Potential Compensatory Changes Research Articles

Gel-permeation chromatography-enzyme-linked immunosorbent assay method for systematic mass distribution profiling of plant cell wall matrix polysaccharides.

Cell walls are dynamic and multi-component materials that play important roles in many areas of plant biology. The composition and interactions of the structural elements give rise to material properties, which are modulated by the activity of wall-related enzymes. Studies of the genes and enzymes that determine wall composition and function have made great progress, but rarely take account of potential compensatory changes in wall polymers that may accompany and accommodate changes in other components, particularly for specific polysaccharides. Here, we present a method that allows the simultaneous examination of the mass distributions and quantities of specific cell wall matrix components, allowing insight into direct and indirect consequences of cell wall manipulations. The method employs gel-permeation chromatography fractionation of cell wall polymers followed by enzyme-linked immunosorbent assay to identify polymer types. We demonstrate the potential of this method using glycan-directed monoclonal antibodies to detect epitopes representing xyloglucans, heteromannans, glucuronoxylans, homogalacturonans (HGs) and methyl-esterified HGs. The method was used to explore compositional diversity in different Arabidopsis organs and to examine the impacts of changing wall composition in a number of previously characterized cell wall mutants. As demonstrated in this article, this methodology allows a much deeper understanding of wall composition, its dynamism and plasticity to be obtained, furthering our knowledge of cell wall biology.

Altered Prefrontal-Basal Ganglia Effective Connectivity in Patients With Poststroke Cognitive Impairment.

We investigated the association between poststroke cognitive impairment and a specific effective network connectivity in the prefrontal–basal ganglia circuit. The resting-state effective connectivity of this circuit was modeled by employing spectral dynamic causal modeling in 11 poststroke patients with cognitive impairment (PSCI), 8 poststroke patients without cognitive impairment (non-PSCI) at baseline and 3-month follow-up, and 28 healthy controls. Our results showed that different neuronal models of effective connectivity in the prefrontal–basal ganglia circuit were observed among healthy controls, non-PSCI, and PSCI patients. Additional connected paths (extra paths) appeared in the neuronal models of stroke patients compared with healthy controls. Moreover, changes were detected in the extra paths of non-PSCI between baseline and 3-month follow-up poststroke, indicating reorganization in the ipsilesional hemisphere and suggesting potential compensatory changes in the contralesional hemisphere. Furthermore, the connectivity strengths of the extra paths from the contralesional ventral anterior nucleus of thalamus to caudate correlated significantly with cognitive scores in non-PSCI and PSCI patients. These suggest that the neuronal model of effective connectivity of the prefrontal–basal ganglia circuit may be sensitive to stroke-induced cognitive decline, and it could be a biomarker for poststroke cognitive impairment 3 months poststroke. Importantly, contralesional brain regions may play an important role in functional compensation of cognitive decline.

Influence of Perinatal Polychlorinated Biphenyl or Thiouracil on Dopamine Function

Objective: Dopamine function is sensitive to toxin exposure. The environmental toxin polychlorinated biphenyl (PCB) alters dopamine physiology in several, harmful ways. Intermediary signals include thyroid hormones as PCB exposure alters thyroid function leading to changes in dopamine neurochemistry. To compare PCB and thyroid alterations directly, we exposed rats perinatally to either PCB (25 ppm) or thiouracil (THIO; 0.625%) from gestational day 1 to separation from the dam at postnatal day (PND) 25 and examined a set of tests sensitive to dopamine function. Methods: We measured behaviors including prepulse inhibition (PPI) of the acoustic startle response (ASR) in adulthood (60-90 PND) and ultrasonic vocalizations (USVs) during pup and adult periods. Dopamine levels in striatum were estimated using tyrosine hydroxylase immunohistochemistry and thyroid hormone levels were assayed in adulthood. Results: Animals exposed to thiouracil had significantly elevated startle response and impaired PPI relative to controls and PCB exposed animals. This group also had significant reductions in both USV emission during PPI and tyrosine hydroxylase staining within striatum. Conversely, PCB exposure during the perinatal period did not lead to alterations in gating or dopamine levels in adulthood. Similar to previous studies using perinatal exposure to PCB or THIO, thyroid hormone levels were unchanged (THIO group) relative to controls or actually increased (PCB group) by adulthood. Conclusion: The findings support an important role for thyroid function in dopamine-dependent behaviors. Results suggest PCB exposure leads to different outcomes in comparison to direct thyroid manipulations suggesting PCB exposure has distinct mechanisms of developmental hormone dysfunction and potential compensatory changes in response to endocrine disruption.

Targeting lifestyle energy expenditure in the management of obesity and health: from biology to built environment.

Increasing lifestyle energy expenditure has long been advocated in the prevention and treatment of obesity, as embodied in the ancient prescription of Hippocrates (the 'father of modern medicine') that people with obesity should eat less and exercise more. However, the long-term outcome of exercise alone or in combination with dieting in obesity management is poor. To understand the reasons underlying these failures and to develop novel strategies that target lifestyle energy expenditure in both prevention and treatment of obesity, research over the past decades has focused on (i) the interactions between physical activity and body weight (and its composition) throughout the lifespan; (ii) the influence of biology and potential compensatory changes in energy expenditure, food intake and food assimilation in response to energy deficits; and (iii) the impact of the built environment (outdoor and indoor) and smart technology on physical activity behaviours, thermoregulatory thermogenesis and metabolic health. It is against this background that recent advances relevant to the theme of 'Targeting Lifestyle Energy Expenditure in the Management of Obesity and Health: From Biology to Built Environment' are addressed in this overview and the nine review articles in this supplement, reporting the proceedings of the 9th Fribourg Obesity Research Conference.

Potential moderators of day-to-day variability in children’s physical activity patterns

ABSTRACTLittle is known about whether physical activity compensation occurs and, if so, what are potential moderators of such responses. This study examined whether children’s physical activity, sedentary time and energy expenditure on one day was associated with these behaviours the following day, and what factors may moderate observed associations. One hundred and twenty-seven children (8–11 years) wore an ActiGraph accelerometer for eight days. Time spent in sedentary time and physical activity was obtained. Daily energy expenditure was also assessed using a SenseWear Armband (n=98). Moderators examined were sex, age, BMI, fitness, and fundamental movement skills (FMS). Multilevel analyses were conducted using generalized mixed models. On any given day, every additional 10 minutes spent in moderate-to-vigorous physical activity (MVPA) was associated with 9.3 minutes less MVPA the following day. Every additional 10kcal expended on one day was associated with 2.9 fewer kcal expended the following day. Additional time spent sedentary on any given day was associated with less light physical activity the following day in children with lower FMS. The results are largely consistent with the compensation hypothesis, with children appearing to compensate their activity between days. Strategies to minimise potential compensatory changes may be needed for children overall rather than for specific population sub-groups.

Conditional knockout of Fgf13 in murine hearts increases arrhythmia susceptibility and reveals novel ion channel modulatory roles

The intracellular fibroblast growth factors (iFGF/FHFs) bind directly to cardiac voltage gated Na+ channels, and modulate their function. Mutations that affect iFGF/FHF-Na+ channel interaction are associated with arrhythmia syndromes. Although suspected to modulate other ionic currents, such as Ca2+ channels based on acute knockdown experiments in isolated cardiomyocytes, the in vivo consequences of iFGF/FHF gene ablation on cardiac electrical activity are still unknown. We generated inducible, cardiomyocyte-restricted Fgf13 knockout mice to determine the resultant effects of Fgf13 gene ablation. Patch clamp recordings from ventricular myocytes isolated from Fgf13 knockout mice showed a ~25% reduction in peak Na+ channel current density and a hyperpolarizing shift in steady-state inactivation. Electrocardiograms on Fgf13 knockout mice showed a prolonged QRS duration. The Na+ channel blocker flecainide further prolonged QRS duration and triggered ventricular tachyarrhythmias only in Fgf13 knockout mice, suggesting that arrhythmia vulnerability resulted, at least in part, from a loss of functioning Na+ channels. Consistent with these effects on Na+ channels, action potentials in Fgf13 knockout mice, compared to Cre control mice, exhibited slower upstrokes and reduced amplitude, but unexpectedly had longer durations. We investigated candidate sources of the prolonged action potential durations in myocytes from Fgf13 knockout mice and found a reduction of the transient outward K+ current (Ito). Fgf13 knockout did not alter whole-cell protein levels of Kv4.2 and Kv4.3, the Ito pore-forming subunits, but did decrease Kv4.2 and Kv4.3 at the sarcolemma. No changes were seen in the sustained outward K+ current or voltage-gated Ca2+ current, other candidate contributors to the increased action potential duration. These results implicate that FGF13 is a critical cardiac Na+ channel modulator and Fgf13 knockout mice have increased arrhythmia susceptibility in the setting of Na+ channel blockade. The unanticipated effect on Ito revealed new FGF13 properties and the unexpected lack of an effect on voltage-gated Ca2+ channels highlight potential compensatory changes in vivo not readily revealed with acute Fgf13 knockdown in cultured cardiomyocytes.

P2X6 Knockout Mice Exhibit Normal Electrolyte Homeostasis.

ATP-mediated signaling is an important regulator of electrolyte transport in the kidney. The purinergic cation channel P2X6 has been previously localized to the distal convoluted tubule (DCT), a nephron segment important for Mg2+ and Na+ reabsorption, but its role in ion transport remains unknown. In this study, P2x6 knockout (P2x6-/-) mice were generated to investigate the role of P2X6 in renal electrolyte transport. The P2x6-/- animals displayed a normal phenotype and did not differ physiologically from wild type mice. Differences in serum concentration and 24-hrs urine excretion of Na+, K+, Mg2+ and Ca2+ were not detected between P2x6+/+, P2x6+/- and P2x6-/- mice. Quantitative PCR was applied to examine potential compensatory changes in renal expression levels of other P2x subunits and electrolyte transporters, including P2x1-5, P2x7, Trpm6, Ncc, Egf, Cldn16, Scnn1, Slc12a3, Slc41a1, Slc41a3, Cnnm2, Kcnj10 and Fxyd2. Additionally, protein levels of P2X2 and P2X4 were assessed in P2x6+/+ and P2x6-/- mouse kidneys. However, significant changes in expression were not detected. Furthermore, no compensatory changes in gene expression could be demonstrated in heart material isolated from P2x6-/- mice. Except for a significant (P<0.05) upregulation of P2x2 in the heart of P2x6-/- mice compared to the P2x6+/+ mice. Thus, our data suggests that purinergic signaling via P2X6 is not significantly involved in the regulation of renal electrolyte handling under normal physiological conditions.

The Midwest Exercise Trial for the Prevention of Weight Regain: MET POWeR

Weight reduction in overweight and obese individuals results in physiological and behavioral changes that make the prevention of weight regain more difficult than either initial weight loss or the prevention of weight gain. Exercise is recommended for the prevention of weight regain by both governmental agencies and professional organizations. To date, the effectiveness of exercise recommendations for the prevention of weight regain has not been evaluated in a properly designed, adequately powered trial. Therefore, we will conduct a randomized trial to evaluate the effectiveness of 3 levels of exercise on the prevention of weight regain, in initially overweight and obese sedentary men and women. Participants will complete a 3month weight loss intervention of decreased energy intake (EI) and increased exercise (100min/week). Participants achieving clinically significant weight loss (≥5% of initial weight), will then be randomly assigned to 12months of verified exercise at 3 levels (150, 225 or 300min/week). This study will evaluate: 1) the effectiveness of 3 levels of exercise on the prevention of weight regain over 12months subsequent to clinically significant weight loss (≥5%); 2) gender differences in weight regain in response to 3 levels of exercise; and 3) potential compensatory changes in daily physical activity (PA) and EI on weight regain in response to the 3 levels of exercise. The results of this investigation will provide information to develop evidence-based recommendations for the level of exercise associated with the prevention of weight regain.

A randomized, controlled, supervised, exercise trial in young overweight men and women: The Midwest Exercise Trial II (MET2)

We evaluated weight loss response to 16months of supervised exercise (45min/day, 5days/week, 75% heart-rate-reserve) in sedentary, overweight/obese participants without energy restriction in the Midwest Exercise Trial (MET1). Results indicated men lost weight, women did not. The gender differences were associated with differences in the energy expenditure of exercise (EEEx) (men=667±116; women=439±88kcal/session) when exercise was prescribed by frequency, intensity and duration. MET2 is a randomized control trial designed and powered to examine differences in weight loss and gender in response to EEEx for men and women of 400 or 600kcal/session, 5days/week, for 10months without energy restriction. One hundred forty-one participants will be randomized to 1 of 2 exercise groups or a non-exercise control. EEEx will be verified by indirect calorimetry monthly during the intervention. This study will evaluate: (1) the weight change response to two levels of EEEx versus non-exercise control; (2) gender differences in weight response to two levels of EEEx; (3) potential compensatory changes in energy intake and/or daily physical activity that may explain the observed weight changes. Results from this study may impact how exercise is prescribed for weight loss and prevention of weight regain and may clarify if men and women differ in response to exercise.

Abstract P078: Dysregulated Calcium Handling in a Conditional Cardiac Myosin Binding Protein C Knockout Model of Hypertrophic Cardiomyopathy

Heritable cardiomyopathy (HCM) is the leading cause of sudden cardiac arrest (SCA) in young people, affecting 1 in 500 individuals. HCM is chiefly caused by mutations in myofibrillar proteins of the cardiac sarcomere, and cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3) is one of the most commonly affected. cMyBP-C, an accessory protein that binds tightly to myosin, has an important role in thick filament regulation. Mice with genetic ablation of MYBPC3 exhibit cardiac hypertrophy, reduced ejection fraction, and increased relaxation times in vivo . Experiments with explanted hearts from these mice exhibit greater susceptibility to arrhythmias compared to WT, suggesting derangement of Ca 2+ handling. The molecular mechanisms underlying the progression of HCM are poorly understood, and are difficult to tease apart in constitutive knock out models due to potential compensatory changes that can mask important aspects of the disease phenotype. We used a tamoxifen-induced conditional MYBPC3 knock out mouse to investigate the onset and progression of the disease before development of overt hypertrophy. We recorded Ca 2+ transients in enzymatically isolated cardiomyocytes at several pacing frequencies using a META LSM 510 confocal microscope. We found that cell shortening in conditional CMs (con-CMs) was reduced by as much as 54% (e.g., 5.46% ± 0.869 in con-CMs, vs. 11.91% ± 0.423 shortening in WT-CMs). Ca 2+ release was often dissynchronous, possibly indicating remodeling at the diads. Ca 2+ transient amplitude was significantly lower in con-CMs across all pacing frequencies (reduced by at least 22%; e.g., fluorescence intensity ratios of 7.983 ± 0.537 in con-CMs vs. 10.332 ± 0.502 in WT CMs). Further, the time constant of transient decay (tau) was dramatically increased in con-CMs (mean 217.27 ± 18.052 msec for con-CMs vs. 107.44 ± 4.045 msec in WT CMs). In some cells (∼5%), this prolongation of transient decay was so profound (e.g., up to 600 milliseconds) that a second Ca 2+ release occurred before [Ca 2+ ] i could return to baseline. These data suggest that conditional knock out of cMyBP-C produces not only contractile dysfunction, but also pro-arrhythmic alterations in Ca 2+ handling.

Brain Neuroimaging in Cannabis Use: A Review

In this study, the authors systematically reviewed structural and functional neuroimaging studies of cannabis use. Structural abnormalities generally have not been identified with chronic use. Regular users demonstrate reciprocal changes in brain activity globally and in cerebellar and frontal regions. Abstinence results in decreases, and administration results in increases correlating with subjective intoxication. Chronic use and cannabis administration result in attenuated brain activity in task-activated regions or activation of compensatory regions. Findings correlate partially with neuropsychological data, but generalization is limited by the lack of use of diagnostic criteria, appropriately paired neuropsychological testing or means to better quantify cannabis use and abstinence.

Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery

Functional neuroimaging experiments targeting personal recall of emotional events may help elucidate neural substrates underlying posttraumatic stress disorder (PTSD). Studies suggest that limbic and paralimbic function might be altered in PTSD, as compared with trauma-exposed control subjects; however, little is known about functional changes resulting from traumatic experience itself. The present study examined both PTSD-specific and trauma-specific regional cerebral blood flow (rCBF) patterns during script-driven imagery. Sixteen combat veterans with PTSD (PP); 15 combat veterans without PTSD (CC); and 14 healthy, aged-matched noncombat control subjects (NC) underwent [15O] H20 positron emission tomography (PET) scanning during script-driven imagery of emotionally evocative and neutral autobiographic events. Differential patterns of activation were detected in amygdala and medial frontal cortex. Past trauma experience was associated with decreased amygdala activity (i.e., less activity than healthy control subjects); however, combat control subjects deactivated this region (i.e., greater activity to neutral scripts). All subjects deactivated medial frontal cortex; PTSD patients had greater rostral anterior cingulate (rACC) deactivation compared with control groups, who deactivated ventromedial prefrontal cortex (vmPFC). Trauma-specific patterns may represent potential compensatory changes to traumatic reminders, while patterns observed only in the PTSD group may reflect neural substrates specific to PTSD pathophysiology.

Estimating incidental takes of shearwaters in driftnet fisheries: lessons for the conservation of seabirds

We consider estimation of the magnitude of incidental fisheries ‘bycatch’ for two petrel species, sooty shearwaters ( Puffinus griseus) and short-tailed shearwaters ( Puffinus tenuirostris). There are clear statistical advantages in estimating bycatch for abundant species such as these, and our results may also guide the conservation and management of rarer species. We used fisheries statistics and observer data to estimate retrospectively the total numbers of sooty and short-tailed shearwaters bycatch in seven large-scale pelagic North Pacific driftnet fisheries between 1952 and 2001. Sensitivity analysis greatly simplified estimation of uncertainty by identifying four driftnet fisheries to be of particular importance in determining the magnitude and precision of the estimated bycatch totals. We estimated that between 1.0 and 12.8 million (95% CI) sooty shearwaters were killed by driftnets between 1952 and 2001. For short-tailed shearwaters we estimated between 4.6 and 21.2 million (95% CI) over the same period. More precise estimation was hampered by the paucity of available observer data, lack of reported detail and inconsistencies among data sources. Estimates may be strongly biased because some dead birds are misidentified or drop out of nets before hauling, or because some records were of live captures that were subsequently released. Improved estimation of overall take and its impact on populations of seabirds requires standardisation of reporting, allowance for potential sampling bias, as well as a clearer definition of the sampling unit and underlying bycatch probability distribution model, and knowledge of potential compensatory changes in population parameters.

Subject Index

This paper focuses on the contributions of the gluteus maximus, biceps femoris, gastrocnemius and soleus in maintaining the stability of the stance limb in the sagittal plane during the mid-stance phase of gait. In the absence of any one of these muscles, the potential compensatory changes in muscle activation are explored, the aim being to restore stability to the stance limb. The investigation was carried out by integrating musculoskeletal modelling, forward simulation and optimization techniques. We concluded that maintenance of stance limb stability requires a subtle interplay of muscle activations. Weakness in a single muscle is unlikely to be adequately compensated for by increasing or decreasing the activation of one muscle alone.

The complementary role of the plantarflexors, hamstrings and gluteus maximus in the control of stance limb stability during gait.

This paper focuses on the contributions of the gluteus maximus, biceps femoris, gastrocnemius and soleus in maintaining the stability of the stance limb in the sagittal plane during the mid-stance phase of gait. In the absence of any one of these muscles, the potential compensatory changes in muscle activation are explored, the aim being to restore stability to the stance limb. The investigation was carried out by integrating musculoskeletal modelling, forward simulation and optimization techniques. We concluded that maintenance of stance limb stability requires a subtle interplay of muscle activations. Weakness in a single muscle is unlikely to be adequately compensated for by increasing or decreasing the activation of one muscle alone.

Regulation of cholanglocyte apical bile acid transporter (ABAT) activity by biliary bile acids: Different potential compensatory changes for intrahepatic and extrahepatic cholestasis

Regulation of Cholangiocyte Apical Bile Acid Transporter (ABAT) Activity by Biliary Bile Acids: Different Potential Compensatory Changes for Intrahepafic and Extrahepatic Cholestasis Gianfranco Alpini, The Texas AM Shannon Glaser, Jo Lynne Phinizy, Scott & White Memorial Hosp, Temple, TX; Noriatsu Kanno, The Texas AM Heather Francis, Scott & White Memorial Hosp, Temple, TX; Mikel Ludvik, The Texas AM Gene Lesage, Scott & White Memorial Hosp, Temple, TX

Regulation of cholanglocyte apical bile acid transporter (ABAT) activity by biliary bile acids: Different potential compensatory changes for intrahepatic and extrahepatic cholestasis

Regulation of cholanglocyte apical bile acid transporter (ABAT) activity by biliary bile acids: Different potential compensatory changes for intrahepatic and extrahepatic cholestasis