rudyvdbrink/CitationDatabase huggingface dataset:
Chronic subdural hematoma: A previously unreported life-threatening complication in adult with Sotos syndrome.
American journal of medical genetics. Part A, 2020

Macrocephaly, defined as head circumference ≥ 2 SDs, is a cardinal feature of Sotos syndrome (SS) and generally persists in adulthood. Subdural fluid collection, typically associated with macrocephaly, is described in children due to anatomical conformation, and in adulthood due to brain atrophy and ex-vacuo hydrocephalus. On the other hand, a true, symptomatic, chronic subdural hematoma (CSH) is a previously unreported complication of SS in adulthood. Here we describe the first SS patient presenting symptomatic CSH, leading to frequent hospitalizations for surgical evacuations that consistently recurred. Middle meningeal artery (MMA) embolization and epidural blood patch (EBP) allowed to resolve the CSH with complete resolution of clinical signs and symptoms. We hypothesize that appearance and recurrences of CSH may be related to pathological biomechanics of brain, cerebro-spinal fluid and skull, secondary to anatomical features of SS. In this context, surgical evacuation may be less efficient than usual to cure CSH. Alternative treatment to avoid blood extravasation, as MMA embolization, or to cure concurrent causes of the pathology, as EBP, may be considered.
Structural Alterations of Mucins Are Associated with Losses in Functionality.
Biomacromolecules, 2021

Commercial mucin glycoproteins are routinely used as a model to investigate the broad range of important functions mucins fulfill in our bodies, including lubrication, protection against hostile germs, and the accommodation of a healthy microbiome. Moreover, purified mucins are increasingly selected as building blocks for multifunctional materials, i.e., as components of hydrogels or coatings. By performing a detailed side-by-side comparison of commercially available and lab-purified variants of porcine gastric mucins, we decipher key molecular motifs that are crucial for mucin functionality. As two main structural features, we identify the hydrophobic termini and the hydrophilic glycosylation pattern of the mucin glycoprotein; moreover, we describe how alterations in those structural motifs affect the different properties of mucins-on both microscopic and macroscopic levels. This study provides a detailed understanding of how distinct functionalities of gastric mucins are established, and it highlights the need for high-quality mucins-for both basic research and the development of mucin-based medical products.
β-arrestin2 recruitment at the β2 adrenergic receptor: A luciferase complementation assay adapted for undergraduate training in pharmacology.
Pharmacology research & perspectives, 2021

In the context of pharmacology teaching, hands-on activities constitute an essential complement to theoretical lectures. Frequently, these activities consist in exposing fresh animal tissues or even living animals to selected drugs and qualitatively or quantitatively evaluating functional responses. However, technological advancements in pharmacological research and the growing concerns for animal experimentation support the need for innovative and flexible in vitro assays adapted for teaching purposes. We herein report the implementation of a luciferase complementation assay (LCA) enabling to dynamically monitor β-arrestin2 recruitment at the β
Rapid-acting and long-lasting antidepressant-like action of (R)-ketamine in Nrf2 knock-out mice: a role of TrkB signaling.
European archives of psychiatry and clinical neuroscience, 2021

The transcription nuclear factor-erythroid factor 2-related factor 2 (Nrf2) plays a key role in inflammation that is involved in depression. We previously reported that Nrf2 knock-out (KO) mice exhibit depression-like phenotypes through systemic inflammation. (R)-ketamine, an enantiomer of ketamine, has rapid-acting and long-lasting antidepressant-like effects in rodents. We investigated whether (R)-ketamine can produce antidepressant-like effects in Nrf2 KO mice. Effects of (R)-ketamine on the depression-like phenotypes in Nrf2 KO mice were examined. Furthermore, the role of TrkB in the antidepressant-like actions of (R)-ketamine was also examined. In the tail-suspension test (TST) and forced swimming test (FST), (R)-ketamine (10 mg/kg) significantly attenuated the increased immobility times of TST and FST in the Nrf2 KO mice. In the sucrose preference test (SPT), (R)-ketamine significantly ameliorated the reduced preference of SPT in Nrf2 KO mice. Decreased expression of synaptic proteins (i.e., GluA1 and PSD-95) in the medial prefrontal cortex (mPFC) of Nrf2 KO mice was significantly ameliorated after a single injection of (R)-ketamine. Furthermore, the pre-treatment with the TrkB antagonist ANA-12 (0.5 mg/kg) significantly blocked the rapid and long-lasting antidepressant-like effects of (R)-ketamine in Nrf2 KO mice. Furthermore, ANA-12 significantly antagonized the beneficial effects of (R)-ketamine on decreased expression of synaptic proteins in the mPFC of Nrf2 KO mice. These findings suggest that (R)-ketamine can produce rapid and long-lasting antidepressant-like actions in Nrf2 KO mice via TrkB signaling.
[FreeSurfer as a Platform for Associating Brain Structure with Function].
Brain and nerve = Shinkei kenkyu no shinpo, 2018

FreeSurfer is open source software used to process and analyze magnetic resonance imaging of the human brain. It is a convenient tool that helps elucidate various structural characteristics the brain. In this review, we introduce the various structural indices of the brain, analyzed using FreeSurfer and magnetoencephalography, which can evaluate neural activity with high temporal and spatial resolution. We consider that the FreeSurfer has great potential as a platform for multimodal neuroimaging studies.
Saccade-induced changes in ocular torsion reveal predictive orientation perception.
Journal of vision, 2019

Natural orienting of gaze often results in a retinal image that is rotated relative to space due to ocular torsion. However, we perceive neither this rotation nor a moving world despite visual rotational motion on the retina. This perceptual stability is often attributed to the phenomenon known as predictive remapping, but the current remapping literature ignores this torsional component. In addition, studies often simply measure remapping across either space or features (e.g., orientation) but in natural circumstances, both components are bound together for stable perception. One natural circumstance in which the perceptual system must account for the current and future eye orientation to correctly interpret the orientation of external stimuli occurs during movements to or from oblique eye orientations (i.e., eye orientations with both a horizontal and vertical angular component relative to the primary position). Here we took advantage of oblique eye orientation-induced ocular torsion to examine perisaccadic orientation perception. First, we found that orientation perception was largely predicted by the rotated retinal image. Second, we observed a presaccadic remapping of orientation perception consistent with maintaining a stable (but spatially inaccurate) retinocentric perception throughout the saccade. These findings strongly suggest that our seamless perceptual stability relies on retinocentric signals that are predictively remapped in all three ocular dimensions with each saccade.
Morphology of the criminal brain: gray matter reductions are linked to antisocial behavior in offenders.
Brain structure & function, 2020

Aggression and psychopathy are multifaceted conditions determined interpersonal and antisocial factors. Only a few studies analyze the link between these separate factors and specific brain morphology distinctively. A voxel-based morphometry (VBM) analysis was performed on 27 violent offenders and 27 controls aiming to associate sub-features of aggressive and psychopathic behavior with specific gray matter volumes. Trait aggression was assessed using two self-report tests (Aggression Questionnaire, AQ, and Reactive-Proactive-Aggression Questionnaire, RPQ) and psychopathy with the Psychopathy Checklist-Revised (PCL-R). Total and sub-scale scores of these tests were correlated to the brain morphometry of the offenders group in separate analyses. It was found that psychopathic behavior was negatively correlated with prefrontal gray matter volume and that this result was primarily driven by the antisocial behavior sub-scale of the PCL-R. Furthermore, less gray matter in right superior frontal and left inferior parietal regions with increasing antisocial behavior could be observed. One cluster comprising the right middle and superior temporal gyrus was negatively correlated with both, reactive aggression and antisocial behavior. These results outline (1) the importance of distinctively analyzing sub-features that contribute to aggressive and psychopathic behavior, given that the negative correlation of psychopathy global scores with prefrontal volume was driven by one single facet of the PCL-R scale (antisocial behavior). Moreover, these results indicate (2) fronto-temporo-parietal network deficits in antisocial, criminal offenders, with a particular strong effect in the temporal lobe.
Identification of sarcopenia and dynapenia in CKD predialysis patients with EGWSOP2 criteria: An observational, cross-sectional study.
Nutrition (Burbank, Los Angeles County, Calif.), 2020

Using the new European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, we identified sarcopenic and dynapenic patients in a cohort of predialysis patients with chronic kidney disease (CKD), and evaluated their clinical and laboratory characteristics.
Amnesia for context fear is caused by widespread disruption of hippocampal activity.
Neurobiology of learning and memory, 2020

The hippocampus plays an essential role in the formation and retrieval of episodic memories in humans and contextual memories in animals. However, amnesia is not always observed when this structure is compromised. To determine why this is the case, we compared the effects of several different circuit manipulations on memory retrieval and hippocampal activity. Mice were first trained on context fear conditioning and then optogenetic and chemogenetic tools were used to alter activity during memory retrieval. We found that retrieval was only impaired when manipulations caused widespread changes (increases or decreases) in hippocampal activity. Widespread increases occurred when pyramidal cells were excited and widespread decreases were found when GABAergic neurons were stimulated. Direct hyperpolarization of excitatory neurons only moderately reduced activity and did not produce amnesia. Surprisingly, widespread decreases in hippocampal activity did not prevent retrieval if they occurred gradually prior to testing. This suggests that intact brain regions can express contextual memories if they are given adequate time to compensate for the loss of the hippocampus.
A ventral striatal prediction error signal in human fear extinction learning.
NeuroImage, 2021

Animal studies have shown that the prediction error (PE) signal that drives fear extinction learning is encoded by phasic activity of midbrain dopamine (DA) neurons. Thus, the extinction PE resembles the appetitive PE that drives reward learning. In humans, fear extinction learning is less well understood. Using computational neuroimaging, a previous study from our group reported hemodynamic activity in the left ventral putamen, a subregion of the ventral striatum (VS), to correlate with a PE function derived from a formal associative learning model. The activity was modulated by genetic variation in a DA-related gene. To conceptually replicate and extend this finding, we here asked whether an extinction PE (EPE) signal in the left ventral putamen can also be observed when genotype information is not taken into account. Using an optimized experimental design for model estimation, we again observed EPE-related activity in the same striatal region, indicating that activation of this region is a feature of human extinction learning. We further observed significant EPE signals across wider parts of the VS as well as in frontal cortical areas. These results may suggest that the prediction errors during extinction learning are available to larger parts of the brain, as has also been observed in human neuroimaging studies of reward PE signaling. Conclusive evidence that the human EPE signal is of DAergic nature is still outstanding.
Multiple sclerosis with intractable vomiting and atypical area postrema lesion.
Multiple sclerosis and related disorders, 2020

Area postrema syndrome is considered as one of the most typical presentations of neuromyelitis optica spectrum disorders (NMOSDs) (Wingerchuk et al., 2015). The involvement of area postrema is rarely seen in multiple sclerosis (MS). We are here report a case of a young woman with multiple sclerosis, presented with intractable vomiting, and her MRI brain showed acute T2 hyperintense signal over the area postrema.
Neurocognitive correlates of self-esteem: From self-related attentional bias to involvement of the ventromedial prefrontal cortex.
Neuroscience research, 2020

Despite growing interest in underlying cognitive mechanisms of self-esteem, its neurocognitive correlates are not fully-understood. Attention bias to self-related stimuli is an example of self-referential processing (SRP) and its association with self-esteem is not well-studied. Moreover, previous studies showed that the medial prefrontal regions are involved in SRP which might suggest its involvement in self-esteem too. We investigated attentional bias to self-related stimuli and its association with the level of self-esteem in the first study (N = 30). In the second study (N = 15), we modulated activity of the ventromedial prefrontal cortex (VMPFC), as one of the medial prefrontal regions, using transcranial direct current stimulation (tDCS) to see how it affects different domains of self-esteem. Results showed that individuals with a higher level of self-esteem have more attentional bias to their own facial pictures (compared to other-facial pictures) and self-related words (compared to self-unrelated words) suggesting an impact of self-esteem on attentional and perceptual processes. Additionally, modulating activity of the VMPFC with 2 mA anodal and cathodal tDCS was associated with significantly higher ratings of global and total self-esteem but not other self-esteem domains. Our findings provide supporting evidence of neurocognitive correlates of self-esteem indicating a biasing influence of self-esteem on attention toward "self" and suggesting self-esteem as a function of SRP at behavioural and neural levels.
Active vision at the foveal scale in the primate superior colliculus.
Journal of neurophysiology, 2021

The primate superior colliculus (SC) has recently been shown to possess both a large foveal representation as well as a varied visual processing repertoire. This structure is also known to contribute to eye movement generation. Here, we describe our current understanding of how SC visual and movement-related signals interact within the realm of small eye movements associated with the foveal scale of visuomotor behavior. Within the SC's foveal representation, there is a full spectrum of visual, visual-motor, and motor-related discharge for fixational eye movements. Moreover, a substantial number of neurons only emit movement-related discharge when microsaccades are visually guided, but not when similar movements are generated toward a blank. This represents a particularly striking example of integrating vision and action at the foveal scale. Beyond that, SC visual responses themselves are strongly modulated, and in multiple ways, by the occurrence of small eye movements. Intriguingly, this impact can extend to eccentricities well beyond the fovea, causing both sensitivity enhancement and suppression in the periphery. Because of large foveal magnification of neural tissue, such long-range eccentricity effects are neurally warped into smaller differences in anatomical space, providing a structural means for linking peripheral and foveal visual modulations around fixational eye movements. Finally, even the retinal-image visual flows associated with tiny fixational eye movements are signaled fairly faithfully by peripheral SC neurons with relatively large receptive fields. These results demonstrate how studying active vision at the foveal scale represents an opportunity for understanding primate vision during natural behaviors involving ever-present foveating eye movements.
Posterior Cranial Fossa Maldevelopment in Infants with Repaired Open Myelomeningoceles: Double Trouble or a Dynamic Process of Posterior Cranial Fossa Abnormalities?
World neurosurgery, 2020

Two degrees of posterior cranial fossa (PCF) maldevelopment can be hypothesized in children with myelomeningocele (MMC). This paper investigates the PCF deformation by quantitative magnetic resonance imaging analysis in MMC subjects with and without Chiari 2 malformation (CM2).
Predictors of the pulsatility index in the middle cerebral artery of acute stroke patients.
Scientific reports, 2020

Cervical and transcranial Doppler (TCD) are widely used as non-invasive methods in the evaluation of acute ischemic stroke (AIS) patients. High-grade carotid artery stenosis induces haemodynamic changes such as collateral flow and a so-called post-stenotic flow pattern of the middle cerebral artery (MCA), which appears flattened, with a reduction of the velocity difference between systole and diastole. We studied the influence of carotid artery stenosis and other variables on the flow pattern in the MCA using the pulsatility index (PI), a quantitative TCD parameter reflecting the flow spectrum in a large of cohort AIS patients. We performed ultrasound examinations of 1825 AIS patients at the CHUV from October 2004 to December 2014. We extracted patient characteristics from the ASTRAL registry. Carotid stenosis severity was classified as < 50%, 50-70%, 70-90% and > 90%, or occlusion, according to Doppler velocity criteria. We first determined variables associated with stenosis grade. Then we performed a multivariate analysis after adjusting for baseline differences, using MCA PI as dependent variable. Carotid stenosis > 70% (- 0.07) and carotid stenosis > 90%, or occlusion (- 0.14) and left side (- 0.02) are associated with lower MCA PI values. Age (+0.006 PI units per decade), diabetes (+0.07), acute ischemic changes on initial CT (+0.03) and severe plaque morphology (+0.18) are associated with higher MCA PI values. We found a number of clinical and radiological conditions that significantly influence the PI of the MCA, including high-grade ipsilateral carotid stenosis in AIS patients. We provide for the first time a quantitative evaluation of the effect of these influencing factors from a large cohort of AIS patients.
p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response.
Nature communications, 2021

Autophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress.
Temporal dynamics of the cerebello-cortical convergence in ventro-lateral motor thalamus.
The Journal of physiology, 2021

Ventrolateral thalamus (VL) integrates information from cerebellar nuclei and motor cortical layer VI. Inputs from the cerebellar nuclei evoke large-amplitude responses that depress upon repetitive stimulation while layer VI inputs from motor cortex induce small-amplitude facilitating responses. We report that the spiking of VL neurons can be determined by the thalamic membrane potential, the frequency of cerebellar inputs and the duration of pauses after cerebellar high frequency stimulation. Inputs from motor cortical layer VI shift the VL membrane potential and modulate the VL spike output in response to cerebellar stimulation.  These results help us to decipher how the cerebellar output is integrated in VL and modulated by motor cortical input.
Host sex and transplanted human induced pluripotent stem cell phenotype interact to influence sensorimotor recovery in a mouse model of cortical contusion injury.
Brain research, 2020

Traumatic brain injury (TBI) is a substantial cause of disability and death worldwide. Primary head trauma triggers chronic secondary injury mechanisms in the brain that are a focus of therapeutic efforts to treat TBI. Currently, there is no successful clinical strategy to repair brain injury. Cell transplantation therapies have demonstrated promise in attenuating secondary injury mechanisms of neuronal death and dysfunction in animal models of brain injury. In this study, we used a unilateral cortical contusion injury (CCI) model of sensorimotor brain injury to examine the effects of human induced pluripotent stem cell (hiPSC) transplantation on pathology in male and female adult mice. We determined transplanted hiPSC-derived neural stem cells (NSCs) and neuroblasts but not astrocytes best tolerate the injured host environment. Surviving NSC and neuroblast cells were clustered at the site of injection within the deep layers of the cortex and underlying corpus callosum. Cell grafts extended neuritic processes that crossed the midline into the contralateral corpus callosum or continued laterally within the external capsule to enter the ipsilateral entorhinal cortex. To determine the effect of transplantation on neuropathology, we performed sensorimotor behavior testing and stereological estimation of host neurons, astrocytes, and microglia within the contused cortex. These measures did not reveal a consistent effect of transplantation on recovery post-injury. Rather the positive and negative effects of cell transplantation were dependent on the host sex, highlighting the importance of developing patient-specific approaches to treat TBI. Our study underscores the complex interactions of sex, neuroimmune responses and cell therapy in a common experimental model of TBI.