Ex vivo proton spectroscopy (1 H-NMR) analysis of inborn errors of metabolism: Automatic and computer-assisted analyses.

There are about 1500 genetic metabolic diseases. A small number of treatable diseases are diagnosed by newborn screening programs, which are continually being developed. However, most diseases can only be diagnosed based on clinical symptoms or metabolic findings. The main biological fluids used are urine, plasma and, in special situations, cerebrospinal fluid. In contrast to commonly used methods such as gas chromatography and high performance liquid chromatography mass spectrometry, ex vivo proton spectroscopy (1 H-NMR) is not yet used in routine clinical practice, although it has been recommended for more than 30 years. Automatic analysis and improved NMR technology have also expanded the applications used for the diagnosis of inborn errors of metabolism. We provide a mini-overview of typical applications, especially in urine but also in plasma, used to diagnose common but also rare genetic metabolic diseases with 1 H-NMR. The use of computer-assisted diagnostic suggestions can facilitate interpretation of the profiles. In a proof of principle, to date, 182 reports of 59 different diseases and 500 reports of healthy children are stored. The percentage of correct automatic diagnoses was 74%. Using the same 1 H-NMR profile-targeted analysis, it is possible to apply an untargeted approach that distinguishes profile differences from healthy individuals. Thus, additional conditions such as lysosomal storage diseases or drug interferences are detectable. Furthermore, because 1 H-NMR is highly reproducible and can detect a variety of different substance categories, the metabolomic approach is suitable for monitoring patient treatment and revealing additional factors such as nutrition and microbiome metabolism. Besides the progress in analytical techniques, a multiomics approach is most effective to combine metabolomics with, for example, whole exome sequencing, to also diagnose patients with nondetectable metabolic abnormalities in biological fluids. In this mini review we also provide our own data to demonstrate the role of NMR in a multiomics platform in the field of inborn errors of metabolism.

Affective Cortical Asymmetry at the Early Developmental Emergence of Emotional Expression.

Emotions have an important survival function. Vast amounts of research have demonstrated how affect-related changes in physiology promote survival by effecting short-term and long-term changes in adaptive behavior. However, if emotions truly serve such an inherent function, they should be pervasive across species and be established early in life. Here, using electroencephalographic (EEG) brain activity we sought to characterize core neurophysiological features underlying affective function at the emergence of emotional expression [i.e., at the developmental age when human infants start to show reliable stimulus-elicited emotional states (4-6 months)]. Using an approach that eschews traditional EEG frequency band delineations (like theta, alpha), we demonstrate that negative emotional states induce a strong right hemispheric increase in the prominence of the resonant frequency (∼5-6 Hz) in the infant frontal EEG. Increased rightward asymmetry was strongly correlated with increased heart rate responses to emotionally negative states compared with neutral states. We conclude that functional frontal asymmetry is a key component of emotional processing and suggest that the rightward asymmetry in prominence of the resonant frequency during negative emotional states might reflect functional asymmetry in the central representation of anatomically driven asymmetry in the autonomic nervous system. Our findings indicate that the specific mode hallmarking emotional processing in the frontal cortex is established in parallel with the emergence of stable emotional states very early during development, despite the well known protracted maturation of frontal cortex.

Effect of the Strawberry Genotype, Cultivation and Processing on the Fra a 1 Allergen Content.

Birch pollen allergic patients show cross-reactivity to vegetables and fruits, including strawberries (Fragaria × ananassa). The objective of this study was to quantify the level of the Fra a 1 protein, a Bet v 1-homologous protein in strawberry fruits by a newly developed ELISA, and determine the effect of genotype, cultivation and food processing on the allergen amount. An indirect competitive ELISA using a specific polyclonal anti-Fra a 1.02 antibody was established and revealed high variability in Fra a 1 levels within 20 different genotypes ranging from 0.67 to 3.97 µg/g fresh weight. Mature fruits of red-, white- and yellow-fruited strawberry cultivars showed similar Fra a 1 concentrations. Compared to fresh strawberries, oven and solar-dried fruits contained slightly lower levels due to thermal treatment during processing. SDS-PAGE and Western blot analysis demonstrated degradation of recombinant Fra a 1.02 after prolonged (>10 min) thermal treatment at 99 °C. In conclusion, the genotype strongly determined the Fra a 1 quantity in strawberries and the color of the mature fruits does not relate to the amount of the PR10-protein. Cultivation conditions (organic and conventional farming) do not affect the Fra a 1 level, and seasonal effects were minor.