rudyvdbrink/CitationDatabase huggingface dataset:
Robust neurocognitive individual differences in grammatical agreement processing: A latent variable approach.
Cortex; a journal devoted to the study of the nervous system and behavior, 2019

Many neurocognitive accounts of language processing presume that neural responses detected in grand mean analyses of cortical electrophysiological activity reflect the normative brain response in the population under investigation. However, emerging work now shows that individuals' brain responses can vary systematically in both the size and type of effect elicited. The present research therefore examined individual differences in neural activity elicited by grammatical agreement anomalies during language comprehension in a large cohort of highly literate, monolingual English speakers (N = 114), a population generally assumed to be relatively homogenous in terms of linguistic knowledge and processing. Results showed systematic variability in event-related brain potentials (ERPs) elicited by subject-verb agreement anomalies, with brain responses varying on a continuum between N400 and P600 dominant responses. Similar variation was found both when agreement was realized via inflectional morphology or via lexical alternations. Individuals' brain response type correlated strongly across these two conditions. Similar variation was also found for ERPs elicited during rapid serial visual presentation and when self-paced ERPs were recorded. Multilevel latent variable regression showed that variation in brain response amplitude and type was not related to individual differences in language experience or verbal working memory capacity, despite high statistical power. These findings indicate that descriptions of processing dynamics predicated solely on grand mean analyses of central tendency can fail to provide an accurate, generalizable account of how processing unfolds in many or most individual members of the population studied. Furthermore, these findings show that systematic individual variation in engagement of neural system supporting grammatical processing is found even in language users at the highest end of the proficiency spectrum and in grammatically simple sentences. This study therefore has implications for studies of language processing in atypical populations.
Microglia Purinoceptor P2Y6: An Emerging Therapeutic Target in CNS Diseases.
Cells, 2020

The purinergic receptor P2Y6 is expressed in immune cells, including the microglia that are implicated in neurological disorders. Its ligand, UDP, is a signaling molecule that can serve as an "find-me" signal when released in significant quantities by damaged/dying cells. The binding of UDP by P2Y6R leads to the activation of different biochemical pathways, depending on the disease context and the pathological environment. Generally, P2Y6R stimulates phagocytosis. However, whether or not phagocytosis coincides with cell activation or the secretion of pro-inflammatory cytokines needs further investigation. The current review aims to discuss the various functions of P2Y6R in some CNS disorders. We present evidence that P2Y6R may have a detrimental or beneficial role in the nervous system, in the context of neurological pathologies, such as ischemic stroke, Alzheimer's disease, Parkinson's disease, radiation-induced brain injury, and neuropathic pain.
Somatostatin, neuronal vulnerability and behavioral emotionality.
Molecular psychiatry, 2015

Somatostatin (SST) deficits are common pathological features in depression and other neurological disorders with mood disturbances, but little is known about the contribution of SST deficits to mood symptoms or causes of these deficits. Here we show that mice lacking SST (Sst(KO)) exhibit elevated behavioral emotionality, high basal plasma corticosterone and reduced gene expression of Bdnf, Cortistatin and Gad67, together recapitulating behavioral, neuroendocrine and molecular features of human depression. Studies in Sst(KO) and heterozygous (Sst(HZ)) mice show that elevated corticosterone is not sufficient to reproduce the behavioral phenotype, suggesting a putative role for Sst cell-specific molecular changes. Using laser capture microdissection, we show that cortical SST-positive interneurons display significantly greater transcriptome deregulations after chronic stress compared with pyramidal neurons. Protein translation through eukaryotic initiation factor 2 (EIF2) signaling, a pathway previously implicated in neurodegenerative diseases, was most affected and suppressed in stress-exposed SST neurons. We then show that activating EIF2 signaling through EIF2 kinase inhibition mitigated stress-induced behavioral emotionality in mice. Taken together, our data suggest that (1) low SST has a causal role in mood-related phenotypes, (2) deregulated EIF2-mediated protein translation may represent a mechanism for vulnerability of SST neurons and (3) that global EIF2 signaling has antidepressant/anxiolytic potential.
Nϵ-lysine acetylation in the lumen of the endoplasmic reticulum: A way to regulate autophagy and maintain protein homeostasis in the secretory pathway.
Autophagy, 2016

