rudyvdbrink/CitationDatabase huggingface dataset:
Caenorhabditis elegans oocyte meiotic spindle pole assembly requires microtubule severing and the calponin homology domain protein ASPM-1.
Molecular biology of the cell, 2014

In many animals, including vertebrates, oocyte meiotic spindles are bipolar but assemble in the absence of centrosomes. Although meiotic spindle positioning in oocytes has been investigated extensively, much less is known about their assembly. In Caenorhabditis elegans, three genes previously shown to contribute to oocyte meiotic spindle assembly are the calponin homology domain protein encoded by aspm-1, the katanin family member mei-1, and the kinesin-12 family member klp-18. We isolated temperature-sensitive alleles of all three and investigated their requirements using live-cell imaging to reveal previously undocumented requirements for aspm-1 and mei-1. Our results indicate that bipolar but abnormal oocyte meiotic spindles assemble in aspm-1(-) embryos, whereas klp-18(-) and mei-1(-) mutants assemble monopolar and apolar spindles, respectively. Furthermore, two MEI-1 functions--ASPM-1 recruitment to the spindle and microtubule severing--both contribute to monopolar spindle assembly in klp-18(-) mutants. We conclude that microtubule severing and ASPM-1 both promote meiotic spindle pole assembly in C. elegans oocytes, whereas the kinesin 12 family member KLP-18 promotes spindle bipolarity.
Evaluation of Hospital-wide Readmission Risk Calculator to Predict 30-Day Readmission in Neurocritical Care Patients.
The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses, 2019

Thirty-day hospital readmissions have been shown to be a measure of quality and result in higher mortality and increased costs. Readmissions are a target for hospitals and payers; thus, several centers have developed predictive readmission scores to identify high-risk patients. The purpose of this study was to evaluate the current hospital-wide readmission risk calculator and the ability of this tool to predict 30-day readmissions in the neurocritical care population.
Deep brain stimulation in the treatment of chorea.
Movement disorders : official journal of the Movement Disorder Society, 2012

Deep brain stimulation has been used as a means of reducing dyskinesias in various conditions, including Parkinson's disease and dystonia for many years. Recently, owing to the clinical similarities between L-dopa induced dyskinesia and chorea, deep brain stimulation has now been implemented as a novel treatment method in both Huntington's disease and neuroacanthocytosis, and a paucity of case studies exist reporting its efficacy. This review will summarize the case studies of deep brain stimulation in both Huntington's disease and neuroacanthocytosis, and discuss the possible implications and limitations associated with these reports. As both these disorders are often refractory to medication and difficult to treat, deep brain stimulation may be a useful treatment option in the future.
A regulatory pathway linking caffeine action, mood and the diurnal clock.
Neuropharmacology, 2020

Depression is a leading cause of disability worldwide. Circadian abnormalities and mood changes are symptoms of depression. The psychostimulant caffeine alters wakefulness and alleviates other depression-related symptoms during chronic intake, but the underlying mechanisms are unclear. It is not known, whether and how acute caffeine administration affects mood. Molecular approaches, transgenic mouse models, pharmacological intervention and behavioral analysis were combined to uncover a regulatory pathway, which connects caffeine action with diurnal signaling via the key dopaminergic protein DARPP-32 and alters mood-related phenotypes in mice, which are often assessed in the context of antidepressant action. We observed that Thr75-DARPP-32 binds to the circadian regulator CLOCK and disrupts CLOCK:BMAL1 chromatin binding, thereby affecting gene expression. T75A-DARPP-32 mutant mice show reduced caffeine effects on CLOCK:BMAL1 and lack caffeine-induced effects on mood. This study provides a link between caffeine, diurnal signaling and mood-related behaviors, which may open new perspectives for our understanding of antidepressant mechanisms in the mouse brain.
Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.
Comprehensive Physiology, 2016

Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016.
Coadministration of lithium and celecoxib attenuates the behavioral alterations and inflammatory processes induced by amphetamine in an animal model of mania.
Pharmacology, biochemistry, and behavior, 2019

The present study evaluated the effects of the coadministration of lithium (Li) and Cel on inflammatory parameters in an animal model of mania induced by dextroamphetamine (D-amph). It was used Wistar rats 60 days old (250-350 g). The animals (n = 10 per group) received D-amph (2 mg/kg) or saline solution of NaCl 0.9% (Sal) intraperitoneally once a day for 14 days. From day eight until 14, the animals from the D-amph and Sal groups received Li (24 mg/kg), Cel (20 mg/kg), Li + Cel or water via gavage. Behavioral analyses were performed using the open-field test. The levels of IL-1β, IL-4, IL-10, and TNF-α were evaluated. The administration of D-amph induced hyperactivity in the rats, as well increased the IL-4, IL-10, and TNF-α levels in the serum, frontal cortex, and striatum of rats compared to those of the controls, and treatment with Li plus Cel reversed these alterations. In general, the administration of Li or Cel per se did not have effects on the behavioral and biochemical parameters. However, the treatment with Cel per se decreased only the IL-10 levels in the serum of animals. Besides, the treatment with Li or Cel decreased the IL-4 levels in the serum and reversed the effects of D-amph on this parameter in the frontal cortex. The treatment with Li reversed the effects of D-amph on the TNF-α levels in all tissues evaluated, and the administration of Cel reversed this alteration only in the striatum. It can be observed that treatment with Li plus Cel was more effective against damages caused by D-amph when compared to the administration of both treatments per se, suggesting that the coadministration can be more effective to treat BD rather than Li or Cel itself. The treatment with Li plus Cel was effective against the inflammation induced by D-amph.
Arrhythmogenic late Ca
Proceedings of the National Academy of Sciences of the United States of America, 2020

Sudden death in heart failure patients is a major clinical problem worldwide, but it is unclear how arrhythmogenic early afterdepolarizations (EADs) are triggered in failing heart cells. To examine EAD initiation, high-sensitivity intracellular Ca
Comparative performance analysis of human iPSC-derived and primary neural progenitor cells (NPC) grown as neurospheres in vitro.
Stem cell research, 2017

Developmental neurotoxicity (DNT) testing performed in rats is resource-intensive (costs, time, animals) and bears the issue of species extrapolation. Thus, reliable alternative human-based approaches are needed for predicting neurodevelopmental toxicity. Human induced pluripotent stem cells (hiPSCs) represent a basis for an alternative method possibly being part of an alternative DNT testing strategy. Here, we compared two hiPSC neural induction protocols resulting in 3D neurospheres: one using noggin and one cultivating cells in neural induction medium (NIM protocol). Performance of Nestin
Establishing regional specificity of neuroestrogen action.
General and comparative endocrinology, 2014

The specificity of estrogen signaling in brain is defined at one level by the types and distributions of receptor molecules that are activated by estrogens. At another level, as our understanding of the neurobiology of the estrogen synthetic enzyme aromatase has grown, questions have emerged as to how neuroactive estrogens reach specific target receptors in functionally relevant concentrations. Here we explore the spatial specificity of neuroestrogen signaling with a focus on studies of songbirds to provide perspective on some as-yet unresolved questions. Studies conducted in both male and female songbirds have helped to clarify these interesting facets of neuroestrogen physiology.
Effects of the serotonin transporter gene, sensitivity of response to alcohol, and parental monitoring on risk for problem alcohol use.
Alcohol (Fayetteville, N.Y.), 2017

The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) has been previously associated with alcohol-related risk. Most findings point to short (S) allele carriers being at increased risk for negative alcohol outcomes relative to long allele homozygotes, although some work indicates a more complex relationship. The current prospective study aimed to clarify how and under what circumstances variations in 5-HTTLPR transmit risk for various alcohol-related outcomes. Participants were 218 adolescents and young adults (29% female) enrolled in the Michigan Longitudinal Study. We tested a moderated mediation model with 5-HTTLPR as the predictor, Self-Rating of the Effects of Alcohol (SRE) score as the mediator, alcohol-related outcomes as the dependent variables, parental monitoring as the moderator of the SRE to alcohol outcomes path, and prior drinks, sex, age, and body mass index as covariates. Four alcohol-related outcomes were tested. The S allele was associated with higher SRE scores (i.e., lower response to alcohol). Parental monitoring was a significant moderator: At low levels of parental monitoring, higher SRE scores predicted more drinks consumed and binge drinking episodes. At high levels of monitoring, higher SRE scores were significantly related to fewer alcohol-related problems. Findings suggest that one mechanism by which 5-HTTLPR variation transmits alcohol-related risk is through level of response to alcohol. Furthermore, the strength and direction of this effect varied by level of parental monitoring, indicating that even in the presence of genetic and physiological vulnerability, parents can influence the likelihood of offspring developing problematic alcohol-related behaviors.
Clinical and cost-effectiveness of an intervention for reducing cholesterol and cardiovascular risk for people with severe mental illness in English primary care: a cluster randomised controlled trial.
The lancet. Psychiatry, 2018

