rudyvdbrink/CitationDatabase huggingface dataset:
MuSK is a BMP co-receptor that shapes BMP responses and calcium signaling in muscle cells.
Science signaling, 2016

Bone morphogenetic proteins (BMPs) function in most tissues but have cell type-specific effects. Given the relatively small number of BMP receptors, this exquisite signaling specificity requires additional molecules to regulate this pathway's output. The receptor tyrosine kinase MuSK (muscle-specific kinase) is critical for neuromuscular junction formation and maintenance. Here, we show that MuSK also promotes BMP signaling in muscle cells. MuSK bound to BMP4 and related BMPs with low nanomolar affinity in vitro and to the type I BMP receptors ALK3 and ALK6 in a ligand-independent manner both in vitro and in cultured myotubes. High-affinity binding to BMPs required the third, alternatively spliced MuSK immunoglobulin-like domain. In myoblasts, endogenous MuSK promoted BMP4-dependent phosphorylation of SMADs and transcription of Id1, which encodes a transcription factor involved in muscle differentiation. Gene expression profiling showed that MuSK was required for the BMP4-induced expression of a subset of genes in myoblasts, including regulator of G protein signaling 4 (Rgs4). In myotubes, MuSK enhanced the BMP4-induced expression of a distinct set of genes, including transcripts characteristic of slow muscle. MuSK-mediated stimulation of BMP signaling required type I BMP receptor activity but was independent of MuSK tyrosine kinase activity. MuSK-dependent expression of Rgs4 resulted in the inhibition of Ca(2+) signaling induced by the muscarinic acetylcholine receptor in myoblasts. These findings establish that MuSK has dual roles in muscle cells, acting both as a tyrosine kinase-dependent synaptic organizing molecule and as a BMP co-receptor that shapes BMP transcriptional output and cholinergic signaling.
Sex differences and Tat expression affect dopaminergic receptor expression and response to antioxidant treatment in methamphetamine-sensitized HIV Tat transgenic mice.
Neuropharmacology, 2020

Methamphetamine (Meth) abuse is a common HIV comorbidity. Males and females differ in their patterns of Meth use, associated behaviors, and responses, but the underlying mechanisms and impact of HIV infection are unclear. Transgenic mice with inducible HIV-1 Tat protein in the brain (iTat) replicate many neurological aspects of HIV infection in humans. We previously showed that Tat induction enhances the Meth sensitization response associated with perturbation of the dopaminergic system, in male iTat mice. Here, we used the iTat mouse model to investigate sex differences in individual and interactive effects of Tat and Meth challenge on locomotor sensitization, brain expression of dopamine receptors (DRDs) and regulatory adenosine receptors (ADORAs). Because Meth administration increases the production of reactive oxygen species (ROS), we also determined whether the effects of Meth could be rescued by concomitant treatment with the ROS scavenger N-acetyl cysteine (NAC). After Meth sensitization and a 7-day abstinence period, groups of Tat+ and Tat-male and female mice were challenged with Meth in combination with NAC. We confirmed that Tat expression and Meth challenge suppressed DRD mRNA and protein in males and females' brains, and showed that females were particularly susceptible to the effects of Meth on D1-like and D2-like DRD subtypes and ADORAs. The expression of these markers differed strikingly between males and females, and between females in different phases of the estrous cycle, in a Tat -dependent manner. NAC attenuated Meth-induced locomotor sensitization and preserved DRD expression in all groups except for Tat + females. These data identify complex interactions between sex, Meth use, and HIV infection on addiction responses, with potential implications for the treatment of male and female Meth users in the context of HIV, especially those with cognitive disorders.
Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes.
Environmental research, 2017

Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6-9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (β^ - 0.13, 95% CI - 0.26, 0.00) but positively associated with Executive Functioning factor scores (β^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (β^ - 0.17, 95% CI - 0.33, - 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision.
Endocannabinoids produced upon action potential firing evoke a Cl(-) current via type-2 cannabinoid receptors in the medial prefrontal cortex.
Pflugers Archiv : European journal of physiology, 2014

The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl(-) current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl(-) channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca(2+) influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl(-) conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.
Neural modeling of antisaccade performance of healthy controls and early Huntington's disease patients.
Chaos (Woodbury, N.Y.), 2021

