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1.
J Strength Cond Res ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39017963

RESUMEN

ABSTRACT: Lim, B, Villalobos, A, Mercer, JA, and Crocker, GH. Energetics and basic stroke kinematics of swimming with different styles of wetsuits. J Strength Cond Res XX(X): 000-000, 2024-This study investigated the physiological responses and basic stroke kinematics while wearing different styles of wetsuits during submaximal intensity front-crawl swimming. Fourteen subjects (6 men and 8 women) completed a swimming-graded exercise test to determine maximal aerobic capacity (V̇O2max) and four 4-minute submaximal front-crawl swims at a pace that elicited 80% of V̇O2max with different wetsuits: regular swimsuit (no wetsuit [NWS]), buoyancy shorts (BS), sleeveless wetsuit (SLW), and full-sleeve wetsuit (FSW). The rate of oxygen consumption (V̇O2), rate of carbon dioxide production (V̇CO2), minute ventilation (V̇E), heart rate (HR), respiratory exchange ratio, and cost of swimming (CS) were determined as the average for the last minute of each trial. The rating of perceived exertion was assessed after each swimming bout. In addition, stroke length and index were determined from swimming pace and stroke rate. V̇O2, V̇CO2, V̇E, HR, and CS differed significantly among wetsuit conditions (p < 0.01). Respiratory exchange ratio and rating of perceived exertion also varied by wetsuit conditions (p < 0.05). However, stroke rate, length, and index were not significantly different across wetsuit conditions (p > 0.05). No differences existed between SLW and FSW for any dependent variable (p > 0.05). Results from this study suggest that swimming at the same pace without a wetsuit is the least economical, and both SLW and FSW are most and equally economical without significant kinematic changes. In addition, BS could be beneficial during training and racing in terms of less physiological demands than a regular swimsuit but not as economical as the SLW or FSW.

2.
Cell ; 135(3): 535-48, 2008 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-18984164

RESUMEN

Learning-related plasticity at excitatory synapses in the mammalian brain requires the trafficking of AMPA receptors and the growth of dendritic spines. However, the mechanisms that couple plasticity stimuli to the trafficking of postsynaptic cargo are poorly understood. Here we demonstrate that myosin Vb (MyoVb), a Ca2+-sensitive motor, conducts spine trafficking during long-term potentiation (LTP) of synaptic strength. Upon activation of NMDA receptors and corresponding Ca2+ influx, MyoVb associates with recycling endosomes (REs), triggering rapid spine recruitment of endosomes and local exocytosis in spines. Disruption of MyoVb or its interaction with the RE adaptor Rab11-FIP2 abolishes LTP-induced exocytosis from REs and prevents both AMPA receptor insertion and spine growth. Furthermore, induction of tight binding of MyoVb to actin using an acute chemical genetic strategy eradicates LTP in hippocampal slices. Thus, Ca2+-activated MyoVb captures and mobilizes REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity.


Asunto(s)
Endosomas/metabolismo , Potenciación a Largo Plazo , Miosina Tipo V/metabolismo , Plasticidad Neuronal , Receptores AMPA/metabolismo , Animales , Calcio/metabolismo , Línea Celular , Dendritas/metabolismo , Espinas Dendríticas/metabolismo , Hipocampo/citología , Hipocampo/metabolismo , Humanos , Ratones , Ratones Endogámicos , Miosina Tipo V/química , Neuronas/metabolismo , Ratas , Sinapsis/metabolismo , Proteínas de Unión al GTP rab/metabolismo
3.
Clin Case Stud ; 21(3): 209-234, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35664370

RESUMEN

Adolescent athletes with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) experience unique challenges that impact their sport performance, such as making errors due to poor concentration. The current multiple-baseline across behaviors case trial (i.e., positive assertion and negative assertion) is an evaluation of The Optimum Performance Program in Sports in an adolescent athlete diagnosed with ADHD and ODD. Intervention skill sets were targeted sequentially in a virtual format to safeguard against COVID-19 contraction. A battery of psychological measures was administered at baseline, post-intervention, and 1-month follow-up. Results indicated negative and positive assertion skills improved, but only when targeted, and severity of ADHD and ODD symptom severity, general mental health symptoms, and factors interfering with sport performance decreased from pre- to post-intervention and these improvements were maintained at 1-month follow-up. Similar improvements occurred in relationships with coaches, teammates, and family. Treatment integrity and consumer satisfaction were high.

