rudyvdbrink/CitationDatabase huggingface dataset:
Stepping forward, stepping backward: a movement-related cortical potential study unveils distinctive brain activities.
Behavioural brain research, 2020

Human locomotion is the product of complex dynamic systems, which rely on physical capacities as well as cognitive functions. In our daily life, we mostly experience forward walking, but also backward stepping can occur, as in protective stepping. In this work, we investigated the electroencephalographic (EEG) correlates of cognitive processing underpinning step initiation by means of movement-related cortical potentials (MRCPs) analysis and force-plates recordings. Healthy young volunteers (N = 11) performed self-paced forward- and backward-oriented steps on two force platforms, which were synchronized to simultaneous EEG recordings. MRCPs and their source localization analyses were computed. Results demonstrate the involvement of cognitive processing during step preparation and execution, as showed by the prefrontal activity, which was enhanced in backward stepping. Further, the parietal activity was larger in forward than backward stepping, while motor-related regions were involved in both step directions. Thus, the neural timing and sources of forward and backward stepping suggest a functional distinction of these two actions, which undergo different cortical organizations. Backward stepping requires enhanced cognitive control and can be regarded as an avoidance behavior, while forward stepping would be assimilated to an oriented-to-action behavior mainly localized over parietal areas. In conclusion, preparing body locomotion involves high cognitive processing, with step direction showing different cortical organization and functional specialization.
The Irritability Questionnaire: a new scale for the measurement of irritability.
Psychiatry research, 2008

Irritability is an important symptom in patients with neuropsychiatric disorders. It is a major source of distress to patients and their carers and can lead to social and family dysfunction. Despite this, there has been little systematic research on irritability in psychiatry. The development of an instrument that captures the various components of irritability is a prerequisite to more detailed research in this area. The aim of this study was to design a scale to measure irritable mood and to explore its nature and subtypes. Following a review of the literature and examination of current theories in affective neuroscience, a new self-rating questionnaire was developed covering a range of subjective experiences, judgements and behaviours deemed to encompass the components of irritability. The items were rated along intensity and frequency dimensions. The questionnaire was administered to patients with affective disorders (n=22), Huntington's disease (n=23), Alzheimer's disease (n=19) and a control group (n=46). The new questionnaire shows good reliability and validity. Preliminary differences in irritability were identified between the diagnostic groups.
Paraspinal muscle asymmetry in Parkinson's disease.
The International journal of neuroscience, 2014

Lateral postural deviation in Parkinson's disease (PD) is not uncommon but has never been radiographically queried to evaluate for specific muscle anatomy. Ten subjects (9 female) were identified with paraspinal asymmetry on examination and MRI. Relative atrophy was seen diffusely in all paraspinal muscles (psoas, interspinalis, quadratus, multifidus, longissimus and ileocostalis). The quadratus, multifidus, longissimus and ileocostalis were the most asymmetric and equally involved. The interspinalis was less asymmetric, whereas the psoas was almost never asymmetric. Fatty infiltrates, consistent with radiographic myopathic degeneration, were often seen in the atrophic muscles. In 8/10 cases, the side of PD symptom onset demonstrated the greatest atrophy. Lateral postural deviation appears to result from ipsilateral paraspinal atrophy with fatty infiltration. Correlation with the most affected side suggests causality.
Characteristics, applications and prospects of mesenchymal stem cells in cell therapy.
Medicina clinica, 2017

Recent advances in the field of cell therapy and regenerative medicine describe mesenchymal stem cells (MSCs) as potential biological products due to their ability to self-renew and differentiate. MSCs are multipotent adult cells with immunomodulatory and regenerative properties, and, given their therapeutic potential, they are being widely studied in order to evaluate their viability, safety and efficacy. In this review, we describe the main characteristics and cellular sources of MSCs, in addition to providing an overview of their properties and current clinical applications, as well offering updated information on the regulatory aspects that define them as somatic cell therapy products. Cell therapy based on MSCs is offered nowadays as a pharmacological alternative, although there are still challenges to be addressed in this regard.
[Sensitive skin, reactive skin].
Annales de dermatologie et de venereologie, 2019

