rudyvdbrink/CitationDatabase huggingface dataset:
A Novel HGF/SF Receptor (MET) Agonist Transiently Delays the Disease Progression in an Amyotrophic Lateral Sclerosis Mouse Model by Promoting Neuronal Survival and Dampening the Immune Dysregulation.
International journal of molecular sciences, 2020

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with no effective treatment. The Hepatocyte Growth Factor/Scatter Factor (HGF/SF), through its receptor MET, is one of the most potent survival-promoting factors for motor neurons (MN) and is known as a modulator of immune cell function. We recently developed a novel recombinant MET agonist optimized for therapy, designated K1K1. K1K1 was ten times more potent than HGF/SF in preventing MN loss in an in vitro model of ALS. Treatments with K1K1 delayed the onset of muscular impairment and reduced MN loss and skeletal muscle denervation of superoxide dismutase 1 G93A (SOD1G93A) mice. This effect was associated with increased levels of phospho-extracellular signal-related kinase (pERK) in the spinal cord and sciatic nerves and the activation of non-myelinating Schwann cells. Moreover, reduced activated microglia and astroglia, lower T cells infiltration and increased interleukin 4 (IL4) levels were found in the lumbar spinal cord of K1K1 treated mice. K1K1 treatment also prevented the infiltration of T cells in skeletal muscle of SOD1G93A mice. All these protective effects were lost on long-term treatment suggesting a mechanism of drug tolerance. These data provide a rational justification for further exploring the long-term loss of K1K1 efficacy in the perspective of providing a potential treatment for ALS.
Personality-cognition associations across the adult life span and potential moderators: Results from two cohorts.
Journal of personality, 2020

Personality and cognitive abilities have been previously linked. However, there are inconsistencies regarding whether this relationship varies as a function of age, and a lack of evidence on whether gender contributes to this relation, particularly across the adulthood. Therefore, this study investigated the association between personality and cognition across the adult life span, accounting for age and gender.
Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease.
Acta neuropathologica communications, 2020

Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta
Neurolight -astonishing advances in brain imaging.
The International journal of neuroscience, 2015

In recent years, significant advances in basic neuroanatomical studies have taken place. Moreover, such classical, clinically-oriented human brain imaging methods such as MRI, PET and DTI have been applied to small laboratory animals allowing improvement in current experimental neuroscience. Contemporary structural neurobiology also uses various technologies based on fluorescent proteins. One of these is optogenetics, which integrates physics, genetics and bioengineering to enable temporal precise control of electrical activity of specific neurons. Another important challenge in the field is the accurate imaging of complicated neural networks. To address this problem, three-dimensional reconstruction techniques and retrograde labeling with modified viruses has been developed. However, a revolutionary step was the invention of the "Brainbow" system, utilizing gene constructs including the sequences of fluorescent proteins and the usage of Cre recombinase to create dozens of colour combinations, enabling visualization of neurons and their connections in extremely high resolution. Furthermore, the newly- introduced CLARITY method should make it possible to visualize three-dimensionally the structure of translucent brain tissue using the hydrogel polymeric network. This original technique is a big advance in neuroscience creating novel viewpoints completely different than standard glass slide immunostaining.
A Pursuit Theory Account for the Perception of Common Motion in Motion Parallax.
Perception, 2016

The visual system uses an extraretinal pursuit eye movement signal to disambiguate the perception of depth from motion parallax. Visual motion in the same direction as the pursuit is perceived nearer in depth while visual motion in the opposite direction as pursuit is perceived farther in depth. This explanation of depth sign applies to either an allocentric frame of reference centered on the fixation point or an egocentric frame of reference centered on the observer. A related problem is that of depth order when two stimuli have a common direction of motion. The first psychophysical study determined whether perception of egocentric depth order is adequately explained by a model employing an allocentric framework, especially when the motion parallax stimuli have common rather than divergent motion. A second study determined whether a reversal in perceived depth order, produced by a reduction in pursuit velocity, is also explained by this model employing this allocentric framework. The results show than an allocentric model can explain both the egocentric perception of depth order with common motion and the perceptual depth order reversal created by a reduction in pursuit velocity. We conclude that an egocentric model is not the only explanation for perceived depth order in these common motion conditions.
Insights into the knowledge, attitude and practices for the treatment of idiopathic inflammatory myopathy from a cross-sectional cohort survey of physicians.
Rheumatology international, 2020

