rudyvdbrink/CitationDatabase huggingface dataset:
On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias.
Science advances, 2020

The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor-related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.
Cluster headache.
Nature reviews. Disease primers, 2018

Cluster headache is an excruciating, strictly one-sided pain syndrome with attacks that last between 15 minutes and 180 minutes and that are accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. The pain is so severe that female patients describe each attack as worse than childbirth. The past decade has seen remarkable progress in the understanding of the pathophysiological background of cluster headache and has implicated the brain, particularly the hypothalamus, as the generator of both the pain and the autonomic symptoms. Anatomical connections between the hypothalamus and the trigeminovascular system, as well as the parasympathetic nervous system, have also been implicated in cluster headache pathophysiology. The diagnosis of cluster headache involves excluding other primary headaches and secondary headaches and is based primarily on the patient's symptoms. Remarkable progress has been achieved in developing effective treatment options for single cluster attacks and in developing preventive measures, which include pharmacological therapies and neuromodulation.
Non-suicidal self-injury and suicidal ideation in relation to eating and general psychopathology among college-age women.
Psychiatry research, 2016

Non-suicidal self-injury (NSSI) and suicidal ideation are potent risk factors for suicide and are associated with general and eating disorder-specific psychopathology. Limited research has examined the effects of combined NSSI+suicidal ideation thus concurrent examination is needed to understand potential differential effects on psychopathology. College-aged women (N=508) completed self-report measures of NSSI, suicidal ideation, general psychopathology, and Eating Disorder-specific psychopathology. MANOVAs determined whether the NSSI/SI status groups differed on general and eating disorder pathology measures as a set. Significant MANOVAs were followed up with univariate ANOVAs and posthoc tests. Thirteen women endorsed NSSI+Suicidal Ideation, 70 endorsed NSSI-only, 25 endorsed Suicidal Ideation-only, and 400 endorsed no NSSI/Suicidal Ideation. Both general and eating disorder-specific psychopathology differed across groups. NSSI+Suicidal Ideation and Suicidal Ideation-only groups typically endorsed higher general psychopathology than the no NSSI/Suicidal Ideation and NSSI-only groups. Regarding eating disorder pathology, the NSSI+Suicidal Ideation group was more pathological than no NSSI/Suicidal Ideation and NSSI-only, except on the weight concerns scale, where NSSI+Suicidal Ideation only differed from no NSSI/Suicidal Ideation. The NSSI+Suicidal Ideation group was only greater than Suicidal Ideation-only on measures of depression and eating concern. Results highlight the importance of screening for both NSSI and suicidal ideation, especially for individuals with eating disorder symptoms. Likewise, screening for eating disorder pathology may be beneficial for individuals presenting with NSSI and suicidal ideation.
Subthalamic nucleus evokes similar long lasting glutamatergic excitations in pallidal, entopeduncular and nigral neurons in the basal ganglia slice.
Neuroscience, 2010

The subthalamic nucleus (STN) modulates the activity of globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr) neurons via its direct glutamatergic projections. To investigate the mechanism by which STN affects activity in these structures and whether STN induced activity is comparable among STN target neurons, we performed patch clamp recordings in a tilted, parasagittal, basal ganglia slice (BGS) that preserves these functional connections. We report that single, brief stimulation of the STN generates a brief monosynaptic AMPA-mediated excitatory postsynaptic current (EPSC) in GP, EP and SNr neurons. A higher intensity, supra-threshold activation evokes a compound EPSC consisting of an early monosynaptic component followed by a slow inward NMDA-mediated current with an overlying barrage of AMPA-mediated EPSCs. These late EPSCs were polysynaptic and gave rise to bursts of spikes that lasted several hundreds of milliseconds. They were eliminated by surgical removal of the STN from the BGS slice, indicating that the STN is required for their generation. Reconstruction of biocytin-filled STN neurons revealed that a third of STN neurons project intra-STN axon collaterals that may underlie polysynaptic activity. We propose that activation of the STN yields comparable long lasting excitations in its target neurons by means of a polysynaptic network.
Moyamoya Vessel Pathology Imaged by Ultra-High-Field Magnetic Resonance Imaging at 7.0 T.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2016

Prompt diagnosis of vessel pathology and appropriate treatment of moyamoya vasculopathy (MMV) are essential to improve long-term prognosis. The aims of our study were to explore the diagnostic value of ultra-high-field (UHF) magnetic resonance imaging at 7.0 T in MMV patients and to compare the applicability of two different 7.0 T vessel imaging modalities to 3.0 T magnetic resonance angiography (MRA) and digital subtraction angiography (DSA).
What do differences between multi-voxel and univariate analysis mean? How subject-, voxel-, and trial-level variance impact fMRI analysis.
NeuroImage, 2014

