AMPK and transcriptional regulation

The AMP-activated protein kinase (AMPK) is an energy sensing enzyme that once activated, promotes energy production and limits energy utilisation to ensure cellular survival. In addition to targeting numerous metabolic enzymes for this purpose, it is becoming apparent that AMPK can also regulate a number of transcriptional processes. These processes ensure cell survival through the inhibition of cell cycle and growth mechanisms, and also prepare the cell for future perturbations in energy balance by increasing the capacity of the cell to produce ATP. While these adaptations might be inextricably linked through regulation of the proliferation-differentiation process, recent studies have identified a number of transcriptional regulators as AMPK substrates that give insights into the regulation of transcription by AMPK in a number of metabolically active tissues.

Genetic and environmental influences on variation in balance performance among female twin pairs aged 21-82 years

Genetic and environmental influences on variation in balance performance were measured in 93 monozygous and 83 dizygous female twin pairs aged 21–82 years (mean age, 50.5 years) in Melbourne, Australia, between 1999 and 2003. The authors administered clinical (Lord's Balance Test and Step Test) and laboratory tests of static and dynamic balance from the Chattecx Balance System with and without distractor tasks. The authors conducted factor analysis and estimated genetic and environmental variance components and heritability (defined as additive genetic variance as a proportion of all variance, after adjustment for age) using a multivariate normal model with the statistical package FISHER. Three factors were identified and adjusted for age. Heritability was 46% (standard error (SE), 9) for the "sensory balance tests" factor and 30% (SE, 9) for the "static and dynamic perturbations" factor. For both factors, the remaining variance was attributed to unique environmental effects. There was no evidence that genetic factors influenced variation in the "dynamic weight shift tests" factor, with environmental effects shared by twins accounting for 38% (SE, 7) of variance. Neither genetic nor environmental proportions of variance differed significantly between twin subgroups by age (≤50/>50 years). An age-related decline in performance measures was found across the whole sample. These results imply that balance impairments may have a heritable element.

Compensatory Ability to Null Mutation in Metabolic Networks

Robustness is an inherent property of biological system. It is still a limited understanding of how it is accomplished at the cellular or molecular level. To this end, this article analyzes the impact degree of each reaction to others, which is defined as the number of cascading failures of following and/or forward reactions when an initial reaction is deleted. By analyzing more than 800 organism’s metabolic networks, it suggests that the reactions with larger impact degrees are likely essential and the universal reactions should also be essential. Alternative metabolic pathways compensate null mutations, which represents that average impact degrees for all organisms are small. Interestingly, average impact degrees of archaea organisms are smaller than other two categories of organisms, eukayote and bacteria, indicating that archaea organisms have strong robustness to resist the various perturbations during the evolution process. The results show that scale-free feature and reaction reversibility contribute to the robustness in metabolic networks. The optimal growth temperature of organism also relates the robust structure of metabolic network.

Mixing characterisation for a serpentine microchannel equipped with embedded barriers

This paper describes the design, simulation, fabrication and experimental analysis of a passive micromixer for the mixing of biological solvents. The mixer consists of a T-junction, followed by a serpentine microchannel. the serpentine has three arcs, each equipped with circular barriers that are patterned as two opposing triangles. >The barriers are engineered to induce periodic perturbations in the flow field and enhance the mixing. CFD (Computational Fluid Dynamics) method is applied to optimise the geometric variables of the mixer before fabrication. The mixer is made from PDMS (Polydimethylsiloxane) using photo- and soft-lithography techniques. Experimental measurements are performed using yellow and blue food dyes as the mixing fluids. The mixing is measured by analysing the composition of the flow's colour across the outlet channel. The performance of the mixer is examined in a wide range of flow rates from 0.5 to 10 µl/min. Mixing efficiencies of higher than 99.4% are obtained in the experiments confirming the results of numerical simulations. The proposed mixer can be employed as a part of lab-on-a-chip for biomedical applications.

Identifying capabilities for the IT function to create agility in information systems

In this paper, we identify the necessary capabilities of the IT function to create agility in existing information systems. Agility is the ability to quickly sense and respond to environment perturbations. We contrast the agility perspective from a widely used industry framework with research perspectives on agility in the IS literature. We suggest Beer’s Viable System Model (VSM) is a useful meta-level theory to house agility elements from IS research literature, and apply VSM principles to identify the capabilities required of the IT function. Indeed, by means of a survey of 34 organisations, we confirm that the meta-level theory better correlates with reported agility measures than existing practice measures do on their own. From a research perspective, the incorporation of the VSM mechanism helps to explain ‘why’ the IT function is capable of creating agility. From a practical perspective of ‘how’, the findings point to a new set of capabilities of the IT function for future versions of the industry frameworks to enable agility.

