rudyvdbrink/CitationDatabase huggingface dataset:
Administration of S-methyl-L-thiocitrulline protects against brain injuries after intracerebral hemorrhage.
Neuroscience, 2014

Although intracerebral hemorrhage (ICH) increases the level of glutamate in the perihematomal area and cerebral spinal fluid (CSF) in the ICH acute phase, it is unclear whether elevated glutamate activates neuronal nitric oxide synthase (nNOS) in the ICH brain and whether nNOS is an important target for ICH treatment. Here, we assessed the role of the nNOS inhibitor S-methyl-l-thiocitrulline (SMTC) in the activity of NADPH-d and ICH-induced brain injuries. An autologous blood intracerebral infusion model in male rats was used. All of the rats were sacrificed 24h after ICH. ICH increased NADPH-d activity in the striatum. Administering SMTC 3h after ICH decreased the activity of NADH-d (p<0.05 vs. the ICH group). The activation of gelatinolytic enzymes in the perihematomal region of the striatum was reduced by SMTC treatment (p<0.01, vs. the ICH group). The loss of laminin- and occludin-stained vessels was significant in perihematomal regions after 24h of ICH and was significantly attenuated by the administration of SMTC (p<0.01 for laminin, p<0.05 for occluding, compared with the ICH group). Neuronal death and neurological deficits after ICH were also decreased in SMTC treatment rats (p<0.01, vs. the ICH group). The results suggest that the administration of the nNOS inhibitor SMTC after ICH protects against ICH-induced brain injuries and improves neurological function.
KCNK18 (TRESK) genetic variants in Italian patients with migraine.
Headache, 2014

To evaluate the prevalence of KCNK18 gene mutations in a dataset of Italian migraineurs, with and without aura, and in healthy controls, and to investigate in silico the functional effects of the mutations.
Preference for attractive faces is species-specific.
Journal of comparative psychology (Washington, D.C. : 1983), 2019

Studies on facial attractiveness in human adults, infants, and newborns have consistently reported a visual preference for faces rated as attractive compared with faces rated as unattractive. Biological accounts of facial attractiveness have typically presented such preferences as arising from adaptations for mate choice or as by-products of general sensory bias. In this cross-species study, we examined whether explicit ratings of attractiveness made by human judges would predict implicit visual preferences in other humans and also in rhesus macaques and, if they do, whether such preferences would extend beyond conspecific faces. Results showed that human ratings of attractiveness can predict implicit preferences in nonhuman primates (macaque monkeys;
Neuronal Protein Farnesylation Regulates Hippocampal Synaptic Plasticity and Cognitive Function.
Molecular neurobiology, 2021

Protein prenylation is a post-translational lipid modification that governs a variety of important cellular signaling pathways, including those regulating synaptic functions and cognition in the nervous system. Two enzymes, farnesyltransferase (FT) and geranylgeranyltransferase type I (GGT), are essential for the prenylation process. Genetic reduction of FT or GGT ameliorates neuropathology but only FT haplodeficiency rescues cognitive function in transgenic mice of Alzheimer's disease. A follow-up study showed that systemic or forebrain neuron-specific deficiency of GGT leads to synaptic and cognitive deficits under physiological conditions. Whether FT plays different roles in shaping neuronal functions and cognition remains elusive. This study shows that in contrast to the detrimental effects of GGT reduction, systemic haplodeficiency of FT has little to no impact on hippocampal synaptic plasticity and cognition. However, forebrain neuron-specific FT deletion also leads to reduced synaptic plasticity, memory retention, and hippocampal dendritic spine density. Furthermore, a novel prenylomic analysis identifies distinct pools of prenylated proteins that are affected in the brain of forebrain neuron-specific FT and GGT knockout mice, respectively. Taken together, this study uncovers that physiological levels of FT and GGT in neurons are essential for normal synaptic/cognitive functions and that the prenylation status of specific signaling molecules regulates neuronal functions.
Scalable Semisupervised Functional Neurocartography Reveals Canonical Neurons in Behavioral Networks.
Neural computation, 2016

Large-scale data collection efforts to map the brain are underway at multiple spatial and temporal scales, but all face fundamental problems posed by high-dimensional data and intersubject variability. Even seemingly simple problems, such as identifying a neuron/brain region across animals/subjects, become exponentially more difficult in high dimensions, such as recognizing dozens of neurons/brain regions simultaneously. We present a framework and tools for functional neurocartography-the large-scale mapping of neural activity during behavioral states. Using a voltage-sensitive dye (VSD), we imaged the multifunctional responses of hundreds of leech neurons during several behaviors to identify and functionally map homologous neurons. We extracted simple features from each of these behaviors and combined them with anatomical features to create a rich medium-dimensional feature space. This enabled us to use machine learning techniques and visualizations to characterize and account for intersubject variability, piece together a canonical atlas of neural activity, and identify two behavioral networks. We identified 39 neurons (18 pairs, 3 unpaired) as part of a canonical swim network and 17 neurons (8 pairs, 1 unpaired) involved in a partially overlapping preparatory network. All neurons in the preparatory network rapidly depolarized at the onsets of each behavior, suggesting that it is part of a dedicated rapid-response network. This network is likely mediated by the S cell, and we referenced VSD recordings to an activity atlas to identify multiple cells of interest simultaneously in real time for further experiments. We targeted and electrophysiologically verified several neurons in the swim network and further showed that the S cell is presynaptic to multiple neurons in the preparatory network. This study illustrates the basic framework to map neural activity in high dimensions with large-scale recordings and how to extract the rich information necessary to perform analyses in light of intersubject variability.
Chemical and thermal unfolding of glypican-1: protective effect of heparan sulfate against heat-induced irreversible aggregation.
Biochemistry, 2009

Glypicans are cell-surface heparan sulfate proteoglycans that influence Wnt, hedgehog, decapentaplegic, and fibroblast growth factor activity via their heparan sulfate chains. However, recent studies have shown that glypican core proteins also have a role in growth factor signaling. Here, we expressed secreted recombinant human glypican-1 in eukaryotic cells. Recombinant glypican-1 was expressed as two glycoforms, one as proteoglycan substituted with heparan sulfate chains and one as the core protein devoid of glycosaminoglycans. Far-UV circular dichroism (CD) analysis of glypican-1 isolated under native conditions showed that the glypican-1 core protein is predominantly alpha-helical in structure, with identical spectra for the core protein and the proteoglycan form. The conformational stability of glypican-1 core protein to urea and guanidine hydrochloride denaturation was monitored by CD and fluorescence spectroscopy and showed a single unfolding transition at high concentrations of the denaturant (5.8 and 2.6 M, respectively). Renaturation from guanidine hydrochloride gave far-UV CD and fluorescence spectra identical to the spectra of native glypican-1. Thermal denaturation monitored by CD and differential scanning calorimetry (DSC) showed a single structural transition at a temperature of approximately 70 degrees C. Refolding of the heat-denatured glypican-1 core protein was dependent on protein concentration, suggesting that intermolecular interactions are involved in irreversible denaturation. However, refolding was concentration-independent for the proteoglycan form, suggesting that O-glycosylation protects the protein from irreversible aggregation. In summary, we have shown that the glypican-1 core protein is a stable alpha-helical protein and that the proteoglycan form of glypican-1 is protected from heat-induced aggregation.
A study of bio-hybrid silsesquioxane/yeast: Biosorption and neuronal toxicity of lead.
Journal of biotechnology, 2017

Lead is a heavy metal of high impact for the environment as well as for human health, being cause of several diseases. Considering the importance of obtaining an effective treatment for lead removal, a new hybrid material was developed for sorption of Pb
Sensory Cortical Control of a Visually Induced Arrest Behavior via Corticotectal Projections.
Neuron, 2015

Innate defense behaviors (IDBs) evoked by threatening sensory stimuli are essential for animal survival. Although subcortical circuits are implicated in IDBs, it remains largely unclear whether sensory cortex modulates IDBs and what the underlying neural pathways are. Here, we show that optogenetic silencing of corticotectal projections from layer 5 (L5) of the mouse primary visual cortex (V1) to the superior colliculus (SC) significantly reduces an SC-dependent innate behavior (i.e., temporary suspension of locomotion upon a sudden flash of light as short as milliseconds). Surprisingly, optogenetic activation of SC-projecting neurons in V1 or their axon terminals in SC sufficiently elicits the behavior, in contrast to other major L5 corticofugal projections. Thus, via the same corticofugal projection, visual cortex not only modulates the light-induced arrest behavior, but also can directly drive the behavior. Our results suggest that sensory cortex may play a previously unrecognized role in the top-down initiation of sensory-motor behaviors.
SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker.
Nature neuroscience, 2010

Sleep is a whole-organism phenomenon accompanied by global changes in neural activity. We previously identified SLEEPLESS (SSS) as a glycosylphosphatidyl inositol-anchored protein required for sleep in Drosophila. Here we found that SSS is critical for regulating the sleep-modulating potassium channel Shaker. SSS and Shaker shared similar expression patterns in the brain and specifically affected each other's expression levels. sleepless (sss) loss-of-function mutants exhibited altered Shaker localization, reduced Shaker current density and slower Shaker current kinetics. Transgenic expression of sss in sss mutants rescued defects in Shaker expression and activity cell-autonomously and suggested that SSS functions in wake-promoting, cholinergic neurons. In heterologous cells, SSS accelerated the kinetics of Shaker currents and was co-immunoprecipitated with Shaker, suggesting that SSS modulates Shaker activity via a direct interaction. SSS is predicted to belong to the Ly-6/neurotoxin superfamily, suggesting a mechanism for regulation of neuronal excitability by endogenous toxin-like molecules.
Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson's disease.
Experimental brain research, 2013

It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson's disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.
Neurophysiological, linguistic, and cognitive predictors of children's ability to perceive speech in noise.
Developmental cognitive neuroscience, 2019

Hearing in noisy environments is a complicated task that engages attention, memory, linguistic knowledge, and precise auditory-neurophysiological processing of sound. Accumulating evidence in school-aged children and adults suggests these mechanisms vary with the task's demands. For instance, co-located speech and noise demands a large cognitive load and recruits working memory, while spatially separating speech and noise diminishes this load and draws on alternative skills. Past research has focused on one or two mechanisms underlying speech-in-noise perception in isolation; few studies have considered multiple factors in tandem, or how they interact during critical developmental years. This project sought to test complementary hypotheses involving neurophysiological, cognitive, and linguistic processes supporting speech-in-noise perception in young children under different masking conditions (co-located, spatially separated). Structural equation modeling was used to identify latent constructs and examine their contributions as predictors. Results reveal cognitive and language skills operate as a single factor supporting speech-in-noise perception under different masking conditions. While neural coding of the F0 supports perception in both co-located and spatially separated conditions, neural timing predicts perception of spatially separated listening exclusively. Together, these results suggest co-located and spatially separated speech-in-noise perception draw on similar cognitive/linguistic skills, but distinct neural factors, in early childhood.
A Novel Mechanism for Zika Virus Host-Cell Binding.
Viruses, 2019

Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic peptides representing the region containing ASN154 from strains PRVABC59 (Puerto Rico 2015) and MR_766 (Uganda 1947) were exposed to neuronal cells and fibroblasts to model ZIKV E protein/cell interactions and bound MDCK or Vero cells and primary neurons significantly. Peptides significantly inhibited Vero cell infectivity by ZIKV strains MR_766 and PRVABC59, indicating that this region represents a putative binding mechanism of ancestral African ZIKV strains and emergent Western Hemisphere strains. Pretreatment of ZIKV strains MR_766 and PRVABC59 with the PS-binding protein annexin V significantly inhibited replication of PRVABC59 but not MR_766, suggesting that Western hemisphere strains may additionally be capable of utilizing PS-mediated entry to infect host cells. These data indicate that the region surrounding E protein ASN154 is capable of binding fibroblasts and primary neuronal cells and that PS-mediated entry may be a secondary mechanism for infectivity utilized by Western Hemisphere strains.
On simplicity and complexity in the brave new world of large-scale neuroscience.
Current opinion in neurobiology, 2015

Technological advances have dramatically expanded our ability to probe multi-neuronal dynamics and connectivity in the brain. However, our ability to extract a simple conceptual understanding from complex data is increasingly hampered by the lack of theoretically principled data analytic procedures, as well as theoretical frameworks for how circuit connectivity and dynamics can conspire to generate emergent behavioral and cognitive functions. We review and outline potential avenues for progress, including new theories of high dimensional data analysis, the need to analyze complex artificial networks, and methods for analyzing entire spaces of circuit models, rather than one model at a time. Such interplay between experiments, data analysis and theory will be indispensable in catalyzing conceptual advances in the age of large-scale neuroscience.
The lateral septum and anterior hypothalamus act in tandem to regulate burying in the shock-probe test but not open-arm avoidance in the elevated plus-maze.
Behavioural brain research, 2016

Both the lateral septum (LS) and anterior hypothalamus (AHA) regulate behavioural defense. We tested whether those two interconnected structures act in serial in that regard. Infusions of the GABAA agonist muscimol into one side of the LS and the contralateral (but not ipsilateral) AHA suppressed rats' burying in the shock-probe test whereas none of our muscimol infusion approaches altered their open-arm avoidance in the elevated plus-maze. These results suggest that the LS-AHA circuit serves a specialized role in defensive responses towards discrete, localizable threat stimuli but not towards potential threats.
Incidence of traumatic brain injury in New Zealand: a population-based study.
The Lancet. Neurology, 2013

Traumatic brain injury (TBI) is the leading cause of long-term disability in children and young adults worldwide. However, accurate information about its incidence does not exist. We aimed to estimate the burden of TBI in rural and urban populations in New Zealand across all ages and TBI severities.
The Lhx4 homeobox transcript in the rat pineal gland: Adrenergic regulation and impact on transcripts encoding melatonin-synthesizing enzymes.
Journal of pineal research, 2020

Homeobox genes generally encode transcription factors involved in regulating developmental processes. In the pineal gland, a brain structure devoted to nocturnal melatonin synthesis, a number of homeobox genes are also expressed postnatally; among these is the LIM homeobox 4 gene (Lhx4). We here report that Lhx4 is specifically expressed in the postnatal pineal gland of rats and humans. Circadian analyses revealed a fourfold rhythm in Lhx4 expression in the rat pineal gland, with rhythmic expression detectable from postnatal day 10. Pineal Lhx4 expression was confirmed to be positively driven by adrenergic signaling, as evidenced by in vivo modulation of Lhx4 expression by pharmacological (isoprenaline injection) and surgical (superior cervical ganglionectomy) interventions. In cultured pinealocytes, Lhx4 expression was upregulated by cyclic AMP, a second messenger of norepinephrine. By use of RNAscope technology, Lhx4 transcripts were found to be exclusively localized in melatonin-synthesizing pinealocytes. This prompted us to investigate the possible role of Lhx4 in regulation of melatonin-producing enzymes. By use of siRNA technology, we knocked down Lhx4 by 95% in cultured pinealocytes; this caused a reduction in transcripts encoding the melatonin-producing enzyme arylalkylamine N-acetyl transferase (Aanat). Screening the transcriptome of siRNA-treated pinealocytes by RNAseq revealed a significant impact of Lhx4 on the phototransduction pathway and on transcripts involved in development of the nervous system and photoreceptors. These data suggest that rhythmic expression of Lhx4 in the pineal gland is controlled via an adrenergic-cyclic AMP mechanism and that Lhx4 acts to promote nocturnal melatonin synthesis.
Mature myelin maintenance requires Qki to coactivate PPARβ-RXRα-mediated lipid metabolism.
The Journal of clinical investigation, 2020

Lipid-rich myelin forms electrically insulating, axon-wrapping multilayers that are essential for neural function, and mature myelin is traditionally considered metabolically inert. Surprisingly, we discovered that mature myelin lipids undergo rapid turnover, and quaking (Qki) is a major regulator of myelin lipid homeostasis. Oligodendrocyte-specific Qki depletion, without affecting oligodendrocyte survival, resulted in rapid demyelination, within 1 week, and gradually neurological deficits in adult mice. Myelin lipids, especially the monounsaturated fatty acids and very-long-chain fatty acids, were dramatically reduced by Qki depletion, whereas the major myelin proteins remained intact, and the demyelinating phenotypes of Qki-depleted mice were alleviated by a high-fat diet. Mechanistically, Qki serves as a coactivator of the PPARβ-RXRα complex, which controls the transcription of lipid-metabolism genes, particularly those involved in fatty acid desaturation and elongation. Treatment of Qki-depleted mice with PPARβ/RXR agonists significantly alleviated neurological disability and extended survival durations. Furthermore, a subset of lesions from patients with primary progressive multiple sclerosis were characterized by preferential reductions in myelin lipid contents, activities of various lipid metabolism pathways, and expression level of QKI-5 in human oligodendrocytes. Together, our results demonstrate that continuous lipid synthesis is indispensable for mature myelin maintenance and highlight an underappreciated role of lipid metabolism in demyelinating diseases.
Effectiveness of simulation in psychiatry for initial and continuing training of healthcare professionals: protocol for a systematic review.
BMJ open, 2018

Although most healthcare professionals must deal with patients with mental illness, many are not prepared for the various situations that can ensue. Simulation may be a powerful pedagogical tool for simultaneously teaching knowledge, skills and attitudes. We aim to assess the effectiveness of simulation for initial and continuous training in psychiatry for healthcare professionals.
Sound-contingent visual motion aftereffect.
BMC neuroscience, 2011

After a prolonged exposure to a paired presentation of different types of signals (e.g., color and motion), one of the signals (color) becomes a driver for the other signal (motion). This phenomenon, which is known as contingent motion aftereffect, indicates that the brain can establish new neural representations even in the adult's brain. However, contingent motion aftereffect has been reported only in visual or auditory domain. Here, we demonstrate that a visual motion aftereffect can be contingent on a specific sound.
The effect of aging on the spatial frequency selectivity of the human visual system.
Vision research, 2010

Changes in the physiological properties of senescent V1 neurons suggest that the mechanisms encoding spatial frequency in primate cortex may become more broadly tuned in old age (Zhang et al., European Journal of Neuroscience, 2008, 28, 201-207). We examined this possibility in two psychophysical experiments that used masking to estimate the bandwidth of spatial frequency-selective mechanisms in younger (age approximately 22years) and older (age approximately 65years) human adults. Contrary to predictions from physiological studies, in both experiments, the spatial frequency selectivity of masking was essentially identical in younger and older subjects.