Effect of dietary fibre type on physical activity and behaviour in kennelled dogs

Dog diets may differ in their effectiveness of maintaining satiety after a meal. Consequently, sensations of hunger, feeding motivation, physical activity, and sensitivity to environmental stressors may be increased. Dietary fibre may be effective in prolonging postprandial satiety depending on type and inclusion level. This study evaluated the effect of fibre fermentability on behaviour in dogs. Sixteen healthy adult dogs were housed individually and fed a low-fermentable fibre (LFF) diet containing 8.5% cellulose or a high-fermentable fibre (HFF) diet containing 8.5% sugar beet pulp and 2% inulin. Dogs were fed two equal portions at 8:30 and 18:30 according to energy requirements. Behaviour of dogs in their home-cage was recorded and analyzed by instantaneous scan sampling (2 × 24 h with 15 min intervals) and focal sampling continuous recordings (10 min per animal per hour, from 9:00 until 18:00). Dogs were subjected to a behaviour test composed of the subtests open-field, sudden-silence, novel-object, and acoustic-startle. The behavioural responses of each dog were recorded. Scores for the scan and focal samples were expressed per clock hour and DIET × TIME effects were tested statistically using Residual Maximum Likelihood (REML). Data from the tests were examined using principal component analysis resulting in the compilation of two components. Data were tested statistically for DIET and DIET × SUBTEST effects using REML. Variables specific for the open-field and novel-object test were analyzed using analysis of variance. For the scans, a significant DIET × TIME effect was found for resting. At night and in the morning, HFF dogs rested more compared to LFF dogs, but they rested less between 14:00 and 17:00. For the continuous recordings, the main findings were a tendency for DIET × TIME effect for time spent resting with a pattern consistent with that for the scans. The interaction was significant for inactive-alert (lie with head up or sitting) with HFF-fed dogs having lower values around 10:00–11:00 and higher values hereafter. Finally, time spent tail wagging was significantly higher for LFF-fed dogs just before the evening meal that may indicate higher level of arousal. For the behaviour tests, no significant DIET or DIET × SUBTEST effects were detected. It is concluded that compared to the LFF diet, the HFF diet increased inactivity in kennelled beagle dogs likely through the prolongation of postprandial satiety. This effect did not change the reaction to stressful events in kennelled laboratory dogs. Enhanced susceptibility to environmental stressors at times of hunger in sensitive companion dogs may occur but requires further study.     

NepA is a structural cell wall protein involved in maintenance of spore dormancy in Streptomyces coelicolor

Streptomycetes have a complex morphogenetic programme culminating in the formation of aerial hyphae that develop into chains of spores. After spore dispersal, environmental signals trigger dormant spores to germinate to establish a new colony. We here compared whole genome expression of a wild-type colony of Streptomyces coelicolor forming aerial hyphae and spores with that of the chp null mutant that forms few aerial structures. This revealed that expression of 244 genes was significantly altered, among which genes known to be involved in development. One of the genes that was no longer expressed in the Δ chpABCDEFGH mutant was nepA , which was previously shown to be expressed in a compartment connecting the substrate mycelium with the sporulating parts of the aerial mycelium. We here show that expression is also detected in developing spore chains, where NepA is secreted to end up as a highly insoluble protein in the cell wall. Germination of spores of a nepA deletion mutant was faster and more synchronous, resulting in colonies with an accelerated morphogenetic programme. Crucially, spores of the Δ nepA mutant also germinated in water, unlike those of the wild-type strain. Taken together, NepA is the first bacterial structural cell wall protein that is important for maintenance of spore dormancy under unfavourable environmental conditions.     