The idiopathic inflammatory myopathies (IIM) are heterogeneous and lead to high morbidity and mortality. Knowledge deficits among healthcare professionals could be detrimental to clinical care. Identifying areas of deficient Knowledge, Attitude and Practice (KAP) of IIM can improve physician education and patient outcomes. To assess the proportion of physicians treating IIM with poor KAP and identify the key areas of deficit. An anonymised and validated e-survey (57 questions) was circulated among physicians treating IIM (purposive sampling). Responses were evaluated using the Likert scale for good (> 70% correct response), poor (> 20% chose > 2 answers) and the rest as intermediate consensus. Descriptive statistics were used. Intergroup comparisons were done using non-parametric tests. Of 80 (9.1% of 883) respondents, 90% were rheumatologists and 37.5% academicians. The knowledge base of treating physicians was good in specific domains such as triggers (80-90%), clinical presentation (MDA5, statin myositis, steroid myopathy, anti-synthetase syndrome) (82-92%), IIM mimics (41-89%), investigations (23-92%) and risk of osteoporosis in IIM (79%). There is also an intermediate knowledge base/consensus for outcome measures (30-56%) and response criteria (30-53%). There was poor knowledge and consensus on trials (27-34%), EULAR/ACR criteria (31%) and exercise-based interventions (17-62%). While 90% agree on the need for muscle biopsy to diagnose polymyositis, only one-third advocated it for juvenile and adult DM. Physicians have a good understanding of the triggers, clinical presentation and mimics of IIM. Poor to intermediate knowledge and consensus exists regarding muscle biopsy, outcome measures, response criteria and exercise-based interventions, which could be addressed through future focussed educational initiatives.
Mental health and caregiving experiences of family carers supporting people with psychosis.
Epidemiology and psychiatric sciences, 2021

Family carers supporting an individual with psychosis often experience poorer mental health, however, little is known about specific risk factors among these carers. We investigated the associations between demographic, caregiving characteristics and mental health outcomes in family carers supporting an individual with psychosis and compared carers' outcomes with general population norms.
Preoperative ultraviolet B inflammation in skin: Modelling individual differences in acute postoperative pain and neuro-immune interactions.
European journal of pain (London, England), 2018

Neuroimmune interactions play a vital role in many of the most common pain conditions, such as arthritis. There have been many attempts to derive clinically predictive information from an individual's inflammatory response in order to gauge subsequent pain perception.
Effects of CD20 antibodies and kinase inhibitors on B-cell receptor signalling and survival of chronic lymphocytic leukaemia cells.
British journal of haematology, 2021

Recently, clinical trial results have established inhibitors of B-cell receptor (BCR)-associated kinase (BAKi), with or without CD20 moniclonal antibodies (mAbs), as the preferred first-line treatment for most chronic lymphocytic leukaemia (CLL) patients. Using phosphospecific flow cytometry, we showed that in leukaemic cells from CLL patients the CD20 therapeutic antibodies - rituximab, ofatumumab, and obinutuzumab - inhibited BCR signalling pathways targeting preferentially pBTK
Designing artificial senses: steps from physiology to clinical implementation.
Swiss medical weekly, 2019

Our senses are the main information channels through which we perceive and interact with the world. Consequently, the physical and social functioning of patients suffering from severe sensory disabilities is limited on several levels. This has motivated the development of a novel therapeutic alternative: &ldquo;artificial senses&rdquo;, more commonly known as sensory neuroprostheses. In order to restore lost function, sensory neuroprostheses attempt to take advantage of the information transfer pathway common to all senses: (i) transduction of the physical stimulus by sensory receptors, (ii) transmission of relevant information to primary sensory areas in the brain by sensory afferents, and (iii) analysis and integration of the information at multiple levels in the central nervous system. Neurosensory deficits might occur upon damage to any of the structures involved in this process. However, damage to the peripheral sensory receptor is often the cause of neurosensory loss. Most sensory neuroprostheses attempt to &ldquo;replace&rdquo; the malfunctioning or missing peripheral sensory organ by directly delivering basic sensory information to the brain using electrical currents. If the prosthesis is able to deliver enough consistent information, the brain will be able to correctly interpret it and useful rehabilitation can be achieved. This review presents the main challenges related to the development, implementation and translation to clinical practice of these devices: (i) sensory information needs to be efficiently delivered to specific neural targets (e.g., peripheral afferents or specific central nuclei); (ii) then the expected physiological response must be evoked and quantified; (iii) the restoration of basic sensory abilities can lead to useful rehabilitation in meaningful everyday activities; (iv) optimal prospects require specific rehabilitation therapy and lifelong medico-technical follow-up. To conclude, the current state and future of sensory neuroprostheses will be discussed. This will include current clinical and technical challenges, future prospects, and the potential of these devices to improve our fundamental knowledge of sensory physiology and neurosensory deficits.
Conscious Movement Processing, Fall-Related Anxiety, and the Visuomotor Control of Locomotion in Older Adults.
The journals of gerontology. Series B, Psychological sciences and social sciences, 2020

Older adults anxious about falling will often consciously process walking movements in an attempt to avoid falling. They also fixate their gaze on the present step rather than looking ahead to plan future actions. The present work examined whether conscious movement strategies result in such restricted visual planning.
A comparative analysis of the dopaminergic innervation of the executive caudal nidopallium in pigeon, chicken, zebra finch, and carrion crow.
The Journal of comparative neurology, 2020

Despite the long, separate evolutionary history of birds and mammals, both lineages developed a rich behavioral repertoire of remarkably similar executive control generated by distinctly different brains. The seat for executive functioning in birds is the nidopallium caudolaterale (NCL) and the mammalian equivalent is known as the prefrontal cortex (PFC). Both are densely innervated by dopaminergic fibers, and are an integration center of sensory input and motor output. Whereas the variation of the PFC has been well documented in different mammalian orders, we know very little about the NCL across the avian clade. In order to investigate whether this structure adheres to species-specific variations, this study aimed to describe the trajectory of the NCL in pigeon, chicken, carrion crow and zebra finch. We employed immunohistochemistry to map dopaminergic innervation, and executed a Gallyas stain to visualize the dorsal arcopallial tract that runs between the NCL and the arcopallium. Our analysis showed that whereas the trajectory of the NCL in the chicken is highly comparable to the pigeon, the two Passeriformes show a strikingly different pattern. In both carrion crow and zebra finch, we identified four different subareas of high dopaminergic innervation that span the entire caudal forebrain. Based on their sensory input, motor output, and involvement in dopamine-related cognitive control of the delineated areas here, we propose that at least three morphologically different subareas constitute the NCL in these songbirds. Thus, our study shows that comparable to the PFC in mammals, the NCL in birds varies considerably across species.
Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics.
International journal of environmental research and public health, 2020

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by disruptions in social communication and behavioral flexibility. Both genetic and environmental factors contribute to ASD risk. Epidemiologic studies indicate that roadway vehicle exhaust and in utero exposure to diesel particulate matter (DPM) are associated with ASD. Using the Comparative Toxicogenomics Database (CTD), we identified genes connected to DPM exposure and ASD, extracted the known enhancers/promoters of the identified genes, and integrated this with Assay for Transposase Accessible Chromatin (ATAC-seq) data from DPM-exposed human neural progenitor cells. Enhancer/promoter elements with significantly different chromosome accessibility revealed enriched DNA sequence motifs with transcription factor binding sites for EGR1. Variant extraction for linkage disequilibrium blocks of these regions followed by analysis through Genome Wide Association Studies (GWAS) revealed multiple neurological trait associations including exploratory eye movement and brain volume measurement. This approach highlights the effects of pollution on the regulatory regions of genes implicated in ASD by genetic studies, indicating convergence of genetic and environmental factors on molecular networks that contribute to ASD. Integration of publicly available data from the CTD, cell culture exposure studies, and phenotypic genetics synergize extensive evidence of chemical exposures on gene regulation for altered brain development.
Multiple memories can be simultaneously reactivated during sleep as effectively as a single memory.
Communications biology, 2021

Memory consolidation involves the reactivation of memory traces during sleep. If different memories are reactivated each night, how much do they interfere with one another? We examined whether reactivating multiple memories incurs a cost to sleep-related benefits by contrasting reactivation of multiple memories versus single memories during sleep. First, participants learned the on-screen location of different objects. Each object was part of a semantically coherent group comprised of either one, two, or six items (e.g., six different cats). During sleep, sounds were unobtrusively presented to reactivate memories for half of the groups (e.g., "meow"). Memory benefits for cued versus non-cued items were independent of the number of items in the group, suggesting that reactivation occurs in a simultaneous and promiscuous manner. Intriguingly, sleep spindles and delta-theta power modulations were sensitive to group size, reflecting the extent of previous learning. Our results demonstrate that multiple memories may be consolidated in parallel without compromising each memory's sleep-related benefit. These findings highlight alternative models for parallel consolidation that should be considered in future studies.
Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome.
mSystems, 2020