Sensitive skin (or reactive skin) is defined as a syndrome involving the onset of unpleasant sensations (stinging sensation, burning sensation, pain, pruritus, tingling) in response to stimuli that do not normally produce such sensations. These unpleasant sensations cannot be accounted for by lesions attributable to any specific skin disease. The skin may appear normal or erythema may be present. Sensitive skin can occur on any part of the skin but particularly affects the face. Sensitive skin is very common and affects around half of the population to different degrees. The diagnosis is based primarily on clinical examination. The physiopathology of the condition is becoming better known: it appears to be caused by hyperreactivity of the cutaneous nervous system and is associated in particular with activation of sensorial proteins present on keratinocytes and nerve endings. However, there is still no consensus regarding treatment.
Tissue Transglutaminase Appears in Monocytes and Macrophages but Not in Lymphocytes in White Matter Multiple Sclerosis Lesions.
Journal of neuropathology and experimental neurology, 2019

Leukocyte infiltration is an important pathological hallmark of multiple sclerosis (MS) and is therefore targeted by current MS therapies. The enzyme tissue transglutaminase (TG2) contributes to monocyte/macrophage migration and is present in MS lesions and could be a potential therapeutic target. We examined the cellular identity of TG2-expressing cells by immunohistochemistry in white matter lesions of 13 MS patients; 9 active and chronic active lesions from 4 patients were analyzed in detail. In these active MS lesions, TG2 is predominantly expressed in leukocytes (CD45+) but not in cells of the lymphocyte lineage, that is, T cells (CD3+) and B cells (CD20+). In general, cells of the monocyte/macrophage lineage (CD11b+ or CD68+) are TG2+ but no further distinction could be made regarding pro- or anti-inflammatory macrophage subtypes. In conclusion, TG2 is abundantly present in cells of the monocyte/macrophage lineage in active white matter MS lesions. We consider that TG2 can play a role in MS as it is associated with macrophage infiltration into the CNS. As such, TG2 potentially presents a novel target for therapeutic intervention that can support available MS therapies targeting lymphocyte infiltration.
Potential involvement of DSCAML1 mutations in neurodevelopmental disorders.
Genes to cells : devoted to molecular & cellular mechanisms, 2021

The molecular mechanisms underlying neurodevelopmental disorders (NDDs) remain unclear. We previously identified Down syndrome cell adhesion molecule like 1 (Dscaml1) as a responsible gene for Ihara epileptic rat (IER), a rat model for human NDDs with epilepsy. However, the relationship between NDDs and DSCAML1 in humans is still elusive. In this study, we screened databases of autism spectrum disorders (ASD), intellectual disability (ID)/developmental disorders (DD) and schizophrenia for genomic mutations in human DSCAML1. We then performed in silico analyses to estimate the potential damage to the mutated DSCAML1 proteins and chose three representative mutations (DSCAML1
Are there any robust predictors of "sudden gainers," and how is sustained improvement in treatment outcome achieved following a gain?
Journal of consulting and clinical psychology, 2019

It has been widely demonstrated that the process of change many patients undergo in therapy is not linear. Some patients benefit greatly from large sudden improvements, commonly referred to as "sudden gains." It is less clear whether certain baseline characteristics make patients more prone to displaying sudden gains, as well as what mechanisms are responsible for the lasting effects of sudden gains.
The significance of intercalated discs in the pathogenesis of Friedreich cardiomyopathy.
Journal of the neurological sciences, 2016

Friedreich ataxia (FRDA) is an autosomal recessive disorder with a complex clinical and neuropathological phenotype, but the most frequent cause of death is cardiomyopathy. The principal autopsy findings in FRDA hearts are concentric hypertrophy, enlargement of cardiomyocytes, myofiber necrosis, inflammatory infiltration, scarring, and random accumulation of iron. In addition, the myocardium shows generalized disorganization of intercalated discs (ICD), the Velcro-like end-to-end connections of heart fibers that provide mechanical cohesion and ionic coupling. The principal components of ICD are fascia adherens junctions (FAJ), desmosomes, and gap junctions. Frataxin deficiency in FRDA may cause improper assembly of ICD early in life, making hearts vulnerable to mechanical stress in childhood and adolescence. We studied the ICD in the myocardium of left ventricular wall (LVW), right ventricular wall, and ventricular septum in 18 genetically confirmed FRDA patients (age of death, 10 to 87years) and 12 normal controls (age of death, 13 to 69years). In cases with juvenile onset, electron microscopy and immunohistochemistry of N-cadherin and vinculin, two abundant FAJ proteins, showed enlargement of ICD, discontinuity, and hyperconvolution. Reaction product of the desmosomal protein desmoglein 2 was similar. The distribution of the gap junction protein connexin 43 at ICD was also irregular and displayed abnormal lateralization to the plasma membranes of cardiomyocytes. Confocal immunofluorescence microscopy of α-actinin, affinity fluorescence microscopy of actin with rhodamine-labeled phalloidin, and electron microscopy, revealed the principal integrity of sarcomeres of the myocardium in FRDA. In two late-onset long-surviving FRDA patients (ages 79 and 87), clinical cardiomyopathy was absent, and ICD were normal. The described observations in patients with a broad range of disease onset and duration allow us to conclude that faulty assembly of ICD interferes with proper end-to-end adhesion of cardiomyocytes of the growing heart and contributes to the pathogenesis of FRDA cardiomyopathy.
CANDOCK: Chemical Atomic Network-Based Hierarchical Flexible Docking Algorithm Using Generalized Statistical Potentials.
Journal of chemical information and modeling, 2020

Small-molecule docking has proven to be invaluable for drug design and discovery. However, existing docking methods have several limitations such as improper treatment of the interactions of essential components in the chemical environment of the binding pocket (e.g., cofactors, metal ions, etc.), incomplete sampling of chemically relevant ligand conformational space, and the inability to consistently correlate docking scores of the best binding pose with experimental binding affinities. We present CANDOCK, a novel docking algorithm, that utilizes a hierarchical approach to reconstruct ligands from an atomic grid using graph theory and generalized statistical potential functions to sample biologically relevant ligand conformations. Our algorithm accounts for protein flexibility, solvent, metal ions, and cofactor interactions in the binding pocket that are traditionally ignored by current methods. We evaluate the algorithm on the PDBbind, Astex, and PINC proteins to show its ability to reproduce the binding mode of the ligands that is independent of the initial ligand conformation in these benchmarks. Finally, we identify the best selector and ranker potential functions such that the statistical score of the best selected docked pose correlates with the experimental binding affinities of the ligands for any given protein target. Our results indicate that CANDOCK is a generalized flexible docking method that addresses several limitations of current docking methods by considering all interactions in the chemical environment of a binding pocket for correlating the best-docked pose with biological activity. CANDOCK along with all structures and scripts used for benchmarking is available at https://github.com/chopralab/candock_benchmark.
Behavioral despair associated with a mouse model of Crohn's disease: Role of nitric oxide pathway.
Progress in neuro-psychopharmacology & biological psychiatry, 2016

