38 research outputs found
At the crossroads of biomacromolecular research: highlighting the interdisciplinary nature of the field
Due to their complexity and wide-ranging utility, biomacromolecular research is an especially interdisciplinary branch of chemistry. It is my goal that the Biomacromolecules subject area of Chemistry Central Journal will parallel this richness and diversity. In this inaugural commentary, I attempt to set the stage for achieving this by highlighting several areas where biomacromolecular research overlaps more traditional chemistry sub-disciplines. Specifically, it is discussed how Materials Science and Biotechnology, Analytical Chemistry, Cell Biology and Chemical Theory are each integral to modern biomacromolecular research. Investigators with reports in any of these areas, or any other dealing with biomacromolecules, are encouraged to submit their research papers to Chemistry Central Journal
Serotonin synthesis, release and reuptake in terminals: a mathematical model
<p>Abstract</p> <p>Background</p> <p>Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system.</p> <p>Methods</p> <p>We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data.</p> <p>Results</p> <p>We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct <it>in silico </it>experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine.</p> <p>Conclusions</p> <p>Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.</p
Advancing a Conceptual Model of Evidence-Based Practice Implementation in Public Service Sectors
Implementation science is a quickly growing discipline. Lessons learned from business and medical settings are being applied but it is unclear how well they translate to settings with different historical origins and customs (e.g., public mental health, social service, alcohol/drug sectors). The purpose of this paper is to propose a multi-level, four phase model of the implementation process (i.e., Exploration, Adoption/Preparation, Implementation, Sustainment), derived from extant literature, and apply it to public sector services. We highlight features of the model likely to be particularly important in each phase, while considering the outer and inner contexts (i.e., levels) of public sector service systems
Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth
This is the final version. Available on open access from Nature Research via the DOI in this record. Data availability:
Individual cohorts contributing to the meta-analysis should be contacted directly as each cohort has different data access policies. GWAS summary statistics from this study are available via the EGG website (https://egg-consortium.org/placental-weight-2023.html, https://www.ebi.ac.uk/gwas/), as well as the GWAS catalog (https://www.ebi.ac.uk/gwas/, accession numbers GCST90275189, GCST90275190, GCST90275191, GCST90275192, GCST90275193, GCST90275194, GCST90275195, GCST90275196, GCST90275197, GCST90275198, GCST90275199). Access to personal-level information from Gen3G (including methylation array data) is subject to controlled access according to participants’ consent concerning sharing of personal data. Request for conditions of access and for data access should be addressed to Center Hospitalier Universitaire de Sherbrooke institutional ethics committee: [email protected] availability:
Analysis code is available from https://github.com/EarlyGrowthGenetics/placental_weight_codeA well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.Wellcome Trus
Parent-Endorsed Sex Differences in Toddlers with and Without ASD: Utilizing the M-CHAT
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites