Publications by authors named "Scott Collier"

51 Publications

Measures of ejection duration and subendocardial viability ratio in normal weight and overweight adolescent children.

Physiol Rep 2021 05;9(9):e14852

Department of Health and Exercise Science, Appalachian State University, Boone, NC, USA.

The aim of our study was to determine how being overweight (OW) affects measures of ejection duration (ED), subendocardial viability ratio (SEVR), and central arterial health in a sample of adolescent children. Thirty-four sex and age-matched adolescent children (n = 34, 17 OW, age = 14 ± 2 years) participated in one laboratory visit. Anthropometric measures, body composition, and cardiovascular measures including resting heart rate, aortic systolic blood pressure (ASBP), carotid-femoral pulse wave velocity (cf-PWV), ED (EDms absolute vs. relative ED%), and the SEVR were ascertained. Transfer functions were applied to obtain ASBP. ED was measured as the time from the beginning of the upstroke of the pulse wave and the dicrotic notch, SEVR as the quotient of the diastolic pressure-time area to the systolic pressure-time area, and cf-PWV as the quotient of distance between carotid-femoral measurement sites and the transit time of the pulse wave. cf-PWV was significantly higher in OW compared to normal weight participants (5.13 ± 0.85 vs. 4.53 ± 0.46 m/s respectively; p = 0.015, d = 0.51). OW adolescents also reported significantly higher values for ASBP (103.1 ± 11.8 vs. 95.7 ± 8.2 mmHg respectively; p = 0.043, d = 0.72) and significantly lower values of SEVR (114.4 ± 25.9% vs. 132.2 ± 22.0% respectively; p = 0.038; d = 0.33). Overweight adolescents demonstrated higher cf-PWV, ASBP, and SEVR then normal weight peers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123553PMC
May 2021

Correlation Between Heart Rate at Maximal Fat Oxidation and Aerobic Threshold in Healthy Adolescent Boys and Girls.

Pediatr Exerc Sci 2021 May 6:1-5. Epub 2021 May 6.

Appalachian State University.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1123/pes.2020-0210DOI Listing
May 2021

Opposite Surfaces of the Cdc15 F-BAR Domain Create a Membrane Platform That Coordinates Cytoskeletal and Signaling Components for Cytokinesis.

Cell Rep 2020 12;33(12):108526

Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address:

Many eukaryotes assemble an actin- and myosin-based cytokinetic ring (CR) on the plasma membrane (PM) for cell division, but how it is anchored there remains unclear. In Schizosaccharomyces pombe, the F-BAR protein Cdc15 links the PM via its F-BAR domain to proteins in the CR's interior via its SH3 domain. However, Cdc15's F-BAR domain also directly binds formin Cdc12, suggesting that Cdc15 may polymerize a protein network directly adjacent to the membrane. Here, we determine that the F-BAR domain binds Cdc12 using residues on the face opposite its membrane-binding surface. These residues also bind paxillin-like Pxl1, promoting its recruitment with calcineurin to the CR. Mutation of these F-BAR domain residues results in a shallower CR, with components localizing ∼35% closer to the PM than in wild type, and aberrant CR constriction. Thus, F-BAR domains serve as oligomeric membrane-bound platforms that can modulate the architecture of an entire actin structure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.108526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775634PMC
December 2020

Bicelles Rich in both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins.

J Am Chem Soc 2020 07 8;142(29):12715-12729. Epub 2020 Jul 8.

Center for Structural Biology, Department of Biochemistry, and Department of Medicine, Vanderbilt University School of Medicine, Nashville 37240, Tennessee, United States.

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 phingomyelin and hlesterol-ich (SCOR) lipid mixtures with phosphatidylcholine can be cosolubilized by -dodecyl-β-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.0c04669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924963PMC
July 2020

The effect of acute alcohol ingestion on systemic hemodynamics and sleep architecture in young, healthy men.

J Am Coll Health 2020 May 5:1-8. Epub 2020 May 5.

Vascular Biology & Autonomic Studies Lab, Appalachian State University, Boone, North Carolina, USA.

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 ( = 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. 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. An acute bout of heavy alcohol consumption may attenuate nocturnal BP dipping that, in turn, may hasten the progression of hypertension-related cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07448481.2020.1756826DOI Listing
May 2020

Comprehensive Clinicopathologic Analyses of Acquired Cystic Disease-associated Renal Cell Carcinoma With Focus on Adverse Prognostic Factors and Metastatic Lesions.

Am J Surg Pathol 2020 08;44(8):1031-1039

Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN.

Acquired cystic disease of kidney-associated renal cell carcinoma (ACD-RCC) is a distinct subtype of renal cell carcinoma with unique morphologic and clinicopathologic features. Generally, ACD-RCC is regarded as an indolent tumor; however, prognostic and outcomes data have been conflicted by the limited and relatively low number of cases with patient follow-up or adverse events. In this study, we focused on the histology of metastatic lesions and identifying prognostic factors associated with metastatic progression. From 32 cases in the cohort, 9 patients had metastasis [ACD-RCC (M+)] and 23 patients were without metastasis [ACD-RCC (M-)]. The median age of patients was 52 years; right side, n=10; left side, n=18; bilateral, n=4; median tumor size=2.6 cm; median hemodialysis duration=17 y; and the median duration of follow-up was 50 mo. Immunohistochemistry showed ACD-RCC to be racemase positive and CK7 negative to focally positive within tumor cells, with consistent positivity for renal histogenesis-associated markers (PAX8 and RCC antigen); S100A1 was a less reliable marker at metastatic sites. All metastatic ACD-RCC except 2 cases involved lymph nodes (para-aortic, renal hilar, subclavicular). Overall, 6/9 (67%) had visceral metastasis to sites including lung (n=3), liver (n=3), bone (n=5), stomach (n=1), and brain (n=1). In total, 5/9 (56%) metastatic tumors had distinctive cystic growth pattern at the metastatic site; intriguingly metastatic tumors had intrametastatic oxalate crystal deposition, a pathognomonic feature associated with primary tumors. Four of nine (44%) patients with ACD-RCC (M+) had fatal outcomes due to metastatic disease. Clinically significant adverse prognostic features associated with metastasis [median follow-up 47 mo, ACD-RCC (M+) vs. ACD-RCC (M-), 50 mo] included: duration of hemodialysis (≥20 vs. <20 y, P=0.0085) and tumor necrosis (P=0.049). Because of sufficient overlap between these parameters, the study was not able to identify parameters that would be reliable in further management strategies, in clinical settings. Our data indicate that ACD-RCC is a tumor which has distinct metastatic potential with nodal and visceral tropism and proclivity for cystic morphology at metastatic sites; this is the first report of the presence of oxalate crystals in metastatic tumors. Our data suggest that ACD-RCC patients with prolonged hemodialysis and tumoral coagulative necrosis require additional surveillance in view of the association of these parameters with metastatic progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0000000000001482DOI Listing
August 2020

Withings Body Cardio versus Gold Standards of Pulse-Wave Velocity and Body Composition.

J Pers Med 2020 Mar 11;10(1). Epub 2020 Mar 11.

Department of Health and Exercise Science, Appalachian State University Boone, NC. 28608, USA.

Home blood pressure monitors are widely used by consumers yet cardiovascular health may be better defined by pulse-wave velocity (PWV). So far, the Withings Body Cardio scale is the only consumer device that has been designed to measure PWV and body composition, including fat mass (FM) and fat-free mass (FFM), in the home setting. While one study has demonstrated that this device meets the acceptable accuracy standards of the ARTERY Society, no study has accounted for the gravitational effect of standing on a scale on aortic-leg PWV.

Purpose: The purpose of this study was to assess the accuracy of PWV and body composition as determined by the Body Cardio scale.

Methods: Measurements of PWV and body composition in healthy, young males and females ( = 20) using the Body Cardio device were compared to PWV assessed by applanation tonometry (SphygmoCor) and body composition analysis determined by air displacement plethysmography (Bod Pod). Bland-Altman analysis and mean absolute percent error (MAPE) were used to assess accuracy.

Results: Data are reported as the mean bias (95% confidence interval). The Body Cardio overestimated PWV by 0.68 m/s (-0.16, 1.51) and FM by 2.91 kg (-2.91, 8.73). Body Cardio PWV and FM estimations had a MAPE of 9.7% and 25.8%, respectively. The Body Cardio underestimated body mass (BM) and FFM by 0.11 kg (-0.41, 0.18) and 2.87 kg (-9.04, 3.30), respectively. Body Cardio BM and FFM estimations had a MAPE of 0.15% and 5.6%, respectively.

Conclusions: The Body Cardio scale provides accurate measures of BM and PWV; however, it should be used cautiously for measures of FM and FFM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm10010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151625PMC
March 2020

Effects of Continuous vs Discontinuous Aerobic Training on Cardiac Autonomic Remodeling.

Int J Sports Med 2019 Mar 10;40(3):180-185. Epub 2019 Jan 10.

HES, Appalachian State University, Boone, United States.

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 VO 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 VO (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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0044-100921DOI Listing
March 2019

Extreme Conditioning Program Induced Acute Hypotensive Effects are Independent of the Exercise Session Intensity.

Int J Exerc Sci 2017;10(8):1165-1173. Epub 2017 Dec 1.

Universidade Federal de Mato Grosso - Faculdade de Educação Física - Campus Cuiabá/Mato Grosso/MT/BRAZIL.

The aim of the study was to determine the acute systolic (SBP) and diastolic (DBP) blood pressure, rating of perceived exertion (RPE) and heart rate (HR) responses following two intense training sessions (24 hours apart). Nine male extreme conditioning program (ECP) practitioners with more than 6 months of experience (age 26.7 ± 6.6 years; body mass 78.8 ± 13.2 kg; body fat 13.5 ± 6.2 %) completed two experimental ECP sessions. Cardiovascular variables were measured before, immediately after and every 15 min during a 45 min recovery following each experimental session. Compared with pre-exercise data, our results showed a SBP decrease at 30 min post exercise session 1 (P≤0.05) and at 45 min following exercise session 2. DBP decreased (P≤0.05) at 15 min and 30 min following exercise session 1 and at 30 min after the exercise session 2, respectively. HR remained significantly higher (P≤0.05) 45 min following the first and second exercise session compared with pre-exercise values. Exercise session 1 induced a higher increase in HR (86 ± 11% of HR versus 82 ± 12% of HR, = 0.01) and RPE (8.8 ± 1.2 versus 8.0 ± 1.2, = 0.02) when compared to exercise session 2. In conclusion, post-exercise hypotension occurs following strenuous exercise sessions, regardless of the session design, which may have an important role in the prevention of cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786200PMC
December 2017

Metabolomic Shifts Following Play-Based Activity in Overweight Preadolescents.

Curr Pediatr Rev 2017 ;13(2):144-151

Vascular Biology and Autonomic Studies Laboratory, Appalachian State University, Boone, NC. United States.

Background: Play-based activities can be a positive intervention to increase participation of overweight children. Metabolomics can reveal elemental shifts in the metabolome, lending to potential mechanistic explanations behind improvements in physiological systems.

Objective: To elucidate dose-response urinary metabolomic signature shifts in overweight preadolescents following four or eight weeks of supervised play-based activity versus a typical summer break control group. We hypothesized that eight weeks of activity would cause the greatest shift in the metabolites.

Study Design: Twenty-two recreationally active preadolescents (12 males, 10 females) were randomly assigned to a four-week (4w) or eight-week (8w) activity group or to a control group (C). Participants reported to the laboratory on two separate occasions during which descriptive characteristics were recorded and urine samples were obtained. Children in the 4w and 8w cohort were tested at the beginning and end of the four and eight weeks of a supervised play-based physical activity program where they were active for 6 hours a day, 5 days a week. Children in the C group were tested before and after eight weeks of an unsupervised summer break.

Results: A valid supervised partial least squares discriminant analysis model was obtained between post-exercise subjects in 8w and C (3 components, R2X = 0.332, R2Y = 0.976, Q2 = 0.091). The eight week intervention yielded significant metabolomic changes in several identified compounds.

Conclusion: When compared to a typical unsupervised summer break, a supervised play-based intervention provides enough of a stimulus for a shift in the metabolome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1573396313666170113145553DOI Listing
February 2018

How consumer physical activity monitors could transform human physiology research.

Am J Physiol Regul Integr Comp Physiol 2017 03 4;312(3):R358-R367. Epub 2017 Jan 4.

Department of Medicine, Georgetown University, Washington, D.C.

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 O, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpregu.00349.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401997PMC
March 2017

Effects of tai chi chuan on anxiety and sleep quality in young adults: lessons from a randomized controlled feasibility study.

Nat Sci Sleep 2016 14;8:305-314. Epub 2016 Nov 14.

Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA.

Objective: To determine feasibility and estimate the effect of a 10-week tai chi chuan (TCC) intervention on anxiety and sleep quality in young adults.

Participants: Seventy-five adults (18-40 years) from a predominately undergraduate midsized university.

Methods: This was an assessor blinded, randomized feasibility trial, and participants were randomized into one of three groups: 10 weeks of TCC meeting 2 times per week, 10 weeks of TCC with a DVD of the curriculum, and control group receiving a handout on anxiety management. Anxiety and sleep quality were assessed 4 times: baseline, 4 weeks, 10 weeks (immediate post-intervention), and 2 months post-intervention. Retention was defined as a participant attending the baseline assessment and at least one other assessment. Adherence to the intervention was set a priori as attendance at 80% of the TCC classes.

Results: Eighty-five percent of participants were retained during the intervention and 70% completed the 2 month follow-up assessments. To increase statistical power, the two TCC groups were combined in the analyses of anxiety and sleep quality measures. No significant changes in anxiety were found in the control group, while levels of anxiety decreased significantly over time in the two TCC groups. Sleep quality scores improved across time for all three groups, but adherent TCC participants reported greater improvement than control participants.

Conclusion: TCC may be an effective nonpharmaceutical means of improving anxiety and poor sleep quality in young adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NSS.S117392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118018PMC
November 2016

Differential Effects of Continuous Versus Discontinuous Aerobic Training on Blood Pressure and Hemodynamics.

J Strength Cond Res 2018 Jan;32(1):97-104

Department of Health and Exercise Science, Vascular Biology and Autonomic Studies Laboratory, College of Health Sciences, Appalachian State University, Boone, North Carolina.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1519/JSC.0000000000001661DOI Listing
January 2018

Tai Chi and Kung-Fu practice maintains physical performance but not vascular health in young versus old participants.

Phys Sportsmed 2016 17;44(2):184-9. Epub 2016 Mar 17.

a Department of Health, Leisure, and Exercise Science , Appalachian State University , Boone , NC , USA.

Objectives: Kung-Fu and Tai Chi along with other martial arts are gaining popularity but studies examining the benefits of martial arts on physical fitness, vascular health, nutrition, and psychological wellness are limited. Aging is associated with declines in these health components. The objectives of this study were to examine whether Tai Chi and Kung-Fu training would maintain physical fitness, vascular health, and psychological wellness components on older versus younger practitioners.

Methods: Seventeen subjects were recruited and divided into Young (age <40 years, n=9) and Old (age 40 years and above, n=8). Participants reported twice for health screens, vascular and nutrition assessment, and fitness tests. Mean differences were compared between groups for all tests using Student's t-tests.

Results: Age, months of practice, systolic blood pressure, and cardiovascular augmentation index were significantly greater in Old versus Young (p=0.001, p=0.007, p=0.049, and p=0.011, respectively). Psychologically, old practitioners experienced greater sleep interference (p=0.035) and overall pain (p=0.036). No other differences existed for any variable.

Conclusion: Our study indicates that the practice of Tai Chi and Kung-Fu maintains physical fitness in older compared to younger practitioners. However, age associated changes in cardiovascular stiffness, systolic blood pressure, and pain were not prevented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00913847.2016.1158623DOI Listing
November 2016

Biased Brownian motion as a mechanism to facilitate nanometer-scale exploration of the microtubule plus end by a kinesin-8.

Proc Natl Acad Sci U S A 2015 Jul 6;112(29):E3826-35. Epub 2015 Jul 6.

Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232;

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1500272112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517267PMC
July 2015

Mobile phones in residential treatment: implications for practice.

J Subst Abuse Treat 2015 Aug 12;55:45-51. Epub 2015 Mar 12.

Healthright 360, 1735 Mission St., San Francisco, CA 94103, USA.

A nonprofit primary care, substance abuse and mental health treatment provider that operates nine separate residential treatment facilities in both northern and southern California began allowing clients to keep their mobile phones while in treatment. From the advent of mobile phone technology and its widespread adoption through early 2013, the organization prohibited clients from having phones while in treatment. Calls to and from clients needed to be made and received at the house phone. After years of enforcing the policy with diminished success as phones became cheaper, smaller, and more prevalent, agency leadership decided to experiment with allowing the clients to keep their phones while in treatment. Elopement data as they relate to the policy are examined along with data from staff interviews about its implementation and impact. Results show that elopements resulting from being caught with a mobile phone were eliminated and some clients were able to be returned to treatment using the devices. All seven (100%) of the interviewees were supportive of the new policy and thought it should be continued. The impact of the policy on clinical disruptions, lost/stolen property liability, and confidentiality issues are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsat.2015.02.004DOI Listing
August 2015

Acute Sodium Ingestion Before Exercise Increases Voluntary Water Consumption Resulting In Preexercise Hyperhydration and Improvement in Exercise Performance in the Heat.

Int J Sport Nutr Exerc Metab 2015 Oct 26;25(5):456-62. Epub 2015 Mar 26.

Dept. of Kinesiology, University of Texas of the Permian Basin, Odessa, TX.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1123/ijsnem.2014-0212DOI Listing
October 2015

Glycolytic enzymes localize to ribonucleoprotein granules in Drosophila germ cells, bind Tudor and protect from transposable elements.

EMBO Rep 2015 Mar 18;16(3):379-86. Epub 2015 Jan 18.

Department of Biological Sciences, Murray State University, Murray, KY, USA

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embr.201439694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364877PMC
March 2015

Effects of exercise timing on sleep architecture and nocturnal blood pressure in prehypertensives.

Vasc Health Risk Manag 2014 12;10:691-8. Epub 2014 Dec 12.

Vascular Biology and Autonomic Studies Laboratory, Department of Health and Exercise Science, Appalachian State University, Boone, NC, USA.

Background: During nocturnal sleep, blood pressure (BP) "dips" compared to diurnal BP, reducing stress on the cardiovascular system. Both the hypotensive response elicited by acute aerobic exercise and sleep quality can impact this dipping response.

Purpose: The purpose of this study was to investigate the effects of aerobic exercise timing on circadian BP changes and sleep architecture.

Materials And Methods: Twenty prehypertensive subjects completed the study. During four test sessions, participants first completed a graded exercise test to exhaustion and then performed 30 minutes of treadmill exercise at 7 am (7A), 1 pm (1P), and 7 pm (7P) in a random, counterbalanced order at 65% of the heart rate obtained at peak oxygen uptake. An ambulatory cuff was used to monitor BP responses during 24 hours following exercise, and an ambulatory sleep-monitoring headband was worn during sleep following each session.

Results: Aerobic exercise at 7A invoked a greater dip in nocturnal systolic BP than exercise at 1P or 7P, although the greatest dip in nocturnal diastolic BP occurred following 7P. Compared to 1P, 7A also invoked greater time spent in deep sleep.

Conclusion: These data indicate that early morning may be the most beneficial time to engage in aerobic exercise to enhance nocturnal BP changes and quality of sleep.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/VHRM.S73688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270305PMC
August 2015

Impact of obesity and Down syndrome on peak heart rate and aerobic capacity in youth and adults.

Res Dev Disabil 2015 01 24;36C:198-206. Epub 2014 Oct 24.

Integrative Physiology Laboratory, Department of Kinesiology and Nutrition University of Illinois at Chicago, Chicago, IL 60612, United States. Electronic address:

Individuals with Down syndrome (DS) exhibit reduced aerobic capacity with reduced peak heart rate (HR). This condition is often coexistent with higher level of obesity compared to individuals without DS. The purpose of this study is to investigate the effects of obesity and Down syndrome (DS) on peak heart rate (HR) and peak oxygen consumption (VO) in children and adults both with and without intellectual disabilities (ID)s. VO and HR from individualized treadmill tests on 654 individuals were analyzed. Body mass index was used to categorize individuals' weight status using standard cut-offs. DS groups had the lowest HR (167bpm±14, p<0.05) compared to individuals with (183bpm±12) without ID (187bpm±12). Obesity did not affect HR among adults and children with DS. VO was lower among individuals with DS (25.2mL/kg/min±6.3, p<0.05) when compared individuals with (37.0mL/kg/min±10.5) and without ID (36.1mL/kg/min±10.4). Obese adults with DS had lower VO (24.3mL/kg/min±6.9, p=0.001) compared to the normal weight (26.7±7.1mL/kg/min) and overweight groups (27.0mL/kg/min±6.1) with DS. Conversely, in children, obesity level did not impact VO in individuals with DS. Our results suggest that DS attenuates both VO and HR, regardless of obesity status and age group. However, obesity was associated with lower VO in all adults, but not in children with DS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ridd.2014.10.002DOI Listing
January 2015

Effects of resistance exercise timing on sleep architecture and nocturnal blood pressure.

J Strength Cond Res 2015 May;29(5):1378-85

Vascular Biology and Autonomic Studies Laboratory, Department of Health and Exercise Science, Appalachian State University, Boone, North Carolina.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1519/JSC.0000000000000750DOI Listing
May 2015

Kinesin-12 Kif15 targets kinetochore fibers through an intrinsic two-step mechanism.

Curr Biol 2014 Oct 25;24(19):2307-13. Epub 2014 Sep 25.

Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address:

Proteins that recognize and act on specific subsets of microtubules (MTs) enable the varied functions of the MT cytoskeleton. We recently discovered that Kif15 localizes exclusively to kinetochore fibers (K-fibers) or bundles of kinetochore-MTs within the mitotic spindle. It is currently speculated that the MT-associated protein TPX2 loads Kif15 onto spindle MTs, but this model has not been rigorously tested. Here, we show that Kif15 accumulates on MT bundles as a consequence of two inherent biochemical properties. First, Kif15 is self-repressed by its C terminus. Second, Kif15 harbors a nonmotor MT-binding site, enabling dimeric Kif15 to crosslink and slide MTs. Two-MT binding activates Kif15, resulting in its accumulation on and motility within MT bundles but not on individual MTs. We propose that Kif15 targets K-fibers via an intrinsic two-step mechanism involving molecular unfolding and two-MT binding. This work challenges the current model of Kif15 regulation and provides the first account of a kinesin that specifically recognizes a higher-order MT array.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2014.08.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207087PMC
October 2014

Structural and functional insights into the N-terminus of Schizosaccharomyces pombe Cdc5.

Biochemistry 2014 Oct 8;53(41):6439-51. Epub 2014 Oct 8.

Department of Cell and Developmental Biology, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/bi5008639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204884PMC
October 2014

Six weeks daily ingestion of whole blueberry powder increases natural killer cell counts and reduces arterial stiffness in sedentary males and females.

Nutr Res 2014 Jul 8;34(7):577-84. Epub 2014 Jul 8.

Dept. of Health and Exercise Science Appalachian State University, Boone, NC, 28608.

Evidence suggests that berries contain bioactive compounds, which reduce certain cancers and hypertension. Our hypothesis was that daily blueberry (BB) consumption would increase natural killer (NK) cells and plasma redox capacity and reduce blood pressure, augmentation index (AIx), central pulse wave velocity, and aortic systolic pressures (ASPs). Twenty-five men and postmenopausal women aged 18 to 50 years were recruited and randomized to BB (n, 13) or placebo groups (n, 12). Participants were provided with BB (equivalent to 250 g berries) or placebo powders each day for 6 weeks. Blood pressure, vascular performance testing, and blood samples were taken at baseline (presupplementation). Participants returned after 6 weeks and repeated all procedures. Presupplementation to postsupplementation comparisons for the main effects of treatment, time, and treatment-time interaction were made using a 2 (treatment) × 2 (times) repeated-measures analysis of variance for all vascular measures, redox status, and NK cell counts. Anthropometric measures were compared using t tests. Body mass, composition, and overall blood pressures were not affected in either group. Overall, AIx and ASPs were decreased in BB (treatment effect, P = .024 and P = .046, respectively). Plasma redox was not affected. Absolute NK cells were increased in BB (time, P = .001 and interaction, P = .012). Subjects (n, 9) with prehypertensive pressures (≥120/80 mm Hg, respectively) were examined as a subset using t tests and exhibited significant reductions in diastolic pressure (P = .038) from presupplementation to postsupplementation in BB. We conclude that BB ingestion for 6 weeks increases NK cells and reduces AIx, ASP, and diastolic pressures in sedentary males and females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nutres.2014.07.002DOI Listing
July 2014

Similar hypotensive effects of combined aerobic and resistance exercise with 1 set versus 3 sets in women with metabolic syndrome.

Clin Physiol Funct Imaging 2015 Nov 15;35(6):443-50. Epub 2014 Aug 15.

Graduation Program on Physical Education, Catholic University of Brasilia, Brasilia, Brazil.

The aim of the present study was to compare the response of systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP) following combined training with 1 set or with 3 sets of resistance exercise (RE). Sixteen women with metabolic syndrome (MetS) were randomly assigned to perform two combined exercise protocols and a control session (CON): 1-set, 30 min of aerobic exercise (AE) at 65-70% of reserve heart rate and 1 set of 8-12 repetitions at 80% of 10-RM in six resistance exercises; 3-sets, same protocol but with 3 sets; and CON, 30 min of seated rest. The SBP, MBP and DBP were measured before and every 15 min during 90 min following the experimental sessions. The SBP displayed a decrease (P ≤ 0.05) during the 90 min following the RE session with 1-set and 3-set, while MBP was decreased (P ≤ 0.05) up to 75 min after 1-set and up to 30 min after the 3-set exercise session compared with pre-intervention values. There was a decrease in DBP only for the greatest individual decrease following 1-set (-6.1 mmHg) and 3-set (-4.9 mmHg) combined exercise sessions, without differences between them. The rate-pressure product and heart rate remained significantly higher (P ≤ 0.05) 75 min and 90 min after the combined exercise session with 1- and 3-sets compared with the CON, respectively. In conclusion, a low-volume RE combined with AE resulted in similar decrease of SBP when compared with RE with 3-sets in women with MetS, which could be beneficial in situations of limited time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpf.12182DOI Listing
November 2015

Normal HR with tilt, yet autonomic dysfunction in persons with Down syndrome.

Med Sci Sports Exerc 2015 Feb;47(2):250-6

1Integrative Physiology Laboratory, Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL; 2Department of Physiology, Georgia Regents University, Augusta, GA; 3Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, NC; 4Department of Nutrition, Food, and Exercise Sciences, Florida State University, Tallahassee, FL; and 5Department of Physical Therapy, Wichita State University, Wichita, KS.

Unlabelled: Persons with Down syndrome (DS) exhibit altered autonomic function at rest and in response to adrenergic stimuli. It is unknown whether a subset of persons with DS that have similar HR responses to a task would have similar responses in HR variability (HRV).

Purpose: This study aimed to compare cardiac autonomic function during upright tilt using HRV analysis in persons with and without DS when persons with and without DS were matched for the change in HR.

Methods: Persons with (25 ± 2 yr; 30.4 ± 1.9 kg·m, n = 15) and without DS (27 ± 2 yr; 24.7 ± 1.1 kg·m, n = 15) were matched on their HR response to a 5-min tilt at 80°, whereas a subset of persons with DS (28 ± 3 yr; 33.5 ± 2.0 kg·m, n = 11) were not matched for the change in HR. HRV was assessed in both the frequency (natural log transformation (Ln) of low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP)) and time domains (root mean square of successive differences [RMSSD]).

Results: Changes in HR were similar in DS-matched and control but lower in DS-not matched. Tilt effects were observed for LnHF, LNTP, and RMSSD in all groups (P < 0.05). Both groups of persons with DS exhibited reduction in LnLF, with no change in the control group (P < 0.05). The increase in LF/HF was greater in the group without DS when compared with that in DS-not matched (8.71 ± 2.38 vs 2.34 ± 1.39, P < 0.05) but not when compared with that in DS-matched (3.59 ± 1.10, P = 0.075).

Conclusions: Despite similar HR response to passive upright tilt in the DS-matched, we still observed reduced sympathetic dominance in response to upright tilt in persons with DS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1249/MSS.0000000000000411DOI Listing
February 2015

Acute and chronic cardiovascular response to 16 weeks of combined eccentric or traditional resistance and aerobic training in elderly hypertensive women: a randomized controlled trial.

J Strength Cond Res 2014 Nov;28(11):3073-84

1Graduate Program on Physical Education, Catholic University of Brasilia, Brasilia, Brazil; 2Research Group in Exercise Physiology (GEFEFIS), North-Northeast Cardiology Institute, Bahia, Brazil; 3Dom Pedro of Alcantara Hospital, Bahia, Brazil; and 4Vascular Biology and Autonomic Studies Laboratory, Appalachian State University, Boone, North Carolina.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1519/JSC.0000000000000537DOI Listing
November 2014

Gle1 functions during mRNA export in an oligomeric complex that is altered in human disease.

Cell 2013 Oct 24;155(3):582-93. Epub 2013 Oct 24.

Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2013.09.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855398PMC
October 2013

Effects of supervised exercise program on metabolic function in overweight adolescents.

World J Pediatr 2013 Nov 14;9(4):307-11. Epub 2013 Nov 14.

Health Science Department, University of Rome "Foro Italico", Boone, NC, USA.

Background: Inactivity is a primary factor related to childhood obesity, yet aerobic exercise has been shown to prevent weight gain and improve fitness in adolescents. Moreover, children become less active during their summer break from school. This study compared the effects of 4 and 8 weeks of supervised summer activity versus an unsupervised summer break on metabolic function and fitness in adolescents.

Methods: Twenty-two adolescents were divided into 4-week (n=6, weight 48.1±14.9 kg, body fat 27.4±8.4%) and 8-week exercise groups (n=6, weight 43.4±10.9 kg, body fat 28.5±12.8%), that performed supervised, play-based physical activity, versus an age-matched 8 week control group that maintained their typical summer break (n=10, weight 41.7±10.0 kg, body fat 23.7±8.0%). Anthropometrics, resting energy expenditure (REE), resting heart rate (RHR) and peak aerobic capacity (VO(2peak)) were evaluated before and after the intervention (4 or 8 weeks).

Results: REE showed group differences in posttraining conditions (the 4-week group vs. the control group, 1220±169 vs. 1067±144 kcal/die, and the 8-week group vs. the control group, 1202±151 vs. 1067±144 kcal/die, P=0.047), but RHR decreased (pre-program vs. post program: 97±22 vs. 80±8 beat/min, P=0.001) and VO(2peak) significantly increased (pre-program vs. post program: 27.8±7.8 vs. 34.8±6.5 mL/kg/min, P=0.001) in the 8-week group compared to the control group.

Conclusions: Eight weeks of supervised play-based activity increased REE and VO(2peak) in adolescents with concomitant decreases in RHR. These data suggest that this novel model of exercise prescription could be considered world-wide by clinicians to improve fitness base in adolescents and help to combat the growing epidemic of childhood obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12519-013-0440-2DOI Listing
November 2013

Structural and functional characterization of the N terminus of Schizosaccharomyces pombe Cwf10.

Eukaryot Cell 2013 Nov 6;12(11):1472-89. Epub 2013 Sep 6.

Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/EC.00140-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837936PMC
November 2013
-->