rudyvdbrink/CitationDatabase huggingface dataset:
Accurate metacognition for visual sensory memory representations.
Psychological science, 2014

The capacity to attend to multiple objects in the visual field is limited. However, introspectively, people feel that they see the whole visual world at once. Some scholars suggest that this introspective feeling is based on short-lived sensory memory representations, whereas others argue that the feeling of seeing more than can be attended to is illusory. Here, we investigated this phenomenon by combining objective memory performance with subjective confidence ratings during a change-detection task. This allowed us to compute a measure of metacognition--the degree of knowledge that subjects have about the correctness of their decisions--for different stages of memory. We show that subjects store more objects in sensory memory than they can attend to but, at the same time, have similar metacognition for sensory memory and working memory representations. This suggests that these subjective impressions are not an illusion but accurate reflections of the richness of visual perception.
Exocytotic release of ATP from cultured astrocytes.
The Journal of biological chemistry, 2007

Astrocytes appear to communicate with each other as well as with neurons via ATP. However, the mechanisms of ATP release are controversial. To explore whether stimuli that increase [Ca(2+)](i) also trigger vesicular ATP release from astrocytes, we labeled ATP-containing vesicles with the fluorescent dye quinacrine, which exhibited a significant co-localization with atrial natriuretic peptide. The confocal microscopy study revealed that quinacrine-loaded vesicles displayed mainly non-directional spontaneous mobility with relatively short track lengths and small maximal displacements, whereas 4% of vesicles exhibited directional mobility. After ionomycin stimulation only non-directional vesicle mobility could be observed, indicating that an increase in [Ca(2+)](i) attenuated vesicle mobility. Total internal reflection fluorescence (TIRF) imaging in combination with epifluorescence showed that a high percentage of fluorescently labeled vesicles underwent fusion with the plasma membrane after stimulation with glutamate or ionomycin and that this event was Ca(2+)-dependent. This was confirmed by patch-clamp studies on HEK-293T cells transfected with P2X(3) receptor, used as sniffers for ATP release from astrocytes. Glutamate stimulation of astrocytes was followed by an increase in the incidence of small transient inward currents in sniffers, reminiscent of postsynaptic quantal events observed at synapses. Their incidence was highly dependent on extracellular Ca(2+). Collectively, these findings indicate that glutamate-stimulated ATP release from astrocytes was most likely exocytotic and that after stimulation the fraction of quinacrine-loaded vesicles, spontaneously exhibiting directional mobility, disappeared.
Dopamine Signaling Modulates the Stability and Integration of Intrinsic Brain Networks.
Cerebral cortex (New York, N.Y. : 1991), 2019

Dopaminergic projections are hypothesized to stabilize neural signaling and neural representations, but how they shape regional information processing and large-scale network interactions remains unclear. Here we investigated effects of lowered dopamine levels on within-region temporal signal variability (measured by sample entropy) and between-region functional connectivity (measured by pairwise temporal correlations) in the healthy brain at rest. The acute phenylalanine and tyrosine depletion (APTD) method was used to decrease dopamine synthesis in 51 healthy participants who underwent resting-state functional MRI (fMRI) scanning. Functional connectivity and regional signal variability were estimated for each participant. Multivariate partial least squares (PLS) analysis was used to statistically assess changes in signal variability following APTD as compared with the balanced control treatment. The analysis captured a pattern of increased regional signal variability following dopamine depletion. Changes in hemodynamic signal variability were concomitant with changes in functional connectivity, such that nodes with greatest increase in signal variability following dopamine depletion also experienced greatest decrease in functional connectivity. Our results suggest that dopamine may act to stabilize neural signaling, particularly in networks related to motor function and orienting attention towards behaviorally-relevant stimuli. Moreover, dopamine-dependent signal variability is critically associated with functional embedding of individual areas in large-scale networks.
Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity.
NeuroImage, 2017