Agility in information systems : enabling capabilities for the IT function

This research identifies how the IT function can create agility in existing information systems. Agility is the capability to quickly sense and respond to environmental perturbations. We contrasted perspectives on agility from a widely used industry framework and that of the IS research literature. Beer’s Viable System Model was a useful meta-level theory to house agility elements from IS research and it introduced cybernetic principles to identify the processes required of the IT function. Indeed, our surveys of 70 organizations confirmed that the applied theory better correlates with reported agility than does existing industry best practice.

The research conducted two quantitative surveys to test the applied theory. The first survey mailed a Likert-type questionnaire to the clients of an Australian IT consultancy. The second survey invited international members of professional interest groups to complete a web-based questionnaire. The responses from the surveys were analyzed using partial-least-squares modeling. The data analysis positively correlated the maturity of IT function processes prescribed by the VSM and the likelihood of agility in existing information systems. We claim our findings generalize to other large organizations in OECD member countries.

The research offers an agility-capability model of the IT function to explain and predict agility in existing information systems. A further contribution is to improve industry ‘best practice’ frameworks by prescribing processes of the IT function to develop in maturity.

Trophic responses to nutrient enrichment in a temperate seagrass food chain

Simple ecological models that predict trophic responses to bottom-up forcing are valuable tools for ecosystem managers. Traditionally, theoretical ecologists have used resource-dependent functional responses to explain the modification of food chains exposed to bottom-up perturbations. These models predict alternating positive, negative and zero responses at each trophic level. More recently, ratio-dependent functional response models that predict proportional increases at each level have challenged this paradigm. The present study tested the predictions of the 2 hypotheses empirically by comparing the relative biomasses of 4 trophic levels of an estuarine seagrass food chain in relatively undisturbed, low-nutrient catchments and ‘developed’ catchments subjected to a prolonged period of nutrient enrichment. We found that nutrient-enriched sites had significantly greater biomass of both epiphytic algae and grazing invertebrates; however, the bottom-up forcing of nutrients was attenuated at higher trophic levels (occupied by juvenile and piscivorous fish), with no significant effect of catchment development. This disconnect in the upward cascade of energy may be due to a number of possible reasons including high levels of diversity and omnivory, trophic subsidy within the system or the strength or nature of perturbations. Although the predictions of both hypotheses failed to hold across all trophic groups, ratio dependence was prevalent at the lower levels of the food chain, which has implications for catchment management.

Two hundred years after a commercial marine turtle fishery: the current status of marine turtles nesting in the Cayman Islands

Large populations of marine turtles breeding in the Cayman Islands were drastically reduced in the early 1800s. However, marine turtle nesting still occurs in the islands. The present-day status of this nesting population provides insight into the conservation of marine turtles, a long-lived species. In 1998 and 1999, the first systematic survey of marine turtle nesting in the Cayman Islands found 38 nests on 22 beaches scattered through the three islands. Three species were found: the green Chelonia mydas, hawksbill Eretmochelys imbricata and loggerhead Caretta caretta turtles. Comparison with other rookeries suggests that the small number of sexually mature adults surviving Cayman’s huge perturbations may be impeding population recovery. This shows the need to implement conservation measures prior to massive reductions in population size.

Invader impact clarifies the roles of top-down and bottom-up effects on tropical snake populations

Disentangling the effects of prey limitation (bottom-up) and predation (top-down) processes on natural populations is difficult, but the perturbations introduced by an invasive species can provide pseudo-experimental evidence on this issue.

A design-based method for estimating glomerular number in the developing kidney

Low glomerular (nephron) endowment has been associated with an increased risk of cardiovascular and renal disease in adulthood. Nephron endowment in humans is determined by 36 wk of gestation, while in rats and mice nephrogenesis ends several days after birth. Specific genes and environmental perturbations have been shown to regulate nephron endowment. Until now, design-based method for estimating nephron number in developing kidneys was unavailable. This was due in part to the difficulty associated with unambiguously identifying developing glomeruli in histological sections. Here, we describe a method that uses lectin histochemistry to identify developing glomeruli and the physical disector/fractionator principle to provide unbiased estimates of total glomerular number (Nglom). We have characterized Nglom throughout development in kidneys from 76 rats and model this development with a 5-parameter logistic equation to predict Nglom from embryonic day 17.25 to adulthood (r2 = 0.98). This approach represents the first design-based method with which to estimate Nglom in the developing kidney.

Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes: evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism

To examine whether genes associated with cellular defense against oxidative stress are associated with insulin sensitivity, patients with type 2 diabetes (n = 7) and age-matched (n = 5) and young (n = 9) control subjects underwent a euglycemic-hyperinsulinemic clamp for 120 min. Muscle samples were obtained before and after the clamp and analyzed for heat shock protein (HSP)72 and heme oxygenase (HO)-1 mRNA, intramuscular triglyceride content, and the maximal activities of β-hyroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase (CS). Basal expression of both HSP72 and HO-1 mRNA were lower (P < 0.05) by 33 and 55%, respectively, when comparing diabetic patients with age-matched and young control subjects, with no differences between the latter groups. Both basal HSP72 (r = 0.75, P < 0.001) and HO-1 (r = 0.50, P < 0.05) mRNA expression correlated with the glucose infusion rate during the clamp. Significant correlations were also observed between HSP72 mRNA and both β-HAD (r = 0.61, P < 0.01) and CS (r = 0.65, P < 0.01). HSP72 mRNA was induced (P < 0.05) by the clamp in all groups. Although HO-1 mRNA was unaffected by the clamp in both the young and age-matched control subjects, it was increased (P < 0.05) ∼70-fold in the diabetic patients after the clamp. These data demonstrate that genes involved in providing cellular protection against oxidative stress are defective in patients with type 2 diabetes and correlate with insulin-stimulated glucose disposal and markers of muscle oxidative capacity. The data provide new evidence that the pathogenesis of type 2 diabetes involves perturbations to the antioxidant defense mechanism within skeletal muscle.

Skeletal muscle mitochondria : a major player in exercise, health and disease.

Maintaining skeletal muscle mitochondrial content and function is important for sustained health throughout the lifespan. Exercise stimulates important key stress signals that control skeletal mitochondrial biogenesis and function. Perturbations in mitochondrial content and function can directly or indirectly impact skeletal muscle function and consequently whole-body health and wellbeing.

Skeletal muscle reactive oxygen species: a target of good cop/bad cop for exercise and disease

Metabolic stresses associated with disease, ageing, and exercise increase the levels of reactive oxygen species (ROS) in skeletal muscle. These ROS have been linked mechanistically to adaptations in skeletal muscle that can be favourable (i.e. in response to exercise) or detrimental (i.e. in response to disease). The magnitude, duration (acute versus chronic), and cellular origin of the ROS are important underlying factors in determining the metabolic perturbations associated with the ROS produced in skeletal muscle. In particular, insulin resistance has been linked to excess ROS production in skeletal muscle mitochondria. A chronic excess of mitochondrial ROS can impair normal insulin signalling pathways and glucose disposal in skeletal muscle. In contrast, ROS produced in skeletal muscle in response to exercise has been linked to beneficial metabolic adaptations including mitochondrial biogenesis and muscle hypertrophy. Moreover, unlike insulin resistance, exercise-induced ROS appears to be primarily of non-mitochondrial origin. The present review summarizes the diverse ROS-targeted metabolic outcomes associated with insulin resistance versus exercise in skeletal muscle, thus, presenting two contrasting perspectives of pathologically harmful versus physiologically beneficial ROS. Here, we discuss the key sites of ROS production during exercise and the effect of ROS in skeletal muscle of people with type 2 diabetes.

Full-order observer design for nonlinear complex large-scale systems with unknown time-varying delayed interactions

This article is concerned with the problem of state observer for complex large-scale systems with unknown time-varying delayed interactions. The class of large-scale interconnected systems under consideration is subjected to interval time-varying delays and nonlinear perturbations. By introducing a set of argumented Lyapunov–Krasovskii functionals and using a new bounding estimation technique, novel delay-dependent conditions for existence of state observers with guaranteed exponential stability are derived in terms of linear matrix inequalities (LMIs). In our design approach, the set of full-order Luenberger-type state observers are systematically derived via the use of an efficient LMI-based algorithm. Numerical examples are given to illustrate the effectiveness of the result

Efficient design of polarization insensitive polymer optical waveguide devices considering stress-induced effects

We present an approach for the efficient design of polarization insensitive polymeric optical waveguide devices considering stress-induced effects. In this approach, the stresses induced in the waveguide during the fabrication process are estimated first using a more realistic model in the finite element analysis. Then we determine the perturbations in the material refractive indices caused by the stress-optic effect. It is observed that the stresses cause non-uniform optical anisotropy in the waveguide materials, which is then incorporated in the modal analysis considering a multilayer structure of waveguide. The approach is exploited in the design of a Bragg grating on strip waveguide. Excellent agreement between calculated and published experimental results confirms the feasibility of our approach in the accurate design of polarization insensitive polymer waveguide devices.