Griet Dewitte

Stability of motor problems in young children with or at risk of autism spectrum disorders, ADHD, and or developmental coordination disorder

Aim  The aim of this study was to investigate the stability of motor problems in a clinically referred sample of children with, or at risk of, autism spectrum disorders (ASDs), attention‐deficit–hyperactivity disorder (ADHD), and/or developmental coordination disorder (DCD).

Neonatal and neurodevelopmental outcome of children aged 3–10 years born following assisted oocyte activation

Assisted oocyte activation (AOA) using a calcium ionophore has been used for more than a decade following intracytoplasmic sperm injection (ICSI) fertilization failure. However, since AOA does not mimic precisely the physiological fertilization process, concerns exist about its use in human assisted reproduction. This study assessed the neonatal and neurodevelopmental outcome of children aged ≥ 3 years who had been born following AOA in our centre. Twenty-one children participated in the study (81% response rate; mean age 63.6 ± 21.07 months). Neonatal data were collected via questionnaires. Neurodevelopmental outcome was tested using the Reynell Developmental Language Scales or Clinical Evaluation of Language Fundamentals, Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children, and the Movement Assessment Battery for Children III. Behaviour was scored by the Social Communication Questionnaire, the Child Behaviour Checklist and the Teachers Report Form. For all tests and questionnaires, the mean outcomes lay within the expected ranges. These are first data on the developmental outcome of AOA children. The high response rate and the robustness of the tests support the data, which are reassuring although still considered preliminary. Therefore, AOA should still be performed only in selected couples.

Screening of recombinant glycosyltransferases reveals the broad acceptor specificity of stevia UGT-76G1

UDP-glycosyltransferases (UGTs) are a promising class of biocatalysts that offer a sustainable alternative for chemical glycosylation of natural products. In this study, we aimed to characterize plant-derived UGTs from the GT-1 family with an emphasis on their acceptor promiscuity and their potential application in glycosylation processes. Recombinant expression in E. coli provided sufficient amounts of enzyme for the in-depth characterization of the salicylic acid UGT from Capsella rubella (UGT-SACr) and the stevia UGT from Stevia rebaudiana (UGT-76G1Sr). The latter was found to have a remarkably broad specificity with activities on a wide diversity of structures, from aliphatic and branched alcohols, over small phenolics to larger flavonoids, terpenoids and even higher glycoside compounds. As an example for its industrial potential, the glycosylation of curcumin was thoroughly evaluated. Under optimized conditions, 96% of curcumin was converted within 24h into the corresponding curcumin β-glycosides. In addition, the reaction was performed in a coupled system with sucrose synthase from Glycine max, to enable the cost-efficient (re)generation of UDP-Glc from sucrose as abundant and renewable resource.

Enzymatic Glycosylation of Phenolic Antioxidants: Phosphorylase-Mediated Synthesis and Characterization.

Although numerous biologically active molecules exist as glycosides in nature, information on the activity, stability, and solubility of glycosylated antioxidants is rather limited to date. In this work, a wide variety of antioxidants were glycosylated using different phosphorylase enzymes. The resulting antioxidant library, containing α/β-glucosides, different regioisomers, cellobiosides, and cellotriosides, was then characterized. Glycosylation was found to significantly increase the solubility and stability of all evaluated compounds. Despite decreased radical-scavenging abilities, most glycosides were identified to be potent antioxidants, outperforming the commonly used 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT). Moreover, the point of attachment, the anomeric configuration, and the glycosidic chain length were found to influence the properties of these phenolic glycosides.

Sequence determinants of nucleotide binding in Sucrose Synthase : improving the affinity of a bacterial Sucrose Synthase for UDP by introducing plant residues

Sucrose Synthase (SuSy) catalyzes the reversible conversion of sucrose and a nucleoside diphosphate (NDP) into NDP-glucose and fructose. Biochemical characterization of several plant and bacterial SuSys has revealed that the eukaryotic enzymes preferentially use UDP whereas prokaryotic SuSys prefer ADP as acceptor. In this study, SuSy from the bacterium Acidithiobacillus caldus, which has a higher affinity for ADP as reflected by the 25-fold lower Km value compared to UDP, was used as a test case to scrutinize the effect of introducing plant residues at positions in a putative nucleotide binding motif surrounding the nucleobase ring of NDP. All eight single to sextuple mutants had similar activities as the wild-type enzyme but significantly reduced Km values for UDP (up to 60 times). In addition, we recognized that substrate inhibition by UDP is introduced by a methionine at position 637. The affinity for ADP also increased for all but one variant, although the improvement was much smaller compared to UDP. Further characterization of a double mutant also revealed more than 2-fold reduction in Km values for CDP and GDP. This demonstrates the general impact of the motif on nucleotide binding. Furthermore, this research also led to the establishment of a bacterial SuSy variant that is suitable for the recycling of UDP during glycosylation reactions. The latter was successfully demonstrated by combining this variant with a glycosyltransferase in a one-pot reaction for the production of the C-glucoside nothofagin, a health-promoting flavonoid naturally found in rooibos (tea).

Effectiveness of a self-regulated remedial program for handwriting difficulties

Abstract Background: Handwriting difficulties may have pervasive effects on a child’s school performance. I Can! is a remedial handwriting program with a focus on self-regulated learning and applying motor learning principles combined with a behavioural approach. It is developed for typically developing children with handwriting problems. Objective: The study aim was to evaluate the program’s effectiveness. Materials and methods: Thirty-one children aged 7–8 year participated in a cross-over study. Handwriting quality and speed were repeatedly assessed by means of the Systematic Screening of Handwriting Difficulties test. Difficulties addressed were fluency in letter formation, fluency in letter connections, letter height, regularity of letter height, space between words, and line path. Results: Mixed model analysis revealed improved quality of writing and speed for all children but significantly more improvement in handwriting quality for the children participating in the program. Although writing speed improved over time, no additional effects of the program occurred. Conclusions and significance: ‘I Can!’ is found to be an effective instructive program to ameliorate handwriting quality in typically developing children with handwriting difficulties. The program’s success was by a therapy burst of only 7 weeks focusing on the child’s self-regulated learning capacities, within an individualized education plan according to their needs and goals.