rudyvdbrink/CitationDatabase huggingface dataset:
The computation of relative numerosity, size and density.
Vision research, 2016

To investigate the mechanisms for the perception of relative numerosity, we used two-interval forced-choice (temporal 2AFC) to measure thresholds for area, density and numerosity differences between dot textures, and a 2×2 FC task to measure the ability of observers to distinguish changes in area from changes in density. To prevent the use of a one-dimensional size signal we used textures in which dots were scattered within irregular polygonal areas. Numerosity thresholds were similar in the area and density-varying conditions, consistent with a single numerosity mechanism. Thresholds for area and density discriminations were raised when number was held constant, consistent with numerosity thresholds being lower than those for size and density. Also, area thresholds for polygonal outlines were increased when no dots were present in the outline. However, a single numerosity mechanism cannot account for all the data, because we find that observers in randomly-interleaved size-varying and density-varying conditions are also able to discriminate between changes in size and density with a precision predicted from independently-noisy size and density channels that have similar noise to that in the putative numerosity channel. A complication, previously noted with circular shapes, is that denser textures tend to be confused with larger textures, and vice versa. This could explain why thresholds rise when density and size changes are in opposition, in the constant-number case. These findings taken together do not rule out an independent numerosity mechanism, but they are equally compatible with a flexible computation of numerosity from size and density cues.
Activation of GABA
Experimental neurology, 2016

Mesiotemporal lobe Epilepsy (MTLE), the most frequent form of focal epilepsy, is often drug-resistant. Enriching the epileptic focus with GABA-releasing engineered cells has been proposed as a strategy to prevent seizures. However, ex vivo data from animal models and MTLE patients suggest that, due to changes in chloride homeostasis, GABA
Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice.
Nature, 2015

Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility. Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.
Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Glutamate is the major excitatory neurotransmitter in the brain. The NMDA subtype of glutamate receptors (NMDAR) is known to mediate many physiological neural functions. However, excessive activation of NMDARs contributes to neuronal damage in various acute and chronic neurological disorders. To avoid unwanted adverse side effects, blockade of excessive NMDAR activity must therefore be achieved without affecting its physiological function. Memantine, an adamantane derivative, has been used for the treatment of Alzheimer's disease with an excellent clinical safety profile. We previously showed that memantine preferentially blocked neurotoxicity mediated by excessive NMDAR activity while relatively sparing normal neurotransmission, in part because of its uncompetitive antagonism with a fast off-rate. Here, using rat autaptic hippocampal microcultures, we show that memantine at therapeutic concentrations (1-10 microM) preferentially blocks extrasynaptic rather than synaptic currents mediated by NMDARs in the same neuron. We found that memantine blocks extrasynaptic NMDAR-mediated currents induced by bath application of 100 microM NMDA/10 microM glycine with a twofold higher potency than its blockade of the NMDAR component of evoked EPSCs (EPSCs(NMDAR)); this effect persists under conditions of pathological depolarization in the presence of 1 mm extracellular Mg(2+). Thus, our findings provide the first unequivocal evidence to explain the tolerability of memantine based on differential extrasynaptic/synaptic receptor blockade. At therapeutic concentrations, memantine effectively blocks excessive extrasynaptic NMDAR-mediated currents, while relatively sparing normal synaptic activity.
Deconstructing the synapse.
Nature neuroscience, 2018

While the role of protein synthesis in synaptic plasticity and memory is well-established, protein degradation processes have been less studied. A seminal 2003 Nature Neuroscience paper showed that ubiquitin-dependent degradation of synaptic proteins is engaged during activity-regulated synaptic remodeling.
E-cigarette use and associated factors among smokers with severe mental illness.
Addictive behaviors, 2020

Smoking is more prevalent among people with severe mental illness (SMI) than the general population. E-cigarettes could provide an effective means of helping people to quit smoking. The aim of this paper is to explore the use of e-cigarettes and factors related to their use in people smokers with SMI.
Dopamine modulation of GABA tonic conductance in striatal output neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

We previously reported greater GABAA receptor-mediated tonic currents in D2+ striatopallidal than D1+ striatonigral medium spiny neurons (MSNs) are mediated by alpha5-subunit-containing receptors. Here, we used whole-cell recordings in slices from bacterial artificial chromosome transgenic mice to investigate the link between subunit composition, phosphorylation, and dopamine receptor activation. Whole-cell recordings in slices from delta-subunit knock-out mice demonstrate that while MSNs in wild-type mice do express delta-subunit-containing receptors, this receptor subtype is not responsible for tonic conductance observed in the acute slice preparation. We assessed the contribution of the beta1- and beta3-subunits expressed in MSNs by their sensitivity to etomidate, an agonist selective for beta2- or beta3-subunit-containing GABAA receptors. Although etomidate produced substantial tonic current in D2+ neurons, there was no effect in D1+ neurons. However, with internal PKA application or dopamine modulation, D1+ neurons expressed tonic conductance and responded to etomidate application. Our results suggest that distinct phosphorylation of beta3-subunits may cause larger tonic current in D2+ striatopallidal MSNs, and proper intracellular conditions can reveal tonic current in D1+ cells.
The use of medical grade cannabis in Italy for drug-resistant epilepsy: a case series.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2020

In Italy, medical grade cannabis (MGC) can be prescribed for different medical conditions, including drug-resistant epilepsy (DRE), once standard and approved therapies have failed, or caused non-tolerable side effects. Here, we present a retrospective case series report of five patients with DRE who started therapy with MGC. Authorized ISO 9001:2008 pharmacies prepared MGC according to Italian laws. Olive oil extracts (OOEs) were prepared following standard extraction protocols, and cannabinoids were measured on each OOE to check for successful extraction.After treatment with MGC, all patients reported a reduction in seizure frequency and severity, and some reported improved mood, sleep quality, and general well-being without relevant side effects. Despite the small sample size and open-label nature of the data, we show that MGC may be successfully used to treat DRE. This is especially true when considering that no valid therapeutic option exists for these patients and that MGC was extremely well tolerated.
Characterizing heat-sensitization responses in suspended moxibustion with high-density EEG.
Pain medicine (Malden, Mass.), 2014

We have reported "heat-sensitization" responses during suspended moxibustion, whose occurrence is associated with significantly better therapeutic effects. The present study aimed to characterize the electrophysiological features of this interesting phenomenon with high-density electroencephalography (EEG).
Assessment of cell line competence for studies of pharmacological GPR30 modulation.
Journal of receptor and signal transduction research, 2017

Cell lines used to study the role of the G protein-coupled receptor 30 (GPR30) or G protein-coupled estrogen receptor (GPER) as a mediator of estrogen responses have yielded conflicting results. This work identified a simple assay to predict cell line competence for pharmacological studies of GPR30.
Association of Variants in BAG3 With Cardiomyopathy Outcomes in African American Individuals.
JAMA cardiology, 2018

The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants.
The role of GABA in human motor learning.
Current biology : CB, 2011

GABA modification plays an important role in motor cortical plasticity. We therefore hypothesized that interindividual variation in the responsiveness of the GABA system to modification influences learning capacity in healthy adults. We assessed GABA responsiveness by transcranial direct current stimulation (tDCS), an intervention known to decrease GABA. The magnitude of M1 GABA decrease induced by anodal tDCS correlated positively with both the degree of motor learning and the degree of fMRI signal change within the left M1 during learning. This study therefore suggests that the responsiveness of the GABAergic system to modification may be relevant to short-term motor learning behavior and learning-related brain activity.
Pair bond formation leads to a sustained increase in global cerebral glucose metabolism in monogamous male titi monkeys (Callicebus cupreus).
Neuroscience, 2017

Social bonds, especially attachment relationships, are crucial to our health and happiness. However, what we know about the neural substrates of these bonds is almost exclusively limited to rodent models and correlational experiments in humans. Here, we used socially monogamous non-human primates, titi monkeys (Callicebus cupreus) to experimentally examine changes in regional and global cerebral glucose metabolism (GCGM) during the formation and maintenance of pair bonds. Baseline positron emission tomography (PET) scans were taken of thirteen unpaired male titi monkeys. Seven males were then experimentally paired with females, scanned and compared, after one week, to six age-matched control males. Five of the six control males were then also paired and scanned after one week. Scans were repeated on all males after four months of pairing. PET scans were coregistered with structural magnetic resonance imaging (MRI), and region of interest (ROI) analysis was carried out. A primary finding was that paired males showed a significant increase in [
Surprising origins of sex differences in the brain.
Hormones and behavior, 2015

This article is part of a Special Issue "SBN 2014". Discerning the biologic origins of neuroanatomical sex differences has been of interest since they were first reported in the late 60's and early 70's. The centrality of gonadal hormone exposure during a developmental critical window cannot be denied but hormones are indirect agents of change, acting to induce gene transcription or modulate membrane bound signaling cascades. Sex differences in the brain include regional volume differences due to differential cell death, neuronal and glial genesis, dendritic branching and synaptic patterning. Early emphasis on mechanism therefore focused on neurotransmitters and neural growth factors, but by and large these endpoints failed to explain the origins of neural sex differences. More recently evidence has accumulated in favor of inflammatory mediators and immune cells as principle regulators of brain sexual differentiation and reveal that the establishment of dimorphic circuits is not cell autonomous but instead requires extensive cell-to-cell communication including cells of non-neuronal origin. Despite the multiplicity of cells involved the nature of the sex differences in the neuroanatomical endpoints suggests canalization, a process that explains the robustness of individuals in the face of intrinsic and extrinsic variability. We propose that some neuroanatomical endpoints are canalized to enhance sex differences in the brain by reducing variability within one sex while also preventing the sexes from diverging too greatly. We further propose mechanisms by which such canalization could occur and discuss what relevance this may have to sex differences in behavior.
ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells.
Science (New York, N.Y.), 2017

The chromatin structure of DNA determines genome compaction and activity in the nucleus. On the basis of in vitro structures and electron microscopy (EM) studies, the hierarchical model is that 11-nanometer DNA-nucleosome polymers fold into 30- and subsequently into 120- and 300- to 700-nanometer fibers and mitotic chromosomes. To visualize chromatin in situ, we identified a fluorescent dye that stains DNA with an osmiophilic polymer and selectively enhances its contrast in EM. Using ChromEMT (ChromEM tomography), we reveal the ultrastructure and three-dimensional (3D) organization of individual chromatin polymers, megabase domains, and mitotic chromosomes. We show that chromatin is a disordered 5- to 24-nanometer-diameter curvilinear chain that is packed together at different 3D concentration distributions in interphase and mitosis. Chromatin chains have many different particle arrangements and bend at various lengths to achieve structural compaction and high packing densities.
Proteinase 3 Induces Neuronal Cell Death Through Microglial Activation.
Neurochemical research, 2015

Proteinase 3 (PR3) is released from neutrophil granules and is involved in the inflammatory process. PR3 is implicated in antimicrobial defense and cell death, but the exact role of PR3 in the brain is less defined. Microglia is the major immune effector cells in the CNS and is activated by brain injury. In the present study, the effect of PR3 on glial activation was investigated. Microglial activation was assessed by the intracellular level of reactive oxygen species and expression of inflammatory cytokines. The conditioned media from activated microglia by PR3 was used for measuring the neurotoxic effects of PR3-stimulated microglia. The effects of PR3 in vivo were measured by microinjecting PR3 into the rat brain. Herein we show that PR3 increased the inflammatory responses including the intracellular ROS and pro-inflammatory cytokine production in rat primary microglia. Conditioned media from PR3-treated microglia induced neuronal cell death in a concentration dependent manner. Furthermore, microinjected PR3 into the striatum of the rat brain induced microglial activation and neuronal cell death. Interestingly treatment with anti-PR3 monoclonal antibody and protease inhibitors ameliorated microglial activation induced by PR3 in primary microglia and striatum, which also prevented neuronal cell death in both conditions. The data presented here suggest that PR3 is a direct modulator of microglial activation and causes neuronal death through the augmentation of inflammatory responses. We suggest that PR3 could be a new modulator of neuroinflammation, and blocking PR3 would be a promising novel therapeutic target for neuroinflammatory disease such as stroke and Alzheimer's disease.
Evolution of central pattern generators and rhythmic behaviours.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2016

Comparisons of rhythmic movements and the central pattern generators (CPGs) that control them uncover principles about the evolution of behaviour and neural circuits. Over the course of evolutionary history, gradual evolution of behaviours and their neural circuitry within any lineage of animals has been a predominant occurrence. Small changes in gene regulation can lead to divergence of circuit organization and corresponding changes in behaviour. However, some behavioural divergence has resulted from large-scale rewiring of the neural network. Divergence of CPG circuits has also occurred without a corresponding change in behaviour. When analogous rhythmic behaviours have evolved independently, it has generally been with different neural mechanisms. Repeated evolution of particular rhythmic behaviours has occurred within some lineages due to parallel evolution or latent CPGs. Particular motor pattern generating mechanisms have also evolved independently in separate lineages. The evolution of CPGs and rhythmic behaviours shows that although most behaviours and neural circuits are highly conserved, the nature of the behaviour does not dictate the neural mechanism and that the presence of homologous neural components does not determine the behaviour. This suggests that although behaviour is generated by neural circuits, natural selection can act separately on these two levels of biological organization.
The impact of Ly6Clow monocytes after cerebral hypoxia-ischemia in adult mice.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2014

After an ischemic stroke, mononuclear phagocytic cells such as microglia, macrophages, and monocytes migrate to the lesion site and coordinate an immune response. Monocytes, which are recruited from the bloodstream after ischemic brain injury, can be categorized into two subsets in mice: inflammatory and patrolling monocytes. Although inflammatory monocytes (Ly6C(hi)) seem to have a protective role in stroke progression, the impact of patrolling monocytes (Ly6C(low)) is unknown. To address the role of Ly6C(low) monocytes in stroke, we generated bone marrow chimeric mice in which their hematopoietic system was replaced by Nr4a1(-/-) cells, allowing the complete and permanent ablation of Ly6C(low) monocytes without affecting the Ly6C(hi) subset. We then subjected adult mice to cerebral hypoxia-ischemia using the Levine/Vannucci model. Functional outcomes after stroke such as body weight change, neurologic score, motor functions and spatial learning were not affected. Moreover, depletion in Ly6C(low) monocytes did not change significantly the total infarct size, cell loss, atrophy, the number, or the activation state of microglia/macrophages at the lesion site. These data suggest that Ly6C(low) patrolling monocytes are redundant in the progression and recovery of ischemic stroke.
The covariation between burnout and sick leave due to mental disorders is explained by a shared genetic liability: a prospective swedish twin study with a five-year follow-up.
Twin research and human genetics : the official journal of the International Society for Twin Studies, 2014

This study aims to assess whether the associations between burnout and sick leave due to stress-related mental disorders, other mental disorders, and somatic conditions are influenced by familial (genetic and shared environmental) factors.
Environmental enrichment: a cure for cancer? It's all in the mind.
Journal of molecular cell biology, 2010

Environmental enrichment is used to enhance mental stimulation and physical activity and has been shown to delay onset and progression of a range of brain disorders. Now, Cao et al. (2010) report in Cell that this paradigm also exerts strong influences beyond the brain and is capable of suppressing tumor growth in mice.
Social-cognitive correlates of risky adolescent cycling behavior.
BMC public health, 2010

Bicycle use entails high safety and health risks especially for adolescents. Most safety education programs aimed at adolescents focus on accident statistics and risk perceptions. This paper proposes the investigation of the social-cognitive correlates of risky cycling behaviors of adolescents prior to developing safety education programs.
SUITer: An Automated Method for Improving Segmentation of Infratentorial Structures at Ultra-High-Field MRI.
Journal of neuroimaging : official journal of the American Society of Neuroimaging, 2020

The advent of high and ultra-high-field MRI has significantly improved the investigation of infratentorial structures by providing high-resolution images. However, none of the publicly available methods for cerebellar image analysis has been optimized for high-resolution images yet.
Cerebral Microbleeds: Imaging and Clinical Significance.
Radiology, 2018

Cerebral microbleeds (CMBs), also referred to as microhemorrhages, appear on magnetic resonance (MR) images as hypointense foci notably at T2*-weighted or susceptibility-weighted (SW) imaging. CMBs are detected with increasing frequency because of the more widespread use of high magnetic field strength and of newer dedicated MR imaging techniques such as three-dimensional gradient-echo T2*-weighted and SW imaging. The imaging appearance of CMBs is mainly because of changes in local magnetic susceptibility and reflects the pathologic iron accumulation, most often in perivascular macrophages, because of vasculopathy. CMBs are depicted with a true-positive rate of 48%-89% at 1.5 T or 3.0 T and T2*-weighted or SW imaging across a wide range of diseases. False-positive "mimics" of CMBs occur at a rate of 11%-24% and include microdissections, microaneurysms, and microcalcifications; the latter can be differentiated by using phase images. Compared with postmortem histopathologic analysis, at least half of CMBs are missed with premortem clinical MR imaging. In general, CMB detection rate increases with field strength, with the use of three-dimensional sequences, and with postprocessing methods that use local perturbations of the MR phase to enhance T2* contrast. Because of the more widespread availability of high-field-strength MR imaging systems and growing use of SW imaging, CMBs are increasingly recognized in normal aging, and are even more common in various disorders such as Alzheimer dementia, cerebral amyloid angiopathy, stroke, and trauma. Rare causes include endocarditis, cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and radiation therapy. The presence of CMBs in patients with stroke is increasingly recognized as a marker of worse outcome. Finally, guidelines for adjustment of anticoagulant therapy in patients with CMBs are under development.