Multi-voxel pattern analysis (MVPA) has led to major changes in how fMRI data are analyzed and interpreted. Many studies now report both MVPA results and results from standard univariate voxel-wise analysis, often with the goal of drawing different conclusions from each. Because MVPA results can be sensitive to latent multidimensional representations and processes whereas univariate voxel-wise analysis cannot, one conclusion that is often drawn when MVPA and univariate results differ is that the activation patterns underlying MVPA results contain a multidimensional code. In the current study, we conducted simulations to formally test this assumption. Our findings reveal that MVPA tests are sensitive to the magnitude of voxel-level variability in the effect of a condition within subjects, even when the same linear relationship is coded in all voxels. We also find that MVPA is insensitive to subject-level variability in mean activation across an ROI, which is the primary variance component of interest in many standard univariate tests. Together, these results illustrate that differences between MVPA and univariate tests do not afford conclusions about the nature or dimensionality of the neural code. Instead, targeted tests of the informational content and/or dimensionality of activation patterns are critical for drawing strong conclusions about the representational codes that are indicated by significant MVPA results.
Pharmacogenetics of antidepressant drugs: State of the art and clinical implementation - recommendations from the French National Network of Pharmacogenetics.
Therapie, 2017

Tailoring antidepressant drug therapy to each individual patient is a complex process because these drugs have adverse effects leading to discontinuation. Pharmacogenetics may provide useful information in routine practice for optimizing antidepressant treatment by helping limit toxic effects while maintaining efficacy. This review presents the usefulness of pharmacogenetic tests for P450 cytochromes CYP2C19 and CYP2D6 in psychiatric patients taking antidepressants. Depending on the level of evidence, the French National Network of Pharmacogenetics (RNPGx) has issued recommendations stating that pharmacogenetic tests for CYP2D6 and CYP2C19 genes are potentially useful in psychiatric patients treated with antidepressant drugs.
Aminophospholipids are signal-transducing TREM2 ligands on apoptotic cells.
Scientific reports, 2019

Variants of triggering receptor expressed on myeloid cells 2 (TREM2) are associated with an increased incidence of Alzheimer's disease, as well as other neurodegenerative disorders. Using a newly developed, highly sensitive reporter cell model, consisting of Jurkat T cells stably overexpressing a reporter gene and a gene encoding TREM2DAP12 fusion protein, we show here that TREM2-dependent signal transduction in response to apoptotic Neuro2a cells is mediated by aminophospholipid ligands, phosphatidylserine and phosphatidylethanolamine, which are not exposed on the intact cell surface, but become exposed upon apoptosis. We also show that signal-transducing TREM2 ligands different from aminophospholipids, which appear to be derived from neurons, might be present in membrane fractions of mouse cerebral cortex. These results may suggest that TREM2 regulates microglial function by transducing intracellular signals from aminophospholipids on apoptotic cells, as well as unidentified ligands in the membranes of the cerebral cortex.
Shaping the Output of Lumbar Flexor Motoneurons by Sacral Neuronal Networks.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

The ability to improve motor function in spinal cord injury patients by reactivating spinal central pattern generators (CPGs) requires the elucidation of neurons and pathways involved in activation and modulation of spinal networks in accessible experimental models. Previously we reported on adrenoceptor-dependent sacral control of lumbar flexor motoneuron firing in newborn rats. The current work focuses on clarification of the circuitry and connectivity involved in this unique modulation and its potential use. Using surgical manipulations of the spinal gray and white matter, electrophysiological recordings, and confocal microscopy mapping, we found that methoxamine (METH) activation of sacral networks within the ventral aspect of S2 segments was sufficient to produce alternating rhythmic bursting (0.15-1 Hz) in lumbar flexor motoneurons. This lumbar rhythm depended on continuity of the ventral funiculus (VF) along the S2-L2 segments. Interrupting the VF abolished the rhythm and replaced it by slow unstable bursting. Calcium imaging of S1-S2 neurons, back-labeled via the VF, revealed that ∼40% responded to METH, mostly by rhythmic firing. All uncrossed projecting METH responders and ∼70% of crossed projecting METH responders fired with the concurrent ipsilateral motor output, while the rest (∼30%) fired with the contralateral motor output. We suggest that METH-activated sacral CPGs excite ventral clusters of sacral VF neurons to deliver the ascending drive required for direct rhythmic activation of lumbar flexor motoneurons. The capacity of noradrenergic-activated sacral CPGs to modulate the activity of lumbar networks via sacral VF neurons provides a novel way to recruit rostral lumbar motoneurons and modulate the output required to execute various motor behaviors.
Benign tremulous parkinsonism of the young-consider Parkin.
Parkinsonism & related disorders, 2019

Benign tremulous parkinsonism is generally considered a disease of the elderly, characterised by dominance of tremor over other motor manifestations, and by slower disease progression. Herein, we draw attention to a different clinical syndrome, benign tremulous parkinsonism of the young, which we have observed in Parkin disease.
Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic β1-integrin.
The Journal of comparative neurology, 2012

β1-containing integrins are required for persistent synaptic potentiation in hippocampus and regulate hippocampal-dependent learning. Based largely on indirect evidence, there is a prevailing assumption that β1-integrins are localized at synapses, where they contribute to synapse adhesion and signaling, but this has not been examined directly. Here we investigate the fine localization of β1-integrin in adult mouse hippocampus using high-resolution immunogold labeling, with a particular emphasis on synaptic labeling patterns. We find that β1-integrins localize to synapses in CA1 and are concentrated postsynaptically. At the postsynaptic membrane, β1-integrins are found more commonly clustered near active zone centers rather than at the peripheral edges. In mice harboring a conditional deletion of β1-integrins, labeling for N-cadherin and neuroligins increases. Western blots show increased levels of N-cadherin in total lysates and neuroligins increase selectively in synaptosomes. These data suggest there is a dynamic, compensatory adjustment of synaptic adhesion. Such adjustment is specific only for certain cell adhesion molecules (CAMs), because labeling for SynCAM is unchanged. Together, our findings demonstrate unequivocally that β1-integrin is an integral synaptic adhesion protein, and suggest that adhesive function at the synapse reflects a cooperative and dynamic network of multiple CAM families.
The intention to get vaccinated against influenza and actual vaccination uptake of Dutch healthcare personnel.
Vaccine, 2014

Health Authorities recommend annual vaccination of healthcare personnel (HCP) against influenza to protect vulnerable patients. Nevertheless, vaccination rates have been low among European HCP. Here we report on a longitudinal survey study to identify social cognitive predictors of the motivation to obtain influenza vaccination, and to test whether intention is a good predictor of actual vaccination behaviour. Dutch HCP (N=1370) were invited to participate in a survey (baseline). To link intention to behaviour, participants who completed the first survey (N=556) were sent a second survey after vaccinations were offered (follow-up). Multinominal regression analysis showed that HCP with a positive attitude and a higher frequency of past vaccinations were more likely to have a high intention to get vaccinated. A negative attitude, high feelings of autonomy in the decision whether to get vaccinated, a preference of inaction over vaccination, a lesser sense of personal responsibility, and high self-protection motives increased the probability of no intention to get vaccinated. Social cognitive predictors were identified that explain the intention to get vaccinated against influenza of HCP, which in turn proved to be a good predictor of behaviour. Future interventions should focus on these variables to increase vaccination coverage rates.
A Comprehensive Review of the Diagnosis, Treatment, and Management of Postmastectomy Pain Syndrome.
Current pain and headache reports, 2020

Postmastectomy pain syndrome (PMPS) remains poorly defined, although it is applied to chronic neuropathic pain following surgical procedures of the breast, including mastectomy and lumpectomy in breast-conserving surgery. It is characterized by persistent pain affecting the anterior thorax, axilla, and/or medial upper arm following mastectomy or lumpectomy. Though the onset of pain is most likely to occur after surgery, there may also be a new onset of symptoms following adjuvant therapy, including chemotherapy or radiation therapy.
Low-Intensity Pulsed Ultrasound Stimulation Induces Coupling Between Ripple Neural Activity and Hemodynamics in the Mouse Visual Cortex.
Cerebral cortex (New York, N.Y. : 1991), 2019

Several studies have separately investigated neural activities and hemodynamic responses induced by low-intensity pulsed ultrasound stimulation (LIPUS), less is known about their coupling under LIPUS. This study aims to investigate the neurovascular coupling with LIPUS by measuring neural activity and hemodynamics. We found that the relative power and sample entropy of local field potential at the ripple band have a significant correlation to relative cerebral blood flow over time (correlation coefficients: 0.66 ± 0.13 [P < 0.01] and -0.58 ± 0.11 [P < 0.05]). These results demonstrate that LIPUS can induce neurovascular coupling in the mouse visual cortex.
Detection of neuron membranes in electron microscopy images using a serial neural network architecture.
Medical image analysis, 2010

Study of nervous systems via the connectome, the map of connectivities of all neurons in that system, is a challenging problem in neuroscience. Towards this goal, neurobiologists are acquiring large electron microscopy datasets. However, the shear volume of these datasets renders manual analysis infeasible. Hence, automated image analysis methods are required for reconstructing the connectome from these very large image collections. Segmentation of neurons in these images, an essential step of the reconstruction pipeline, is challenging because of noise, anisotropic shapes and brightness, and the presence of confounding structures. The method described in this paper uses a series of artificial neural networks (ANNs) in a framework combined with a feature vector that is composed of image intensities sampled over a stencil neighborhood. Several ANNs are applied in series allowing each ANN to use the classification context provided by the previous network to improve detection accuracy. We develop the method of serial ANNs and show that the learned context does improve detection over traditional ANNs. We also demonstrate advantages over previous membrane detection methods. The results are a significant step towards an automated system for the reconstruction of the connectome.
Characterization of the Inflammatory Properties of Actively Released HMGB1 in Juvenile Idiopathic Arthritis.
Antioxidants & redox signaling, 2016

Pathogenic effects of the endogenous inflammatory mediator high mobility group box protein 1 (HMGB1) have been described in several inflammatory diseases. Recent reports have underlined the importance of post-translational modifications (PTMs) in determination of HMGB1 function and release mechanisms. We investigated the occurrence of PTMs of HMGB1 obtained from synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients.
Combined Toxoplasma gondii seropositivity and high blood kynurenine--Linked with nonfatal suicidal self-directed violence in patients with schizophrenia.
Journal of psychiatric research, 2016

Toxoplasma gondii (T. gondii) chronic infection and elevated kynurenine (KYN) levels have been individually associated with non-fatal suicidal self-directed violence (NF-SSDV). We aimed to test the hypothesis that the association between T. gondii seropositivity and history of NF-SSDV would be stronger in schizophrenia patients with high plasma KYN levels than in those with lower KYN levels. We measured anti-T. gondii IgG antibodies and plasma KYN in 950 patients with schizophrenia, and used logistic regression to evaluate the relationship between NF-SSDV and KYN in patients who were either seropositive or seronegative for T. gondii. For those with KYN levels in the upper 25th percentile, the unadjusted odds ratio for the association between NF-SSDV history and KYN in T. gondii seropositive patients was 1.63 (95% CI 1.01 to 2.66), p = 0.048; the adjusted odds ratio was 1.95 (95% CI 1.15 to 3.30), p = 0.014. Plasma KYN was not associated with a history of NF-SSDV in T. gondii seronegative patients. The results suggest that T. gondii and KYN may have a nonlinear cumulative effect on the risk of NF-SSDV among those with schizophrenia. If confirmed by future longitudinal studies, this result is expected to have both theoretical and clinical implications for the prevention and treatment of suicidal behavior.
Maternal vaccination and protective immunity against Zika virus vertical transmission.
Nature communications, 2019

An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3'UTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3'UTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3'UTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3'UTR-∆10-LAV may also be considered for maternal vaccination.
Noncoding Microdeletion in Mouse 
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in
On the detection of cerebral metabolic depression in experimental traumatic brain injury using Chemical Exchange Saturation Transfer (CEST)-weighted MRI.
Scientific reports, 2018

Metabolic abnormalities are commonly observed in traumatic brain injury (TBI) patients exhibiting long-term neurological deficits. This study investigated the feasibility and reproducibility of using chemical exchange saturation transfer (CEST) MRI to detect cerebral metabolic depression in experimental TBI. Phantom and in vivo CEST experiments were conducted at 9.4 Tesla to optimize the selective saturation for enhancing the endogenous contrast-weighting of the proton exchanges over the range of glucose proton chemical shifts (glucoCEST) in the resting rat brain. The optimized glucoCEST-weighted imaging was performed on a closed-head model of diffuse TBI in rats with 2-deoxy-D-[
Persistent firing supported by an intrinsic cellular mechanism in a component of the head direction system.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

The rat postsubiculum has head direction cells that fire persistently when the rat's head is oriented in particular directions. This persistent firing is maintained even if the rat is motionless, when spatial cues are removed from the environment and in the dark, but the mechanism that supports persistent firing of the head direction cells is still unclear. Here, using in vitro whole-cell patch recording, we found that a short-triggering stimulus (as few as five induced spikes) can initiate persistent firing in cells of the postsubiculum. Pharmacological results indicated that this persistent firing is driven by a calcium-sensitive nonselective cation current. The distribution of cells with persistent firing in superficial and deep layers in the postsubiculum was similar to that of head direction cells. These results suggest that persistent firing of head direction cells in the postsubiculum could be supported by an intrinsic mechanism.