4.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34576157

RESUMEN

DNA damage and mitochondrial dysfunction are defining characteristics of aged vascular smooth muscle cells (VSMCs) found in atherosclerosis. Pink1 kinase regulates mitochondrial homeostasis and recycles dysfunctional organelles critical for maintaining energetic homeostasis. Here, we generated a new vascular-specific Pink1 knockout and assessed its effect on VSMC-dependent atherogenesis in vivo and VSMC energetic metabolism in vitro. A smooth muscle cell-specific and MHC-Cre-inducible flox'd Pink1f/f kinase knockout was made on a ROSA26+/0 and ApoE-/- C57Blk6/J background. Mice were high fat fed for 10 weeks and vasculature assessed for physiological and pathogical changes. Mitochondrial respiratory activity was then assessed in wild-type and knockout animals vessels and isolated cells for their reliance on oxidative and glycolytic metabolism. During atherogenesis, we find that Pink1 knockout affects development of plaque quality rather than plaque quantity by decreasing VSMC and extracellular matrix components, collagen and elastin. Pink1 protein is important in the wild-type VSMC response to metabolic stress and induced a compensatory increase in hexokinase II, which catalyses the first irreversible step in glycolysis. Pink1 appears to play an important role in VSMC energetics during atherogenesis but may also provide insight into the understanding of mitochondrial energetics in other diseases where the regulation of energetic switching between oxidative and glycolytic metabolism is found to be important.


Asunto(s)
Músculo Liso Vascular/metabolismo , Proteínas Quinasas/metabolismo , Animales , Aterosclerosis/metabolismo , Aterosclerosis/fisiopatología , Daño del ADN/genética , Daño del ADN/fisiología , Glucólisis/genética , Glucólisis/fisiología , Ratones , Ratones Noqueados , Microdisección , Músculo Liso Vascular/citología , Miocitos del Músculo Liso , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Fosforilación/genética , Fosforilación/fisiología , Proteínas Quinasas/genética , Transducción de Señal/genética , Transducción de Señal/fisiología
5.
Int J Mol Sci ; 23(1)2021 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-35008643

RESUMEN

The cardiovascular disease of atherosclerosis is characterised by aged vascular smooth muscle cells and compromised cell survival. Analysis of human and murine plaques highlights markers of DNA damage such as p53, Ataxia telangiectasia mutated (ATM), and defects in mitochondrial oxidative metabolism as significant observations. The antiageing protein Klotho could prolong VSMC survival in the atherosclerotic plaque and delay the consequences of plaque rupture by improving VSMC phenotype to delay heart attacks and stroke. Comparing wild-type VSMCs from an ApoE model of atherosclerosis with a flox'd Pink1 knockout of inducible mitochondrial dysfunction we show WT Pink1 is essential for normal cell viability, while Klotho mediates energetic switching which may preserve cell survival. METHODS: Wild-type ApoE VSMCs were screened to identify potential drug candidates that could improve longevity without inducing cytotoxicity. The central regulator of cell metabolism AMP Kinase was used as a readout of energy homeostasis. Functional energetic switching between oxidative and glycolytic metabolism was assessed using XF24 technology. Live cell imaging was then used as a functional readout for the WT drug response, compared with Pink1 (phosphatase-and-tensin-homolog (PTEN)-induced kinase-1) knockout cells. RESULTS: Candidate drugs were assessed to induce pACC, pAMPK, and pLKB1 before selecting Klotho for its improved ability to perform energetic switching. Klotho mediated an inverse dose-dependent effect and was able to switch between oxidative and glycolytic metabolism. Klotho mediated improved glycolytic energetics in wild-type cells which were not present in Pink1 knockout cells that model mitochondrial dysfunction. Klotho improved WT cell survival and migration, increasing proliferation and decreasing necrosis independent of effects on apoptosis. CONCLUSIONS: Klotho plays an important role in VSMC energetics which requires Pink1 to mediate energetic switching between oxidative and glycolytic metabolism. Klotho improved VSMC phenotype and, if targeted to the plaque early in the disease, could be a useful strategy to delay the effects of plaque ageing and improve VSMC survival.


