Polymerase-catalyzed synthesis of DNA from phosphoramidate conjugates of deoxynucleotides and amino acids

Some selected amino acids, in particular l-aspartic acid (l-Asp) and l-histidine (l-His), can function as leaving group during polymerase-catalyzed incorporation of deoxyadenosine monophosphate (dAMP) in DNA. Although l-Asp-dAMP and l-His-dAMP bind, most probably, in a different way in the active site of the enzyme, aspartic acid and histidine can be considered as mimics of the pyrophosphate moiety of deoxyadenosine triphosphate. l-Aspartic acid is more efficient than d-aspartic acid as leaving group. Such P-N conjugates of amino acids and deoxynucleotides provide a novel experimental ground for diversifying nucleic acid metabolism in the field of synthetic biology

Elastic modulus of tree frog adhesive toe pads

Previous work using an atomic force microscope in nanoindenter mode indicated that the outer, 10- to 15-μm thick, keratinised layer of tree frog toe pads has a modulus of elasticity equivalent to silicone rubber (5–15 MPa) (Scholz et al. 2009), but gave no information on the physical properties of deeper structures. In this study, micro-indentation is used to measure the stiffness of whole toe pads of the tree frog, Litoria caerulea. We show here that tree frog toe pads are amongst the softest of biological structures (effective elastic modulus 4–25 kPa), and that they exhibit a gradient of stiffness, being stiffest on the outside. This stiffness gradient results from the presence of a dense network of capillaries lying beneath the pad epidermis, which probably has a shock absorbing function. Additionally, we compare the physical properties (elastic modulus, work of adhesion, pull-off force) of the toe pads of immature and adult frogs

A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project

Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don't always mimic human physiology due to species-specific differences. Several efforts have been made to predict medication transfer into the milk based on physicochemical characteristics. However, the role of transporter proteins and several physiological factors (e.g., variable milk lipid content) are not accounted for by these methods. Physiologically-based pharmacokinetic (PBPK) modelling offers a mechanism-oriented strategy with bio-relevance. Recently, lactation PBPK models have been reported for some medications, showing at least the feasibility and value of PBP

Gender‐dependent association between exhaled nitric oxide and the CC16 38AA genotype in young school children

Background Studies that investigated the association between the CC16 A38G polymorphism and the risk of asthma yielded conflicting results. The aim of this study among schoolchildren was to assess the relationships of CC16 A38G polymorphism with aeroallergen sensitization and fractional exhaled nitric oxide (FeNO), two outcomes predicting asthma later in&nbsp;life. Methods The study included 139 children (72 boys), median age of 7.7. Information on each child&#8217;s health, lifestyle, and environment was collected through a questionnaire completed by their parents. CC16 genotypes were determined using urinary DNA. We measured FeNO, the CC16 protein in urine and nasal lavage fluid and aeroallergen‐specific immunoglobulin E in nasal mucosa&nbsp;fluid. Results Children with the homozygous mutant CC16 38AA genotype had higher odds of increased FeNO (&gt;30 ppb) compared with their peers with the wild‐type genotype 38GG (OR, 9.85; 95% CI, 2.09‐46.4;&nbsp;P = .004). This association was female gender specific (P = .002) not being observed in boys (P = .40). It was also independent of allergic sensitization, which yet emerged as the strongest predictor of FeNO along with the use of bleach for house cleaning. Children with the CC16 38AA genotype had lower covariates‐adjusted urinary CC16 levels than those with 38GG (median, μg/L, 1.17 vs&nbsp;2.08,&nbsp;P = .02). Conclusion Our study suggests that the CC16 38AA allele promotes airway inflammation as measured by FeNO through a gender‐dependent association. Deficient levels of CC16 in the deep lung, measured noninvasively in urine, as a possible proxy for serum CC16, might underlie this promoting&nbsp;effect.</p