Biocatalytic cascade oxidation using laccase for pyranose 2-oxidase regeneration

The interactions between two oxidoreductases coupled by an artificial redox mediator have been described quantitatively to increase both stability and productivity. In this cascade oxidation, pyranose 2-oxidase oxidizes several aldoses at the C-2 position to 2-ketoaldoses. A redox mediator is used as electron acceptor for pyranose 2-oxidase because it shows more favourable kinetics in comparison to oxygen. The reduced redox mediator is in turn re-oxidized by laccase, which uses oxygen as the terminal electron acceptor, reducing it fully to water. However, pyranose 2-oxidase is capable of using oxygen as an electron acceptor in a competing side reaction, leading to the formation of hydrogen peroxide, which is detrimental for both enzymes and seriously limits the operational stability of both enzymes.The experimental results showed full conversion of the aldose to the 2-ketoaldose and a good agreement with the simulations of the process.     

Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed.     

Reduced Glomerular Filtration Rate and Its Association with Clinical Outcome in Older Patients at Risk of Vascular Events: Secondary Analysis

Background

Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

Methods and Findings

Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ([20–40], [40–50], [50–60]) ≥ 60 ml/min/1.73 m². Baseline risk factors were analysed by category of eGFR, with and without adjustment for other risk factors. The associations between baseline eGFR and morbidity and mortality outcomes, accrued after an average of 3.2 y, were investigated using Cox proportional hazard models adjusting for traditional risk factors. We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status. Age, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index, fasting glucose, female sex, histories of hypertension and vascular disease were associated with eGFR (p = 0.001 or less) after adjustment for other risk factors. Low eGFR was independently associated with risk of all cause mortality, vascular mortality, and other noncancer mortality and with fatal and nonfatal coronary and heart failure events (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals [CIs]) for eGFR < 40 ml/min/1.73m² relative to eGFR ≥ 60 ml/min/1.73m² respectively 2.04 (1.48–2.80), 2.37 (1.53–3.67), 3.52 (1.78–6.96), 1.64 (1.18–2.27), 3.31 (2.03–5.41). There were no nominally statistically significant interactions (p < 0.05) between randomized treatment allocation and eGFR for clinical outcomes, with the exception of the outcome of coronary heart disease death or nonfatal myocardial infarction (p = 0.021), with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs.

Conclusions

We have established that, in an elderly population over the age of 70 y, impaired GFR is associated with female sex, with presence of vascular disease, and with levels of other risk factors that would be associated with increased risk of vascular disease. Further, impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes. Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin.     

Genetical metabolomics of flavonoid biosynthesis in Populus: a case study

Genetical metabolomics [metabolite profiling combined with quantitative trait locus (QTL) analysis] has been proposed as a new tool to identify loci that control metabolite abundances. This concept was evaluated in a case study with the model tree Populus. Using HPLC, the peak abundances were analyzed of 15 closely related flavonoids present in apical tissues of two full-sib poplar families, Populus deltoides cv. S9-2 x P. nigra cv. Ghoy and P. deltoides cv. S9-2 x P. trichocarpa cv. V24, and correlation and QTL analysis were used to detect flux control points in flavonoid biosynthesis. Four robust metabolite quantitative trait loci (mQTL), associated with rate-limiting steps in flavonoid biosynthesis, were mapped. Each mQTL was involved in the flux control to one or two flavonoids. Based on the identities of the affected metabolites and the flavonoid pathway structure, a tentative function was assigned to three of these mQTL, and the corresponding candidate genes were mapped. The data indicate that the combination of metabolite profiling with QTL analysis is a valuable tool to identify control points in a complex metabolic pathway of closely related compounds.     

Specific Visualization of Glioma Cells in Living Low-Grade Tumor Tissue

Background

The current therapy of malignant gliomas is based on surgical resection, radio-chemotherapy and chemotherapy. Recent retrospective case-series have highlighted the significance of the extent of resection as a prognostic factor predicting the course of the disease. Complete resection in low-grade gliomas that show no MRI-enhanced images are especially difficult. The aim in this study was to develop a robust, specific, new fluorescent probe for glioma cells that is easy to apply to live tumor biopsies and could identify tumor cells from normal brain cells at all levels of magnification.

Methodology/Principal Findings

In this investigation we employed brightly fluorescent, photostable quantum dots (QDs) to specifically target epidermal growth factor receptor (EGFR) that is upregulated in many gliomas. Living glioma and normal cells or tissue biopsies were incubated with QDs coupled to EGF and/or monoclonal antibodies against EGFR for 30 minutes, washed and imaged. The data include results from cell-culture, animal model and ex vivo human tumor biopsies of both low-grade and high-grade gliomas and show high probe specificity. Tumor cells could be visualized from the macroscopic to single cell level with contrast ratios as high as 1000: 1 compared to normal brain tissue.

Conclusions/Significance

The ability of the targeted probes to clearly distinguish tumor cells in low-grade tumor biopsies, where no enhanced MRI image was obtained, demonstrates the great potential of the method. We propose that future application of specifically targeted fluorescent particles during surgery could allow intraoperative guidance for the removal of residual tumor cells from the resection cavity and thus increase patient survival.     

Extended foot-ankle musculoskeletal models for application in movement analysis

Multibody simulations of human motion require representative models of the anatomical structures. A model that captures the complexity of the foot is still lacking. In the present work, two detailed 3D multibody foot-ankle models generated based on CT scans using a semi-automatic tool are described. The proposed models consists of five rigid segments (talus, calcaneus, midfoot, forefoot and toes), connected by five joints (ankle, subtalar, midtarsal, tarsometatarsal and metatarsophalangeal), one with 15DOF and the other with 8DOF. The calculated kinematics of both models were evaluated using gait trials and compared against literature, both presenting realistic results. An inverse dynamic analysis was performed for the 8DOF model, again presenting feasible dynamic results.     

Dynamics of a <Emphasis Type="Italic">Limecola</Emphasis> (<Emphasis Type="Italic">Macoma</Emphasis>) <Emphasis Type="Italic">balthica</Emphasis> population in a tidal flat area in the western Wadden Sea: effects of declining survival and recruitment

We followed the dynamics of the population of the bivalve Limecola (Macoma) balthica in the westernmost part of the Wadden Sea by monitoring for 44 years (1973–2016) its numbers and age composition at 15 sites in a 50-km² tidal-flat area. During the first half of this period, the annual recruitment and adult survival were at a relatively constant level, resulting in rather constant numbers. During the second half of the observation period, annual recruitment and adult survival showed declining trends, resulting in seriously reduced adult abundance. Sudden substantial reductions in adult survival started around 1996 at a few sites to spread over the entire area within 5 years, like an infectious disease. The resulting small adult stocks produced small numbers of recruits. The stock–recruitment curve showed an increasing part up to about 30 adults m^?2, followed by invariably successful recruitments at > 40 adults m^?2. Both recruitment and adult survival were negatively related to water temperatures. However, elevated temperatures after 1997 could not explain the very low survival rates observed after 1996 and the very low recruitment success after 2003. So far, recovery of the population has hardly taken place, with both recruitment and adult survival at lower levels than observed for the initial stable period.     

A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle

Clinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has been lacking. Herein, we mapped, fine-mapped, and discovered the putative causal variant underlying this CM resistance QTL in the Dutch dairy cattle population. We identified a ~12 kb multi-allelic copy number variant (CNV), that is in perfect linkage disequilibrium with a lead SNP, as a promising candidate variant. By implementing a fine-mapping and through expression QTL mapping, we showed that the group-specific component gene (GC), a gene encoding a vitamin D binding protein, is an excellent candidate causal gene for the QTL. The multiplicated alleles are associated with increased GC expression and low CM resistance. Ample evidence from functional genomics data supports the presence of an enhancer within this CNV, which would exert cis-regulatory effect on GC. We observed that strong positive selection swept the region near the CNV, and haplotypes associated with the multiplicated allele were strongly selected for. Moreover, the multiplicated allele showed pleiotropic effects for increased milk yield and reduced fertility, hinting that a shared underlying biology for these effects may revolve around the vitamin D pathway. These findings together suggest a putative causal variant of a CM resistance QTL, where a cis-regulatory element located within a CNV can alter gene expression and affect multiple economically important traits.