Antiseizure medication use during pregnancy and children's neurodevelopmental outcomes.

The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.

Genetic Insights Into Perinatal Outcomes of Maternal Antihypertensive Therapy During Pregnancy.

Importance: Limited information exists regarding the impact of pharmacotherapy in pregnancy due to ethical concerns of unintended fetal harm. Yet, maternal prescriptive drug use for chronic conditions such as hypertension is common.

Objective: To investigate potential causal relationships between perturbing maternal genetic variants influencing antihypertensive drug targets and perinatal outcomes among offspring using mendelian randomization (MR).

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806).

Schistosomiasis in Burkina Faso: review on 60 years' research.

Schistosomiasis is a common neglected helminthic disease in the tropics and sub-tropics particularly in sub-Saharan countries including Burkina Faso. It is the second world parasitic endemic disease after malaria. The two prevalent species infecting human in Burkina Faso are are Schistosoma haematobium and Schistosoma mansoni which cause respectively the urogenital schistosomiasis and the intestinal schistosomiasis.

Redirecting tropane alkaloid metabolism reveals pyrrolidine alkaloid diversity in Atropa belladonna.

Plant-specialized metabolism is complex, with frequent examples of highly branched biosynthetic pathways, and shared chemical intermediates. As such, many plant-specialized metabolic networks are poorly characterized. The N-methyl Δ -pyrrolinium cation is a simple pyrrolidine alkaloid and precursor of pharmacologically important tropane alkaloids.

How to estimate heritability: a guide for genetic epidemiologists.

Traditionally, heritability has been estimated using family-based methods such as twin studies. Advancements in molecular genomics have facilitated the development of methods that use large samples of (unrelated or related) genotyped individuals. Here, we provide an overview of common methods applied in genetic epidemiology to estimate heritability, i.

Correction: Fruity, sticky, stinky, spicy, bitter, addictive, and deadly: evolutionary signatures of metabolic complexity in the Solanaceae.

Correction for 'Fruity, sticky, stinky, spicy, bitter, addictive, and deadly: evolutionary signatures of metabolic complexity in the Solanaceae' by Paul D. Fiesel , , 2022, , 1438-1464, https://doi.org/10.

Efficacy, Tolerability, and Pharmacokinetic Studies of Antibody-Drug Conjugates Containing a Low-Potency Pyrrolobenzodiazepine Dimer.

Antibody-drug conjugate (ADC) research has typically focused on the release of highly potent cytotoxic agents to achieve antitumor efficacy. However, recently approved ADCs trastuzumab deruxtecan and sacituzumab govitecan release lower-potency topoisomerase inhibitors. This has prompted interest in ADCs that release lower-potency cytotoxic drugs to potentially enhance therapeutic index and reduce unwanted toxicity.

Using Mendelian Randomisation to Prioritise Candidate Maternal Metabolic Traits Influencing Offspring Birthweight.

Marked physiological changes in pregnancy are essential to support foetal growth; however, evidence on the role of specific maternal metabolic traits from human studies is limited. We integrated Mendelian randomisation (MR) and metabolomics data to probe the effect of 46 maternal metabolic traits on offspring birthweight ( = 210,267). We implemented univariable two-sample MR (UVMR) to identify candidate metabolic traits affecting offspring birthweight.

Investigating how the accuracy of teacher expectations of pupil performance relate to socioeconomic and genetic factors.

Teacher expectations of pupil ability can influence educational progression, impacting subsequent streaming and exam level. Systematic discrepancies between teacher expectations of pupil achievement may therefore have a detrimental effect on children's education. Associations between socioeconomic and demographic factors with teacher expectation accuracy have been demonstrated, but it is not known how teacher expectations of achievement may relate to genetic factors.

Fruity, sticky, stinky, spicy, bitter, addictive, and deadly: evolutionary signatures of metabolic complexity in the Solanaceae.

Covering: 2000-2022Plants collectively synthesize a huge repertoire of metabolites. General metabolites, also referred to as primary metabolites, are conserved across the plant kingdom and are required for processes essential to growth and development. These include amino acids, sugars, lipids, and organic acids.

Simultaneous monitoring of multiple attributes of pyrrolobenzodiazepine antibody-drug conjugates by size exclusion chromatography - high resolution mass spectrometry.

Antibody-drug conjugates (ADCs) are an emerging class of oncology treatments combining the unique specificity of monoclonal antibodies with the highly cytotoxic properties of small molecule compounds. Pyrrolobenzodiazepines (PBDs) are highly potent agents capable of inhibiting cellular DNA replication which leads to apoptosis. To ensure efficacy and patient safety upon administration of such toxic and heterogeneous molecules, their structure and quality attributes must be closely monitored.

Optimising the use of gene expression data to predict plant metabolic pathway memberships.

Plant metabolites from diverse pathways are important for plant survival, human nutrition and medicine. The pathway memberships of most plant enzyme genes are unknown. While co-expression is useful for assigning genes to pathways, expression correlation may exist only under specific spatiotemporal and conditional contexts.

Within- and cross-species predictions of plant specialized metabolism genes using transfer learning.

Plant specialized metabolites mediate interactions between plants and the environment and have significant agronomical/pharmaceutical value. Most genes involved in specialized metabolism (SM) are unknown because of the large number of metabolites and the challenge in differentiating SM genes from general metabolism (GM) genes. Plant models like have extensive, experimentally derived annotations, whereas many non-model species do not.

QTL and Transcriptomic Analyses Implicate Cuticle Transcription Factor as a Source of Natural Variation for Epidermal Traits in Cucumber Fruit.

The fruit surface is a unique tissue with multiple roles influencing fruit development, post-harvest storage and quality, and consumer acceptability. Serving as the first line of protection against herbivores, pathogens, and abiotic stress, the surface can vary markedly among species, cultivars within species, and developmental stage. In this study we explore developmental changes and natural variation of cucumber ( L.

Synthesis and evaluation of pyrrolobenzodiazepine dimer antibody-drug conjugates with dual β-glucuronide and dipeptide triggers.

Antibody-drug conjugates (ADCs) containing pyrrolobenzodiazepine (PBD) dimers are currently being evaluated in human oncology clinical trials with encouraging results. To further improve the therapeutic window, next-generation PBD drug-linker design has focused on the inclusion of additional tumor-selective triggers and use of lower-potency PBDs. β-Glucuronidase is a well-known target for discovery prodrugs due to increased presence in tumor cells and microenvironment.

A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis.

Infections of humans and livestock with African trypanosomes are treated with drugs introduced decades ago that are not always fully effective and often have severe side effects. Here, the trypanosome haptoglobin-haemoglobin receptor (HpHbR) has been exploited as a route of uptake for an antibody-drug conjugate (ADC) that is completely effective against Trypanosoma brucei in the standard mouse model of infection. Recombinant human anti-HpHbR monoclonal antibodies were isolated and shown to be internalised in a receptor-dependent manner.

An Automated Data-Driven Pipeline for Improving Heterologous Enzyme Expression.

Enzymes are the ultimate entities responsible for chemical transformations in natural and engineered biosynthetic pathways. However, many natural enzymes suffer from suboptimal functional expression due to poor intrinsic protein stability. Further, stability enhancing mutations often come at the cost of impaired function.

Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization.

Tropinone is the first intermediate in the biosynthesis of the pharmacologically important tropane alkaloids that possesses the 8-azabicyclo[3.2.1]octane core bicyclic structure that defines this alkaloid class.

Coexpression Analysis Identifies Two Oxidoreductases Involved in the Biosynthesis of the Monoterpene Acid Moiety of Natural Pyrethrin Insecticides in .

Flowers of produce a set of compounds known collectively as pyrethrins, which are commercially important pesticides that are strongly toxic to flying insects but not to most vertebrates. A pyrethrin molecule is an ester consisting of either trans-chrysanthemic acid or its modified form, pyrethric acid, and one of three alcohols, jasmolone, pyrethrolone, and cinerolone, that appear to be derived from jasmonic acid. Chrysanthemyl diphosphate synthase (CDS), the first enzyme involved in the synthesis of trans-chrysanthemic acid, was characterized previously and its gene isolated.

Characterization of Trichome-Expressed BAHD Acyltransferases in Reveals Distinct Acylsugar Assembly Mechanisms within the Solanaceae.

Acylsugars are synthesized in the glandular trichomes of the Solanaceae family and are implicated in protection against abiotic and biotic stress. Acylsugars are composed of either sucrose or glucose esterified with varying numbers of acyl chains of differing length. In tomato (), acylsugar assembly requires four acylsugar acyltransferases (ASATs) of the BAHD superfamily.

Insight into the evolution of the Solanaceae from the parental genomes of Petunia hybrida.

Petunia hybrida is a popular bedding plant that has a long history as a genetic model system. We report the whole-genome sequencing and assembly of inbred derivatives of its two wild parents, P. axillaris N and P.

Transcriptome-enabled marker discovery and mapping of plastochron-related genes in Petunia spp.

Background: Petunia (Petunia × hybrida), derived from a hybrid between P. axillaris and P. integrifolia, is one of the most economically important bedding plant crops and Petunia spp.

A root-expressed L-phenylalanine:4-hydroxyphenylpyruvate aminotransferase is required for tropane alkaloid biosynthesis in Atropa belladonna.

The tropane alkaloids, hyoscyamine and scopolamine, are medicinal compounds that are the active components of several therapeutics. Hyoscyamine and scopolamine are synthesized in the roots of specific genera of the Solanaceae in a multistep pathway that is only partially elucidated. To facilitate greater understanding of tropane alkaloid biosynthesis, a de novo transcriptome assembly was developed for Deadly Nightshade (Atropa belladonna).