Asunto(s)
Proteínas Klotho/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Animales , Apolipoproteínas E/metabolismo , Apoptosis/fisiología , Aterosclerosis/metabolismo , Proliferación Celular/fisiología , Supervivencia Celular/fisiología , Células Cultivadas , Glucólisis/fisiología , Ratones , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Fenotipo , Placa Aterosclerótica/metabolismo , Proteínas Quinasas/metabolismo
6.
J Strength Cond Res ; 35(2): 332-339, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33306594

RESUMEN

ABSTRACT: Barker, L, Siedlik, J, and Mercer, J. The influence of countermovement strategy and external load on amortization forces during jump squats. J Strength Cond Res 35(2): 332-339, 2021-The purpose of this study was to investigate the influence of countermovement strategy on amortization forces when performing jump squats. To gather a range of deceleration demands, jump squats were performed across a range of external loads (0, 15, 30, 45, and 60% of repetition maximum [1RM]) and verbally cued countermovement depths (preferred: PREF; quarter: QTR; and full: FULL). Dual force platform ground reaction force data were collected from 12 subjects. Amortization Fz, amortization time, and countermovement depth were analyzed using a 3 × 5 (technique × load) repeated measures analysis of variance. To assess countermovement strategy and amortization Fz, correlations and regression analysis were used to assess relationships among system mass, countermovement kinetic energy and depth, and amortization Fz. Amortization Fz was greater with QTR than PREF (p < 0.05), but similar between PREF and FULL (p > 0.05), and between QTR and FULL (p > 0.05). Amortization Fz was different between 0 and 15% 1RM (p < 0.05) and between 0 and 30% 1RM (p < 0.05). All loaded conditions (15-60% 1-RM) were similar (p > 0.05). As a group, countermovement kinetic energy and system mass were significantly, but weakly, correlated (r = 0.29, p < 0.01). Regression analysis revealed amortization Fz did not change in relation to countermovement kinetic energy but did change in relation to depth. These results suggest that preferred countermovement depths were associated with lesser amortization Fz (strain energy) during maximal effort unloaded and loaded countermovement jumps. Strength and conditioning professionals selecting exercises to maximize amortization Fz should consider the jump squat with light loads (or no load) and short countermovement depths.


Asunto(s)
Fuerza Muscular , Postura , Ejercicio Físico , Humanos
7.
Eur J Appl Physiol ; 120(7): 1519-1530, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32350595

RESUMEN

PURPOSE: We investigated the influence of a change in stride frequency on physiological and perceptual responses during forward and backward running at different body weight support (BWS) levels. METHODS: Participants ran forward and backward at 0% BWS, 20% BWS, and 50% BWS conditions on a lower body positive pressure treadmill. The stride frequency conditions consisted of forward and backward running at preferred stride frequency (PSF), PSF + 10%, and PSF-10%. We measured oxygen uptake ([Formula: see text]O2), carbon dioxide production, heart rate (HR), muscle activity from the lower extremity, and rating of perceived exertion (RPE). Furthermore, we calculated the metabolic cost of transport (CoT). RESULTS: [Formula: see text]O2, HR, CoT, and muscle activity from the rectus femoris were significantly different between stride frequency conditions (P < 0.05). [Formula: see text]O2, HR, and CoT during running at PSF + 10% were significantly higher than when running at PSF, regardless of running direction and BWS (P < 0.05). However, RPE was not different between stride frequency conditions (P > 0.05: e.g., 12.8-13.8 rankings in RPE for backward running at 0% BWS). CONCLUSIONS: Manipulation of stride frequency during running may have a greater impact on physiological responses than on perceptual responses at a given speed, regardless of running direction and BWS. Individuals who need to increase their physiological demands during running may benefit from a 10% increase in stride frequency from the PSF, regardless of BWS and running direction.


Asunto(s)
Peso Corporal/fisiología , Músculo Esquelético/fisiología , Esfuerzo Físico/fisiología , Carrera/fisiología , Adulto , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Aparatos Ortopédicos , Consumo de Oxígeno/fisiología , Músculo Cuádriceps/fisiología , Adulto Joven
8.
Proc Natl Acad Sci U S A ; 114(42): 11115-11120, 2017 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-28973951

RESUMEN

Point mutations in genes encoding sarcomeric proteins are the leading cause of inherited primary cardiomyopathies. Among them are mutations in the TNNT2 gene that encodes cardiac troponin T (TnT). These mutations are clustered in the tropomyosin (Tm) binding region of TnT, TNT1 (residues 80-180). To understand the mechanistic changes caused by pathogenic mutations in the TNT1 region, six hypertrophic cardiomyopathy (HCM) and two dilated cardiomyopathy (DCM) mutants were studied by biochemical approaches. Binding assays in the absence and presence of actin revealed changes in the affinity of some, but not all, TnT mutants for Tm relative to WT TnT. HCM mutants were hypersensitive and DCM mutants were hyposensitive to Ca2+ in regulated actomyosin ATPase activities. To gain better insight into the disease mechanism, we modeled the structure of TNT1 and its interactions with Tm. The stability predictions made by the model correlated well with the affinity changes observed in vitro of TnT mutants for Tm. The changes in Ca2+ sensitivity showed a strong correlation with the changes in binding affinity. We suggest the primary reason by which these TNNT2 mutations between residues 92 and 144 cause cardiomyopathy is by changing the affinity of TnT for Tm within the TNT1 region.