Huntington's disease (HD), a genetically determined neurodegenerative disease, is positively correlated with eye movement abnormalities in decision making. The antisaccade conflict paradigm has been widely used to study response inhibition in eye movements, and reliable performance deficits in HD subjects have been observed, including a greater number and timing of direction errors. We recorded the error rates and response latencies of early HD patients and healthy age-matched controls performing the mirror antisaccade task. HD participants displayed slower and more variable antisaccade latencies and increased error rates relative to healthy controls. A competitive accumulator-to-threshold neural model was then employed to quantitatively simulate the controls' and patients' reaction latencies and error rates and uncover the mechanisms giving rise to the observed HD antisaccade deficits. Our simulations showed that (1) a more gradual and noisy rate of accumulation of evidence by HD patients is responsible for the observed prolonged and more variable antisaccade latencies in early HD; (2) the confidence level of early HD patients making a decision is unaffected by the disease; and (3) the antisaccade performance of healthy controls and early HD patients is the end product of a neural lateral competition (inhibition) between a correct and an erroneous decision process, and not the end product of a third top-down stop signal suppressing the erroneous decision process as many have speculated.
Solid phase assays versus automated indirect immunofluorescence for detection of antinuclear antibodies.
Autoimmunity reviews, 2018

Solid phase assays (SPAs) and automated microscope systems are increasingly used to screen for antinuclear antibodies (ANAs). The goal of this study was to evaluate the performance of three automated ANA screening assays; NOVA Lite HEp-2 using NOVA View® (NV, Inova Diagnostics), an automated indirect immunofluorescence method, EliA™ CTD Screen (Fluorescence Enzyme Immunoassay, FEIA; Thermo Fisher) and QUANTA Flash® CTD Screen Plus (Chemiluminescence immunoassay, CIA; Inova Diagnostics). The assays were performed on 480 diagnostic samples from patients with an ANA-associated rheumatic disease (AARD; systemic lupus erythematosus, primary Sjögren's syndrome, systemic sclerosis, inflammatory myopathy, mixed connective tissue disease) and on 767 samples from diseased and healthy controls. Using cut-offs proposed by the manufacturers, the sensitivity was 95%, 80.5% and 86% for NV, FEIA and CIA, respectively. The corresponding specificity was 61% (NV), 97.5% (FEIA) and 88% (CIA). The sensitivity associated with a specificity of ~95% was 79%, 82% and 78% for NV, FEIA, and CIA, respectively. Receiver operating characteristics (ROC) curve analysis revealed no differences in area under the curve (AUC) between the 3 assays when all diseases were grouped. For Sjögren's syndrome, the AUC was higher for SPAs than for NV, whereas for systemic sclerosis, the AUC was higher for NV than for CIA. For all assays, the likelihood ratio for AARD increased with increasing antibody levels and for double positivity of NV with SPA. In conclusion, the performance of automated SPA and IIF was assay- and disease-dependent. Taking into account antibody levels and combining IIF with SPA adds value.
Sensory-motor integration in focal dystonia.
Neuropsychologia, 2015

Traditional definitions of focal dystonia point to its motor component, mainly affecting planning and execution of voluntary movements. However, focal dystonia is tightly linked also to sensory dysfunction. Accurate motor control requires an optimal processing of afferent inputs from different sensory systems, in particular visual and somatosensory (e.g., touch and proprioception). Several experimental studies indicate that sensory-motor integration - the process through which sensory information is used to plan, execute, and monitor movements - is impaired in focal dystonia. The neural degenerations associated with these alterations affect not only the basal ganglia-thalamic-frontal cortex loop, but also the parietal cortex and cerebellum. The present review outlines the experimental studies describing impaired sensory-motor integration in focal dystonia, establishes their relationship with changes in specific neural mechanisms, and provides new insight towards the implementation of novel intervention protocols. Based on the reviewed state-of-the-art evidence, the theoretical framework summarized in the present article will not only result in a better understanding of the pathophysiology of dystonia, but it will also lead to the development of new rehabilitation strategies.
Breathe: Your Mitochondria Will Do the Rest… If They Are Healthy!
Cell metabolism, 2019

Dysfunctions of the mitochondrial electron transport chain cause severe, currently untreatable, diseases in humans. A new study by Jain et al. (2019) reports increased oxygen levels in the brain of complex-I-deficient mice. Reducing the O
Cognitive impairment and McArdle disease: Is there a link?
Neuromuscular disorders : NMD, 2011

