Contribution of stretch to the change of activation properties of muscle fibers in the diaphragm at the transition from fetal to neonatal life

The transition from fetal to postnatal life involves clearance of liquid from the lung and airways, and rapid formation of a functional residual capacity. Despite the importance of the diaphragm in this process, the impact of birth on the mechanical and functional activity of its muscle fibers is not known. This study determined the contractile characteristics of individual “skinned” diaphragm fibers from 70 days (0.47) gestation to after birth in sheep. Based on differential sensitivity to the divalent ions calcium (Ca²⁺) and strontium (Sr²⁺), all fibers in the fetal diaphragm were classified as “fast,” whereas fibers from the adult sheep diaphragm exhibited a “hybrid” phenotype where both “fast” and “slow” characteristics were present within each single fiber. Transition to the hybrid phenotype occurred at birth, was evident after only 40 min of spontaneous breathing, and could be induced by simple mechanical stretch of diaphragm fibers from near-term fetuses (∼147 days gestation). Both physical stretch of isolated fibers, and mechanical ventilation of the fetal diaphragm in situ, significantly increased sensitivity to Ca²⁺ and Sr²⁺, maximum force generating capacity, and decreased passive tension in near-term and preterm fetuses; however, only fibers from near-term fetuses showed a complete transition to a “hybrid” activation profile. These findings suggest that stretch associated with the transition from a liquid to air-filled lung at birth induces physical changes of proteins determining the activation and elastic properties of the diaphragm. These changes may allow the diaphragm to meet the increased mechanical demands of breathing immediately after birth.

The effect of resistance training on functional capacity and quality of life in individuals with high and low number of metabolic risk factors

OBJECTIVE—There are limited data on the effects of resistance training on the capacity to perform activities of daily living (ADLs) and quality of life (QoL) for individuals with a high number of metabolic risk factors (HiMF). In this study, we examined the effect of resistance training on the capacity to perform ADLs and QoL in individuals with HiMF and compared any benefits with individuals with a low number of metabolic risk factors (LoMF).

RESEARCH DESIGN AND METHODS—Fifty-five untrained individuals, aged 50.8 ± 6.5 years, were randomized to four groups: HiMF training (HiMFT), HiMF control, LoMF training (LoMFT), and LoMF control. At baseline and after 10 weeks of resistance training, participants underwent anthropometric measurements and assessments of aerobic power (Vo2peak), muscle strength, capacity to perform ADLs, and a self-perceived QoL questionnaire. A repeated-measures ANOVA was used to examine the effect of training over time among groups.

RESULTS—Training increased lean body mass in both HiMFT (P = 0.03) and LoMFT (P = 0.03) groups. Total fat content and Vo2peak improved in the LoMFT group only. Muscle strength improved in both training groups (P < 0.01). Time to complete ADLs was reduced by 8.8% in the LoMFT group (P < 0.01) and 9.7% in the HiMF group (P < 0.01). Only the HiMFT group reported improvement in QoL.

CONCLUSIONS— Resistance training improved muscle strength and the capacity to perform ADLs in individuals with HiMF and LoMF. Resistance training improved QoL for the HiMF group, and this result was independent of changes in body fat content or aerobic power. Longer training regimens may be needed to improve QoL in individuals with LoMF.

Functional capacity and quality of life in middle-age men and women with high and low number of metabolic risk factors

It is not clear if men and women with high numbers of risk factors (HiMF) for metabolic syndrome (MetS) have impaired capacities to perform activities of daily living (ADL's) and lower quality of life (QoL) in the absence of symptomatic heart disease. Our results indicate that in women there is a correlation between the number of risk factors and the capacity to perform ADL's and QoL. This was not evident for men. These findings may partly explain why women tend to consult healthcare practitioners earlier in the disease process than men.

Minimal-order functional observer-based residual generators for fault detection and isolation of dynamical systems

This paper examines the design of minimal-order residual generators for the purpose of detecting and isolating actuator and/or component faults in dynamical systems. We first derive existence conditions and design residual generators using only first-order observers to detect and identify the faults. When the first-order functional observers do not exist, then based on a parametric approach to the solution of a generalized Sylvester matrix equation, we develop systematic procedures for designing residual generators utilizing minimal-order functional observers. Our design approach gives lower-order residual generators than existing results in the literature. The advantages for having such lower-order residual generators are obvious from the economical and practical points of view as cost saving and simplicity in implementation can be achieved, particularly when dealing with high-order complex systems. Numerical examples are given to illustrate the proposed fault detection and isolation schemes. In all of the numerical examples, we design minimum-order residual generators to effectively detect and isolate actuator and/or component faults in the system.

Functional analysis of natriuretic peptide receptors in the bladder of the toad, bufo marinus

This study aimed to localize and characterize natriuretic peptide binding sites in the urinary bladder of Bufo marinus and to then examine the effect of natriuretic peptides on the bladder vascular tone and water reabsorption in isolated perfused bladder preparations. Specific ¹²⁵I-rat atrial natriuretic peptide (¹²⁵I-rANP) binding sites were present on blood vessels, muscle, and epithelium. In tissue sections and/or isolated membranes, the binding was completely displaced by frog ANP, rat ANP, and porcine C-type natriuretic peptide (CNP; membranes only). However, a reduction in binding was observed after incubation with ¹²⁵I-rANP and 1 μM of the natriuretic peptide receptor-C (NPR-C) ligand C-ANF, but residual binding remained suggesting the presence of two distinct binding sites. Electrophoresis of bladder membranes cross-linked to ¹²⁵I-rANP identified two bands at approximately 70 and 140 kDa that correspond to the monomeric mass of NPR-C and the guanylate cyclase receptors, respectively. Furthermore, the presence of natriuretic peptide receptor-A and NPR-C mRNA in the bladder was demonstrated with reverse transcription–polymerase chain reaction. In addition, rat ANP, frog ANP, and porcine CNP stimulated a significant increase in cGMP generation in bladder membrane preparations, which indicated the presence of guanylate cyclase-linked receptors. In perfused bladder preparations, arginine vasotocin increased perfusion pressure and water permeability. The infusion of frog ANP or porcine CNP failed to alter perfusion pressure or water reabsorption in the presence or absence of arginine vasotocin. This study identified a well-developed natriuretic peptide receptor system in the urinary bladder of B. marinus but the function of the receptors remains unclear.

Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia

Most severe congenital neutropenia (SCN) cases possess constitutive neutrophil elastase mutations; a smaller cohort has acquired mutations truncating the granulocyte colony-stimulating factor receptor (G-CSF-R). We have described a case with constitutive extracellular G-CSF-R mutation hyporesponsive to ligand. Here we report two independent acquired G-CSF-R truncation mutations and a novel constitutive neutrophil elastase mutation in this patient. Co-expression of a truncated receptor chain restored STAT5 signalling responses of the extracellular G-CSF-R mutant, while constitutively-active STAT5 enhanced its proliferative capacity. These data add to our knowledge of SCN and further highlight the importance of STAT5 in mediating proliferative responses to G-CSF.

Retrodicting patch use by foraging swans in a heterogeneous environment using a set of functional responses

Effective conservation of important bird areas requires insight in the number of birds an area can support, and how this carrying capacity changes with habitat modifications. When food depletion is the dominant mechanism of competition, it should in principle be possible to calculate the total time foragers can spend per patch from their functional response (intake rate as a function of food density). However, in the field there are likely to be factors modulating the functional response. In this study previously published results of experiments on captive Bewick's swans were used to obtain functional responses of swans digging for tubers of Fennel pondweed on different foraging substrates: sandy and clayey sediment, and in shallow and deep water. In a field study, four 250×250 m sections belonging to different types (sandy–shallow, clayey–shallow, sandy–deep and clayey–deep) were delineated. Here tubers were sampled with sediment corers in three years, both before and after swan exploitation in autumn, and swans were observed and mapped from a hide in two of these years. Giving-up tuber biomass densities varied among sections. Substitution of these giving-up densities in the derived patch-type-specific functional responses yielded the quitting net energy intake rates in the four sections. As expected from the marginal value theorem, the quitting net energy intake rates did not vary among sections. Moreover, the observed foraging pressure (total foraging time per area) per patch type was in quantitative agreement with the integrated functional responses. These results suggest that in spatially heterogeneous environments, patch exploitation by foragers can be predicted from their functional responses after accounting for foraging substrate.

COMT Val158Met and 5HTTLPR functional loci interact to predict anxiety across adolescence : results from the Victorian Adolescent Health Cohort Study (1992-2006)

We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val158Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose–response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met158 [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76–0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79–0.99, P = 0.033). There was no evidence for a dose–response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29–0.70, P < 0.001) among carriers homozygous for both the COMT Met158 and the 5HTTLPR Short alleles (Met158Met + Short-Short) compared with the remaining cohort. The double-recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.

Functional characterization of the twin ZIP/SLC39 metal transporters, NpunF3111 and NpunF2202 in Nostoc punctiforme

The ZIP family of metal transporters is involved in the transport of Zn2+ and other metal cations from the extracellular environment and/or organelles into the cytoplasm of prokaryotes, eukaryotes and archaeotes. In the present study, we identified twin ZIP transporters, Zip11 (Npun_F3111) and Zip63 (Npun_F2202) encoded within the genome of the filamentous cyanobacterium, Nostoc punctiforme PCC73120. Sequence-based analyses and structural predictions confirmed that these cyanobacterial transporters belong to the SLC39 subfamily of metal transporters. Quantitative real-time (QRT)-PCR analyses suggested that the enzymes encoded by zip11 and zip63 have a broad allocrite range that includes zinc as well as cadmium, cobalt, copper, manganese and nickel. Inactivation of either zip11 or zip63 via insertional mutagenesis in N. punctiforme resulted in reduced expression of both genes, highlighting a possible co-regulation mechanism. Uptake experiments using 65Zn demonstrated that both zip mutants had diminished zinc uptake capacity, with the deletion of zip11 resulting in the greatest overall reduction in 65Zn uptake. Over-expression of Zip11 and Zip63 in an E. coli mutant strain (ZupT736::kan) restored divalent metal cation uptake, providing further evidence that these transporters are involved in Zn uptake in N. punctiforme. Our findings show the functional role of these twin metal uptake transporters in N. punctiforme, which are independently expressed in the presence of an array of metals. Both Zip11 and Zip63 are required for the maintenance of homeostatic levels of intracellular zinc N. punctiforme, although Zip11 appears to be the primary zinc transporter in this cyanobacterium, both ZIP's may be part of a larger metal uptake system with shared regulatory elements.

Effect of sorghum flour addition on resistant starch content, phenolic profile and antioxidant capacity of durum wheat pasta

Foods containing elevated levels of health functional components such as resistant starch and polyphenolic antioxidants may have beneficial effects on human health. Pasta incorporating either red sorghum flour (RSF) or white sorghum flour (WSF) each at 20%, 30% and 40% substitution of durum wheat semolina (DWS) was prepared and compared to pasta made from 100% DWS (control) for content of starch fractions, phenolic profile and antioxidant capacity, before and after cooking. Total, digestible and resistant starch contents were determined by the AOAC method; individual phenolic acids and anthocyanins by reverse phase-HPLC analysis; total phenolic content by the Folin–Ciocalteu method and antioxidant capacity by the ABTS assay. The addition of both RSF and WSF increased the resistant starch content, bound phenolic acids, total phenolic content and antioxidant capacity at all incorporation levels compared to the control pasta; while free phenolic acids and anthocyanins were higher in the RSF-containing pasta only. Cooking did not change the resistant starch content of any of the pasta formulations. Cooking did however decrease the free phenolic acids, anthocyanins, total phenolic content and antioxidant capacity and increased the bound phenolic acids of the sorghum-containing pastas. The study suggests that these sorghum flours may be very useful for the preparation of pasta with increased levels of resistant starch and polyphenolic antioxidants.

Fault detection for dynamical systems using first-order functional observers

This paper reports a new result on the fault detection of dynamical systems by employing only first-order functional observers. Indeed, we show that fault detection can be achieved by utilizing first-order functional observers. The advantages for having such simple structured observers are obvious from the economical and practical points of view as significant cost saving can be achieved. We derive existence conditions and an algorithm for the generation of residual signals to detect faults using firstorder functional observers. Two numerical examples are given to illustrate the proposed fault detection scheme. In one of the examples, a two-area interconnected power system with reheat thermal turbines is considered where only a first-order functional observer is designed to detect faults in the power system.

The A622 gene in Nicotiana glauca (tree tobacco): evidence for a functional role in pyridine alkaloid synthesis

Nicotiana glauca (Argentinean tree tobacco) is atypical within the genus Nicotiana, accumulating predominantly anabasine rather than nicotine and/or nornicotine as the main component of its leaf pyridine alkaloid fraction. The current study examines the role of the A622 gene from N. glauca (NgA622) in alkaloid production and utilises an RNAi approach to down-regulate gene expression and diminish levels of A622 protein in transgenic tissues. Results indicate that RNAi-mediated reduction in A622 transcript levels markedly reduces the capacity of N. glauca to produce anabasine resulting in plants with scarcely any pyridine alkaloids in leaf tissues, even after damage to apical tissues. In addition, analysis of hairy roots containing the NgA622-RNAi construct shows a substantial reduction in both anabasine and nicotine levels within these tissues, even if stimulated with methyl jasmonate, indicating a role for the A622 enzyme in the synthesis of both alkaloids in roots of N. glauca. Feeding of Nicotinic Acid (NA) to hairy roots of N. glauca containing the NgA622-RNAi construct did not restore capacity for synthesis of anabasine or nicotine. Moreover, treatment of these hairy root lines with NA did not lead to an increase in anatabine levels, unlike controls. Together, these results strongly suggest that A622 is an integral component of the final enzyme complex responsible for biosynthesis of all three pyridine alkaloids in Nicotiana.

Legal issues: minors' decision-making capacity to refuse life-saving and life-sustaining treatment: legal and psychiatric perspectives

Laws in Belgium and the Netherlands permit euthanasia and assisted suicide for seriously ill children who experience "constant and unbearable suffering" – they have the capacity to request death by lethal injection if they convey a "reasonable understanding of the consequences" of that request. The child's capacity to understand death is therefore a prerequisite to the implementation of the request. However, modern neuro-psychological and fMRI (functional Magnetic Resonance Imaging) studies of the relationship between the neuro-anatomical development of the brain in human beings and their emotional and experiential capacity, demonstrates that both are not fully developed until the early 20s for girls and mid-20s for boys. Unlike Belgium and the Netherlands, the clinical and legal implications of the immaturity of the brain on medical decision-making of minors, in particular life and death decisions, have been implicit in the Australian courts' approach to the refusal of life-saving and life-sustaining treatment by minors. This approach is exemplified by X v Sydney Children's Hospitals Network [2013] NSWCA 320 (and a series of earlier cases).

Improved contact load-bearing capacity of ultra-fine grained titanium : Multilayering and grading

The contact load-bearing response and surface damage resistance of multilayered hierarchical structured (MHSed) titanium were determined and compared to monolithic nanostructured titanium. The MHS structure was formed by combining cryorolling with a subsequent Surface Mechanical Attrition Treatment (SMAT) producing a surface structure consisted of an outer amorphous layer containing nanocrystals, an inner nanostructured layer and finally an ultra-fine grained core. The combination of a hard outer layer, a gradual transition layer and a compliant core results in reduced indentation depth, but a deeper and more diffuse sub-surface plastic deformation zone, compared to the monolithic nanostructured Ti. The redistribution of surface loading between the successive layers in the MHS Ti resulted in the suppression of cracking, whereas the monolithic nanograined (NG) Ti exhibited sub-surface cracks at the boundary of the plastic strain field. Finite element models with discrete layers and mechanically graded layersrepresenting the MHS system confirmed the absence of cracking and revealed a 38% decrease in shear stress in the sub-surface plastic strain field, compared to the monolithic NG Ti. Further, the mechanical gradation achieves a more gradual stress distribution which mitigates the interface failure and increases the interfacial toughness, thus providing strong resistance to loading damage. © 2014 Elsevier Ltd.