Asunto(s)
Cardiomiopatía Dilatada/genética , Cardiomiopatía Hipertrófica/genética , Tropomiosina/metabolismo , Troponina T/genética , Troponina T/metabolismo , Actinas/metabolismo , Calcio/metabolismo , Escherichia coli , Humanos , Modelos Químicos , Estructura Molecular , Mutación
9.
Int J Sports Med ; 40(4): 269-275, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30716782

RESUMEN

We investigated metabolic costs, rating of perceived exertion (RPE), stride frequency (SF), and preferred speed (PS) during forward and backward running at different levels of body weight support (BWS). Participants completed forward and backward running on a lower body positive pressure treadmill at their preferred speed for forward and backward running at 0%BWS, 20%BWS, and 50%BWS. Oxygen uptake (V̇O2), heart rate (HR), RPE, SF, and PS were measured. HR, RPE, and SF during forward and backward running decreased with increasing BWS (P<0.05).V̇O2 during both forward and backward running at 50%BWS was significantly lower than when running at 0%BWS (P<0.01). However, PS during forward and backward running increased with increasing BWS (P<0.01). Furthermore,V̇O2 was different between running directions only when running at 0%BWS (P<0.01). HR and RPE were not different between running directions (P>0.05). SF during backward running was higher than that of forward running (P<0.01). PS during backward running was lower than when running forward (P<0.001). Our observations suggest that individuals may select PS and SF during running with BWS in a way that resulted in similar metabolic costs, regardless of direction of locomotion.


Asunto(s)
Metabolismo Energético , Prueba de Esfuerzo/métodos , Marcha/fisiología , Carrera/fisiología , Adulto , Peso Corporal , Prueba de Esfuerzo/instrumentación , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Percepción , Esfuerzo Físico/fisiología
10.
Sensors (Basel) ; 18(7)2018 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-29932154

RESUMEN

Cardiovascular disease remains the leading cause of death in Western society. Recent technological advances have opened the opportunity of developing new and innovative smart stent devices that have advanced electrical properties that can improve diagnosis and even treatment of previously intractable conditions, such as central line access failure, atherosclerosis and reporting on vascular grafts for renal dialysis. Here we review the latest advances in the field of cardiovascular medical implants, providing a broad overview of the application of their use in the context of cardiovascular disease rather than an in-depth analysis of the current state of the art. We cover their powering, communication and the challenges faced in their fabrication. We focus specifically on those devices required to maintain vascular access such as ones used to treat arterial disease, a major source of heart attacks and strokes. We look forward to advances in these technologies in the future and their implementation to improve the human condition.


Asunto(s)
Enfermedades Cardiovasculares/diagnóstico , Prótesis e Implantes/tendencias , Aterosclerosis/diagnóstico , Terapia de Resincronización Cardíaca , Humanos , Monitoreo Ambulatorio/instrumentación , Monitoreo Ambulatorio/tendencias , Telemetría/instrumentación , Telemetría/tendencias , Tecnología Inalámbrica/instrumentación , Tecnología Inalámbrica/tendencias
11.
J Strength Cond Res ; 32(7): 1960-1967, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28682935