The Nϵ-lysine acetylation of cargo proteins in the lumen of the endoplasmic reticulum (ER) requires a membrane transporter (SLC33A1) and 2 acetyltransferases (NAT8B and NAT8). The ER acetylation machinery regulates the homeostatic balance between quality control/efficiency of the secretory pathway and autophagy-mediated disposal of toxic protein aggregates. We recently reported that the autophagy pathway that acts downstream of the ER acetylation machinery specifically targets protein aggregates that form within the secretory pathway. Genetic and biochemical manipulation of ER acetylation in a mouse model of Alzheimer disease is able to restore normal proteostasis and rescue the disease phenotype. Here we summarize these findings and offer an overview of the ER-acetylation machinery.
Thermal Hyperalgesia and Mechanical Allodynia Elicited by Histamine and Non-histaminergic Itch Mediators: Respective Involvement of TRPV1 and TRPA1.
Neuroscience, 2020

Acute itch is elicited by histamine, as well as non-histaminergic itch mediators including chloroquine, BAM8-22 and Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL). When injected intradermally, histamine binds to histamine H1 and H4 receptors that activate transient receptor potential vanilloid 1 (TRPV1) to depolarize pruriceptors. Chloroquine, BAM8-22, and SLIGRL, respectively, bind to Mas-related G-protein-coupled receptors MrgprA3, MrgprC11, and MrgprC11/PAR2 that in turn activate transient receptor potential ankyrin 1 (TRPA1). In this study we tested if histamine, chloroquine, BAM8-22 and SLIGRL elicit thermal hyperalgesia and mechanical allodynia in adult male mice. We measured the latency of hindpaw withdrawal from a noxious heat stimulus, and the threshold for hindpaw withdrawal from a von Frey mechanical stimulus. Intraplantar injection of histamine resulted in significant thermal hyperalgesia (p < 0.001) and mechanical allodynia (p < 0.001) ipsilaterally that persisted for 1 h. Pretreatment with the TRPV1 antagonist AMG-517 (10 or 20 μg), but not the TRPA1 antagonist HC-030031 (50 or 100 μg), significantly attenuated the magnitude and time course of thermal hyperalgesia and mechanical allodynia elicited by histamine (p < 0.001 for both), indicating that these effects are mediated by TRPV1. In contrast, pretreatment with the TRPA1 antagonist significantly reduced thermal hyperalgesia and mechanical allodynia elicited by chloroquine (p < 0.001 for both ), BAM-822 (p < 0.01, p < 0.001, respectively) and SLGRL (p < 0.05, p < 0.001, respectively), indicating that effects elicited by these non-histaminergic itch mediators require TRPA1. TRPV1 and TRPA1 channel inhibitors thus may have potential use in reducing hyperalgesia and allodynia associated with histaminergic and non-histaminergic itch, respectively.
High impulsivity predicts the switch to compulsive cocaine-taking.
Science (New York, N.Y.), 2008

Both impulsivity and novelty-seeking have been suggested to be behavioral markers of the propensity to take addictive drugs. However, their relevance for the vulnerability to compulsively seek and take drugs, which is a hallmark feature of addiction, is unknown. We report here that, whereas high reactivity to novelty predicts the propensity to initiate cocaine self-administration, high impulsivity predicts the development of addiction-like behavior in rats, including persistent or compulsive drug-taking in the face of aversive outcomes. This study shows experimental evidence that a shift from impulsivity to compulsivity occurs during the development of addictive behavior, which provides insights into the genesis and neural mechanisms of drug addiction.
[Sleep and Psychological Functioning of Children and Adolescents - a Narrative Review].
Praxis der Kinderpsychologie und Kinderpsychiatrie, 2019

Sleep and Psychological Functioning of Children and Adolescents - a Narrative Review Children and adolescents need sufficient and restoring sleep to improve their cognitive, emotional, social and behavioral performance. The present narrative review describes the associations between children's and adolescents' sleep patterns and a broad variety of topics; these topics were chosen at the authors' discretion and does not claim to be exhaustive. After a short introduction, we describe the associations between (adolescent) children's sleep in tight relation to the family functioning. Specifically, (adolescent) children's sleep and psychological functioning appears to be related to mothers' sleep and psychological functioning. Findings from longitudinal studies are reported, which underline that poor sleep at childhood increases the risk of poor sleep and somatic and psychological health issues later in life. Excessive screen time in the evening increases the risk of shorter sleep duration and increased daytime sleepiness; on the flip side, it also appears the excessive screen time might be a coping strategy to deal with symptoms of anxiety; further, using social media in the evening seems to be associated with the adolescents' need to stay in touch with their peers. While physical inactivity and sedentary behavior is a serious health concern, in children and adolescents, regular physical activity is associated with improved subjective and objective sleep and a broad variety of psychological health outcomes. Further selective topics are: While children and adolescents with repaired cleft did not show disadvantages in their sleep and psychological functioning compared to their counterparts without clefts, at the age of seven to nine years, very preterm children show unfavorable sleep patterns and psychological functioning, compared to typically developing children.
MEG Insight into the Spectral Dynamics Underlying Steady Isometric Muscle Contraction.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