McArdle disease is caused by deficiency of myophosphorylase, the muscle isoform of glycogen phosphorylase. This isoform is also expressed in astrocytes, where it seems to have a key role in neural energy metabolism. Whereas in other glycogen storage diseases cognitive impairment has been rarely reported, it has not been previously observed in McArdle disease. Here we report the case of an Italian 55-year-old woman with McArdle disease and cognitive impairment with bilateral dysfunction of prefrontal and frontal cortex (shown by neuropsychological assessment and fluorodeoxyglucose PET). Further studies are needed to assess the prevalence of central neurological manifestations in this disease.
(-)-Epigallocatechin-3-Gallate Antihyperalgesic Effect Associates With Reduced CX3CL1 Chemokine Expression in Spinal Cord.
Phytotherapy research : PTR, 2017

(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the neuropathic pain alleviation in animal models. Because chemokine fractalkine (CX3CL1) has been suggested as an important signal during neuropathic pain development, this study aimed to investigate whether CX3CL1 expression may be modulated by EGCG treatment reducing hyperalgesia in chronic constriction injured mice. To this end, Balb/c mice were subjected to a chronic constriction injury of sciatic nerve (CCI) and treated with EGCG or vehicle once a day during the first week following surgery. Thermal hyperalgesia was tested at 7 and 14 days post-surgery, and the expression of CX3CL1 and its mRNA were analyzed in spinal cord at the end of the experimental period. Results revealed that EGCG treatment significantly reduced thermal hyperalgesia in CCI-injured mice at short time, and this antihyperalgesic effect was associated with a down-regulation of CX3CL1 protein expression in the spinal cord. On the other hand, EGCG treatment did not affect the CX3CL1 transcription. Overall, our results suggest a new role of EGCG-treatment in an experimental model of neuropathic pain as a mediator of nociceptive signaling cross talk between neurons and glial cells in the dorsal horn of the spinal cord. Copyright © 2016 John Wiley & Sons, Ltd.
Considering factors affecting the connectome-based identification process: Comment on Waller et al.
NeuroImage, 2018

A recent study by Waller and colleagues evaluated the reliability, specificity, and generalizability of using functional connectivity data to identify individuals from a group. The authors note they were able to replicate identification rates in a larger version of the original Human Connectome Project (HCP) dataset. However, they also report lower identification accuracies when using historical neuroimaging acquisitions with low spatial and temporal resolution. The authors suggest that their results indicate connectomes derived from historical imaging data may be similar across individuals, to the extent that this connectome-based approach may be inappropriate for precision psychiatry and the goal of drawing inferences based on subject-level data. Here we note that the authors did not take into account factors affecting data quality and hence identification rates, independent of whether a low spatiotemporal resolution acquisition or a high spatiotemporal resolution acquisition is used. Specifically, we show here that the amount of data collected per subject and in-scanner motion are the predominant factors influencing identification rates, not the spatiotemporal resolution of the acquisition. To do this, we investigated identification rates in the HCP dataset as a function of the amount of data and motion. Using a dataset from the Consortium for Reliability and Reproducibility (CoRR), we investigated the impact of multiband versus non-multiband imaging parameters; that is, high spatiotemporal resolution versus low spatiotemporal resolution acquisitions. We show scan length and motion affect identification, whereas the imaging protocol does not affect these rates. Our results suggest that motion and amount of data per subject are the primary factors impacting individual connectivity profiles, but that within these constraints, individual differences in the connectome are readily observable.
Facial and bodily emotion recognition in multiple sclerosis: the role of alexithymia and other characteristics of the disease.
Journal of the International Neuropsychological Society : JINS, 2014

Multiple sclerosis (MS) may be associated with impaired perception of facial emotions. However, emotion recognition mediated by bodily postures has never been examined in these patients. Moreover, several studies have suggested a relation between emotion recognition impairments and alexithymia. This is in line with the idea that the ability to recognize emotions requires the individuals to be able to understand their own emotions. Despite a deficit in emotion recognition has been observed in MS patients, the association between impaired emotion recognition and alexithymia has received little attention. The aim of this study was, first, to investigate MS patient's abilities to recognize emotions mediated by both facial and bodily expressions and, second, to examine whether any observed deficits in emotions recognition could be explained by the presence of alexithymia. Thirty patients with MS and 30 healthy matched controls performed experimental tasks assessing emotion discrimination and recognition of facial expressions and bodily postures. Moreover, they completed questionnaires evaluating alexithymia, depression, and fatigue. First, facial emotion recognition and, to a lesser extent, bodily emotion recognition can be impaired in MS patients. In particular, patients with higher disability showed an impairment in emotion recognition compared with patients with lower disability and controls. Second, their deficit in emotion recognition was not predicted by alexithymia. Instead, the disease's characteristics and the performance on some cognitive tasks significantly correlated with emotion recognition. Impaired facial emotion recognition is a cognitive signature of MS that is not dependent on alexithymia.
Neuromuscular adaptability of male and female rats to muscle unloading.
Journal of neuroscience research, 2018