Transcranial magnetic stimulation (TMS) is a powerful non-invasive technique for the modulation of brain activity. While the precise mechanism of action is still unknown, TMS is applied in cognitive neuroscience to establish causal relationships between stimulation and subsequent changes in cerebral function and behavioral outcome. In addition, TMS is an FDA-approved therapeutic agent in psychiatric disorders, especially major depression. Successful repetitive TMS in such disorders is usually applied over the left dorso-lateral prefrontal cortex (DLPFC) and treatment response mechanism was therefore supposed to be based on modulations in functional networks, particularly the meso-cortico-limbic reward circuit. However, mechanistic evidence for the direct effects of rTMS over DLPFC is sparse. Here we show the specificity and temporal evolution of rTMS effects by comparing connectivity changes within 20 common independent components in a sham-controlled study. Using an unbiased whole-brain resting-state network (RSN) approach, we successfully demonstrate that stimulation of left DLPFC modulates anterior cingulate cortex (ACC) connectivity in one specific meso-cortico-limbic network, while all other networks are neither influenced by rTMS nor by sham treatment. The results of this study show that the neural correlates of TMS treatment response are also traceable in DLPFC stimulation of healthy brains and therefore represent direct effects of the stimulation procedure.
Comparison of cerebral perfusion in perimesencephalic subarachnoid hemorrhage and aneurysmal subarachnoid hemorrhage.
Neuroradiology, 2018

Perimesencephalic hemorrhage (PMH) is a benign subtype of nonaneurysmal subarachnoid hemorrhage (SAH). We aimed to investigate if cerebral perfusion in PMH is less affected than in aneurysmal SAH (aSAH).
The Epigenetic Reader BRD2 as a Specific Modulator of PAI-1 Expression in Lipopolysaccharide-Stimulated Mouse Primary Astrocytes.
Neurochemical research, 2015

The post translational modification of lysine acetylation is a key mechanism that regulates chromatin structure. Epigenetic readers, such as the BET domains, are responsible for reading histone lysine acetylation which is a hallmark of open chromatin structure, further providing a scaffold that can be accessed by RNA polymerases as well as transcription factors. Recently, several reports have assessed and highlighted the roles of epigenetic readers in various cellular contexts. However, little is known about their role in the regulation of inflammatory genes, which is critical in exquisitely tuning inflammatory responses to a variety of immune stimuli. In this study, we investigated the role of epigenetic readers BRD2 and BRD4 in the lipopolysaccharide (LPS)-induced immune responses in mouse primary astrocytes. Inflammatory stimulation by LPS showed that the levels of Brd2 mRNA and protein were increased, while Brd4 mRNA levels did not change. Knocking down of Brd2 mRNA using specific small interfering RNA (siRNA) in cultured mouse primary astrocytes inhibited LPS-induced mRNA expression and secretion of plasminogen activator inhibitor-1 (PAI-1). However, no other pro-inflammatory cytokines, such as Il-6, Il-1β and Tnf-α, were affected. Indeed, treatment with bromodomain-containing protein inhibitor, JQ1, blocked Pai-1 mRNA expression through the inhibition of direct BRD2 protein-binding and active histone modification on Pai-1 promoter. Taken together, our data suggest that BRD2 is involved in the modulation of neuroinflammatory responses through PAI-1 and via the regulation of epigenetic reader BET protein, further providing a potential novel therapeutic strategy in neuroinflammatory diseases.
A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).
International journal of molecular sciences, 2015

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.
QSAR design of triazolopyridine mGlu2 receptor positive allosteric modulators.
Journal of molecular graphics & modelling, 2014

Two QSAR approaches were applied to assist the design and to prioritise the synthesis of new active mGlu2 receptor positive allosteric modulators (PAMs). With the aim to explore a particular point of substitution the models successfully prioritised molecules originating from chemistry ideas and a large virtual library. The two methods, 3D topomer CoMFA and support vector machines with 2D ECFP6 fingerprints, delivered good correlation and success in this prospective application. Fourteen molecules with different substituent decoration were identified by the in silico models and synthesised. They were found to be highly active and their mGlu2 receptor PAM activity (pEC50) was predicted within 0.3 and 0.4log units of error with the two methods. The value of the molecules and the models for the future of the project is discussed.
Alpha synuclein in hematopoiesis and immunity.
Heliyon, 2019