Crohn's disease (CD) is associated with increased psychiatric co-morbidities. Nitric oxide (NO) is implicated in inflammation and tissue injury in CD, and it may also play a central role in pathogenesis of the accompanying behavioral despair. This study investigated the role of the NO pathway in behavioral despair associated with a mouse model of CD. Colitis was induced by intrarectal (i.r.) injection of 2,4,6-trinitrobenzenesulfonic acid (10mg TNBS in 50% ethanol). Forced swimming test (FST), pharmacological studies and tissues collection were performed 72 h following TNBS administration. To address a possible inflammatory origin for the behavioral despair following colitis induction, tumor necrosis factor-alpha (TNF-α) level was measured in both the hippocampal and colonic tissue samples. In parallel, hippocampal inducible nitric oxide synthase (iNOS) and nitrite level were evaluated. Pharmacological studies targeting the NO pathway were performed 30-60 min before behavioral test. Colitis was confirmed by increased colonic TNF-α level and microscopic score. Colitic mice demonstrated a significantly higher immobility time in the FST associated to a significant increase of hippocampal TNF-α, iNOS expression and nitrite content. Acute NOS inhibition using either Nω-nitro-l-arginine methyl ester (a non-specific NOS inhibitor) or aminoguanidine hydrochloride (a specific iNOS inhibitor) decreased the immobility time in colitic groups. Moreover, acute treatment with both NOS inhibitors decreased the TNF-α level and nitrite content in the hippocampal samples. This study suggests that the NO pathway may be involved in the behavioral effects in the mouse TNBS model of CD. These findings endow new insights into the gut-brain communication during the development of colonic inflammation, which may ultimately lead to improved therapeutic strategies to combat behavior changes associated with gastrointestinal disorders.
Evoked potentials as a translatable biomarker to track functional remyelination.
Molecular and cellular neurosciences, 2019

Enhancing remyelination is a key therapeutic strategy for demyelinating diseases such as multiple sclerosis. To achieve this goal, a central challenge is being able to quantitatively and longitudinally track functional remyelination, especially with translatable biomarkers that can be performed in both preclinical models and in the clinic. We developed the methodology to stably measure multi-modal sensory evoked potentials from the skull surface over the course of months in individual mice and applied it to a genetic mouse model of oligodendrocyte ablation and demyelination. We found that auditory and somatosensory evoked potential latencies reliably increased over time during the early phase of the model and recovered spontaneously and almost completely during a later phase. Histological examination supported the interpretation that the evoked potential latency changes dynamically reflect changes in CNS myelination. Specifically, we found reduction of myelination in corresponding brain regions at the time that sensory evoked potentials were maximally impacted. Importantly, we also found that myelination levels recovered when evoked potential latencies recovered. Other changes known to associate with demyelination were also observed at the time of delayed evoked potentials, including the emergence of white matter vacuoles and increased markers for activated microglia and macrophages; these changes also fully reversed by the time that evoked potentials recovered. Our results support the hypothesis that skull-surface recorded evoked potential latencies can dynamically track CNS myelination changes. The methods developed here allow for longitudinally tracking functional myelination changes in vivo in preclinical rodent models with a quantitative biomarker that can also be applied clinically and will facilitate translational development of CNS remyelinating therapies.
Lateral Prefrontal Cortex Contributes to Fluid Intelligence Through Multinetwork Connectivity.
Brain connectivity, 2015

Our ability to effectively adapt to novel circumstances--as measured by general fluid intelligence--has recently been tied to the global connectivity of lateral prefrontal cortex (LPFC). Global connectivity is a broad measure that summarizes both within-network connectivity and across-network connectivity. We used additional graph theoretical measures to better characterize the nature of LPFC connectivity and its relationship with fluid intelligence. We specifically hypothesized that LPFC is a connector hub with an across-network connectivity that contributes to fluid intelligence independent of within-network connectivity. We verified that LPFC was in the top 10% of brain regions in terms of across-network connectivity, suggesting it is a strong connector hub. Importantly, we found that the LPFC across-network connectivity predicted individuals' fluid intelligence and this correlation remained statistically significant when controlling for global connectivity (which includes within-network connectivity). This supports the conclusion that across-network connectivity independently contributes to the relationship between LPFC connectivity and intelligence. These results suggest that LPFC contributes to fluid intelligence by being a connector hub with a truly global multisystem connectivity throughout the brain.
Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR DNA binding protein-43 C-terminal fragments.
Molecular neurodegeneration, 2010