People with severe mental illnesses, including psychosis, have an increased risk of cardiovascular disease. We aimed to evaluate the effects of a primary care intervention on decreasing total cholesterol concentrations and cardiovascular disease risk in people with severe mental illnesses.
Methods to measure, model and manipulate fluid flow in brain.
Journal of neuroscience methods, 2020

The brain consists of a complex network of cells and matrix that is cushioned and nourished by multiple types of fluids: cerebrospinal fluid, blood, and interstitial fluid. The movement of these fluids through the tissues has recently gained more attention due to implications in Alzheimer's Disease and glioblastoma. Therefore, methods to study these fluid flows are necessary and timely for the current study of neuroscience. Imaging modalities such as magnetic resonance imaging have been used clinically and pre-clinically to image flows in healthy and diseased brains. These measurements have been used to both parameterize and validate models of fluid flow both computational and in vitro. Both of these models can elucidate the changes to fluid flow that occur during disease and can assist in linking the compartments of fluid flow with one another, a difficult challenge experimentally. In vitro models, though in limited use with fluid flow, allow the examination of cellular responses to physiological flow. To determine causation, in vivo methods have been developed to manipulate flow, including both physical and pharmacological manipulations, at each point of fluid movement of origination resulting in exciting findings in the preclinical setting. With new targets, such as the brain-draining lymphatics and glymphatic system, fluid flow and tissue drainage within the brain is an exciting and growing research area. In this review, we discuss the methods that currently exist to examine and test hypotheses related to fluid flow in the brain as we attempt to determine its impact on neural function.
Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains.
Brain sciences, 2015

Dystrophin-glycoprotein complex (DGC) is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin) of a muscle fiber to the extracellular matrix (ECM). Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies), and limb-girdle muscular dystrophies (sarcoglycanopathies), are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS), which is localized at the muscle membrane by DGC members (dystrophin and syntrophins), plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ) and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain.
Effect of long-term GH replacement therapy on cardiovascular outcomes in isolated GH deficiency compared with multiple pituitary hormone deficiencies: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults.
European journal of endocrinology, 2014

Isolated GH deficiency (IGHD) could provide a model to investigate the influence of GH deficiency per se and the effect of GH replacement therapy without the influence from other pituitary hormone deficiencies or their treatment. The aim of this study is to address the questions about differences between IGHD and multiple pituitary hormone deficiencies (MPHDs) in clinical presentation and in responsiveness to GH treatment.
The Biology of Forgetting-A Perspective.
Neuron, 2017

Pioneering research studies, beginning with those using Drosophila, have identified several molecular and cellular mechanisms for active forgetting. The currently known mechanisms for active forgetting include neurogenesis-based forgetting, interference-based forgetting, and intrinsic forgetting, the latter term describing the brain's chronic signaling systems that function to slowly degrade molecular and cellular memory traces. The best-characterized pathway for intrinsic forgetting includes "forgetting cells" that release dopamine onto engram cells, mobilizing a signaling pathway that terminates in the activation of Rac1/Cofilin to effect changes in the actin cytoskeleton and neuron/synapse structure. Intrinsic forgetting may be the default state of the brain, constantly promoting memory erasure and competing with processes that promote memory stability like consolidation. A better understanding of active forgetting will provide insights into the brain's memory management system and human brain disorders that alter active forgetting mechanisms.
Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice.
Scientific reports, 2017

Soybean oil consumption is increasing worldwide and parallels a rise in obesity. Rich in unsaturated fats, especially linoleic acid, soybean oil is assumed to be healthy, and yet it induces obesity, diabetes, insulin resistance, and fatty liver in mice. Here, we show that the genetically modified soybean oil Plenish, which came on the U.S. market in 2014 and is low in linoleic acid, induces less obesity than conventional soybean oil in C57BL/6 male mice. Proteomic analysis of the liver reveals global differences in hepatic proteins when comparing diets rich in the two soybean oils, coconut oil, and a low-fat diet. Metabolomic analysis of the liver and plasma shows a positive correlation between obesity and hepatic C18 oxylipin metabolites of omega-6 (ω6) and omega-3 (ω3) fatty acids (linoleic and α-linolenic acid, respectively) in the cytochrome P450/soluble epoxide hydrolase pathway. While Plenish induced less insulin resistance than conventional soybean oil, it resulted in hepatomegaly and liver dysfunction as did olive oil, which has a similar fatty acid composition. These results implicate a new class of compounds in diet-induced obesity-C18 epoxide and diol oxylipins.
Deciphering Sounds Through Patterns of Vibration on the Skin.
Neuroscience, 2021