Parkinson's disease (PD) is the second most common neurodegenerative condition and intracellular deposition of Lewy bodies in the substantia nigra (SN), which can cause dopaminergic neuronal death, is the hallmark of this syndrome. α-synuclein (syn) is a small protein expressed mainly in neurons but can also be found in a number of tissues. It can be present as a soluble monomer under normal physiological conditions, but can be toxic in its oligomeric or fibrillary forms. Most of the available literature has focused on the effects of α-syn pathology in the mechanisms leading to PD. However, the normal functions of α-syn still remain to be fully elucidated. Notably, α-syn in the hematopoietic system seems to mediate important functions as indicated by anemia and incomplete cell maturation when this protein is absent. This review will summarize basic genetic and structural findings, and critical information that suggests an essential role of α-syn in the development and activation of the hematopoietic system and immunity.
Development and characterisation of novel fentanyl-delta opioid receptor antagonist based bivalent ligands.
British journal of anaesthesia, 2015

Opioid tolerance is a limiting factor in chronic pain. Delta opioid peptide (DOP)(δ) receptor antagonism has been shown to reduce tolerance. Here, the common clinical mu opioid peptide (MOP)(µ) receptor agonist fentanyl has been linked to the DOP antagonist Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydrisoquinoline-3-carboxylic acid) to create new bivalent compounds.
Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?
Trends in neurosciences, 2016

Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals: evaluating (i) associations and plausible mechanisms linking non-rapid-eye-movement (NREM) sleep disruption, Aβ, and AD; (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation; (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD; and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits.
The need for research maps to navigate published work and inform experiment planning.
Neuron, 2013

The increasing volume, complexity, and interconnectedness of published studies in neuroscience make it difficult to determine what is known, what is uncertain, and how to contribute effectively to one's field. There is a pressing need to develop automated strategies to help researchers navigate the vastness of the published record. Simplified, interactive, and unbiased representations of previous findings (i.e., research maps) would be invaluable in preparing research surveys, in guiding experiment planning, and in evaluating research plans and contributions. Principles normally used in weighing research findings, including reproducibility and convergence, could be automated and incorporated into research maps. Here, we discuss a series of recent advances that are bringing us closer than ever to being able to derive systematic, comprehensive, but also interactive and user-friendly research maps. These maps could revolutionize the way we review the literature, plan experiments, and fund and publish science.
Psychological status after insulo-opercular resection in patients with epilepsy: Depression, anxiety, and quality of life.
Epilepsy & behavior : E&B, 2021

Insular epilepsy is increasingly recognized in epilepsy surgery centers. Recent studies suggest that resection of an epileptogenic zone that involves the insula as a treatment for drug-resistant seizures is associated with good outcomes in terms of seizure control. However, despite the existing evidence of a role of the insula in emotions and affective information processing, the long-term psychological outcome of patients undergoing these surgeries remain poorly documented. A group of 27 adults (18 women) who underwent an insulo-opercular resection (in combination with a part of the temporal lobe in 10, and of the frontal lobe in 5) as part of epilepsy surgery at our center between 2004 and 2019 completed psychometric questionnaires to assess depression (Beck Depression Inventory - 2nd edition; BDI-II), anxiety (State-Trait Anxiety Inventory, Trait Version; STAI-T), and quality of life (Patient Weighted Quality of Life In Epilepsy; QOLIE-10-P). Scores were compared to those of patients who had standard temporal lobe epilepsy (TLE) surgery with similar socio-demographic and disease characteristics. Seizure control after insular epilepsy surgery was comparable to that observed after TLE surgery, with a majority of patients reporting being seizure free (insular: 63.0%; temporal: 63.2%) or having rare disabling seizures (insular: 7.4%; temporal: 18.4%) at the time of questionnaire completion. Statistical comparisons revealed no significant group difference on scores of depression, anxiety, or quality of life. Hemisphere or extent of insular resection had no significant effect on the studied variables. In the total sample, employment status and seizure control, but not location of surgery, significantly predicted quality of life. Self-reported long-term psychological status after insulo-opercular resection as part of epilepsy surgery thus appears to be similar to that observed after TLE surgery, which is commonly performed in epilepsy surgery centers.
Immediate effect of spinal magnetic stimulation on camptocormia in Parkinson's disease.
Journal of neurology, neurosurgery, and psychiatry, 2014

Spinal cord stimulation is a potential therapeutic option for the treatment of Parkinson's disease (PD)-associated symptoms. Repetitive trans-spinal magnetic stimulation (rTSMS) is a non-invasive and safe alternative for stimulation of spinal pathways that has not been studied for therapeutic efficacy in PD. We assessed the benefits of rTSMS on camptocormia, an often treatment-resistant postural abnormality observed in PD patients.
Exploring physicians, nurses and ward-based pharmacists working relationships in a Swedish inpatient setting: a mixed methods study.
International journal of clinical pharmacy, 2019

Background In Sweden there has been limited work investigating the integration and nature of collaborative relationships between pharmacists and other healthcare practitioners. Objective To explore the working relationships of physicians, nurses and ward-based pharmacists in a rural hospital after the introduction of a clinical pharmacy service. Setting General medical ward in a rural hospital in northern Sweden. Method Mixed methods involving face-to-face semi-structured interviews with nurses, physicians and pharmacists, and a physician survey using the Physician-Pharmacist Collaboration Index to measure the extent of physician-reported collaborative working relationships. Main outcome measure Perceptions about collaborative working relationships between physician, nurses and pharmacists. Results All physicians (n = 9) who interacted with the clinical pharmacists completed the survey. The mean total score was 78.6 ± 4.7, total 92 (higher scores represent a more advanced relationship). Mean domain scores were highest for relationship initiation (13.0 ± 1.3, total 15), and trustworthiness (38.9 ± 3.4, total 42), followed by role specification (26.3 ± 2.6, total 30). The interviews (with nurses and physicians), showed how communication, collaboration and joint knowledge-exchange in the intervention changed and developed over time. Conclusion This study provides new insights into collaborative working relationships from the perspectives of physicians and nurses. The Physician-Pharmacist Collaboration Index scores suggest that physicians felt that clinical pharmacists were active in providing patient care; could be trusted to follow up on recommendations; and were credible. The interviews suggest that the team-based intervention provided good conditions for creating new ways to work to achieve commitment to professional working relationships.
Interaction of dopamine D1 with NMDA NR1 receptors in rat prefrontal cortex.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2009

Despite the tremendous importance of D1 and NMDA receptors to cognition (working memory, executive functions) and synaptic plasticity in the prefrontal cortex (PFC), little is known about the molecular mechanisms underlying D1-NMDA receptors interactions in this brain area. Here, we show that D1 receptors and the NMDA receptor co-localize in single pyramidal neurons and interneurons in adult rat PFC. NR1 and NR2A expression are found in different neuronal types. Conversely, D1 receptors are predominantly localized in pyramidal-like cells and parvalbumin positive cells. NR1 co-immunoprecipitates with D1 receptor in adult medial PFC. In prefrontal primary cultures, NMDA does not affect the D1 receptor dependent-cAMP production. In contrast, activation of D1 receptor potentiates the NMDA mediated increase in cytosolic Ca2+, an effect that was blocked by a PKA inhibitor. We conclude that D1 receptor potentiates the NMDA-Ca2+ signal by a PKA-dependent mechanism.
Regional specific alterations in brain acetylcholinesterase activity after repeated blast exposures in mice.
Neuroscience letters, 2012

Acetylcholinesterase (AChE) which catalyzes the hydrolysis of the neurotransmitter acetylcholine has been recognized as one of the major regulators of stress responses after traumatic brain injury (TBI). Repeated blast exposure induces TBI (blast TBI) with a variable neuropathology at different brain regions. Since AChE inhibitors are being used as a line of treatment for TBI, we sought to determine the time course of AChE activity in the blood and different brain regions after repeated blast exposures using modified Ellman assay. Our data showed that repeated blast exposures significantly reduced AChE activity in the whole-blood and erythrocytes by 3-6h, while plasma AChE activity was significantly increased by 3h post-blast. In the brain, significant increase in AChE activity was observed at 6h in the frontal cortex, while hind cortex and hippocampus showed a significant decrease at 6h post-blast, which returned to normal levels by 7 days. AChE activity in the cerebellum and mid brain showed a decrease at 6h, followed by significant increase at 3 days and that was decreased significantly at 14 days post-blast. Medulla region showed decreased AChE activity at 24h post-blast, which was significantly increased at 14 days. These results suggest that there are brain regional and time-related changes in AChE activity after tightly coupled repeated blast exposures in mice. In summary, acute and chronic regional specific changes in the AChE activity after repeated blast exposures warrant systematic evaluation of the possibility of AChE inhibitor therapeutics against blast TBI.
Applications and efficiencies of the first cat 63K DNA array.
Scientific reports, 2018

The development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array's genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50-1,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations.