rudyvdbrink/CitationDatabase huggingface dataset:
Elevating EGFR-MAPK program by a nonconventional Cdc42 enhances intestinal epithelial survival and regeneration.
JCI insight, 2020

The regulatory mechanisms enabling the intestinal epithelium to maintain a high degree of regenerative capacity during mucosal injury remain unclear. Ex vivo survival and clonogenicity of intestinal stem cells (ISCs) strictly required growth response mediated by cell division control 42 (Cdc42) and Cdc42-deficient enteroids to undergo rapid apoptosis. Mechanistically, Cdc42 engaging with EGFR was required for EGF-stimulated, receptor-mediated endocytosis and sufficient to promote MAPK signaling. Proteomics and kinase analysis revealed that a physiologically, but nonconventionally, spliced Cdc42 variant 2 (V2) exhibited stronger MAPK-activating capability. Human CDC42-V2 is transcriptionally elevated in some colon tumor tissues. Accordingly, mice engineered to overexpress Cdc42-V2 in intestinal epithelium showed elevated MAPK signaling, enhanced regeneration, and reduced mucosal damage in response to irradiation. Overproducing Cdc42-V2 specifically in mouse ISCs enhanced intestinal regeneration following injury. Thus, the intrinsic Cdc42-MAPK program is required for intestinal epithelial regeneration, and elevating this signaling cascade is capable of initiating protection from genotoxic injury.
Toxoplasma infection induces microglia-neuron contact and the loss of perisomatic inhibitory synapses.
Glia, 2020

Infection and inflammation within the brain induces changes in neuronal connectivity and function. The intracellular protozoan parasite, Toxoplasma gondii, is one pathogen that infects the brain and can cause encephalitis and seizures. Persistent infection by this parasite is also associated with behavioral alterations and an increased risk for developing psychiatric illness, including schizophrenia. Current evidence from studies in humans and mouse models suggest that both seizures and schizophrenia result from a loss or dysfunction of inhibitory synapses. In line with this, we recently reported that persistent T. gondii infection alters the distribution of glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes GABA synthesis in inhibitory synapses. These changes could reflect a redistribution of presynaptic machinery in inhibitory neurons or a loss of inhibitory nerve terminals. To directly assess the latter possibility, we employed serial block face scanning electron microscopy (SBFSEM) and quantified inhibitory perisomatic synapses in neocortex and hippocampus following parasitic infection. Not only did persistent infection lead to a significant loss of perisomatic synapses, it induced the ensheathment of neuronal somata by myeloid-derived cells. Immunohistochemical, genetic, and ultrastructural analyses revealed that these myeloid-derived cells included activated microglia. Finally, ultrastructural analysis identified myeloid-derived cells enveloping perisomatic nerve terminals, suggesting they may actively displace or phagocytose synaptic elements. Thus, these results suggest that activated microglia contribute to perisomatic inhibitory synapse loss following parasitic infection and offer a novel mechanism as to how persistent T. gondii infection may contribute to both seizures and psychiatric illness.
Frequency distribution in intraoperative stimulation-evoked EMG responses during selective dorsal rhizotomy in children with cerebral palsy-part 2: gender differences and left-biased asymmetry.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2020

Spinal reflexes reorganize in cerebral palsy (CP), producing hyperreflexia and spasticity. CP is more common among male infants, and gender might also influence brain and spinal-cord reorganization. This retrospective study investigated the frequency of higher-graded EMG responses elicited by electrical nerve-root stimulation during selective dorsal rhizotomy (SDR), prior to partial nerve- root deafferentation, considering not only segmental level and body side, but also gender.
Learning to predict: Neuronal signatures of auditory expectancy in human event-related potentials.
NeuroImage, 2021

Learning to anticipate future states of the world based on statistical regularities in the environment is a key component of perception and is vital for the survival of many organisms. Such statistical learning and prediction are crucial for acquiring language and music appreciation. Importantly, learned expectations can be implicitly derived from exposure to sensory input, without requiring explicit information regarding contingencies in the environment. Whereas many previous studies of statistical learning have demonstrated larger neuronal responses to unexpected versus expected stimuli, the neuronal bases of the expectations themselves remain poorly understood. Here we examined behavioral and neuronal signatures of learned expectancy via human scalp-recorded event-related brain potentials (ERPs). Participants were instructed to listen to a series of sounds and press a response button as quickly as possible upon hearing a target noise burst, which was either reliably or unreliably preceded by one of three pure tones in low-, mid-, and high-frequency ranges. Participants were not informed about the statistical contingencies between the preceding tone 'cues' and the target. Over the course of a stimulus block, participants responded more rapidly to reliably cued targets. This behavioral index of learned expectancy was paralleled by a negative ERP deflection, designated as a neuronal contingency response (CR), which occurred immediately prior to the onset of the target. The amplitude and latency of the CR were systematically modulated by the strength of the predictive relationship between the cue and the target. Re-averaging ERPs with respect to the latency of behavioral responses revealed no consistent relationship between the CR and the motor response, suggesting that the CR represents a neuronal signature of learned expectancy or anticipatory attention. Our results demonstrate that statistical regularities in an auditory input stream can be implicitly learned and exploited to influence behavior. Furthermore, we uncover a potential 'prediction signal' that reflects this fundamental learning process.
The biology of aggressive behavior in bipolar disorder: A systematic review.
Neuroscience and biobehavioral reviews, 2020

Aggressive behavior (AB) represents a public health concern often associated with severe psychiatric disorders. Although most psychiatric patients are not aggressive, untreated psychiatric illness, including bipolar disorder (BD), may associate with an increased risk of AB. Accurate predictive models of AB are still lacking and it is crucial to delineate AB biomarkers state of the art in BD. We performed a systematic review according to PRISMA guidelines to identify biological correlates of AB in BD. Final results included 20 studies: 10 involving genetic and 10 other biological AB biomarkers (total sample size N = 5,181). Our results pointed to a serotoninergic hypoactivation in violent suicidal BD patients. Similarly, BD violent suicide attempters had a blunted hypothalamic-pituitary-adrenal (HPA) activity. Violent behavior in BD was associated with a chronic inflammatory state. While the role of lipids as biomarkers for AB remains equivocal, uric acid appears as a potential biomarker for hetero-AB in BD. Available data can be useful in the fulfill of specific biomarkers of AB in BD, ultimately leading to the development of accurate predictive models.
Frequency and methylation status of selected retrotransposition competent L1 loci in amyotrophic lateral sclerosis.
Molecular brain, 2020

Long interspersed element-1 (LINE-1/L1) is the only autonomous transposable element in the human genome that currently mobilises in both germline and somatic tissues. Recent studies have identified correlations between altered retrotransposon expression and the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) in a subset of patients. The risk of an individual developing ALS is dependent on an interaction of genetic variants and subsequent modifiers during life. These modifiers could include environmental factors, which can lead to epigenetic and genomic changes, such as somatic mutations, occurring in the neuronal cells that degenerate as the disease develops. There are more than 1 million L1 copies in the human genome today, but only 80-100 L1 loci in the reference genome are considered to be retrotransposition-competent (RC) and an even smaller number of these RC-L1s loci are highly active. We hypothesise that RC-L1s could affect normal cellular function through their mutagenic potential conferred by their ability to retrotranspose in neuronal cells and through DNA damage caused by the endonuclease activity of the L1-encoded ORF2 protein. To investigate whether either an increase in the genomic burden of RC-L1s or epigenetic changes to RC-L1s altering their expression, could play a role in disease development, we chose a set of seven well characterised genomic RC-L1 loci that were reported earlier to be highly active in a cellular L1 retrotransposition reporter assay or serve as major source elements for germline and/or somatic retrotransposition events. Analysis of the insertion allele frequency of five polymorphic RC-L1s, out of the set of seven, for their presence or absence, did not identify an increased number individually or when combined in individuals with the disease. However, we did identify reduced levels of methylation of RC-L1s in the motor cortex of those individuals with both familial and sporadic ALS compared to control brains. The changes to the regulation of the loci encompassing these RC-L1s demonstrated tissue specificity and could be related to the disease process.
Video Modeling and Social Skills Learning in ASD-HF.
Children (Basel, Switzerland), 2020

Autism spectrum disorders represent a heterogeneous group of clinical situations, and are mainly represented by a deficit of social communication. In this study, we compare two strategies to enhance communicative/social skills, namely self-video modeling and peer video modeling. The subjects were divided into two groups treated via the method of self-video modeling (group 1) or peer video modeling (group 2). For both groups of subjects affected by ASD-HF (Autism Spectrum Disorder-high-functioning), three different activities were proposed: (a) interacting with a salesperson while making a purchase, (b) initiating and maintaining a conversation with peers, and (c) starting and maintaining an enjoyable activity with a peer. The ability to rapidly accomplish the task was used as the main criteria to appraise the groups' responses to the proposed activities. In group 1, the use of self-video modeling procedures demonstrated a faster and correct execution of the three proposed tasks (especially task 3) when compared to group 2. In group 2, the use of peer video modeling has instead led to a slower acquisition of abilities to process and perform the tasks. The use of self-video modeling speeds up the acquisition of skills to perform communicative/social tasks, compared to peer video modeling's slower performance in subjects with ASD-HF. Results could be related to either the amount of time the subject is exposed to the task or to the capacity of ASD-HF subjects to self-value one's own actions more than others. In our work, we have tried to reset the differences in exposure time. Therefore, self-video modeling is demonstrated to be more effective, as it produces a response to the signification/mirroring characteristic of ASD-HF.
[New results of neuroscience research - the background of symptomatological and etiological diversity of mental disorders].
Ideggyogyaszati szemle, 2020

Nowadays, the focus of genetic, neurobiological, neuropsychological and psychosocial research is on a more accurate discovery of the etiology of mental illnesses, especially with regard to the role and complex interactions of certain risk factors. It is increasingly challenging to interpret the results of different aspects and methodologies in a coherent theoretical framework, as this can only lead to a more accurate understanding of the complexity and mechanism of the psychiatric disorders. The main aim of this paper to overview recent studies on etiological background of mental disorders and to present the most important aspects of the Research Domain Criteria (RDoC) system.
Vimentin's side gig: Regulating cellular proteostasis in mammalian systems.
Cytoskeleton (Hoboken, N.J.), 2020

Intermediate filaments (IFs) perform a diverse set of well-known functions including providing structural support for the cell and resistance to mechanical stress, yet recent evidence has revealed unexpected roles for IFs as stress response proteins. Previously, it was shown that the type III IF protein vimentin forms cage-like structures around centrosome-associated proteins destined for degradation, structures referred to as aggresomes, suggesting a role for vimentin in protein turnover. However, vimentin's function at the aggresome has remained largely understudied. In a recent report, vimentin was shown to be dispensable for aggresome formation, but played a critical role in protein turnover at the aggresome through localizing proteostasis-related machineries, such as proteasomes, to the aggresome. Here, we review evidence for vimentin's function in proteostasis and highlight the organismal implications of these findings.
The Fidia-Georgetown Institute for the Neurosciences (FGIN) 1985-1994.
Pharmacological research, 2011

This article describes briefly the history and activities of the Fidia-Georgetown Institute for the Neurosciences (FGIN), from its establishment in 1985 to its closure in 1994. It also provides a list of those colleagues and students who worked at FGIN and contributed to various research projects.
[Information flow between medical and social sciences].
Orvosi hetilap, 2014

In order to reveal impacts of natural and social sciences on each other, the authors examined connections between fields of medical and social sciences using a search for references and citations of scientific publication. 1. The largest affinity between the medical and social sciences was found between neurosciences and psychology, but there was a significant affinity between clinical sciences and general social sciences, as well. 2. The example of General & Internal Medicine papers in the topics of "diabetes" suggests that in the period 2001-2010 the share of references to social sciences was significantly increased. In the meantime, social science papers in the same topics contained references to Clinical Medicine papers in a constantly high percentage. 3. In the sample under study, the age distribution of social science papers in the references did not differ significantly from that of the other sources. 4. Share of references to social science papers was found to be extremely high among Hungarian General & Internal Medicine papers in the topics of "diabetes". This finding still requires clarification, nevertheless, since e.g. it was not supported by an institutional comparison including the largest Hungarian medical research university. 5. The intensity of the reference/citation mediated information flows between the Hungarian Medical Journal, Orvosi Hetilap and social sciences appears to be in accordance with the current international trends.
Parsimonious modelling allows generation of the dendrograms of primate striatal medium spiny and pallidal type II neurons using a stochastic algorithm.
Brain research, 2008

Data from quantitative three-dimensional analysis of primate striatal medium spiny neurons (MSNs) and pallidal type I and type II neurons were used to search for possible rules underlying the dendritic architecture of these cells. Branching and terminating probabilities per unit length of dendrite were computed from all available measurement points. In the three neuronal groups, terminating probabilities were found to be exponentially increasing functions of the path distance to soma. MSNs and type II branching probabilities could be accurately modelled with decreasing functions of both the metrical (exponential functions) and topological (power functions of the centrifugal branch order) distances to soma. Additionally, type II branching also slightly depended on the distance to the proximal tip of the supporting branches. Type I branching probabilities did not follow these rules accurately. Embedding the modelled probability functions in a stochastic algorithm allowed generation of dendrograms close to those of the real MSNs and pallidal type II neurons, while the algorithm failed to simulate type I dendrites. MSN and pallidal type II neuron branching and terminating probabilities are thus highly dependent on the position in the dendritic arbor. This relationship can be modelled with simple functions and has a strong incidence on the dendrogram structure of the cells concerned. The additional dependence of the branching probability on the within-branch position led us to propose an extension of a previous modelling study by Nowakowski and co-workers which could account for a large range of topological and metrical (length) dendritic tree structures.
The effect of complex cognitive training on subsequent night sleep.
Journal of sleep research, 2020

Using a nap design, we have recently shown that training at a complex cognitive task at bedtime improves objective sleep quality by reducing sleep fragmentation. In order to extend our findings to nighttime sleep, here we assess the impact of a multi-componential cognitive task at bedtime on the subsequent sleep episode of subjects reporting habitual bad sleep, allegedly characterized by high sleep fragmentation. In a within-subjects design, 20 subjective bad sleepers underwent polysomnographic recording in three conditions: (a) baseline sleep (BL); (b) post-training sleep (TR), preceded by a complex ecological task, i.e. a modified version of the word game Ruzzle; (c) post-active control sleep (AC), preceded by a control task. Sleep in TR was more organized (higher number of cycles and longer time spent in cycles) and showed lower microarousal frequency than in AC and BL. As for sleep continuity (total and brief awakening frequency) and other stability measures (state transition and functional uncertainty period frequency, time in functional uncertainty), both TR and AC showed significant improvements compared with BL. Arousal frequency was also reduced in TR relative to BL. Our results show a clear impact of cognitive training on subsequent night sleep, basically consisting of an increase in sleep continuity, stability and organization. In our sample of bad sleepers, these post-training changes end up representing a notable sleep improvement, also consistently reflected in subjective sleep quality perception. Therefore, ecological pre-sleep cognitive training should be further studied as an easily accessible complementary approach in standard therapies for sleep-disordered populations.
Does the Beck Cognitive Insight Scale predict change in delusional beliefs?
Psychology and psychotherapy, 2020

The Beck Cognitive Insight Scale (BCIS) is composed of two subscales, self-reflectiveness and self-certainty, assessing reflectiveness and openness to feedback, and mental flexibility. Delusions have previously been associated with low cognitive insight. The aim of this study was to determine whether changes in BCIS scores predict changes in delusional beliefs.
Safety and efficacy of ticagrelor as single antiplatelet therapy in prevention of thromboembolic complications associated with the Pipeline Embolization Device (PED): multicenter experience.
Journal of neurointerventional surgery, 2020

Flow diversion (FD) is a common treatment modality for complex intracranial aneurysms. A major concern regarding the use of FD is thromboembolic events (TEE). There is debate surrounding the optimal antiplatelet regimen to prevent TEE. We aim to evaluate the safety and efficacy of ticagrelor as a single antiplatelet therapy (SAPT) for the prevention of TEE following FD for complex aneurysm treatment.
Plasticity in olfactory bulb circuits.
Current opinion in neurobiology, 2020

Olfaction is crucial for animal survival and human well-being. The olfactory bulb is the obligatory input station for olfactory information. In contrast to the traditional view as a static relay station, recent evidence indicates that the olfactory bulb dynamically processes olfactory information in an experience-dependent and context-dependent manner. Here, we review recent studies on experience-dependent plasticity of the main circuit components within the olfactory bulb of rodents. We argue that the olfactory bulb plasticity allows optimal representations of behaviorally-relevant odors in the continuously changing olfactory environment.
Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update.
Medicina (Kaunas, Lithuania), 2019

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of the pathophysiology of the disease. The diagnostic criteria have been modified several times over the years. Basically, they include clinical symptoms, presence of typical lesions detected by magnetic resonance imaging (MRI), and laboratory findings. The analysis of cerebrospinal fluid (CSF) allows an evaluation of inflammatory processes circumscribed to the CNS and reflects changes in the immunological pattern due to the progression of the pathology, being fundamental in the diagnosis and monitoring of MS. The detection of the oligoclonal bands (OCBs) in both CSF and serum is recognized as the "gold standard" for laboratory diagnosis of MS, though presents analytical limitations. Indeed, current protocols for OCBs assay are time-consuming and require an operator-dependent interpretation. In recent years, the quantification of free light chain (FLC) in CSF has emerged to assist clinicians in the diagnosis of MS. This article reviews the current knowledge on CSF biomarkers used in the diagnosis of MS, in particular on the validated assays and on the alternative biomarkers of intrathecal synthesis.
Hypersensitivity to amphetamine's psychomotor and reinforcing effects in serotonin transporter knockout rats: Glutamate in the nucleus accumbens.
British journal of pharmacology, 2020

Amphetamine (AMPH) use disorder is a serious health concern, but, surprisingly, little is known about the vulnerability to the moderate and compulsive use of this psychostimulant and its underlying mechanisms. Previous research showed that inherited serotonin transporter (SERT) down-regulation increases the motor response to cocaine, as well as moderate (as measured during daily 1-h self-administration sessions) and compulsive (as measured during daily 6-h self-administration sessions) intake of this psychostimulant. Here, we sought to investigate whether these findings generalize to AMPH and the underlying mechanisms in the nucleus accumbens.
Azathioprine immunosuppression and disease modification in Parkinson's disease (AZA-PD): a randomised double-blind placebo-controlled phase II trial protocol.
BMJ open, 2020

The immune system is implicated in the aetiology and progression of Parkinson's disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a 'proof of concept' trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.