Enhanced Lacto-Tri-Peptide Bio-Availability by Co-Ingestion of Macronutrients

Some food-derived peptides possess bioactive properties, and may affect health positively. For example, the C-terminal lacto-tri-peptides Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP) and Val-Pro-Pro (VPP) (together named here XPP) are described to lower blood pressure. The bioactivity depends on their availability at the site of action. Quantitative trans-organ availability/kinetic measurements will provide more insight in C-terminal tri-peptides behavior in the body. We hypothesize that the composition of the meal will modify their systemic availability. We studied trans-organ XPP fluxes in catheterized pigs (25 kg; n=10) to determine systemic and portal availability, as well as renal and hepatic uptake of a water-based single dose of synthetic XPP and a XPP containing protein matrix (casein hydrolyte, CasH). In a second experiment (n=10), we compared the CasH-containing protein matrix with a CasH-containing meal matrix and the modifying effects of macronutrients in a meal on the availability (high carbohydrates, low quality protein, high fat, and fiber). Portal availability of synthetic XPP was 0.08 ± 0.01% of intake and increased when a protein matrix was present (respectively 3.1, 1.8 and 83 times for IPP, LPP and VPP). Difference between individual XPP was probably due to release from longer peptides. CasH prolonged portal bioavailability with 18 min (absorption half-life, synthetic XPP: 15 ± 2 min, CasH: 33 ± 3 min, p<0.0001) and increased systemic elimination with 20 min (synthetic XPP: 12 ± 2 min; CasH: 32 ± 3 min, p<0.0001). Subsequent renal and hepatic uptake is about 75% of the portal release. A meal containing CasH, increased portal 1.8 and systemic bioavailability 1.2 times. Low protein quality and fiber increased XPP systemic bioavailability further (respectively 1.5 and 1.4 times). We conclude that the amount and quality of the protein, and the presence of fiber in a meal, are the main factors that increase the systemic bioavailability of food-derived XPP.     

Some Like It Hot: Camera Traps Unravel the Effects of Weather Conditions and Predator Presence on the Activity Levels of Two Lizards

It is generally assumed that favourable weather conditions determine the activity levels of lizards, because of their temperature-dependent behavioural performance. Inactivity, however, might have a selective advantage over activity, as it could increase survival by reducing exposure to predators. Consequently, the effects of weather conditions on the activity patterns of lizards should be strongly influenced by the presence of predators. Using remote camera traps, we test the hypothesis that predator presence and weather conditions interact to modulate daily activity levels in two sedentary cordylid lizards, Karusasaurus polyzonus and Ouroborus cataphractus. While both species are closely related and have a fully overlapping distribution, the former is a fast-moving lightly armoured lizard, whereas the latter is a slow-moving heavily armoured lizard. The significant interspecific difference in antipredator morphology and consequently differential vulnerability to aerial and terrestrial predators, allowed us to unravel the effects of predation risk and weather conditions on activity levels. Our results demonstrate that K. polyzonus is predominantly active during summer, when ambient temperatures are favourable enough to permit activity. In contrast, a peak in activity during spring was observed in O. cataphractus, with individuals being inactive during most of summer. While favourable weather conditions had a strong effect on the activity levels of K. polyzonus, no such relationship was present in O. cataphractus. Contrary to our hypothesis, the presence of terrestrial predators does not seem to affect daily activity levels or alter the influence of weather conditions on activity levels. We conclude that inactivity in O. cataphractus appears to be related to seasonal differences in vulnerability to predators, rather than the presence of predators, and highlight the importance of additional selective pressures, such as food abundance, in determining the species’ activity levels.     

The Impact of Conservation Management on the Community Composition of Multiple Organism Groups in Eutrophic Interconnected Man-Made Ponds

Ponds throughout the world are subjected to a variety of management measures for purposes of biodiversity conservation. Current conservation efforts typically comprise a combination of multiple measures that directly and indirectly impact a wide range of organism groups. Knowledge of the relative impact of individual measures on different taxonomic groups is important for the development of effective conservation programs. We conducted a field study of 28 man-made ponds, representing four management types differing in the frequency of periodic pond drainage and the intensity of fish stock management. We disentangled the relative importance of direct and indirect effects of pond management measures on the community composition of phytoplankton, zooplankton, aquatic macro-invertebrates, submerged and emergent vascular plants. With the exception of phytoplankton, pond management had strong effects on the community composition of all investigated biota. Whether management affected communities directly or indirectly through its impact on fish communities or local environmental conditions in the pond varied between organism groups. Overall, the impact of pond drainage regime and fish community characteristics on the community composition of target organism groups were more important than local environmental conditions. The majority of taxa were negatively associated with fish density, whereas multiple emergent plant species and several taxa of aquatic macro-invertebrates were positively affected by increased drainage frequency. The effects of fish community and drainage tended to be largely independent. The present study indicates that pond drainage is an important element for biodiversity conservation in eutrophicated shallow and interconnected man-made ponds.     

Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers – Is There a Specific Role for Mast Cells?

Background

Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath.

Methods

Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test), measurement of fractional exhaled nitric oxide (FeNO) and pH/8-isoprostane in exhaled breath condensate (EBC). Lung tissue sections containing cancer-free large (LA) and small airways (SA) were stained for inflammatory cells. Mucosal (MC_T) respectively connective tissue mast cells (MC_TC) and interleukin-17A (IL-17A) expression by mast cells was analysed using a double-staining protocol.

Results

The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MC_T were higher in the lamina propria of SA compared to LA (MC_TC: 49 vs. 27.4 cells/mm²; MC_T: 162.5 vs. 35.4 cells/mm²; P<0.005 for both instances). IL-17A expression was predominantly detected in MC_TC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (r_s= -0.39), for the FEV₁% pred. (r_s= 0.37) and for FEV₁/FVC ratio (r_s=0.38) with MC_T in SA (P<0.05 for all instances). 8-isoprostane concentration correlated with the mast cells in the SA (r_s=0.44), there was no correlation for pH or FeNO with cellular distribution in SA.

Conclusions

Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the lack of correlation with lung function and exhaled breath parameters.     

The Berg-Purcell Limit Revisited

Biological systems often have to measure extremely low concentrations of chemicals with high precision. When dealing with such small numbers of molecules, the inevitable randomness of physical transport processes and binding reactions will limit the precision with which measurements can be made. An important question is what the lower bound on the noise would be in such measurements. Using the theory of diffusion-influenced reactions, we derive an analytical expression for the precision of concentration estimates that are obtained by monitoring the state of a receptor to which a diffusing ligand can bind. The variance in the estimate consists of two terms, one resulting from the intrinsic binding kinetics and the other from the diffusive arrival of ligand at the receptor. The latter term is identical to the fundamental limit derived by Berg and Purcell (Biophys. J., 1977), but disagrees with a more recent expression by Bialek and Setayeshgar. Comparing the theoretical predictions against results from particle-based simulations confirms the accuracy of the resulting expression and reaffirms the fundamental limit established by Berg and Purcell.     

Development of acaricide resistance in Pacific spider mite (<Emphasis Type="Italic">Tetranychus pacificus</Emphasis>) from California vineyards

In recent years, grape growers in California reported failures of acaricides against Tetranychus pacificus McGregor. We collected T. pacificus populations from four vineyards and tested them for resistance to bifenazate, propargite and pyridaben. In addition, we sequenced part of the cytochrome b gene of bifenazate-resistant and -susceptible T. pacificus to test for the presence of mutations reported to confer resistance to the congeneric T. urticae. None of the mutations conferring resistance to bifenazate in T. urticae were present in resistant T. pacificus. Resistance levels ranged from full susceptibility to statistically significant 11-fold resistance to pyridaben, sevenfold resistance to bifenazate and fourfold resistance to propargite compared to a susceptible population. Despite the relatively low levels of resistance detected, we estimated that under the conditions of our study the highest field rates of bifenazate and pyridaben application would cause less than 58 and 66% mortality of adult females in the most resistant populations, respectively. In contrast, field rates of propargite application would cause close to 100% mortality in the least susceptible population. These results highlight a potential link between resistance development and reduced field effectiveness for bifenazate and pyridaben. Finally, T. pacificus may be more tolerant to bifenazate and propargite than T. urticae, since the LC₅₀ values for the susceptible population of T. pacificus were several times higher than LC₅₀’s reported for susceptible T. urticae.     