Previously, it has been shown that following muscle unloading, males and females experience different maladaptations in neuromuscular function. As a follow-up, the present investigation sought to determine if male and female neuromuscular systems demonstrated similar, or disparate morphological adaptations to muscle unloading. Twenty young adult male, and 20 young adult female rats were randomly assigned to one of two treatment protocols: muscle unloading, or control conditions. Following the 2-week intervention period, immunofluorescent procedures were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs), and to assess myofiber profiles (size and fiber type composition) of the soleus, plantaris, and EDL muscles. A 2-way ANOVA with main effects for sex and treatment was then used to identify statistically significant (p ≤ .05) differences among structural parameters. Analysis of NMJs showed a consistent lack of differences between males and females. Overall, NMJs were also found to be resistant to the effects of unloading. When examining myofiber profiles, however, male myofibers were revealed to be significantly larger than female ones in each of the muscles examined. Unloading resulted in significant myofiber atrophy only in the primarily weight-bearing soleus muscle. Only the EDL showed unloading-induced differences in myofiber type distribution (Type II → I). These data indicate that different components of the neuromuscular system (NMJs, myofibers) respond uniquely to unloading, and that sex affects myofiber type profiles, but not NMJs. Moreover, it appears that only muscles that have their habitual activity patterns disturbed by unloading (i.e., the soleus, adapt to that intervention).
The difference of apparent diffusion coefficient in the middle cerebellar peduncle among parkinsonian syndromes: Evidence from a meta-analysis.
Journal of the neurological sciences, 2016

The measurement of middle cerebellar peduncle (MCP) width allows for differential diagnosis between Parkinson's disease (PD) and multiple system atrophy with predominant parkinsonian features (MSA-P). However, it remains controversial whether apparent diffusion coefficient (ADC) value in the MCP of MSA-P is elevated or not. In the present study, we aimed to assess the usefulness of ADC value in the MCP for differential diagnosis between PD and MSA-P. An on-line literature search yielded 5 eligible studies. We expressed between-group difference of ADC value as the standardized mean difference (SMD). The proportion of variation due to heterogeneity was computed and expressed as I(2). ADC in the MCP of MSA-P was significantly increased compared with PD with heterogeneous studies (P=0.0007, I(2)=81%). A meta-regression analysis of MSA-P was conducted for "UPDRS III", and revealed a significant correlation between UPDRS III and SMD (P=0.01). Our meta-regression analysis has clarified the contribution of severity of MSA-P to heterogeneity of the included studies for ADC in the MCP. This finding raised the possibility that ADC in the MCP depended on severity of MSA-P, and less severe patients with MSA-P should be mainly enrolled in future study to assess the ability for differential diagnostic tool.
GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries.
American journal of physiology. Heart and circulatory physiology, 2016

We investigated the acute effects of glucagon-like peptide-1 (GLP-1), GLP-1(1-36), and GLP-1(7-36) on vascular endothelial growth factor-A (VEGFA)-induced endothelium-dependent signaling and vasodilation. Our hypothesis was that GLP-1 released from intestinal l-cells modulates processes related to PLCγ activation, Src, and endothelial NOS (eNOS) signaling, thereby controlling endothelial vessel tone. By using RT-PCR analysis, we found mRNA for the GLP-1 receptor (GLP-1R) in human dermal microvascular endothelial cells (HDMEC), human retinal microvascular endothelial cells, and rat arteries. In isolated rat mesenteric resistance arteries precontracted with the thromboxane analog U46619 to 80-90% of maximum contraction, VEGFA (25 ng/ml) caused a small and gradual relaxation (28.9 ± 3.9%). Pretreatment of arteries with either GLP-1(1-36) (500 nM) or GLP-1(7-36) (1 nM) abolished the VEGFA-induced relaxation. VEGFA-induced relaxations were also inhibited in endothelial-denuded arteries and in arteries pretreated with the nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (100 μM). In vivo studies on male Wistar rats also revealed that GLP-1(7-36) inhibited VEGFA-induced vasodilation of the same arteries. In isolated endothelial cells, GLP-1(1-36) and GLP-1(7-36) caused a reduction in VEGFA-induced phosphorylation of PLCγ. Ca