Nicola Lai - Academia.edu (original) (raw)

Papers by Nicola Lai

Oxford University Press eBooks, Sep 22, 2015

Background: Integration of metabolic pathways resources and regulatory metabolic network models, ... more Background: Integration of metabolic pathways resources and regulatory metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation in metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks. Description: PathCase Systems Biology (PathCase-SB) is built and released. The PathCase-SB database provides data and API for multiple user interfaces and software tools. The current PathCase-SB system provides a databaseenabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate data of selected biological data sources on the web (currently, BioModels database an...

Bulletin of the American Physical Society, 2017

PLOS ONE, 2017

Skeletal muscle resistance to insulin is related to accumulation of lipid-derived products, but i... more Skeletal muscle resistance to insulin is related to accumulation of lipid-derived products, but it is not clear whether this accumulation is caused by skeletal muscle mitochondrial dysfunction. Diabetes and obesity are reported to have a selective effect on the function of subsarcolemmal and interfibrillar mitochondria in insulin-resistant skeletal muscle. The current study investigated the role of the subpopulations of mitochondria in the pathogenesis of insulin resistance in the absence of obesity. A non-obese spontaneous rat model of type 2 diabetes mellitus, (Goto-Kakizaki), was used to evaluate function and biochemical properties in both populations of skeletal muscle mitochondria. In subsarcolemmal mitochondria, minor defects are observed whereas in interfibrillar mitochondria function is preserved. Subsarcolemmal mitochondria defects characterized by a mild decline of oxidative phosphorylation efficiency are related to ATP synthase and structural alterations of inner mitochondria membrane but are considered unimportant because of the absence of defects upstream as shown with polarographic and spectrophometric assays. Fatty acid transport and oxidation is preserved in both population of mitochondria, whereas palmitoyl-CoA increased 25% in interfibrillar mitochondria of diabetic rats. Contrary to popular belief, these data provide compelling evidence that mitochondrial function is unaffected in insulin-resistant skeletal muscle from T2DM non-obese rats.

Physiological Reports, 2016

The majority of the studies on _ VO 2 kinetics in pediatric populations investigated gender diffe... more The majority of the studies on _ VO 2 kinetics in pediatric populations investigated gender differences in prepubertal children during submaximal intensity exercise, but studies are lacking in adolescents. The purpose of this study was to test the hypothesis that gender differences exist in the _ VO 2 and heart rate (HR) kinetic responses to moderate (M) and heavy (H) intensity exercise in adolescents. Twenty-one healthy African-American adolescents (9 males, 15.8 AE 1.1 year; 12 females, 15.7 AE 1 year) performed constant work load exercise on a cycle ergometer at M and H. The _ VO 2 kinetics of the male group was previously analyzed (Lai et al., Appl. Physiol. Nutr. Metab. 33:107-117, 2008b). For both genders, _ VO 2 and HR kinetics were described with a single exponential at M and a double exponential at H. The fundamental time constant (s 1) of _ VO 2 was significantly higher in female than male at M (45 AE 7 vs. 36 AE 11 sec, P < 0.01) and H (41 AE 8 vs. 29 AE 9 sec, P < 0.01), respectively. The functional gain (G 1) was not statistically different between gender at M and statistically higher in females than males at H: 9.7 AE 1.2 versus 10.9 AE 1.3 mL min À1 W À1 , respectively. The amplitude of the slow component was not significantly different between genders. The HR kinetics were significantly (s 1 , P < 0.01) slower in females than males at M (61 AE 16 sec vs. 45 AE 20 sec, P < 0.01) and H (42 AE 10 sec vs. 30 AE 8 sec, P = 0.03). The G 1 of HR was higher in females than males at M: 0.53 AE 0.11 versus 0.98 AE 0.2 bpm W À1 and H: 0.40 AE 0.11 versus 0.73 AE 0.23 bpm W À1 , respectively. Gender differences in the _ VO 2 and HR kinetics suggest that oxygen delivery and utilization kinetics of female adolescents differ from those in male adolescents.

Physiological reports, Aug 1, 2016

The study aims to characterize age-associated changes in skeletal muscle bioenergetics by evaluat... more The study aims to characterize age-associated changes in skeletal muscle bioenergetics by evaluating the response to ischemia-reperfusion in the skeletal muscle of the Goto-Kakizaki (GK) rats, a rat model of non-obese type 2 diabetes (T2D). (31)P magnetic resonance spectroscopy (MRS) and blood oxygen level-dependent (BOLD) MRI was performed on the hindlimb of young (12 weeks) and adult (20 weeks) GK and Wistar (control) rats. (31)P-MRS and BOLD-MRI data were acquired continuously during an ischemia and reperfusion protocol to quantify changes in phosphate metabolites and muscle oxygenation. The time constant of phosphocreatine recovery, an index of mitochondrial oxidative capacity, was not statistically different between GK rats (60.8 ± 13.9 sec in young group, 83.7 ± 13.0 sec in adult group) and their age-matched controls (62.4 ± 11.6 sec in young group, 77.5 ± 7.1 sec in adult group). During ischemia, baseline-normalized BOLD-MRI signal was significantly lower in GK rats than in t...

Physiological reports, 2014

Mouse models of human diseases are used to study the metabolic and physiological processes leadin... more Mouse models of human diseases are used to study the metabolic and physiological processes leading to altered whole-body energy expenditure (EE), which is the sum of EE of all body organs and tissues. Isotopic techniques, arterio-venous difference of substrates, oxygen, and blood flow measurements can provide essential information to quantify tissue/organ EE and substrate oxidation. To complement and integrate experimental data, quantitative mathematical model analyses have been applied in the design of experiments and evaluation of metabolic fluxes. In this study, a method is presented to quantify the energy expenditure of the main mouse organs using metabolic flux measurements. The metabolic fluxes and substrate utilization of the main metabolic pathways of energy metabolism in the mouse tissue/organ systems and the whole body are quantified using a mathematical model based on mass and energy balances. The model is composed of six organ/tissue compartments: brain, heart, liver, ga...

Surgery, 2014

One of the goals of modern ventral hernia repair (VHR) is restoring the linea alba by returning t... more One of the goals of modern ventral hernia repair (VHR) is restoring the linea alba by returning the rectus muscles to the midline. Although this practice presumably restores native abdominal wall function, improvement of abdominal wall function has never been measured in a scientific fashion. We hypothesized that a dynamometer could be used to demonstrate an improvement in rectus muscle function after open VHR with restoration of the midline, and that this improvement would be associated with a better quality-of-life. Thirteen patients agreed to dynamometric analysis before and 6 months after an open posterior component separation (Rives-Stoppa technique complimented with a transversus abdominis muscle release) and mesh sublay. Analysis done using a dynamometer (Biodex 3, Corp, Shirley, NY) included measurement of peak torque (PT; N*m) and PT per bodyweight (BW; %) generated during abdominal flexion in 5 settings: Isokinetic analysis at 45°/s and 60°/s as well as isometric analysis at 0°, -15°, and +15°. Power (W) was calculated during isokinetic settings. Quality-of-life was measured using our validated HerQles survey at the time of each dynamometric analysis. Thirteen patients (mean age, 54 ± 9 years; mean body mass index, 31 ± 7 kg/m(2)) underwent repair with restoration of the midline using the aforementioned technique. Mean hernia width was 12.5 cm (range, 5-19). Improvements in PT and PT/BW were significant in all 5 settings (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Improvement in power during isokinetic analyses at 45°/s and 60°/s was also significant (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). All patients reported an improvement in quality-of-life, which was associated positively with each dynamometric parameter. Restoration of the linea alba during VHR is associated with improved abdominal wall functionality. Analysis of rectus muscle function using a dynamometer showed statistical improvement by isokinetic and isometric measurements, all of which were associated with an improvement in quality-of-life.

Advances in Experimental Medicine and Biology, 2009

Muscle oxygenation measurements by near infrared spectroscopy (NIRS) are frequently obtained in h... more Muscle oxygenation measurements by near infrared spectroscopy (NIRS) are frequently obtained in humans to make inferences about mechanisms of metabolic control of respiration in working skeletal muscle. However, these measurements have technical limitations that can mislead the evaluation of tissue processes. In particular, NIRS measurements of working muscle represent oxygenation of a mix of fibers with heterogeneous activation, perfusion and architecture. Specifically, the relative volume distribution of capillaries, small arteries, and venules may affect NIRS data. To determine the effect of spatial volume distribution of components of working muscle on oxygen utilization dynamics and blood flow changes, a mathematical model of oxygen transport and utilization was developed. The model includes blood volume distribution within skeletal muscle and accounts for convective, diffusive, and reactive processes of oxygen transport and metabolism in working muscle. Inputs to the model are arterial O 2 concentration, cardiac output and ATP demand. Model simulations were compared to exercise data from human subjects during a rest-to-work transition. Relationships between muscle oxygen consumption, blood flow, and the rate coefficient of capillary-tissue transport are analyzed. Blood volume distribution in muscle has noticeable effects on the optimal estimates of metabolic flux and blood flow in response to an exercise stimulus.

Skeletal muscle voluntary contractions (VC) and electrical stimulations (ES) were compared in eig... more Skeletal muscle voluntary contractions (VC) and electrical stimulations (ES) were compared in eight healthy men. High-energy phosphates and myoglobin oxygenation were simultaneously monitored in the quadriceps by interleaved 1 Hand 31 P-NMR spectroscopy. For the VC protocol, subjects performed five or six bouts of 5 min with a workload increment of 10% of maximal voluntary torque (MVT) at each step. The ES protocol consisted of a 13-min exercise with a load corresponding to 10% MVT. For both protocols, exercise consisted of 6-s isometric contractions and 6-s rest cycles. For an identical mechanical level (10% MVT), ES induced larger changes than VC in the Pi-to-phosphocreatine ratio [1.38 Ϯ 1.14 (ES) vs. 0.13 Ϯ 0.04 (VC)], pH [6.69 Ϯ 0.11 (ES) vs. 7.04 Ϯ 0.07 (VC)] and myoglobin desaturation [43 Ϯ 15.9 (ES) vs. 6.1 Ϯ 4.6% (VC)]. ES activated the muscle facing the NMR coil to a greater extent than did VCs when evaluated under identical technical conditions. This metabolic pattern can be interpreted in terms of specific temporal and spatial muscle cell recruitment. Furthermore, at identical levels of energy charge, the muscle was more acidotic and cytoplasm appeared more oxygenated during ES than during VC. These results are in accordance with a preferential recruitment of type II fibers and a relative muscle hyperperfusion during ES.

Tissue Engineering, 2006

A novel mathematical model to simulate the growth of engineered cartilage in static systems is pr... more A novel mathematical model to simulate the growth of engineered cartilage in static systems is proposed. This model is based on material balances for the involved species (glycosaminoglycan and collagen, both pertaining to extracellular matrix), as well as mass-structured population balance for simulating cell growth and its proliferation within the scaffold. This model may simulate tissue growth on static culture taking place in Petri dishes, static flasks, and well plates for different types of scaffolds (i.e., poly(glycolic acid) [PGA], PGA/poly(l-lactic acid), and collagen sponge). This work aimed to demonstrate that the model approach proposed in previous works, regarding engineered cartilage growth on PGA scaffolds performed in rotating bioreactors, may also be applied to different scaffolds and system configurations. In particular, the balance equation for simulating collagen production is introduced, as well as the use of spatial averaging over the spatial region to compare experimental data with the model. Experimental data from the literature in terms of cells, glycosaminoglycans, and collagen content have been successfully compared with model results, thus demonstrating the validity of the proposed model, as well as its predictive capability.

Medicine & Science in Sports & Exercise, 2009

Journal of Applied Physiology, 2010

It was the purpose of this study to examine the effect of a priming contractile bout on oxygen up... more It was the purpose of this study to examine the effect of a priming contractile bout on oxygen uptake (V̇o2) on-kinetics in highly oxidative skeletal muscle. Canine gastrocnemii ( n = 12) were stimulated via their sciatic nerves (8 V, 0.2-ms duration, 50 Hz, 200-ms train) at a rate of 2 contractions/3 s (≈70% peak V̇o2) for two 2-min bouts, separated by 2 min of recovery. Blood flow was recorded with an ultrasonic flowmeter, and muscle oxygenation monitored via near-infrared spectroscopy. Compared with the first bout ( bout 2 vs. bout 1), the V̇o2 primary time constant (mean ± SD, 9.4 ± 2.3 vs. 12.0 ± 3.9 s) and slow-component amplitude (5.9 ± 6.3 vs. 12.1 ± 9.0 ml O2·kg wet wt−1·min−1) were significantly reduced ( P < 0.05) during the second bout. Blood flow on-kinetics were significantly speeded during the second bout (time constant = 7.7 ± 2.6 vs. 14.8 ± 5.8 s), and O2 extraction was greater at the onset of contractions (0.050 ± 0.030 vs. 0.020 ± 0.010 ml O2/ml blood). Kinetic...

Journal of Applied Physiology, 2009

Noninvasive, continuous measurements in vivo are commonly used to make inferences about mechanism... more Noninvasive, continuous measurements in vivo are commonly used to make inferences about mechanisms controlling internal and external respiration during exercise. In particular, the dynamic response of muscle oxygenation ([Formula: see text]) measured by near-infrared spectroscopy (NIRS) is assumed to be correlated to that of venous oxygen saturation (SvO2) measured invasively. However, there are situations where the dynamics of [Formula: see text] and SvO2 do not follow the same pattern. A quantitative analysis of venous and muscle oxygenation dynamics during exercise is necessary to explain the links between different patterns observed experimentally. For this purpose, a mathematical model of oxygen transport and utilization that accounts for the relative contribution of hemoglobin (Hb) and myoglobin (Mb) to the NIRS signal was developed. This model includes changes in microvascular composition within skeletal muscle during exercise and integrates experimental data in a consistent ...

Journal of Applied Physiology, 2012

The purpose of this study was to examine O2 uptake (V̇o2) on-kinetics when the spontaneous blood ... more The purpose of this study was to examine O2 uptake (V̇o2) on-kinetics when the spontaneous blood flow (and therefore O2 delivery) on-response was slowed by 25 and 50 s. The isolated gastrocnemius muscle complex (GS) in situ was studied in six anesthetized dogs during transitions from rest to a submaximal metabolic rate (≈50–70% of peak V̇o2). Four trials were performed: 1) a pretrial in which resting and steady-state blood flows were established, 2) a control trial in which the blood flow on-kinetics mean response time (MRT) was set at 20 s (CT20), 3) an experimental trial in which the blood flow on-kinetics MRT was set at 45 s (EX45), and 4) an experimental trial in which the blood flow on-kinetics MRT was set at 70 s (EX70). Slowing O2 delivery via slowing blood flow on-kinetics resulted in a linear slowing of the V̇o2 on-kinetics response ( R = 0.96). Average MRT values for CT20, EX45, and EX70 V̇o2 on-kinetics were (means ± SD) 17 ± 2, 23 ± 4, and 26 ± 3 s, respectively ( P <...