. RESEARCH METHODS AND PROCEDURES: Sixteen obese Zucker rats were studied at 5 to 6 months of age, and 16 age-matched lean Zucker rats served as controls. Heart weight index, myocardial architecture, key components of the Fas receptor-dependent apoptotic pathway, apoptotic activity, and fibrosis in the excised left ventricle of rats were measured by weight scales, hematoxylin and eosin staining, Western blotting, TUNEL assay, and Masson trichrome staining. RESULTS: Body weight, whole heart weight, left ventricular weight, ratio of whole heart weight to tibia length, percentage of TUNEL-positive cardiac myocytes, and percentage of cardiac fibrosis were significantly increased in the obese group. Cardiomyocyte disarray and increased cardiac interstitial space were observed in obese rats. Protein levels of Fas ligand, Fas death receptors, and Fas-associated Death Domain were all significantly increased in the obese group. In addition, pro-caspase-8 and pro-caspase-3 were significantly decreased, whereas activated caspase-8 and activated caspase-3 were significantly increased in the obese group, which implies that pro-forms of caspase-8 and caspase-3 were cleaved into active-forms caspase-8 and caspase-3. CONCLUSIONS: Cardiac Fas receptor-dependent apoptotic pathways were more activated in obese rats' hearts, which may provide one of the possible apoptotic mechanisms for developing cardiac abnormality in obesity.


Asunto(s)
Apoptosis , Cardiomiopatías/etiología , Cardiomiopatías/patología , Miocardio/patología , Obesidad/metabolismo , Receptores de Muerte Celular/agonistas , Receptor fas/agonistas , Animales , Peso Corporal , Cardiomiopatías/metabolismo , Caspasa 3/análisis , Caspasa 3/metabolismo , Caspasa 8/análisis , Caspasa 8/metabolismo , Fibrosis , Masculino , Miocardio/metabolismo , Obesidad/complicaciones , Tamaño de los Órganos , Ratas , Ratas Zucker , Receptores de Muerte Celular/metabolismo , Receptor fas/metabolismo
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