6,774 research outputs found

    UMSL Bulletin 2023-2024

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    The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp

    Placental origins of health & disease:Therapeutic opportunities

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    Splenic nerve bundle stimulation in acute and chronic inflammation

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    Splenic neurovascular bundle stimulation holds potential to treat acute and chronic inflammatory conditions. In the first part of the thesis, the available literature on the interactions between the immune system and nervous system in the intestine is summarized. Then, it is shown that a specialized T-cell, that can produce the neurotransmitter acetylcholine, resides in the gut an plays a dual role in the development of experimental colitis in mice. Furthermore, electrical splenic neurovascular bundle stimulation ameliorated the outcomes of colitis in mice and reversed transcriptomic changes in the gut that were induced by colitis. The second part of the thesis focused on the translation of splenic neurovascular bundle stimulation to the human situation. It is shown that there are significant changes between murine and human innervation of the spleen. Using computed tomography (CT) images the course and the characteristics of the splenic artery were described. These data were used to develop a cuff electrode that could be used for electrical stimulation of the splenic neurovascular bundle in humans. Finally, it was demonstrated that splenic neurovascular bundle stimulation in humans was safe and feasible in a pilot study with patients that underwent esophagectomy

    Studying the interplay between ageing and Parkinson's disease using the zebrafish model

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    Parkinson’s disease (PD) is a neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra. Ageing is the major risk factor for developing PD but the interplay between ageing and PD remains elusive. To investigate the effect of ageing on PD-relevant pathological mechanisms, zebrafish mutant lines harbouring mutations in ageing-associated genes (klotho-/-, sirt1-/-, satb1a-/-, satb1b-/- and satb1a-/-;satb1b-/-) were generated, using CRISPR/Cas9 gene editing. Likewise, a chemical model for SIRT1 deficiency was utilised. klotho-/- zebrafish displayed an accelerated ageing phenotype at 3mpf and reduced survival to 6mpf. Dopaminergic neuron number, MPP+ susceptibility and microglial number were unaffected in klotho-/- larvae. NAD+ levels were decreased in 6mpf klotho-/- brains. However, ATP levels and DNA damage were unaffected. sirt1-/- zebrafish did not display a phenotype through adulthood. il-1β and il-6 were not upregulated in sirt1-/- larvae, and chemical inhibition of sirt1 did not increase microglial number. cdkn1a, il-1β and il-6 were not upregulated in satb1a-/- and satb1b-/- larvae. Dopaminergic neuron number and MPP+ susceptibility were unaffected in satb1a-/- larvae. However, satb1b-/- larvae demonstrated a moderate decrease in dopaminergic neuron number but equal susceptibility to MPP+ as satb1b+/+ larvae. Adult satb1a-/- but not adult satb1b-/- zebrafish were emaciated. satb1a-/-;satb1b-/- zebrafish did not display a phenotype through adulthood. Transgenic zebrafish expressing human wildtype α-Synuclein (Tg(eno2:hsa.SNCA-ires-EGFP)) were crossed with klotho-/- and sirt1-/- zebrafish, and treated with a sirt1-specific inhibitor. Neither genetic cross affected survival. The klotho mutation did not increase microglial number in Tg(eno2:hsa.SNCA-ires-EGFP) larvae. Likewise, sirt1 inhibition did not induce motor impairment or cell death in Tg(eno2:hsa.SNCA-ires-EGFP) larvae. In conclusion, the suitability of zebrafish for studying ageing remains elusive, as only 1 ageing-associated mutant line displayed accelerated ageing. However, zebrafish remain an effective model for studying PD-relevant pathological mechanisms due to the availability of CRISPR/Cas9 gene editing, neuropathological and neurobehavioral tools

    Subject-Independent Detection of Yes/No Decisions Using EEG Recordings During Motor Imagery Tasks: A Novel Machine-Learning Approach with Fine-Graded EEG Spectrum

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    The classification of sensorimotor rhythms in electroencephalography signals can enable paralyzed individuals, for example, to make yes/no decisions. In practice, these approaches are hard to implement due to the variability of electroencephalography signals between and within subjects. Therefore, we report a novel and fast machine learning model, meeting the need for efficiency and reliability as well as low calibration and training time. Our model extracts finely graded frequency bands from motor imagery electroencephalography data by using power spectral density and training a random forest algorithm for classification. The goal was to create a non-invasive generalizable method by training the algorithm with subject-independent EEG data. We evaluate our approach using one of the currently largest publicly available electroencephalography datasets. With a balanced accuracy of 73.94%, our novel algorithm outperforms other state-of-the-art non-subject-dependent algorithms

    Complexity Science in Human Change

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    This reprint encompasses fourteen contributions that offer avenues towards a better understanding of complex systems in human behavior. The phenomena studied here are generally pattern formation processes that originate in social interaction and psychotherapy. Several accounts are also given of the coordination in body movements and in physiological, neuronal and linguistic processes. A common denominator of such pattern formation is that complexity and entropy of the respective systems become reduced spontaneously, which is the hallmark of self-organization. The various methodological approaches of how to model such processes are presented in some detail. Results from the various methods are systematically compared and discussed. Among these approaches are algorithms for the quantification of synchrony by cross-correlational statistics, surrogate control procedures, recurrence mapping and network models.This volume offers an informative and sophisticated resource for scholars of human change, and as well for students at advanced levels, from graduate to post-doctoral. The reprint is multidisciplinary in nature, binding together the fields of medicine, psychology, physics, and neuroscience

    Constitutions of Value

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    Gathering an interdisciplinary range of cutting-edge scholars, this book addresses legal constitutions of value. Global value production and transnational value practices that rely on exploitation and extraction have left us with toxic commons and a damaged planet. Against this situation, the book examines law’s fundamental role in institutions of value production and valuation. Utilising pathbreaking theoretical approaches, it problematizes mainstream efforts to redeem institutions of value production by recoupling them with progressive values. Aiming beyond radical critique, the book opens up the possibility of imagining and enacting new and different value practices. This wide-ranging and accessible book will appeal to international lawyers, socio-legal scholars, those working at the intersections of law and economy and others, in politics, economics, environmental studies and elsewhere, who are concerned with rethinking our current ideas of what has value, what does not, and whether and how value may be revalued

    Molecular modeling of the monoamine transporters and their interactions with psychostimulants and other substances

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    The monoamines (i.e., dopamine, serotonin, and norepinephrine) are vital to the ontogeny, function, and plasticity of the nervous system. These neurotransmitters affect each other and regulate, amongst others, motor function, cognitive state, motivation, and stress reactions. The neurotransmission is mainly terminated by reuptake in monoamine transporters (MATs), i.e., the dopamine-, serotonin-, and norepinephrine transporter. These transporters are the focus of the current study. Imbalance in the monoamine systems in the central nervous system (CNS) is associated with neurological- and psychiatric disorders, where the MATs are targets for several therapeutic drugs. Most of these drugs bind the outward-facing conformation of the MATs, and their effects depend highly on the selectivity for a single MAT. On the other hand, the increased use of illicit stimulants, predominantly acting on DAT, has risen alarms due to their unpredictable effects and high abuse potential. Regarding this, some research standards (atypical inhibitors), suggested to bind the inward-facing conformation of the MATs, have been shown to exert anti-addictive properties – being valuable in future treatment of addiction and withdrawal symptoms. The main aim of this thesis was to construct outward-and inward facing human MAT-models, based on homology modeling, to identify determinants for selective binding to each MAT, by utilizing induced fit docking and molecular dynamics simulations. Therapeutic psychostimulants, illicit psychostimulants, antidepressants, non-stimulants, atypical inhibitors, and some research standards were studied. The results indicate that divergent residues in the S1-site play a key role in MAT-selectivity. These residues shape the polarity and steric environment in the orthosteric (S1) pocket, thus affecting the stabilization, interactions, and orientation of ligands in each MAT. Structural features in the ligands appeared to also play a role in the selectivity for a MAT, concerning the binding mode and formation of interactions
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