rudyvdbrink/CitationDatabase huggingface dataset:
Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A).
Human mutation, 2020

Defects in the motor domain of kinesin family member 1A (KIF1A), a neuron-specific ATP-dependent anterograde axonal transporter of synaptic cargo, are well-recognized to cause a spectrum of neurological conditions, commonly known as KIF1A-associated neurological disorders (KAND). Here, we report one mutation-negative female with classic Rett syndrome (RTT) harboring a de novo heterozygous novel variant [NP_001230937.1:p.(Asp248Glu)] in the highly conserved motor domain of KIF1A. In addition, three individuals with severe neurodevelopmental disorder along with clinical features overlapping with KAND are also reported carrying de novo heterozygous novel [NP_001230937.1:p.(Cys92Arg) and p.(Pro305Leu)] or previously reported [NP_001230937.1:p.(Thr99Met)] variants in KIF1A. In silico tools predicted these variants to be likely pathogenic, and 3D molecular modeling predicted defective ATP hydrolysis and/or microtubule binding. Using the neurite tip accumulation assay, we demonstrated that all novel KIF1A variants significantly reduced the ability of the motor domain of KIF1A to accumulate along the neurite lengths of differentiated SH-SY5Y cells. In vitro microtubule gliding assays showed significantly reduced velocities for the variant p.(Asp248Glu) and reduced microtubule binding for the p.(Cys92Arg) and p.(Pro305Leu) variants, suggesting a decreased ability of KIF1A to move along microtubules. Thus, this study further expanded the phenotypic characteristics of KAND individuals with pathogenic variants in the KIF1A motor domain to include clinical features commonly seen in RTT individuals.
Neuronal functional diversity and collective behaviors: a scientific case.
Cognitive processing, 2009

A major issue in today's neuroscience is how the brain complex and highly flexible organization emerges from its individual components. Robustness of neuronal properties with weak linkages between regulatory processes are suggested to account for the adaptive, tunable, multistable dynamics, the coding schemes and the complexity of neuronal functional (sub)systems. Interneurons and neurotransmitter diversity, resonance phenomena due to properties of the cell or network, time/frequency-dependent activation of dedicated neuronal assemblies, code- and frequency-specific oscillations interact in determining the brain functional setup and operations. Despite the scientific relevance, comprehensive theories are not yet available, but the scenario--however incomplete and incompletely characterized--is promising and warrants further investigation.
Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocol.
BMJ open, 2021

Vaping behaviour has increased in popularity and is particularly important to examine how it effects health outcomes in vulnerable populations, including those with opioid use disorder (OUD). With polysubstance use including cigarette and cannabis use being highly prevalent in the OUD population and cannabis/nicotine increasingly being consumed by vaping, vaping may have an important contribution to health outcomes in these individuals. The primary objective of this review is to systematically assess the literature related to patients with OUD and the effects vaping has shown on their physical and mental health.
The role of SCF
Genes to cells : devoted to molecular & cellular mechanisms, 2020

A proper balance between proliferation and differentiation of cerebellar granule cell precursors (GCPs) is required for appropriate cerebellar morphogenesis. The Skp1-Cullin1-F-box (SCF) complex, an E3 ubiquitin ligase complex, is involved in polyubiquitination and subsequent degradation of various cell cycle regulators and transcription factors. However, it remains unknown how the SCF complex affects proliferation and differentiation of GCPs. In this study, we found that the scaffold protein Cullin1, and F-box proteins Skp2, β-TrCP1 and β-TrCP2 are expressed in the external granule layer (EGL). Knockdown of these molecules in the EGL showed that Cullin1, Skp2 and β-TrCP2 enhanced differentiation of GCPs. We also observed accumulation of cyclin-dependent kinase inhibitor p27 in GCPs when treated with a Cullin1 inhibitor or proteasome inhibitor. Furthermore, knockdown of p27 rescued enhancement of differentiation by Cullin1 knockdown. These results suggest that the SCF complex is involved in the maintenance of the proliferative state of GCPs through p27 degradation. In addition, inhibition of Cullin1 activity also prevented cell proliferation and enhanced accumulation of p27 in Daoy cells, a cell line derived from the sonic hedgehog subtype of medulloblastoma. This suggested that excess degradation of p27 through the SCF complex causes overproliferation of medulloblastoma cells.
Neuroablative surgical treatments for pain due to cancer.
Neuro-Chirurgie, 2021

Cancer pain is common and challenging to manage - it is estimated that approximately 30% of cancer patients have pain that is not adequately controlled by analgesia. This paper discusses safe and effective neuroablative treatment options for refractory cancer pain. Current management of cancer pain predominantly focuses on the use of medications, resulting in a relative loss of knowledge of these surgical techniques and the erosion of the skills required to perform them. Here, we review surgical methods of modulating various points of the neural axis with the aim to expand the knowledge base of those managing cancer pain. Integration of neuroablative approaches may lead to higher rates of pain relief, and the opportunity to dose reduce analgesic agents with potential deleterious side effects. With an ever-increasing population of cancer patients, it is essential that neurosurgeons maintain or train in these techniques in tandem with the oncological multi-disciplinary team.
FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight.
Neurochemistry international, 2020

Fragile X mental retardation protein (FMRP), strongly associated with fragile X syndrome, plays important roles by regulating gene expression via interacting with other RNA binding proteins in the brain. However, the role of FMRP in hypothalamus, a central part responsible for metabolic control, is poorly known. Our study shows that FMRP is primarily located in the hypothalamic arcuate nucleus (ARC). Using proteomic analysis, we identified 56 up-regulated and 22 down-regulated proteins in the hypothalamus of Map1b KO mice, with microtubule-associated protein 1 B (MAP1B) being the most outstanding increased protein (more than 10 folds). Immunofluorescent assays showed that MAP1B significantly increased in the Map1b-KO ARC, in which the number of agouti-related peptide (AgRP)-staining neurons significantly reduced, but not altered for pro-opiomelanocortin (POMC) neurons. We further showed an age-dependent reduces in food intake and body weight of the KO mice, along with the decreases of MAP1B and AgRP at the same time points. In hypothalamic GT1-7 cells, the AgRP expression decreased upon knockdown of FMRP or overexpression of MAP1B, and increased in response to overexpression of FMRP or knockdown of MAP1B. Co-knockdown or co-overexpression of FMRP and MAP1B led to a reverse expression of AgRP compared to overexpression of knockdown of FMRP alone, demonstrating that MAP1B is essential for the regulatory effect of FMRP on AgRP expression. Taken together, these data suggest that FMRP-deficiency-induced increase of hypothalamic MAP1B and decrease of AgRP might be associated with reduces in food intake and body weight.
Treatment Outcome of Carotid Artery Stenting Underwent within 14 Days of Stroke Onset - Consideration of Safety and Efficacy of Urgent Carotid Artery Stenting for Neurologically Progressing Patients.
Neurologia medico-chirurgica, 2017

As the safety and effectiveness of urgent carotid artery stenting (CAS) for neurologically progressing patients remain controversial, we retrospectively analyzed the outcome of urgent CAS based on the patients' pathophysiological condition and neuroimaging findings. We divided 71 patients who underwent CAS within 14 days of stroke onset into two groups. Group 1 (n = 35) was comprised of patients with progressing neurologic signs and a reversible ischemic penumbra on magnetic resonance images (MRI). They were treated by urgent CAS. Group 2 (n = 36) was neurologically stable and underwent prophylactic CAS. In all patients we recorded the National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin scale (mRS). Urgent CAS resulted in significant improvement in the NIHSS score, when compared before and after CAS in group 1 (5.3 ± 4.3, P < 0.01). The rate of good outcomes (mRS 0-2 at 3 months post-CAS) was 48.6% in group 1, and 75% in group 2. The cumulative incidence of ipsilateral stroke between 31 days and 1 year was 5.9% in group 1, and 0% in group 2. The procedural complication rate was similar in both groups (group 1: 5.7%, n = 2; group 2: 5.6%, n = 2). No patient suffered a symptomatic intracerebral hemorrhage. When the pathophysiological status and neuroimaging findings are used to determine patient eligibility for urgent CAS, this treatment improve neurologic outcome and can be performed as safely as prophylactic CAS in our cohort of patients with acute ischemic stroke.
A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small t Mostly Associates with Those Having Phosphatase and Chromatin-Remodeling Functions.
Viruses, 2020

The oncogenic potential of both the polyomavirus large (LT-Ag) and small (Sm t-Ag) tumor antigens has been previously demonstrated in both tissue culture and animal models. Even the contribution of the MCPyV tumor antigens to the development of an aggressive human skin cancer, Merkel cell carcinoma, has been recently established. To date, the known primary targets of these tumor antigens include several tumor suppressors such as pRb, p53, and PP2A. However, a comprehensive list of the host proteins targeted by these proteins remains largely unknown. Here, we report the first interactome of JCV LT-Ag and Sm t-Ag by employing two independent "affinity purification/mass spectroscopy" (AP/MS) assays. The proteomics data identified novel targets for both tumor antigens while confirming some of the previously reported interactions. LT-Ag was found to primarily target the protein complexes with ATPase (v-ATPase and Smc5/6 complex), phosphatase (PP4 and PP1), and ligase (E3-ubiquitin) activities. In contrast, the major targets of Sm t-Ag were identified as Smarca1/6, AIFM1, SdhA/B, PP2A, and p53. The interactions between "LT-Ag and SdhB", "Sm t-Ag and Smarca5", and "Sm t-Ag and SDH" were further validated by biochemical assays. Interestingly, perturbations in some of the LT-Ag and Sm t-Ag targets identified in this study were previously shown to be associated with oncogenesis, suggesting new roles for both tumor antigens in novel oncogenic pathways. This comprehensive data establishes new foundations to further unravel the new roles for JCV tumor antigens in oncogenesis and the viral life cycle.
Spatial primes produce dissociated inhibitory effects on saccadic latencies and trajectories.
Vision research, 2014

In masked priming, a briefly presented prime can facilitate or inhibit responses to a subsequent target. In most instances, targets with an associated response that is congruent with the prime direction speed up reaction times to the target (a positive compatibility effect; PCE). However, under certain circumstances, slower responses for compatible primes are obtained (a negative compatibility effect; NCE). NCEs can be found when a long pre-target delay is used. During the delay, inhibition is assumed to take place, and therefore an effect on saccade trajectories may also be expected. In a previous study, we found the effects of inhibition on response times and trajectories to be dissociated, but this experiment varied the timing of several aspects of the stimulus sequence and it is therefore unclear what caused the dissociation. In the present study, we varied only one aspect of the timing, but replicated the dissociation. By varying just the pre-target delay, we found a PCE for a short delay, and an NCE for a long delay, but saccade trajectories deviated away from prime directions in both conditions. This suggests dissociated inhibitory effects of primes on response times and saccade trajectories.
Multiple lifestyle factors and depressed mood: a cross-sectional and longitudinal analysis of the UK Biobank (N = 84,860).
BMC medicine, 2020

There is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and how these relations may differ in individuals with major depressive disorder (MDD) and those without a depressive disorder, as 'healthy controls' (HC).
Enhanced Validation of Antibodies Enables the Discovery of Missing Proteins.
Journal of proteome research, 2020

The localization of proteins at a tissue- or cell-type-specific level is tightly linked to the protein function. To better understand each protein's role in cellular systems, spatial information constitutes an important complement to quantitative data. The standard methods for determining the spatial distribution of proteins in single cells of complex tissue samples make use of antibodies. For a stringent analysis of the human proteome, we used orthogonal methods and independent antibodies to validate 5981 antibodies that show the expression of 3775 human proteins across all major human tissues. This enhanced validation uncovered 56 proteins corresponding to the group of "missing proteins" and 171 proteins of unknown function. The presented strategy will facilitate further discussions around criteria for evidence of protein existence based on immunohistochemistry and serves as a useful guide to identify candidate proteins for integrative studies with quantitative proteomics methods.
Thinking about Others' Minds: Mental State Inference in Boys with Conduct Problems and Callous-Unemotional Traits.
Journal of abnormal child psychology, 2020

Children with conduct problems (CP) and high levels of callous-unemotional traits (CP/HCU) have been found to have an intact ability to represent other minds, however, they behave in ways that indicate a reduced propensity to consider other people's thoughts and feelings. Here we report findings from three tasks assessing different aspects of mentalising in 81 boys aged 11-16 [Typically developing (TD) n = 27; CP/HCU n = 28; CP and low levels of callous-unemotional traits (CP/LCU) n = 26]. Participants completed the Movie Assessment of Social Cognition (MASC), a task assessing ability/propensity to incorporate judgements concerning an individual's mind into mental state inference; provided a written description of a good friend to assess mind-mindedness; and completed the Social Judgement Task (SJT), a new measure assessing mentalising about antisocial actions. Boys with CP/HCU had more difficulty in accurately inferring others' mental states in the MASC than TD and CP/LCU boys. There were no group differences in the number of mind-related comments as assessed by the mind-mindedness protocol or in responses to the SJT task. These findings suggest that although the ability to represent mental states is intact, CP/HCU boys are less likely to update mental state inferences as a function of different minds.
Disgust: Internal Context Matters.
Current biology : CB, 2021

Novel research suggests the rhythms in our stomachs can influence our response to disgusting stimuli. Monetary reward will only encourage people to engage with disgusting stimuli after a peripherally acting drug alters gastric signals.
The role of interoception in understanding others' affect. Dissociation between superficial and detailed appraisal of facial expressions.
Cortex; a journal devoted to the study of the nervous system and behavior, 2020

Embodied models of social cognition argue that others' emotional states are processed by re-enacting a representation of the same state in the observer, along with associated somatic and physiological responses. In this framework, previous studies tested whether a strong sensitivity to interoceptive signals (i.e., inputs arising from within one's body) facilitates the understanding of others' affect, leading to mixed results. Such heterogeneity in the literature could reflect methodological differences in paradigms employed, with some probing classification of a precise condition, and others requiring the assessment of supra-ordinal dimensions orthogonal to many states. Here, we engaged fifty young women in a study where they evaluated others' naturalistic facial reactions to painful and disgusting stimuli of comparable unpleasantness. Separately, we measured their interoceptive abilities through a well-known heartbeat counting task. We found that individuals that were more accurate in tracking their heartbeats across time were also more prone to judge facial expressions as more unpleasant (supra-ordinal assessment). However, when specifically asked to discriminate between comparably-unpleasant pain and disgust (state-specific assessment), participants' performance was not influenced by their interoceptive abilities. Although confined to a female sample, this study extends our knowledge on the role of interoception in the understanding of others, which influences only the evaluation of general features such as unpleasantness (common between pain and disgust), without extending to the appraisal of a precise state. This finding supports multi-componential models of social cognition, suggesting that only part of our ability to assess others' affect is mediated by a representation of one's affective/somatic responses.
The Effect of Adherence to the Mediterranean Diet on Late-Life Cognitive Disorders: A Systematic Review.
Journal of the American Medical Directors Association, 2020

Although some results are conflicting, numerous investigations have demonstrated that the Mediterranean Diet (MedDiet) has positive effects on brain health. This review intends to provide an update on the scientific evidence regarding the effects of adherence to the MedDiet on late-life cognitive disorders.
Simultaneous two-photon activation and imaging of neural activity based on spectral-temporal modulation of supercontinuum light.
Neurophotonics, 2020

Recent advances in nonlinear optics in neuroscience have focused on using two ultrafast lasers for activity imaging and optogenetic stimulation. Broadband femtosecond light sources can obviate the need for multiple lasers by spectral separation for chromatically targeted excitation.
DNA hypomethylation of the Krüppel-like factor 11 (KLF11) gene promoter: a putative biomarker of depression comorbidity in panic disorder and of non-anxious depression?
Journal of neural transmission (Vienna, Austria : 1996), 2020

Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD. In an effort to further delineate the effects of the KLF11-MAOA pathway in anxiety and affective disorders, KLF11 promoter methylation was analyzed via pyrosequencing of sodium bisulfite-treated DNA isolated from human peripheral blood in two independent samples of PD patients with or without comorbid MDD in a case-control design (sample 1: N = 120) as well as MDD patients with and without anxious depression (sample 2: N = 170). Additionally, in sample 1, KLF11 methylation was correlated with Beck Depression Inventory (BDI-II) scores. No overall association of KLF11 promoter methylation with PD was detected. However, PD patients with comorbid MDD showed significant hypomethylation relative to both healthy controls (p = 0.010) and PD patients without comorbid MDD (p = 0.008). Furthermore, KLF11 methylation was negatively correlated with BDI-II scores in PD patients (p = 0.013). MDD patients without anxious features showed nominally decreased KLF11 methylation in comparison to MDD patients with anxious depression (p = 0.052). The present results suggest KLF11 promoter hypomethylation as a potential epigenetic marker of MDD comorbidity in PD or of non-anxious depression, respectively, possibly constituting a differential pathomechanism in anxiety and mood disorders.
The therapeutic 'make-over' of dementias-an introduction.
Age and ageing, 2018

The online themed collection of 15 papers recently published provides an update on the advances of pharmacological and non-pharmacological interventions in dementia over the last 15 years. The published studies reflect the efficacy of the current anti-dementia treatments, preventive treatments of cardio and cerebrovascular incidents (known to be risk factors for dementia), alongside the use of antidepressant medication and non-pharmacological interventions for treatment of behavioural and psychopathological symptoms of dementia. We also address the future preventative steps and therapeutic strategies currently in development to combat the devastating consequences of dementia.
Knockout serotonin transporter in rats moderates outcome and stimulus generalization.
Translational psychiatry, 2021

Understanding the common dimension of mental disorders (such as anxiety, depression, and drug addiction) might contribute to the construction of biological frameworks (Research Domain Criteria, RDoC) for novel ways of treatment. One common dimension at the behavioral level observed across these disorders is a generalization. Testing generalization in serotonin transporter (5-HTT) knockout (KO) rats, an animal model showing depression/anxiety-like behaviors and drug addiction-like behaviors, could therefore provide more insights into this framework. We tested the outcome and stimulus generalization in wild-type (WT) and 5-HTT KO rats. Using a newly established touchscreen-based task, subjects directly responded to visual stimuli (Gabor patch images). We measured the response time and outcome in a precise manner. We found that 5-HTT KO rats processed visual information faster than WT rats during outcome generalization. Interestingly, during stimulus generalization, WT rats gradually responded faster to the stimuli as the sessions progressed, while 5-HTT KO rats responded faster than WT in the initial sessions and did not change significantly as the sessions progressed. This observation suggests that KO rats, compared to WT rats, may be less able to update changes in information. Taken together, KO 5-HTT modulates information processing when the environment changes.