A5086149000- Plant biochemistry and biosynthesis
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Photosynthetic Processes and Mechanisms
- Essential Oils and Antimicrobial Activity
- Plant Gene Expression Analysis
- Microbial Natural Products and Biosynthesis
- Microbial Metabolic Engineering and Bioproduction
- Heart Failure Treatment and Management
- Phytochemicals and Antioxidant Activities
- RNA modifications and cancer
- Plant Pathogens and Fungal Diseases
- Lipid metabolism and biosynthesis
- Plant Stress Responses and Tolerance
- Plant Molecular Biology Research
- Biochemical and biochemical processes
- Natural product bioactivities and synthesis
- Ion channel regulation and function
- Neurological disorders and treatments
- RNA and protein synthesis mechanisms
- Soft tissue tumor case studies
- GDF15 and Related Biomarkers
- Natural Compounds in Disease Treatment
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Washington State University
2012-2024
University Medical Center Utrecht
2016-2024
Utrecht University
2018-2024
Erasmus MC
2022-2023
Clínica Alemana
2022
Royal Hospital for Children
2022
Universidad del Desarrollo
2022
University of Glasgow
2022
Institute of Biological Chemistry, Academia Sinica
2011
Okanagan University College
2011
Peppermint ( Mentha × piperita L.) was transformed with various gene constructs to evaluate the utility of metabolic engineering for improving essential oil yield and composition. Oil increases were achieved by overexpressing genes involved in supply precursors through 2 C -methyl-D-erythritol 4-phosphate (MEP) pathway. Two-gene combinations enhance both composition a single transgenic line assessed as well. The most promising results obtained transforming plants expressing an antisense...
Summary Objective Pathogenic variants in SCN 1A can give rise to extremely variable disease severities that may be indistinguishable at their first presentation. We aim find clinical features help predict the evolution of seizures into Dravet syndrome and cognitive outcome syndrome. specifically investigate role contraindicated medication ( CIM ) as a possible modifier decline. Methods A cohort 164 Dutch participants with ‐related was evaluated. Clinical data were collected from medical...
Glandular trichomes are specialized anatomical structures that accumulate secretions with important biological roles in plant-environment interactions. These also have commercial uses the flavor, fragrance, and pharmaceutical industries. The capitate-stalked glandular of Cannabis sativa (cannabis), situated on surfaces bracts female flowers, primary site for biosynthesis storage resins rich cannabinoids terpenoids. In this study, we profiled nine cannabis strains purportedly different...
Pathogenic variants in the neuronal sodium channel α1 subunit gene (SCN1A) are most frequent monogenic cause of epilepsy. Phenotypes comprise a wide clinical spectrum, including severe childhood epilepsy; Dravet syndrome, characterized by drug-resistant seizures, intellectual disability, and high mortality; milder genetic epilepsy with febrile seizures plus (GEFS+), normal cognition. Early recognition child's risk for developing syndrome vs GEFS+ is key implementing disease-modifying...
Abstract Objective SCN1A variants are associated with epilepsy syndromes ranging from mild genetic febrile seizures plus (GEFS+) to severe Dravet syndrome (DS). Many de novo, making early phenotype prediction difficult, and genotype–phenotype associations remain poorly understood. Methods We assessed data a retrospective cohort of 1018 individuals SCN1A‐ related epilepsies. explored relationships between variant characteristics (position, in silico scores: Combined Annotation Dependent...
Metabolomics is the methodology that identifies and measures global pools of small molecules (of less than about 1,000 Daltons) a biological sample, which are collectively called metabolome. can therefore reveal metabolic outcome genetic or environmental perturbation regulatory network, thus provide insights into structure regulation network. Because chemical complexity metabolome limitations associated with individual analytical platforms for determining metabolome, it currently difficult...
<h3>Background</h3> Mutations in the <i>KIAA2022</i> gene have been reported male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 who carry a heterozygous de novo mutation share phenotype characterised by disability epilepsy. <h3>Methods</h3> Reported females selected for genetic testing because of substantial developmental problems and/or X-inactivation expression studies performed when possible. <h3>Results</h3> All mutations...
Summary Objective Phenotypes caused by de novo SCN 1A pathogenic variants are very variable, ranging from severely affected patients with Dravet syndrome to much milder genetic epilepsy febrile seizures plus cases. The most important determinant of disease severity is the type variant, that cause a complete loss function protein (α‐subunit neuronal sodium channel Nav1.1) being detected almost exclusively in patients. However, even within ranges greatly, and consequently other modifiers must...
Abstract We have previously reported the use of a combination computational simulations and targeted experiments to build first generation mathematical model peppermint (Mentha × piperita) essential oil biosynthesis. Here, we report on expansion this approach identify key factors controlling monoterpenoid biosynthesis under adverse environmental conditions. also investigated determinants in transgenic lines with modulated profiles. A perturbation analysis, which was implemented variables...
Pathogenic variants in the PCDH19 gene are associated with epilepsy, intellectual disability (ID) and behavioural disturbances. Only heterozygous females mosaic males affected, likely due to a disease mechanism named cellular interference. Until now, only four affected male patients have been described literature. Here, we report five additional patients, of which older than oldest patient reported so far. All were selected for genetic testing because developmental delay and/or epilepsy....
In plants, two spatially separated pathways provide the precursors for isoprenoid biosynthesis. We generated transgenic Arabidopsis (Arabidopsis thaliana) lines with modulated levels of expression each individual gene involved in cytosolic/peroxisomal mevalonate and plastidial methylerythritol phosphate pathways. By assessing correlation transgene marker metabolites (gene-to-metabolite correlation), we determined relative importance transcriptional control at step precursor The accumulation...
Background A neurodevelopmental syndrome was recently reported in four patients with SOX4 heterozygous missense variants the high-mobility-group (HMG) DNA-binding domain. The present study aimed to consolidate clinical and genetic knowledge of this syndrome. Methods We newly identified 17 variants, predicted variant pathogenicity using silico tests vitro functional assays analysed patients’ phenotypes. Results All were novel, distinct heterozygous. Seven HMG-domain five stop-gain classified...
Adventitious root cultures were developed from Tripterygium regelii, and growth conditions optimized for the abundant production of diterpenoids, which can be collected directly medium. An analysis publicly available transcriptome data sets with T. regelii roots indicated presence a large gene family (with 20 members) terpene synthases (TPSs). Nine candidate diterpene synthase genes selected follow-up functional evaluation, two belonged to TPS-c, three TPS-e/f, four TPS-b subfamilies. These...
The commercially important essential oils of peppermint (
SCN1A is one of the most important epilepsy-related genes, with pathogenic variants leading to a range phenotypes varying disease severity. Different modifying factors have been hypothesized influence SCN1A-related phenotypes. We investigate presence rare and more common in genes as potential modifiers
Abstract Mentha longifolia (L.) Huds., a wild, diploid mint species, has been developed as model for genetic and genomic research to aid breeding efforts that target Verticillium wilt disease resistance essential oil monoterpene composition. Here, we present near-complete, chromosome-scale genome assembly M. USDA accession CMEN 585. This new is an update of previously published draft, with dramatic improvements. A total 42,107 protein-coding genes were annotated placed on 12 chromosomal...
Monoterpene synthases (MTSs) catalyze the initial committed step in biosynthesis of monoterpenes. MTSs control challenging reactions that involve highly reactive carbocations through exquisite steric and electrostatic confinement, some cases with remarkable product specificity enantioselectivity. Using two well-characterized as models, (4S)-(−)-limonene synthase (LMNS) (+)-bornyl diphosphate (BPPS), we implemented an iterative approach involves comparative atomistic simulations experimental...
ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) only five individuals and systematic clinical characterisation not available. The aim of this study is to provide a comprehensive description the phenotypic genotypic spectrum ARF1-related neurodevelopmental disorder.We collected detailed phenotypes an international cohort (n=17) with variants assembled through GeneMatcher platform. Missense were structurally modelled, impact several functionally validated.De novo...
The metabolic underpinnings of plant survival under severe drought-induced senescence conditions are poorly understood. In this study, we assessed the morphological, physiological and responses to sustained water deficit in Brachypodium distachyon, a model organism for research on temperate grasses. Relative control plants, fresh biomass, leaf potential, chlorophyll levels decreased rapidly plants grown drought conditions, demonstrating an early onset senescence. C/N ratio protein content...
Taxol (paclitaxel) is a very widely used anticancer drug, but its commercial sources mainly consist of stripped bark or suspension cultures members the plant genus Taxus. accumulates as part complex mixture chemical analogs, termed taxoids, which complicates production in pure form, highlighting need for metabolic engineering approaches high-level cell microbial hosts. Here, we report on characterization acyl-activating enzymes (AAEs) that catalyze formation CoA esters different organic...