To gain fundamental knowledge on how the brain controls motor actions, we studied in detail the interplay between MEG signals from the primary sensorimotor (SM1) cortex and the contraction force of 17 healthy adult humans (7 females, 10 males). SM1 activity was coherent at ∼20 Hz with surface electromyogram (as already extensively reported) but also with contraction force. In both cases, the effective coupling was dominant in the efferent direction. Across subjects, the level of ∼20 Hz coherence between cortex and periphery positively correlated with the "burstiness" of ∼20 Hz SM1 (Pearson
Alcohol drinking and brain morphometry in apparently healthy community-dwelling Japanese men.
Alcohol (Fayetteville, N.Y.), 2021

The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40-79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010-2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of <0.05. The results obtained demonstrated that the amount of alcohol consumed was associated with lower GMV. The VBM analysis showed lower GMV within the parahippocampal, entorhinal, cingulate, insular, temporal, and frontal cortices and cerebellum in very heavy drinkers (≥42 ethanol g/day) than in non-drinkers. Furthermore, alcohol consumption was associated with a higher white matter lesion volume. These results suggest subclinical structural changes similar to alcohol-related neurological diseases.
Seeing mental states: An experimental strategy for measuring the observability of other minds.
Physics of life reviews, 2018

Is it possible to perceive others' mental states? Are mental states visible in others' behavior? In contrast to the traditional view that mental states are hidden and not directly accessible to perception, in recent years a phenomenologically-motivated account of social cognition has emerged: direct social perception. However, despite numerous published articles that both defend and critique direct perception, researchers have made little progress in articulating the conditions under which direct perception of others' mental states is possible. This paper proposes an empirically anchored approach to the observability of others' mentality - not just in the weak sense of discussing relevant empirical evidence for and against the phenomenon of interest, but also, and more specifically, in the stronger sense of identifying an experimental strategy for measuring the observability of mental states and articulating the conditions under which mental states are observable. We conclude this article by reframing the problem of direct perception in terms of establishing a definable and measurable relationship between movement features and perceived mental states.
Spinal cord multi-parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis.
European journal of neurology, 2017

Assessing survival is a critical issue in patients with amyotrophic lateral sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by magnetic resonance imaging (MRI) and disease progression. The aim of the study was to determine the predictive added value of multimodal SC MRI on survival.
Stimulus dependency and mechanisms of surround modulation in cortical area MT.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

The perceptual interpretation of a given visual feature depends on the surrounding context. To explore the neural mechanisms underlying such contextual interactions in the motion domain, we studied responses of neurons in the middle temporal area (MT) of macaque monkeys while presenting a variety of center-surround stimuli that stimulated both the classical receptive visual field (CRF) and the receptive field surround. In human psychophysical experiments, the perceptual impact of the surround stimulus on the center stimulus varied from motion capture ("integration") to motion contrast ("segmentation"). In our neurophysiological experiments, the directional tuning of surround modulation with these stimuli ranged from antagonistic (consistent with motion contrast) to integrative (consistent with motion capture) and agreed qualitatively with perception under some but not all conditions. Most strikingly, for a stimulus that elicited perceptual motion contrast, surround modulation was integrative if the CRF stimulus was ambiguous due to the aperture problem. In addition, we found that surround modulation was linked to response magnitude: stimuli eliciting the largest responses yielded the strongest antagonism and those eliciting the smallest responses yielded the strongest integration. We developed a neural network model that accounts for this finding as well as a previous finding that surround suppression in area MT is contrast-dependent. Our findings suggest that changes in MT surround modulation result from shifts in the balance between directionally tuned excitation and inhibition mediated by changes in input strength. We speculate that input strength is, in turn, linked with the ambiguity of the motion present within the CRF.
Concurrent maternal and pup postnatal tobacco smoke exposure in Wistar rats changes food preference and dopaminergic reward system parameters in the adult male offspring.
Neuroscience, 2015

Children from pregnant smokers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption. Here, we studied the relationship between tobacco smoke exposure during lactation with feeding, behavior and brain dopaminergic reward system parameters at adulthood. Nursing Wistar rats and their pups were divided into two groups: tobacco smoke-exposed (S: 4times/day, from the 3rd to the 21th day of lactation), and ambient air-exposed (C). On PN175, both offspring groups were subdivided for a food challenge: S and C that received standard chow (SC) or that chose between high-fat (HFD) and high-sucrose diets (HSDs). Food intake was recorded after 30min and 12h. Offspring were tested in the elevated plus maze and open field on PN178-179; they were euthanized for dopaminergic analysis on PN180. SSD (self-selected diet) animals presented a higher food intake compared to SC ones. S-SSD animals ate more than C-SSD ones at 30min and 12h. Both groups preferred the HFD. However, S-SSD animals consumed relatively more HFD than C-SSD at 30min. No behavioral differences were observed between groups. S animals presented lower tyrosine hydroxylase (TH) content in the ventral tegmental area, lower TH, dopaminergic receptor 2, higher dopaminergic receptor 1 contents in the nucleus accumbens and lower OBRb in hypothalamic arcuate nucleus. Tobacco-smoke exposure during lactation increases preference for fat in the adult progeny possibly due to alterations in the dopaminergic system.
Ready-to-use food supplement, with or without arginine and citrulline, with daily chloroquine in Tanzanian children with sickle-cell disease: a double-blind, random order crossover trial.
The Lancet. Haematology, 2018

Sickle-cell disease increases the risk of malnutrition. Low arginine and nitric oxide bioavailability are implicated in morbidity related to sickle-cell disease. Simple interventions are required, especially in low-income settings. We aimed to test the hypotheses that: (1) supplementary arginine, citrulline, and daily chloroquine increase bioavailable arginine and flow-mediated dilatation (FMD; maximal diameter change; FMD
Hepatocyte Transfection in Small Pigs After Weaning by Hydrodynamic Intraportal Injection of Naked DNA/Minicircle Vectors.
Human gene therapy methods, 2015

Liver is an attractive organ for gene delivery in order to correct various genetic (metabolic) diseases. Hydrodynamic vein injection of naked DNA/minicircles devoid of viral or plasmid backbones was demonstrated in, for example, murine phenylketonuria to allow sustained therapeutic transduction of hepatocytes. Here we show successful hepatocyte transfusion in domestic small pigs immediately after weaning upon portal vein catheterization and hydrodynamic injection of naked DNA/minicircle vectors expressing the luciferase gene from the CMV or a liver-specific promoter. First, we established a surgical method allowing hydrodynamic portal vein pressurization up to 120 mmHg and infusion of naked DNA in pigs (n = 5) with long-term survival. No acute adverse effects such as changes in liver transaminases or signs of liver cell damage were observed. We then showed efficiency of stable hepatocyte transfection at 10 and 28 days in single experiments (n = 7) where we found that up to 60% of samples (45/75) were polymerase chain reaction (PCR)-positive for minicircle-DNA. Of these samples, 13% of the positive specimen (6/45) showed low but stable luciferase expression when driven by a liver-specific promoter, as well as appropriate copy numbers per diploid genome. In conclusion, we accomplished a safe procedure for stable transfection of liver cells upon hydrodynamic gene delivery using minicircle vectors in small pigs as a prerequisite to potentially treat infants with genetic liver diseases.
Onecut factors control development of the Locus Coeruleus and of the mesencephalic trigeminal nucleus.
Molecular and cellular neurosciences, 2012

The Locus Coeruleus (LC), the main noradrenergic nucleus in the vertebrate CNS, contributes to the regulation of several processes including arousal, sleep, adaptative behaviors and stress. Regulators controlling the formation of the LC have been identified but factors involved in its maintenance remain unknown. Here, we show that members of the Onecut (OC) family of transcription factors, namely HNF-6, OC-2 and OC-3, are required for maintenance of the LC phenotype. Indeed, in embryos lacking any OC proteins, LC neurons properly differentiate but abnormally migrate and eventually lose their noradrenergic characteristics. Surprisingly, the expression of Oc genes in these neurons is restricted to the earliest differentiation stages, suggesting that OC factors may regulate maintenance of the LC in a non cell-autonomous manner. Accordingly, the OC factors are present throughout development in a population directly adjacent to the LC, the rhombencephalic portion of the mesencephalic trigeminal nucleus (MTN). In the absence of OC factors, rhombencephalic MTN neurons fail to be generated, suggesting that OC proteins cell-autonomously control their production. Hence, we propose that OC factors are required at early developmental stages for differentiation of the MTN neurons that are in turn necessary for maintenance of the LC.
Stepwise shortening of agalsidase beta infusion duration in Fabry disease: Clinical experience with infusion rate escalation protocol.
Molecular genetics & genomic medicine, 2021

Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients' quality of life. Moreover, regular infusions are time-consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate.