bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined insulin treatment and intense exercise training improved basal cardiac function and Ca2+-cycling proteins expression in type 1 diabetic rats
Authors: Le Douairon Lahaye Solène , Gratas-Delamarche Arlette , Malardé Ludivine , Zguira Sami , Vincent Sophie , Lemoine Morel Sophie , Carré François , Rannou Bekono Françoise 
Published: February 2012

This study investigated the effects of 8 weeks of intense exercise training combined with insulin treatment on the Ca2+-cycling protein complex expression and their functional consequences on cardiac function in type 1 diabetic rat hearts. Diabetic Wistar rats were randomly assigned into the following groups: received no treatment, insulin-treated diabetic, trained diabetic, and trained insulin-treated diabetic. A control group was also included. Insulin treatment and (or) treadmill intense exercise training were conducted over 8 weeks. Basal cardiac function was evaluated by Langendorff technique. Cardiac expression of the main Ca2+-cycling proteins (RyR2, FKBP 12.6, SERCA2, PLB, NCX1) was assessed by Western blot. Diabetes altered basal cardiac function (±dP/dt) and decrease the expression of the main Ca2+-cycling proteins expression: RyR2, SERCA2, and NCX1 (p < 0.05). Whereas combined treatment was not able to normalize –dP/dt, it succeeded to normalize +dP/dt of diabetic rats (p < 0.05). Moreover, both insulin and intense exercise training, applied solely, increased the expression of the Ca2+-cycling proteins: RyR2, SERCA2, PLB. and NCX1 (p < 0.05). But this effect was higher when the 2 treatments were combined. These data are the first to show that combined insulin treatment and intense exercise training during diabetes synergistically act on the expression of the main Ca2+-cycling proteins, providing insights into mechanisms by which the dual treatment during diabetes improves cardiac function.
Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior
Authors: Larsen Ryan G. , Callahan Damien M. , Foulis Stephen A. , Kent-Braun Jane A. 
Published: February 2012

There is discrepancy in the literature regarding the degree to which old age affects muscle bioenergetics. These discrepancies are likely influenced by several factors, including variations in physical activity (PA) and differences in the muscle group investigated. To test the hypothesis that age may affect muscles differently, we quantified oxidative capacity of tibialis anterior (TA) and vastus lateralis (VL) muscles in healthy, relatively sedentary younger (8 YW, 8 YM; 21–35 years) and older (8 OW, 8 OM; 65–80 years) adults. To investigate the effect of physical activity on muscle oxidative capacity in older adults, we compared older sedentary women to older women with mild-to-moderate mobility impairment and lower physical activity (OIW, n = 7), and older sedentary men with older active male runners (OAM, n = 6). Oxidative capacity was measured in vivo as the rate constant, kPCr, of postcontraction phosphocreatine recovery, obtained by31P magnetic resonance spectroscopy following maximal isometric contractions. While kPCrwas higher in TA of older than activity-matched younger adults (28%; p = 0.03), older adults had lower kPCrin VL (23%; p = 0.04). In OIW compared with OW, kPCrwas lower in VL (∼45%; p = 0.01), but not different in TA. In contrast, OAM had higher kPCrthan OM (p = 0.03) in both TA (41%) and VL (54%). In older adults, moderate-to-vigorous PA was positively associated with kPCrin VL (r = 0.65, p < 0.001) and TA (r = 0.41, p = 0.03). Collectively, these results indicate that age-related changes in oxidative capacity vary markedly between locomotory muscles, and that altered PA behavior may play a role in these changes.
Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction
Authors: Herbst Eric A.F. , Dunford Emily C.E. , Harris Robert A. , Vandenboom Rene , LeBlanc Paul J. , Roy Brian D. , Jeoung Nam Ho , Peters Sandra J. 
Published: February 2012

The oxidation of carbohydrates in mammals is regulated by the pyruvate dehydrogenase (PDH) complex, which is covalently regulated by four PDH kinases (PDK1–4) and two PDH phosphatases (PDP1–2) unique to the PDH complex. To investigate the role that PDK4 plays in regulating PDH activation (PDHa) during muscle contraction, mouse extensor digitorum muscle was removed from wild type (WT) and PDK4-knockout (PDK4-KO) mice after a 24 h fast and stimulated for 3 min either at 10 Hz (low-intensity contraction), 40 Hz (moderate-intensity contraction), or allowed to rest. Force was recorded and muscle PDHa activity and metabolite concentrations were measured. PDHa activity was ∼2.5-fold higher at rest in PDK4-KO mice than WT mice (P = 0.009) and ∼2-fold higher in PDK4-KO mice at both 10 Hz (P < 0.001) and 40 Hz (P < 0.001). Force relative to muscle weight was similar at 10 Hz, but was 5.8 ± 0.7 mN·g–1 in PDK4-KO mice and 3.5 ± 0.7 mN·g–1 in WT mice at 40 Hz (P < 0.001), with a similar rate of fatigue in both genotypes. From these results it was concluded that PDK4 plays a role in reducing PDHa activity during low to moderate-intensity muscle stimulation, and that absence of PDK4 and the subsequent changes in carbohydrate utilization may alter force production.
An evaluation of the physical activity and health status of British Columbian Aboriginal populations
Authors: Foulds Heather J.A. , Bredin Shannon S.D. , Warburton Darren E.R. 
Published: February 2012

Aboriginal people have experienced elevated rates of obesity, diabetes, cardiovascular disease, and other chronic conditions that are disproportionate to the general Canadian population. We sampled British Columbian Aboriginal populations to determine the current health status of this population. A total of 882 Aboriginal adults ≥16 years of age from 25 locations around the province were sampled from 2007–2011. Health measurements evaluated included body mass index, waist circumference, physical activity, smoking behaviours, and resting blood pressure as well as histories of diabetes, cardiovascular disease, and hypertension. Nonfasting measures of blood sugar, total cholesterol, and high-density lipoprotein cholesterol were also recorded. We used logistical regression to quantify variations in diabetes and cardiovascular disease risk factors with age, gender, geographic location, on- and off-reserve and urban–rural areas of residence, smoking, and physical activity behaviour. The prevalence of diabetes, hypertension, and high total cholesterol were found to be greater among males, while females experienced greater rates of abdominal obesity and physical inactivity. Rates of chronic conditions were similar across on- and off-reserve, urban–rural areas, and geographic region residences, though rural, on-reserve, and northern residents experienced greater risk of poor health status. Larger proportions of on-reserve, rural, and interior individuals were found to be more physically inactive. Aboriginal populations still experience substantially poorer health status in comparison with the general population. Initiatives to improve the health of this population are urgently needed addressing all sectors of the Aboriginal population, all geographic regions, and all areas of residence, with special emphasis on rural, on-reserve, and northern populations.
Glucose tolerance is affected by visceral adiposity and sex, but not birth weight, in Yucatan miniature pigs
Authors: McKnight Leslie L. , Myrie Semone B. , MacKay Dylan S. , Brunton Janet A. , Bertolo Robert F. 
Published: February 2012

Epidemiological studies have linked small birth weight and lack of breastfeeding to type 2 diabetes mellitus. This study aimed to determine if (i) small birth weight promotes and (ii) suckling prevents the development of adiposity and diabetes biomarkers in a Yucatan miniature pig model. At 3 days of age, the intrauterine growth-restricted (IUGR) piglet (n = 6) was paired with a normal weight (NW), same-sex littermate (n = 6) and fed milk replacer for 4 weeks. A sow-fed normal weight littermate (n = 6) was also compared with the NW littermate to assess the effects of suckling. All pigs were fed a standard diet ad libitum for 5 h·day–1from week 4. At 9.5 months, pigs underwent intravenous glucose tolerance (IVGTT) and insulin sensitivity tests (IST). At 10 months, tissues were harvested for fat analysis and pancreas histology. IUGR pigs demonstrated compensatory growth before sexual maturity and had greater subcutaneous fat depth; birth weight also negatively correlated with visceral fat content. Visceral and subcutaneous adiposity were greater in females than males. IVGTT and IST outcomes were not different due to birth weight or suckling. However, visceral adiposity was associated with several glucose tolerance outcomes and females were more glucose intolerant due to their greater adiposity. Pancreas insulin content or histology outcomes were not different. This model did not develop markers of type 2 diabetes mellitus because of small birth weight or formula feeding. However, visceral adiposity and sex were associated with glucose intolerance, which is consistent with data in humans.
Acute l-arginine supplementation increases muscle blood volume but not strength performance
Authors: Álvares Thiago Silveira , Conte Carlos Adam , Paschoalin Vânia Margaret Flosi , Silva Joab Trajano , Meirelles Cláudia de Mello , Bhambhani Yagesh N. , Gomes Paulo Sergio Chagas 
Published: February 2012

l-Arginine (L-arg) is an amino acid precursor to nitric oxide (NO). Dietary supplements containing L-arg have been marketed with the purpose of increasing vasodilation, thereby elevating blood flow to the exercising muscle and enhancing the metabolic response to exercise. Our goal was to identify the acute effect of L-arg supplementation on biceps strength performance, indicators of NO production (nitrite and nitrate – NOx), and muscle blood volume (Mbv) and oxygenation (Mox) during recovery from 3 sets of resistance exercise. Fifteen males participated in a randomized, double-blind, placebo-controlled study. After withdrawing resting blood samples, the subjects were supplemented with 6 g of L-arg (ARG) or placebo (PLA). Monitoring of Mbv and Mox with near-infrared spectroscopy began 30 min after supplementation and lasted for 60 min. The exercise protocol (3 sets of 10 maximal voluntary contractions of isokinetic concentric elbow extension at 60°·s–1, 2-min rest between sets) was initiated 80 min after supplementation. Blood samples were drawn at 30, 60, 90, and 120 min after supplementation. Repeated measures ANOVA showed that Mbv significantly (p ≤ 0.05) increased in ARG compared with the PLA during the recovery period of each set of resistance exercise. NOx, Mox, peak torque, total work, and set total work were not significantly different between groups. We found that acute L-arg supplementation increases Mbv during recovery from sets of resistance exercise with no increase in strength performance. It is still premature to recommend nutritional supplements containing L-arg as an ergogenic aid to increase muscle strength during resistance training in healthy subjects.
Benefits of pedometer-measured habitual physical activity in healthy women
Authors: Graff Scheila Karen , Alves Bruna Cherubini , Toscani Mariana Kirjner , Spritzer Poli Mara 
Published: February 2012

This cross-sectional study aimed at (i) characterizing pedometer-determined physical activity and (ii) examining its associations with dietary intake and anthropometric and metabolic profile in healthy women. Anthropometric and metabolic profile was evaluated in 68 healthy women of reproductive age. Habitual physical activity was assessed using a pedometer for 6 consecutive days, including weekends. Participants were stratified into active and inactive according to the mean steps·day–1(≥6000 and <6000, respectively). Food consumption was evaluated by 24-h recall in a subsample of 35 participants. Thirty-eight women were defined as active and had significantly lower body mass index (BMI), fat percentage, waist circumference, sum of skinfold thickness, insulin, and HOMA than the sedentary group. Mean BMI was 27 kg·m–2(overweight) in active participants and 31 kg·m–2(class I obesity) in inactive participants. Active women consumed more carbohydrates (55.5% ± 9.4% vs. 46.3% ± 7.6%) and calories (2138 ± 679 vs. 1664 ± 558 kcal), and less protein (15.4% ± 4.2% vs. 19.9% ± 5.8%) and lipids (29.0% ± 7.2% vs. 33.8% ± 6.2%) than inactive individuals (p < 0.05). Fiber, cholesterol, and fatty acid intake was similar in both groups. The number of steps was lower on Sunday than on weekdays for the overall group. Using a pedometer for 3 days was sufficient to determine habitual physical activity (sensitivity: 94%; specificity 91% vs. 6 days of pedometer use). In the present study, nonstructured physical activity was associated with more adequate dietary consumption and contributed toward a healthier anthropometric and metabolic profile in young women, despite the high prevalence of overweight.
Validation of a new mixing chamber system for breath-by-breath indirect calorimetry
Authors: Kim Do-yeon , Robergs Robert Andrew 
Published: February 2012

Limited validation research exists for applications of breath-by-breath systems of expired gas analysis indirect calorimetry (EGAIC) during exercise. We developed improved hardware and software for breath-by-breath indirect calorimetry (NEW) and validated this system as well as a commercial system (COM) against 2 methods: (i) mechanical ventilation with known calibration gas, and (ii) human subjects testing for 5 min each at rest and cycle ergometer exercise at 100 and 175 W. Mechanical calibration consisted of medical grade and certified calibration gas ((4.95% CO2, 12.01% O2, balance N2), room air (20.95% O2, 0.03% CO2, balance N2), and 100% nitrogen), and an air flow turbine calibrated with a 3-L calibration syringe. Ventilation was mimicked manually using complete 3-L calibration syringe manouvres at a rate of 10·min–1from a Douglas bag reservoir of calibration gas. The testing of human subjects was completed in a counterbalanced sequence based on 5 repeated tests of all conditions for a single subject. Rest periods of 5 and 10 min followed the 100 and 175 W conditions, respectively. COM and NEW had similar accuracy when tested with known ventilation and gas fractions. However, during human subjects testing COM significantly under-measured carbon dioxide gas fractions, over-measured oxygen gas fractions and minute ventilation, and resulted in errors to each of oxygen uptake, carbon dioxide output, and respiratory exchange ratio. These discrepant findings reveal that controlled ventilation and gas fractions are insufficient to validate breath-by-breath, and perhaps even time-averaged, systems of EGAIC. The errors of the COM system reveal the need for concern over the validity of commercial systems of EGAIC.
Impaired superficial femoral artery vasodilation and leg blood flow in young obese women following an oral glucose tolerance test
Authors: Olver T.D. , Hazell T.J. , Hamilton C.D. , Shoemaker J.K. , Lemon P.W.R. 
Published: February 2012

This study was designed to test the hypothesis that glucose ingestion following an overnight fast increases leg vascular conductance (LVCd) and superficial femoral artery (SFA) vasodilation in lean but not obese young women. Obese (23.5 ± 4.0 years, 84.7 ± 14.7 kg, 37.2% ± 6.4% fat; mean ± SD, n = 8) and lean (23.8 ± 2.4 years, 60.6 ± 4.0 kg, 22.3% ± 2.8% fat; n = 8) women arrived in the laboratory at 0830 h after a 12-h overnight fast for body composition (densitometry) assessment. Then, capillary blood glucose (BGlu), plasma insulin, heart rate, cardiac output, mean arterial pressure, leg blood flow (Doppler ultrasound), and LVCd were measured (after 15 min in the supine position), and at 30-min intervals for 2 h following glucose ingestion (75 g glucose load, 12.5% solution). Fasting BGlu concentration was not different between groups (obese = 5.1 ± 0.47 vs. lean = 4.9 ± 0.37 mmol·L–1, p = 0.71) but 60, 90, and 120 min postingestion BGlu was elevated (p ≤ 0.03) in the obese women. Insulin differences were not significant. Fasting LVCd was not different between groups (lean = 0.72 ± 0.49 vs. obese = 0.70 ± 0.19 mL·min–1·mm Hg–1; p = 0.48); however, LVCd, as well as Δ in SFA diameter were significantly elevated (p ≤ 0.04) in the lean compared with the obese group at 60, 90, and 120 min postglucose ingestion (LVCd, peak lean = 1.4 ± 0.5 vs. peak obese = 0.8 ± 0.1 mL·min–1·mm Hg–1; Δ in SFA, peak lean = 0.51 ± 0.30 vs. peak obese = 0.09 ± 0.45 mm). The reduced LVCd following glucose ingestion could contribute to impaired glucose tolerance. Further, the lack of SFA dilation may be evidence of impaired vascular insulin responsiveness in these obese young women.
Cigarette Smoke Induces Aberrant EGF Receptor Activation That Mediates Lung Cancer Development and Resistance to Tyrosine Kinase Inhibitors
Authors: Filosto Simone , Becker Cathleen R. , Goldkorn Tzipora 
Published: February 2012

Abstract
The EGF receptor (EGFR) and its downstream signaling are implicated in lung cancer development. Therefore, much effort was spent in developing specific tyrosine kinase inhibitors (TKI) that bind to the EGFR ATP-pocket, blocking EGFR phosphorylation/signaling. Clinical use of TKIs is effective in a subset of lung cancers with mutations in the EGFR kinase domain, rendering the receptor highly susceptible to TKIs. However, these benefits are limited, and emergence of additional EGFR mutations usually results in TKI resistance and disease progression. Previously, we showed one mechanism linking cigarette smoke to EGFR-driven lung cancer. Specifically, exposure of lung epithelial cells to cigarette smoke-induced oxidative stress stimulates aberrant EGFR phosphorylation/activation with impaired receptor ubiquitination/degradation. The abnormal stabilization of the activated receptor leads to uncontrolled cell growth and tumorigenesis. Here, we describe for the first time a novel posttranslational mechanism of EGFR resistance to TKIs. Exposure of airway epithelial cells to cigarette smoke causes aberrant phosphorylation/activation of EGFR, resulting in a conformation that is different from that induced by the ligand EGF. Unlike EGF-activated EGFR, cigarette smoke-activated EGFR binds c-Src and caveolin-1 and does not undergo canonical dimerization. Importantly, the cigarette smoke-activated EGFR is not inhibited by TKIs (AG1478; erlotinib; gefitinib); in fact, the cigarette smoke exposure induces TKI-resistance even in the TKI-sensitive EGFR mutants. Our findings show that cigarette smoke exposure stimulates not only aberrant EGFR phosphorylation impairing receptor degradation, but also induces a different EGFR conformation and signaling that are resistant to TKIs. Together, these findings offer new insights into cigarette smoke-induced lung cancer development and TKI resistance. Mol Cancer Ther; 11(4); 795–804. ©2012 AACR.
The Thymidine Phosphorylase Inhibitor 5′-O-Tritylinosine (KIN59) Is an Antiangiogenic Multitarget Fibroblast Growth Factor-2 Antagonist
Authors: Liekens Sandra , Bronckaers Annelies , Belleri Mirella , Bugatti Antonella , Sienaert Rebecca , Ribatti Domenico , Nico Beatrice , Gigante Alba , Casanova Elena , Opdenakker Ghislain , Pérez-Pérez María-Jesús , Balzarini Jan , Presta Marco 
Published: February 2012

Abstract
5′-O-Tritylinosine (KIN59) is an allosteric inhibitor of the angiogenic enzyme thymidine phosphorylase. Previous observations showed the capacity of KIN59 to abrogate thymidine phosphorylase–induced as well as developmental angiogenesis in the chicken chorioallantoic membrane (CAM) assay. Here, we show that KIN59 also inhibits the angiogenic response triggered by fibroblast growth factor-2 (FGF2) but not by VEGF in the CAM assay. Immunohistochemical and reverse transcriptase PCR analyses revealed that the expression of laminin, the major proteoglycan of the basement membrane of blood vessels, is downregulated by KIN59 administration in control as well as in thymidine phosphorylase- or FGF2-treated CAMs, but not in CAMs treated with VEGF. Also, KIN59 abrogated FGF2-induced endothelial cell proliferation, FGF receptor activation, and Akt signaling in vitro with no effect on VEGF-stimulated biologic responses. Accordingly, KIN59 inhibited the binding of FGF2 to FGF receptor-1 (FGFR1), thus preventing the formation of productive heparan sulphate proteoglycan/FGF2/FGFR1 ternary complexes, without affecting heparin interaction. In keeping with these observations, systemic administration of KIN59 inhibited the growth and neovascularization of subcutaneous tumors induced by FGF2-transformed endothelial cells injected in immunodeficient nude mice. Taken together, the data indicate that the thymidine phosphorylase inhibitor KIN59 is endowed with a significant FGF2 antagonist activity, thus representing a promising lead compound for the design of multitargeted antiangiogenic cancer drugs. Mol Cancer Ther; 11(4); 817–29. ©2012 AACR.
Modeling of Forecast Sensitivity on the March of Monsoon Isochrones from Kerala to New Delhi: The First 25 Days
Authors: Krishnamurti T. N. , Simon Anu , Thomas Aype , Mishra Akhilesh , Sikka Dev , Niyogi Dev , Chakraborty Arindam , Li Li 
Published: February 2012

Abstract
This study addresses observational and modeling sensitivity on the march of the onset isochrones of the Indian summer monsoon. The first 25 days of the passage of the isochrones of monsoon onset is of great scientific interest. Surface and satellite-based datasets are used for high-resolution modeling of the impact of the motion of the onset isochrones from Kerala to New Delhi. These include the asymmetries across the isochrone such as soil moisture and its temporal variability, moistening of the dry soil to the immediate north of the isochrone by nonconvective anvil rains, and formation of newly forming cloud elements to the immediate north of the isochrone. The region immediately north of the isochrone is shown to carry a spread of buoyancy elements. As these new elements grow, they are continually being steered by the divergent circulations of the parent isochrone to the north and eventually to the northwest. CloudSat was extremely useful for identifying the asymmetric cloud structures across the isochrone. In the modeling sensitivity studies, the authors used a mesoscale Advanced Research Weather Research and Forecasting Model (ARW-WRF) to examine days 1–25 of forecasts of the onset isochrone. Prediction experiments were first modeled during normal, dry, and wet Indian monsoons using default values of model parameters. This study was extended to determine the effects of changes in soil moisture and nonconvective rain parameterizations (the parameters suggested by the satellite observations). These sensitivity experiments show that the motion of the isochrones from Kerala to New Delhi are very sensitive to the parameterization of soil moisture and nonconvective anvil rains immediately north of the isochrone.