RESUMEN

Masumoto, K, Mefferd, KC, Iyo, R, and Mercer, JA. Muscle activity and physiological responses during running in water and on dry land at submaximal and maximal efforts. J Strength Cond Res 32(7): 1960-1967, 2018-We investigated muscle activity, oxygen uptake, heart rate, and rating of perceived exertion during running in water and on dry land at submaximal and maximal efforts. Eleven recreational runners performed deep-water running (DWR) and treadmill running (TMR) graded exercise tests on separate days. On the third-test day, the subjects exercised at their 60, 80, and 100% of maximal oxygen uptake (V[Combining Dot Above]O2max) by matching specific stride frequencies or running speeds. V[Combining Dot Above]O2max, maximal heart rate (HRmax), and rating of perceived exertion at maximal effort (RPEmax) were measured. Furthermore, muscle activity from the rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius were measured. V[Combining Dot Above]O2max (DWR: 48.9 ± 5.7 ml·kg·min; TMR: 59.2 ± 5.6 ml·kg·min; p < 0.001) and HRmax (DWR: 174.1 ± 9.6 beats·min; TMR: 191.2 ± 6.9 beats·min; p < 0.001) were each lower during DWR vs. TMR. In addition, RPEmax was not significantly different between DWR and TMR (DWR: 17.8 ± 1.9; TMR: 18.4 ± 1.3; p > 0.05). Furthermore, muscle activity from all tested muscles was not influenced by the interaction of mode and intensity (p > 0.05). Muscle activity from all tested muscles was different between modes (p < 0.05) and between intensities (p < 0.001). Specifically, muscle activity from the tested muscles during DWR was 29-69% lower than that of TMR at maximal effort. Athletes and coaches should consider that the exercise intensity during DWR can be overestimated, if exercise prescription was made according to the maximal responses during TMR.


Asunto(s)
Prueba de Esfuerzo/métodos , Músculo Esquelético/fisiología , Carrera/fisiología , Adulto , Electromiografía , Terapia por Ejercicio , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Contracción Muscular/fisiología , Consumo de Oxígeno/fisiología , Esfuerzo Físico/fisiología , Agua , Adulto Joven
12.
J Strength Cond Res ; 32(1): 248-254, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28746248

RESUMEN

Barker, LA, Harry, JR, and Mercer, JA. Relationships between countermovement jump ground reaction forces and jump height, reactive strength index, and jump time. J Strength Cond Res 32(1): 248-254, 2018-The purpose of this study was to determine the relationship between ground reaction force (GRF) variables to jump height, jump time, and the reactive strength index (RSI). Twenty-six, Division-I, male, soccer players performed 3 maximum effort countermovement jumps (CMJs) on a dual-force platform system that measured 3-dimensional kinetic data. The trial producing peak jump height was used for analysis. Vertical GRF (Fz) variables were divided into unloading, eccentric, amortization, and concentric phases and correlated with jump height, RSI (RSI = jump height/jump time), and jump time (from start to takeoff). Significant correlations were observed between jump height and RSI, concentric kinetic energy, peak power, concentric work, and concentric displacement. Significant correlations were observed between RSI and jump time, peak power, unload Fz, eccentric work, eccentric rate of force development (RFD), amortization Fz, amortization time, second Fz peak, average concentric Fz, and concentric displacement. Significant correlations were observed between jump time and unload Fz, eccentric work, eccentric RFD, amortization Fz, amortization time, average concentric Fz, and concentric work. In conclusion, jump height correlated with variables derived from the concentric phase only (work, power, and displacement), whereas Fz variables from the unloading, eccentric, amortization, and concentric phases correlated highly with RSI and jump time. These observations demonstrate the importance of countermovement Fz characteristics for time-sensitive CMJ performance measures. Researchers and practitioners should include RSI and jump time with jump height to improve their assessment of jump performance.


Asunto(s)
Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Fútbol/fisiología , Adolescente , Atletas , Fenómenos Biomecánicos , Prueba de Esfuerzo , Humanos , Masculino , Adulto Joven
13.
J Strength Cond Res ; 32(7): 1937-1947, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29939947

RESUMEN

Harry, JR, Silvernail, JF, Mercer, JA, and Dufek, JS. Bilateral comparison of vertical jump landings and step-off landings from equal heights. J Strength Cond Res 32(7): 1937-1947, 2018-The purpose of this investigation was to examine kinetic, kinematic, and temporal parameters during vertical jump landings (VJL) and step-off landings (STL) from equal heights. Five men (25.0 ± 1.6 years; 1.7 ± 0.4 m; 79.7 ± 7.1 kg) and 5 women (20.8 ± 1.6 years; 1.6 ± 0.4 m; 68.5 ± 7.1 kg) performed 15 VJL and 15 STL. Paired-samples t-tests (α = 0.05) compared impact velocity and the times to the first (F1) and second (F2) peak vertical ground reaction force magnitudes (tF1 and tF2) and the end of impact. Two-way analyses of variance (α = 0.05) compared limb and task differences in F1, F2, hip, knee, and ankle joint angles at ground contact, F1, F2, and the end of impact, and hip, knee, and ankle joint displacements between contact and F1, F1 and F2, and F2 and the end of impact. Impact velocity was not different between STL and VJL, although STL produced a greater F1 and a more rapid tF2. Greater hip, knee, and ankle flexion/dorsiflexion occurred during STL throughout the majority of impact regardless of limb. Lesser hip, knee, and ankle joint displacements occurred during STL regardless of limb between F1 and F2, whereas greater joint displacement occurred between F2 and the end of impact. Lastly, knee joint angles at ground contact differed between limbs during STL only. Strength and conditioning professionals aiming to improve an athlete's performance during sport-specific jump landings should consider the likely impact attenuation outcomes before selecting STL or VJL in training.


Asunto(s)
Extremidad Inferior/fisiología , Deportes , Adulto , Articulación del Tobillo/fisiología , Fenómenos Biomecánicos , Prueba de Esfuerzo , Femenino , Articulación de la Cadera/fisiología , Humanos , Articulación de la Rodilla/fisiología , Masculino , Rango del Movimiento Articular , Adulto Joven
14.
Proteomics ; 17(12)2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28508578

RESUMEN

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 6/metabolismo , Ciclofosfamida/farmacología , Linfoma/metabolismo , Lisosomas/metabolismo , Animales , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Fitogénicos/farmacología , Etopósido/farmacología , Femenino , Linfoma/tratamiento farmacológico , Linfoma/patología , Ratones , Ratones Endogámicos C57BL , Proteoma/metabolismo , Proteómica/métodos , Células Tumorales Cultivadas
15.
Circ Res ; 116(5): 816-26, 2015 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-25524056

RESUMEN

RATIONALE: DNA damage and the DNA damage response have been identified in human atherosclerosis, including in vascular smooth muscle cells (VSMCs). However, although double-stranded breaks (DSBs) are hypothesized to promote plaque progression and instability, in part, by promoting cell senescence, apoptosis, and inflammation, the direct effects of DSBs in VSMCs seen in atherogenesis are unknown. OBJECTIVE: To determine the presence and effect of endogenous levels of DSBs in VSMCs on atherosclerosis. METHODS AND RESULTS: Human atherosclerotic plaque VSMCs showed increased expression of multiple DNA damage response proteins in vitro and in vivo, particularly the MRE11/RAD50/NBS1 complex that senses DSB repair. Oxidative stress-induced DSBs were increased in plaque VSMCs, but DSB repair was maintained. To determine the effect of DSBs on atherosclerosis, we generated 2 novel transgenic mice lines expressing NBS1 or C-terminal deleted NBS1 only in VSMCs, and crossed them with apolipoprotein E(-/-) mice. SM22α-NBS1/apolipoprotein E(-/-) VSMCs showed enhanced DSB repair and decreased growth arrest and apoptosis, whereas SM22α-(ΔC)NBS1/apolipoprotein E(-/-) VSMCs showed reduced DSB repair and increased growth arrest and apoptosis. Accelerating or retarding DSB repair did not affect atherosclerosis extent or composition. However, VSMC DNA damage reduced relative fibrous cap areas, whereas accelerating DSB repair increased cap area and VSMC content. CONCLUSIONS: Human atherosclerotic plaque VSMCs show increased DNA damage, including DSBs and DNA damage response activation. VSMC DNA damage has minimal effects on atherogenesis, but alters plaque phenotype inhibiting fibrous cap areas in advanced lesions. Inhibiting DNA damage in atherosclerosis may be a novel target to promote plaque stability.


Asunto(s)
Daño del ADN , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Placa Aterosclerótica/genética , Animales , Aorta/citología , Aorta/patología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/patología , Apolipoproteínas E/deficiencia , Tronco Braquiocefálico/patología , Arterias Carótidas/citología , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , Células Cultivadas , Ensayo Cometa , Roturas del ADN de Doble Cadena , Enzimas Reparadoras del ADN/biosíntesis , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas de Microfilamentos/biosíntesis , Proteínas de Microfilamentos/genética , Proteínas Musculares/biosíntesis , Proteínas Musculares/genética , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Regulación hacia Arriba
16.
J Strength Cond Res ; 31(7): 1780-1786, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27669194

RESUMEN

Harry, JR, Barker, LA, Mercer, JA, and Dufek, JS. Vertical and horizontal impact force comparison during jump landings with and without rotation in NCAA Division I male soccer players. J Strength Cond Res 31(7): 1780-1786, 2017-There is a wealth of research on impact force characteristics when landing from a jump. However, there are no data on impact forces during landing from a jump with an airborne rotation about the vertical axis. We examined impact force parameters in the vertical and horizontal axes during vertical jump (VJ) landings and VJ landings with a 180° rotation (VJR). Twenty-four Division I male soccer players performed 3 VJ and VJR landings on a dual-force platform system. Paired-samples t-tests (α = 0.05) compared differences in the first (F1) and second (F2) peak vertical ground reaction forces, times to F1 (tF1), F2 (tF2), and the end of the impact phase, vertical impulse, and anterior-posterior and medial-lateral force couples. Effect sizes (ES; large >0.8) were computed to determine the magnitude of the differences. Lower jump height (41.60 ± 4.03 cm, VJ landings; 39.40 ± 4.05 cm, VJR landings; p = 0.002; ES = 0.39), greater F2 (55.71 ± 11.95 N·kg, VJ; 68.16 ± 14.82 N·kg; p < 0.001; ES = 0.94), faster tF2 (0.057 ± 0.012 seconds, VJ; 0.047 ± 0.011 seconds, VJR; p = 0.001; ES = 0.89), greater anterior-posterior (0.06 ± 0.03 N·s·kg, VJ; 0.56 ± 0.15 N·s·kg, VJR; p < 0.001; ES = 1.83) and medial-lateral force couples (0.29 ± 0.11 N·s·kg, VJ; 0.56 ± 0.14 N·s·kg, VJR; p < 0.001; ES = 1.46) occurred during VJR landings. No other differences were identified. This kinetic analysis determined that landing from a jump with 180° airborne rotation is different than landing from a jump without an airborne rotation. Male Division I soccer players could benefit from increasing the volume of VJR landings during training to address the differences in jump height and force parameters compared with VJ landings.


Asunto(s)
Atletas , Fútbol/fisiología , Adolescente , Humanos , Cinética , Masculino , Rotación , Adulto Joven
17.
J Strength Cond Res ; 31(4): 932-938, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27398922

RESUMEN

Barker, LA, Harry, JR, Dufek, JS, and Mercer, JA. Aerial rotation effects on vertical jump performance among highly skilled collegiate soccer players. J Strength Cond Res 31(4): 932-938, 2017-In soccer matches, jumps involving rotations occur when attempting to head the ball for a shot or pass from set pieces, such as corner kicks, goal kicks, and lob passes. However, the 3-dimensional ground reaction forces used to perform rotational jumping tasks are currently unknown. Therefore, the purpose of this study was to compare bilateral, 3-dimensional, and ground reaction forces of a standard countermovement jump (CMJ0) with those of a countermovement jump with a 180° rotation (CMJ180) among Division-1 soccer players. Twenty-four participants from the soccer team of the University of Nevada performed 3 trials of CMJ0 and CMJ180. Dependent variables included jump height, downward and upward phase times, vertical (Fz) peak force and net impulse relative to mass, and medial-lateral and anterior-posterior force couple values. Statistical significance was set a priori at α = 0.05. CMJ180 reduced jump height, increased the anterior-posterior force couple in the downward and upward phases, and increased upward peak Fz (p ≤ 0.05). All other variables were not significantly different between groups (p > 0.05). However, we did recognize that downward peak Fz trended lower in the CMJ0 condition (p = 0.059), and upward net impulse trended higher in the CMJ0 condition (p = 0.071). It was concluded that jump height was reduced during the rotational jumping task, and rotation occurred primarily via AP ground reaction forces through the entire countermovement jump. Coaches and athletes may consider additional rotational jumping in their training programs to mediate performance decrements during rotational jump tasks.


Asunto(s)
Atletas , Rendimiento Atlético/fisiología , Rotación , Fútbol/fisiología , Adulto , Femenino , Humanos , Masculino , Adulto Joven
18.
J Biol Chem ; 290(11): 7003-15, 2015 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-25548289

RESUMEN

The most frequent known causes of primary cardiomyopathies are mutations in the genes encoding sarcomeric proteins. Among those are 30 single-residue mutations in TPM1, the gene encoding α-tropomyosin. We examined seven mutant tropomyosins, E62Q, D84N, I172T, L185R, S215L, D230N, and M281T, that were chosen based on their clinical severity and locations along the molecule. The goal of our study was to determine how the biochemical characteristics of each of these mutant proteins are altered, which in turn could provide a structural rationale for treatment of the cardiomyopathies they produce. Measurements of Ca(2+) sensitivity of human ß-cardiac myosin ATPase activity are consistent with the hypothesis that hypertrophic cardiomyopathies are hypersensitive to Ca(2+) activation, and dilated cardiomyopathies are hyposensitive. We also report correlations between ATPase activity at maximum Ca(2+) concentrations and conformational changes in TnC measured using a fluorescent probe, which provide evidence that different substitutions perturb the structure of the regulatory complex in different ways. Moreover, we observed changes in protein stability and protein-protein interactions in these mutants. Our results suggest multiple mechanistic pathways to hypertrophic and dilated cardiomyopathies. Finally, we examined a computationally designed mutant, E181K, that is hypersensitive, confirming predictions derived from in silico structural analysis.


Asunto(s)
Actinas/metabolismo , Calcio/metabolismo , Cardiomiopatías/genética , Mutación Puntual , Tropomiosina/genética , Tropomiosina/metabolismo , Adenosina Trifosfatasas/metabolismo , Cardiomiopatías/metabolismo , Humanos , Modelos Moleculares , Miosinas/metabolismo , Estabilidad Proteica , Tropomiosina/química
19.
Eur J Appl Physiol ; 115(12): 2691-700, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26255289

RESUMEN

PURPOSE: To determine if muscle activity is related to preferred stride frequency (PSF) during deep water running (DWR) and treadmill running on dry land (TMR). METHODS: Subjects (n = 11; 26.2 ± 4.4 years) completed TMR and DWR at their mode-specific preferred stride frequency (PSF mode). They also ran at stride frequencies which were lower and higher than the PSF mode (i.e., PSF mode ± 5, 10, and 15 %). Muscle activity from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and gastrocnemius (GL), SF, and rating of perceived exertion (RPE) were measured. RESULTS: The PSF mode during DWR was significantly lower than that of TMR (i.e., 49.9 ± 11.0 versus 81.9 ± 4.8 strides/min, P < 0.0001). Additionally, muscle activity from the RF, TA, and GL during DWR was significantly lower than during TMR at respective PSF mode (~83.6 % decrease, P < 0.0001). However, RPE while running at the PSF mode during DWR and TMR was similar. During DWR, the RF, TA, and GL muscle activity was not different between PSF mode and any other SF conditions (P > 0.0005). During TMR, there was no significant difference in the RF and GL muscle activity between PSF mode and any other SF conditions during TMR (P > 0.0005). CONCLUSIONS: During DWR, subjects selected a lower PSF than during TMR even though RPE was the same. It was also determined that the relationship between muscle activity and changes in SF relative to the PSF mode was unique during DWR and TMR.


Asunto(s)
Músculo Esquelético/fisiología , Carrera/fisiología , Natación/fisiología , Adolescente , Adulto , Fenómenos Biomecánicos , Prueba de Esfuerzo/métodos , Humanos , Esfuerzo Físico
20.
J Exerc Sci Fit ; 13(1): 29-34, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29541096

RESUMEN

BACKGROUND/OBJECTIVE: It is important to understand the factors that influence the impact force observed during running, since the impact force is likely to be related to overuse injuries. The purpose of this study was to compare the impact force during running when participants were instructed to use different foot strike patterns: obvious heel strike (Obvious-HS), subtle heel strike (Subtle-HS), midfoot strike (Mid-FS), and fore foot strike (Fore-FS) patterns. METHODS: Participants (n = 10, 25 ± 5.7 years, 70.2 ± 12.1 kg, 174.6 ± 7.2 cm) completed four foot strike patterns while running over ground: Obvious-HS, Subtle-HS, Mid-FS, and Fore-FS. Speed was controlled between conditions (random order). Vertical ground reaction forces were recorded (1000 Hz) along with the impact force, peak force, and stance time for analysis. A repeated measures analysis of variance was used to compare each variable across foot strike instructions, with post hoc comparisons contrasting Obvious-HS to each of the other conditions. RESULTS: Impact force was influenced by foot strike instructions, with Obvious-HS being greater than Subtle-HS and Fore-FS (p < 0.05) but not different from Mid-FS (p > 0.05). The peak force was not influenced by foot strike instructions (p > 0.05); stance time was longer during Obvious-HS than during Mid-FS or Fore-FS (p < 0.05), but not different from Subtle-HS (p > 0.05). CONCLUSION: The unique observation of this study was that impact force was different when participants were instructed to run with either an Obvious-HS or a Subtle-HS at contact. Both these foot strike patterns would have been considered rear foot strike patterns, suggesting that something other than which specific part of the foot strikes the ground initially influenced impact force.

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