Accurate SNP and mutation detection by targeted custom microarray-based genomic enrichment of short-fragment sequencing libraries

Microarray-based enrichment of selected genomic loci is a powerful method for genome complexity reduction for next-generation sequencing. Since the vast majority of exons in vertebrate genomes are smaller than 150 nt, we explored the use of short fragment libraries (85–110 bp) to achieve higher enrichment specificity by reducing carryover and adverse effects of flanking intronic sequences. High enrichment specificity (60–75%) was obtained with a relative even base coverage. Up to 98% of the target-sequence was covered more than 20× at an average coverage depth of about 200×. To verify the accuracy of SNP/mutation detection, we evaluated 384 known non-reference SNPs in the targeted regions. At ∼200× average sequence coverage, we were able to survey 96.4% of 1.69 Mb of genomic sequence with only 4.2% false negative calls, mostly due to low coverage. Using the same settings, a total of 1197 novel candidate variants were detected. Verification experiments revealed only eight false positive calls, indicating an overall false positive rate of less than 1 per ∼200 000 bp. Taken together, short fragment libraries provide highly efficient and flexible enrichment of exonic targets and yield relatively even base coverage, which facilitates accurate SNP and mutation detection. Raw sequencing data, alignment files and called SNPs have been submitted into GEO database http://www.ncbi.nlm.nih.gov/geo/ with accession number {"type":"entrez-geo","attrs":{"text":"GSE18542","term_id":"18542"}}GSE18542.     

Mode of action of adjuvants: Implications for vaccine safety and design

For decades, the search for new vaccine adjuvants has been largely empirical. A series of new adjuvants and related formulations are now emerging that are acting through identified immunological mechanisms. Understanding adjuvant mechanism of action is crucial for vaccine design, since this allows for directing immune responses towards efficacious disease-specific effector mechanisms and appropriate memory. It is also of great importance to build new paradigms for assessing adjuvant safety at development stages and at regulatory level. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference, organized by the International Association for Biologicals (IABS), on the mode of action of adjuvants on 29–30 April 2010 in Bethesda, Maryland, USA, particularly focusing on how understanding adjuvants mode of action can impact on the assessment of vaccine safety and help to develop target-specific vaccines. More information on the conference output can be found on the IABS website, http://www.iabs.org/.     

Foetal and adult cardiomyocyte progenitor cells have different developmental potential

In the past years, cardiovascular progenitor cells have been isolated from the human heart and characterized. Up to date, no studies have been reported in which the developmental potential of foetal and adult cardiovascular progenitors was tested simultaneously. However, intrinsic differences will likely affect interpretations regarding progenitor cell potential and application for regenerative medicine. Here we report a direct comparison between human foetal and adult heart‐derived cardiomyocyte progenitor cells (CMPCs). We show that foetal and adult CMPCs have distinct preferences to differentiate into mesodermal lineages. Under pro‐angiogenic conditions, foetal CMPCs form more endothelial but less smooth muscle cells than adult CMPCs. Foetal CMPCs can also develop towards adipocytes, whereas neither foetal nor adult CMPCs show significant osteogenic differentiation. Interestingly, although both cell types differentiate into heart muscle cells, adult CMPCs give rise to electrophysiologically more mature cardiomyocytes than foetal CMPCs. Taken together, foetal CMPCs are suitable for molecular cell biology and developmental studies. The potential of adult CMPCs to form mature cardiomyocytes and smooth muscle cells may be essential for cardiac repair after transplantation into the injured heart.