Depression is influenced by the structure, diversity, and composition of the gut microbiome. Although depression has been described previously in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) monoinfections, and to a lesser extent in HIV-HCV coinfection, research on the interplay between depression and the gut microbiome in these disease states is limited. Here, we characterized the gut microbiome using 16S rRNA amplicon sequencing of fecal samples from 373 participants who underwent a comprehensive neuropsychiatric assessment and the gut metabolome on a subset of these participants using untargeted metabolomics with liquid chromatography-mass spectrometry. We observed that the gut microbiome and metabolome were distinct between HIV-positive and -negative individuals. HCV infection had a large association with the microbiome that was not confounded by drug use. Therefore, we classified the participants by HIV and HCV infection status (HIV-monoinfected, HIV-HCV coinfected, or uninfected). The three groups significantly differed in their gut microbiome (unweighted UniFrac distances) and metabolome (Bray-Curtis distances). Coinfected individuals also had lower alpha diversity. Within each of the three groups, we evaluated lifetime major depressive disorder (MDD) and current Beck Depression Inventory-II. We found that the gut microbiome differed between depression states only in coinfected individuals. Coinfected individuals with a lifetime history of MDD were enriched in primary and secondary bile acids, as well as taxa previously identified in people with MDD. Collectively, we observe persistent signatures associated with depression only in coinfected individuals, suggesting that HCV itself, or interactions between HCV and HIV, may drive HIV-related neuropsychiatric differences.
The Hippocampus and Dorsolateral Striatum Integrate Distinct Types of Memories through Time and Space, Respectively.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Several decades of research have established that different kinds of memories result from the activity of discrete neural networks. Studying how these networks process information in experiments that target specific types of mnemonic representations has provided deep insights into memory architecture and its neural underpinnings. However, in natural settings reality confronts organisms with problems that are not neatly compartmentalized. Thus, a critical problem in memory research that still needs to be addressed is how distinct types of memories are ultimately integrated. Here we demonstrate how two memory networks, the hippocampus and dorsolateral striatum, may accomplish such a goal. The hippocampus supports memory for facts and events, collectively known as declarative memory and often studied as spatial memory in rodents. The dorsolateral striatum provides the basis for habits that are assessed in stimulus-response types of tasks. Expanding previous findings, the current work revealed that in male Long-Evans rats, the hippocampus and dorsolateral striatum use time and space in distinct and largely complementary ways to integrate spatial and habitual representations. Specifically, the hippocampus supported both types of memories when they were formed in temporal juxtaposition, even if the learning took place in different environments. In contrast, the lateral striatum supported both types of memories if they were formed in the same environment, even at temporally distinct points. These results reveal for the first time that by using fundamental aspects of experience in specific ways, the hippocampus and dorsolateral striatum can transcend their attributed roles in information storage.
Evidence for the absence of visceral pain in C57BL6/N mice subjected to therapeutically relevant O
Laboratory animals, 2017

Each different gas that is used to induce a pneumoperitoneum (PP) exhibits individual effects within the peritoneal cavity. This might include adverse effects such as pain and/or inflammatory reactions. The acute effects of ozonized oxygen (O
Ropinirole, a dopamine agonist with high D
Neuropharmacology, 2020

Response inhibition describes the cognitive processes mediating the suppression of unwanted actions. A network involving the basal ganglia mediates two forms of response inhibition: reactive and proactive inhibition. Reactive inhibition serves to abruptly stop motor activity, whereas proactive inhibition is goal-orientated and results in slowing of motor activity in anticipation of stopping. Due to its impairment in several psychiatric disorders, the neurochemistry of response inhibition has become of recent interest. Dopamine has been posed as a candidate mediator of response inhibition due to its role in functioning of the basal ganglia and the observation that patients with Parkinson's disease on dopamine agonists develop impulse control disorders. Although the effects of dopamine on reactive inhibition have been studied, substantial literature on the role of dopamine on proactive inhibition is lacking. To fill this gap, we devised a double-blind, placebo-controlled study of 1 mg ropinirole (a dopamine agonist) on response inhibition in healthy volunteers. We found that whilst reactive inhibition was unchanged, proactive inhibition was impaired when participants were on ropinirole relative to when on placebo. To investigate how ropinirole mediated this effect on proactive inhibition, we used hierarchical drift-diffusion modelling. We found that ropinirole impaired the ability to raise the decision threshold when proactive inhibition was called upon. Our results provide novel evidence that an acute dose of ropinirole selectively reduces proactive inhibition in healthy participants. These results may help explain how ropinirole induces impulse control disorders in susceptible patients with Parkinson's disease.
Mesenchymal Stem Cells Attenuated Blood-Brain Barrier Disruption via Downregulation of Aquaporin-4 Expression in EAE Mice.
Molecular neurobiology, 2020

Blood-brain barrier disruption is one of the hallmarks of multiple sclerosis. Mesenchymal stem cells showed great potential for the multiple sclerosis therapy. However, the effect of mesenchymal stem cells on blood-brain barrier in multiple sclerosis remains unclear. Here, we investigated whether mesenchymal stem cells transplantation protected blood-brain barrier integrity and further explored possible underlying mechanisms. Adult female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptide33-55 (MOG33-55) to induce experimental autoimmune encephalomyelitis (EAE). Mesenchymal stem cells (5 × 10
Association of guideline publication and delays to treatment in pediatric status epilepticus.
Neurology, 2020

To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review.