Sensory substitution refers to the concept of feeding information to the brain via an atypical sensory pathway. We here examined the degree to which participants (deaf and hard of hearing) can learn to identify sounds that are algorithmically translated into spatiotemporal patterns of vibration on the skin of the wrist. In a three-alternative forced choice task, participants could determine the identity of up to 95% and on average 70% of the stimuli simply by the spatial pattern of vibrations on the skin. Performance improved significantly over the course of 1 month. Younger participants tended to score better, possibly because of higher brain plasticity, more sensitive skin, or better skills at playing digital games. Similar results were obtained with pattern discrimination, in which a pattern representing the sound of one word was presented to the skin, followed by that of a second word. Participants answered whether the word was the same or different. With minimal difference pairs (distinguished by only one phoneme, such as "house" and "mouse"), the best performance was 83% (average of 62%), while with non-minimal pairs (such as "house" and "zip") the best performance was 100% (average of 70%). Collectively, these results demonstrate that participants are capable of using the channel of the skin to interpret auditory stimuli, opening the way for low-cost, wearable sensory substitution for the deaf and hard of hearing communities.
Inhibition of the dopamine transporter as an animal model of bipolar disorder mania: Locomotor response, neuroimmunological profile and pharmacological modulation.
Journal of psychiatric research, 2018

Inhibition of dopamine transporter (DAT) by GBR12909 has been proposed as a pharmacological model of mania related to bipolar disorder (BD). Here we tested the hypothesis that GBR12909 injection impairs habituation and induces hyperlocomotion in mice, along with changes in cytokines and neurotrophic factors levels, as observed in BD patients. We also tested if lithium carbonate, sodium valproate and aripiprazole prevent GBR12909-induced locomotion. Male Swiss mice received GBR12909 (15 mg/kg) injections and locomotor responses were quantified in an open field. Cytokines and neurotrophic factors levels were assessed in the prefrontal cortex, striatum and hippocampus 30 min and 24 h after injections. Pre-treatments with lithium, valproate or aripiprazole were performed with single and repeated injection protocols. GBR12909 prevented motoric habituation and increased basal locomotion in habituated mice in the open field. This compound also induced changes in IL-2 and BDNF levels in prefrontal cortex; IL-2, IL-4 and IL-10 in striatum; and IL-10, IL-4, IFN-γ and NGF in hippocampus. GBR12909-induced hyperlocomotion was attenuated by lithium (12.5-100 mg/kg), but not valproate (75-300 mg/kg), and prevented by aripiprazole (0.1-10 mg/kg). Repeated injections of these drugs (twice a day for 3 days), however, failed to inhibit hyperlocomotion. The main limitations of the protocols in this study are the analysis of locomotion as the only behavioral parameter, changes in immune factors that may overlap with other psychiatric disorders and the lack chronic drug injections. Despite of these limitations, this study adds to previous literature suggesting DAT inhibition as a potential animal model of mania related to BD.
NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: a bipartisan affair?
Free radical biology & medicine, 2014

Microglia are the resident immune cells of the brain and play major roles in central nervous system development, maintenance, and disease. Brain insults cause microglia to proliferate, migrate, and transform into one or more activated states. Classical M1 activation triggers the production of proinflammatory factors such as tumor necrosis factor-α, interleukin-1β (IL-1β), nitric oxide, and reactive oxygen species (ROS), which, in excess, can exacerbate brain injury. The mechanisms underlying microglial activation are not fully understood, yet reactive oxygen species are increasingly implicated as mediators of microglial activation. In this review, we highlight studies linking reactive oxygen species, in particular hydrogen peroxide derived from NADPH oxidase-generated superoxide, to the classical activation of microglia. In addition, we critically evaluate controversial evidence suggesting a specific role for mitochondrial reactive oxygen species in the activation of the NLRP3 inflammasome, a multiprotein complex that mediates the production of IL-1β and IL-18. Finally, the limitations of common techniques used to implicate mitochondrial ROS in microglial and inflammasome activation, such as the use of the mitochondrially targeted ROS indicator MitoSOX and the mitochondrially targeted antioxidant MitoTEMPO, are also discussed.