Inclusions of TAR DNA binding protein-43 (TDP-43) are the defining histopathological feature of several neurodegenerative diseases collectively referred to as TDP-43 proteinopathies. These diseases are characterized by the presence of cellular aggregates composed of abnormally phosphorylated, N-terminally truncated and ubiquitinated TDP-43 in the spinal cord and/or brain. Recent studies indicate that C-terminal fragments of TDP-43 are aggregation-prone and induce cytotoxicity. However, little is known regarding the pathways responsible for the degradation of these fragments and how their phosphorylation contributes to the pathogenesis of disease.
Overestimation and contraction biases of depth information stored in working memory depend on spatial configuration.
British journal of psychology (London, England : 1953), 2021

Depth perception is essential for effective interaction with the environment. Although the accuracy of depth perception has been studied extensively, it is unclear how accurate the depth information is stored in working memory. In this study, we investigated the accuracy and systematic biases of depth representation by a delayed estimation task. The memory array consisted of items presented at various stereoscopic depth positions, and the participants were instructed to estimate the depth position of one target item after a retention interval. We examined the effect of spatial configuration by comparing the memory performance in the whole-display condition where non-target memory items were present during retrieval with that in the single-display condition where non-target memory items were absent. In the single-display condition, we found an overestimation bias that the depth estimates were farther than the corresponding depth positions defined by disparity, and a contraction bias that the stored depth positions near the observer were overestimated and those far from the observer were underestimated. The magnitude of these biases increased with the number of to-be-stored items. However, in the whole-display condition, the overestimation bias was corrected and the contraction bias did not increase with the number of to-be-stored items. Our findings suggested that the number of to-be-stored items could affect the accuracy of depth working memory, and its effect depended crucially on whether the information of spatial configuration of memory display was available at the retrieval stage.
Dopamine Modulates the Activity of Sensory Hair Cells.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

The senses of hearing and balance are subject to modulation by efferent signaling, including the release of dopamine (DA). How DA influences the activity of the auditory and vestibular systems and its site of action are not well understood. Here we show that dopaminergic efferent fibers innervate the acousticolateralis epithelium of the zebrafish during development but do not directly form synapses with hair cells. However, a member of the D1-like receptor family, D1b, tightly localizes to ribbon synapses in inner ear and lateral-line hair cells. To assess modulation of hair-cell activity, we reversibly activated or inhibited D1-like receptors (D1Rs) in lateral-line hair cells. In extracellular recordings from hair cells, we observed that D1R agonist SKF-38393 increased microphonic potentials, whereas D1R antagonist SCH-23390 decreased microphonic potentials. Using ratiometric calcium imaging, we found that increased D1R activity resulted in larger calcium transients in hair cells. The increase of intracellular calcium requires Cav1.3a channels, as a Cav1 calcium channel antagonist, isradipine, blocked the increase in calcium transients elicited by the agonist SKF-38393. Collectively, our results suggest that DA is released in a paracrine fashion and acts at ribbon synapses, likely enhancing the activity of presynaptic Cav1.3a channels and thereby increasing neurotransmission.
beta-Alanine elevates dopamine levels in the rat nucleus accumbens: antagonism by strychnine.
Amino acids, 2010

Glycine receptors (GlyRs) in the nucleus accumbens (nAc) have recently been suggested to be involved in the reinforcing and dopamine-elevating properties of ethanol via a neuronal circuitry involving the VTA. Apart from ethanol, both glycine and taurine have the ability to modulate dopamine output via GlyRs in the same brain region. In the present study, we wanted to explore whether yet another endogenous ligand for the GlyR, beta-alanine, had similar effects. To this end, we monitored dopamine in the nAc by means of in vivo microdialysis and found that local perfusion of beta-alanine increased dopamine output. In line with previous observations investigating ethanol, glycine and taurine, the competitive GlyR antagonist strychnine completely blocked the dopamine elevation. The present results suggest that beta-alanine has the ability to modulate dopamine levels in the nAc via strychnine-sensitive GlyRs, and are consistent with previous studies suggesting the importance of this receptor for modulating dopamine output.