rudyvdbrink/CitationDatabase huggingface dataset:
Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia.
Proceedings of the National Academy of Sciences of the United States of America, 2008

Primary cilia are ubiquitous cellular appendages that provide important yet not well understood sensory and signaling functions. Ciliary dysfunction underlies numerous human genetic disorders. However, the precise defects in cilia function and the basis of disease pathophysiology remain unclear. Here, we report that the proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localization of G protein-coupled receptors to primary cilia on central neurons. We demonstrate a lack of ciliary localization of somatostatin receptor type 3 (Sstr3) and melanin-concentrating hormone receptor 1 (Mchr1) in neurons from mice lacking the Bbs2 or Bbs4 gene. Because Mchr1 is involved in the regulation of feeding behavior and BBS is associated with hyperphagia-induced obesity, our results suggest that altered signaling caused by mislocalization of ciliary signaling proteins underlies the BBS phenotypes. Our results also provide a potential molecular mechanism to link cilia defects with obesity.
Characterization of ectopic colonies that form in widespread areas of the nervous system with neural stem cell transplants into the site of a severe spinal cord injury.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

We reported previously the formation of ectopic colonies in widespread areas of the nervous system after transplantation of fetal neural stem cells (NSCs) into spinal cord transection sites. Here, we characterize the incidence, distribution, and cellular composition of the colonies. NSCs harvested from E14 spinal cords from rats that express GFP were treated with a growth factor cocktail and grafted into the site of a complete spinal cord transection. Two months after transplant, spinal cord and brain tissue were analyzed histologically. Ectopic colonies were found at long distances from the transplant in the central canal of the spinal cord, the surface of the brainstem and spinal cord, and in the fourth ventricle. Colonies were present in 50% of the rats, and most rats had multiple colonies. Axons extended from the colonies into the host CNS. Colonies were strongly positive for nestin, a marker for neural precursors, and contained NeuN-positive cells with processes resembling dendrites, GFAP-positive astrocytes, APC/CC1-positive oligodendrocytes, and Ki-67-positive cells, indicating ongoing proliferation. Stereological analyses revealed an estimated 21,818 cells in a colony in the fourth ventricle, of which 1005 (5%) were Ki-67 positive. Immunostaining for synaptic markers (synaptophysin and VGluT-1) revealed large numbers of synaptophysin-positive puncta within the colonies but fewer VGluT-1 puncta. Continuing expansion of NSC-derived cell masses in confined spaces in the spinal cord and brain could produce symptoms attributable to compression of nearby tissue. It remains to be determined whether other cell types with self-renewing potential can also form colonies.
Nerve Growth Factor Gene Delivery across the Blood-Brain Barrier to Reduce Beta Amyloid Accumulation in AD Mice.
Molecular pharmaceutics, 2020

The therapeutic potential of the nerve growth factor (NGF) gene using brain-targeted liposomal nanoparticles was investigated for the treatment of Alzheimer's disease (AD). We designed brain-targeted gene delivery systems with prolonged systemic circulation and enhanced cellular penetration by conjugating the transferrin (Tf) ligand and the penetratin (Pen) peptide to liposomes via a 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) phospholipid. In vitro characterization studies showed that the nanoparticles had homogeneous particle size and positive zeta potential and were able to protect the plasmid DNA against enzymatic degradation. In vivo brain targeting efficiency of designed liposomes was mimicked using an in vitro triple coculture blood-brain barrier (BBB) model. Liposomal nanoparticles dual-modified with Tf and Pen encasing plasmid NGF efficiently crossed the in vitro BBB model and, subsequently, transfected the primary neuronal cells. Increasing NGF expression in primary neuronal cells following treatment with liposomes increased the levels of the presynaptic marker synaptophysin in vitro. A dose-response study in vivo was performed in order to select the appropriate dose of plasmid NGF to induce significant NGF expression and, consequently, a therapeutic effect. Administration of PenTf-liposomes containing pNGF to amyloid precursor protein (APP)/PS1 mice (aged 3 months) for 4 weeks (one injection per week) significantly decreased (
Hemispheric dorsolateral prefrontal cortex lateralization in the regulation of empathy for pain.
Neuroscience letters, 2015

The dorsolateral prefrontal cortex (DLPFC) is involved in the cognitive appraisal and modulation of the pain experience. In this sham-controlled study, with healthy volunteers, we used bi-hemispheric transcranial direct current stimulation (tDCS) over the DLPFC to assess emotional reactions elicited by pain observation. Left-cathodal/right-anodal tDCS decreased valence and arousal evaluations compared to other tDCS conditions. Compared to sham condition, both left-cathodal/right-anodal and left-anodal/right-cathodal tDCS decreased hostility, sadness and self-pain perception. These decreased sensations after both active tDCS suggest a common role for left and right DLPFC in personal distress modulation. However, the differences in arousal and valence evaluations point to distinct roles of lateralized DLPFC in cognitive empathy, probably through distinct emotion regulation mechanisms.
Standardizing Assessment of Spoken Discourse in Aphasia: A Working Group With Deliverables.
American journal of speech-language pathology, 2021

Purpose The heterogeneous nature of measures, methods, and analyses reported in the aphasia spoken discourse literature precludes comparison of outcomes across studies (e.g., meta-analyses) and inhibits replication. Furthermore, funding and time constraints significantly hinder collecting test-retest data on spoken discourse outcomes. This research note describes the development and structure of a working group, designed to address major gaps in the spoken discourse aphasia literature, including a lack of standardization in methodology, analysis, and reporting, as well as nominal data regarding the psychometric properties of spoken discourse outcomes. Method The initial initiatives for this working group are to (a) propose recommendations regarding standardization of spoken discourse collection, analysis, and reporting in aphasia, based on the results of an international survey and a systematic literature review and (b) create a database of test-retest spoken discourse data from individuals with and without aphasia. The survey of spoken discourse collection, analysis, and interpretation procedures was distributed to clinicians and researchers involved in aphasia assessment and rehabilitation from September to November 2019. We will publish survey results and recommend standards for collecting, analyzing, and reporting spoken discourse in aphasia. A multisite endeavor to collect test-retest spoken discourse data from individuals with and without aphasia will be initiated. This test-retest information will be contributed to a central site for transcription and analysis, and data will be subsequently openly curated. Conclusion The goal of the working group is to create recommendations for field-wide standards in methods, analysis, and reporting of spoken discourse outcomes, as has been done across other related disciplines (e.g., Consolidated Standards of Reporting Trials, Enhancing the Quality and Transparency of Health Research, Committee on Best Practice in Data Analysis and Sharing). Additionally, the creation of a database through our multisite collaboration will allow the identification of psychometrically sound outcome measures and norms that can be used by clinicians and researchers to assess spoken discourse abilities in aphasia.
SPP1 genotype and glucocorticoid treatment modify osteopontin expression in Duchenne muscular dystrophy cells.
Human molecular genetics, 2017

Glucocorticoids are beneficial in Duchenne muscular dystrophy (DMD). Osteopontin (OPN), the protein product of SPP1, plays a role in DMD pathology modulating muscle inflammation and regeneration. A polymorphism in the SPP1 promoter (rs28357094) has been recognized as a genetic modifier of DMD, and there is evidence suggesting that it modifies response to glucocorticoid treatment. The effect of the glucocorticoid deflazacort on SPP1 mRNA and protein expression was investigated in DMD primary human myoblasts and differentiated myotubes with defined rs28357094 genotype (TT versus TG). Both healthy and DMD myoblasts/myotubes abundantly express OPN. In immunoblot, OPN was detected as a doublet of 55 and 50 kDa bands, with a shift towards the lighter isoform in the transition from myoblasts to myotubes and to mature muscle. A significant increase in OPN expression was observed in DMD myotubes carrying the TG compared to the TT genotype at rs28357094. Deflazacort treatment led to a significant increase of OPN only in myotubes carrying the TG genotype, leading to OPN overexpression. Our study shows a strong effect of the rs28357094 G allele in increasing OPN expression in the presence of deflazacort, and adds to the evidence that rs28357094 polymorphism may predict response to glucocorticoids in DMD.
COVID-19 in multiple sclerosis: The Dutch experience.
Multiple sclerosis (Houndmills, Basingstoke, England), 2020

Here, we provide an extensive overview of all reported COVID-19 cases in multiple sclerosis (MS) patients in the Netherlands between 27 February and 9 June 2020, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology. A total of 86 MS patients were reported, 43 of whom tested positive for COVID-19. Of 43 patients who tested positive, 22 patients were hospitalized. Three intensive care unit (ICU) admissions and four deaths were reported. Our findings show no apparent difference in disease-modifying treatment (DMT) use and COVID-19 disease course in Dutch MS patients. In addition, a clear link between low lymphocyte count and severe disease was not observed.
Partial maintenance of auditory-based cognitive training benefits in older adults.
Neuropsychologia, 2014

The potential for short-term training to improve cognitive and sensory functions in older adults has captured the public's interest. Initial results have been promising. For example, eight weeks of auditory-based cognitive training decreases peak latencies and peak variability in neural responses to speech presented in a background of noise and instills gains in speed of processing, speech-in-noise recognition, and short-term memory in older adults. But while previous studies have demonstrated short-term plasticity in older adults, we must consider the long-term maintenance of training gains. To evaluate training maintenance, we invited participants from an earlier training study to return for follow-up testing six months after the completion of training. We found that improvements in response peak timing to speech in noise and speed of processing were maintained, but the participants did not maintain speech-in-noise recognition or memory gains. Future studies should consider factors that are important for training maintenance, including the nature of the training, compliance with the training schedule, and the need for booster sessions after the completion of primary training.
Nanobody-directed targeting of optogenetic tools to study signaling in the primary cilium.
eLife, 2020

Compartmentalization of cellular signaling forms the molecular basis of cellular behavior. The primary cilium constitutes a subcellular compartment that orchestrates signal transduction independent from the cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary signaling has been challenging due to the lack of tools to investigate ciliary signaling. Here, we describe a nanobody-based targeting approach for optogenetic tools in mammalian cells and in vivo in zebrafish to specifically analyze ciliary signaling and function. Thereby, we overcome the loss of protein function observed after fusion to ciliary targeting sequences. We functionally localized modifiers of cAMP signaling, the photo-activated adenylyl cyclase bPAC and the light-activated phosphodiesterase LAPD, and the cAMP biosensor mlCNBD-FRET to the cilium. Using this approach, we studied the contribution of spatial cAMP signaling in controlling cilia length. Combining optogenetics with nanobody-based targeting will pave the way to the molecular understanding of ciliary function in health and disease.
Activin receptors regulate the oligodendrocyte lineage in health and disease.
Acta neuropathologica, 2018

The most prevalent neurological disorders of myelin include perinatal brain injury leading to cerebral palsy in infants and multiple sclerosis in adults. Although these disorders have distinct etiologies, they share a common neuropathological feature of failed progenitor differentiation into myelin-producing oligodendrocytes and lack of myelin, for which there is an unmet clinical need. Here, we reveal that a molecular pathology common to both disorders is dysregulation of activin receptors and that activin receptor signaling is required for the majority of myelin generation in development and following injury. Using a constitutive conditional knockout of all activin receptor signaling in oligodendrocyte lineage cells, we discovered this signaling to be required for myelination via regulation of oligodendrocyte differentiation and myelin compaction. These processes were found to be dependent on the activin receptor subtype Acvr2a, which is expressed during oligodendrocyte differentiation and axonal ensheathment in development and following myelin injury. During efficient myelin regeneration, Acvr2a upregulation was seen to coincide with downregulation of Acvr2b, a receptor subtype with relatively higher ligand affinity; Acvr2b was shown to be dispensable for activin receptor-driven oligodendrocyte differentiation and its overexpression was sufficient to impair the abovementioned ligand-driven responses. In actively myelinating or remyelinating areas of human perinatal brain injury and multiple sclerosis tissue, respectively, oligodendrocyte lineage cells expressing Acvr2a outnumbered those expressing Acvr2b, whereas in non-repairing lesions Acvr2b+ cells were increased. Thus, we propose that following human white matter injury, this increase in Acvr2b expression would sequester ligand and consequently impair Acvr2a-driven oligodendrocyte differentiation and myelin formation. Our results demonstrate dysregulated activin receptor signaling in common myelin disorders and reveal Acvr2a as a novel therapeutic target for myelin generation following injury across the lifespan.
Interhemispheric sensorimotor integration; an upper limb phenomenon?
Neuroscience, 2016

Somatosensory information from the limbs reaches the contralateral Primary Sensory Cortex (S1) with a delay of 23ms for finger, and 40ms for leg (somatosensory N20/N40). Upon arrival of this input in the cortex, motor evoked potentials (MEPs) elicited by Transcranial Magnetic Stimulation (TMS) are momentarily inhibited. This phenomenon is called 'short latency afferent inhibition (SAI)' and can be used as a tool for investigating sensorimotor interactions in the brain. We used SAI to investigate the process of sensorimotor integration in the hemisphere ipsilateral to the stimulated limb. We hypothesized that ipsilateral SAI would occur with a delay following the onset of contralateral SAI, to allow for transcallosal conduction of the signal. We electrically stimulated the limb either contralateral or ipsilateral to the hemisphere receiving TMS, using a range of different interstimulus intervals (ISI). We tested the First Dorsal Interosseous (FDI) muscle in the hand, and Tibialis Anterior (TA) in the lower leg, in three separate experiments. Ipsilateral SAI was elicited in the upper limb (FDI) at all ISIs that were greater than N20+18ms (all p<.05) but never at any earlier timepoint. No ipsilateral SAI was detected in the lower limb (TA) at any of the tested ISIs. The delayed onset timing of ipsilateral SAI suggests that transcallosal communication mediates this inhibitory process for the upper limb. The complete absence of ipsilateral SAI in the lower limb warrants consideration of the potential limb-specific differences in demands for bilateral sensorimotor integration.
Sex-specific linkage scans in opioid dependence.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2017

Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD = 3.29; point-wise P = 0.00005; empirical autosome-wide P = 0.042), which significantly differed from the linkage signal at the same location in EA women (empirical P = 0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD = 2.18), 104 cM on chromosome 11 (LOD = 1.85), and 60.9 cM on chromosome 16 (LOD = 1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD = 2.32), 152.9 cM on chromosome 6 (LOD = 1.86), 16.8 cM on chromosome 7 (LOD = 1.95), and 36.1 cM on chromosome 17 (LOD = 1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. © 2016 Wiley Periodicals, Inc.
Prediction of performance level during a cognitive task from ongoing EEG oscillatory activities.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2008

Tracking the level of performance in cognitive tasks may be useful in environments, such as aircraft, in which the awareness of the pilots is critical for security. In this paper, the usefulness of EEG for the prediction of performance is investigated.
'Snail factors in testicular germ cell tumours and their regulation by the BMP4 signalling pathway'.
Andrology, 2020

Snail transcription factors mediate key cellular transitions in many developmental processes, including spermatogenesis, and their production can be regulated by TGF-β superfamily signalling. SNAI1 and SNAI2 support many cancers of epithelial origin. Their functional relevance and potential regulation by TGF-β superfamily ligands in germ cell neoplasia are unknown.
Impact of social status and antidepressant treatment on neurogenesis in the baboon hippocampus.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014

Adult hippocampal neurogenesis is critically implicated in rodent models of stress and anxiety as well as behavioral effects of antidepressants. Whereas similar factors such as psychiatric disorder and antidepressant administration are correlated with hippocampal volume in humans, the relationship between these factors and adult neurogenesis is less well understood. To better bridge the gap between rodent and human physiology, we examined the numbers of proliferating neural precursors and immature cells in the hippocampal dentate gyrus (DG) as well as in vivo magnetic resonance imaging (MRI)-estimated whole hippocampal volume in eight socially dominant- or subordinate-like (SL) baboons administered the antidepressant fluoxetine or vehicle. SL baboons had lower numbers of proliferating cells and immature neurons than socially dominant-like baboons. Fluoxetine treatment was associated with a larger whole hippocampal volume but surprisingly resulted in lower numbers of immature neurons. These findings are the first to indicate that adult neurogenesis in the baboon hippocampal DG may be functionally relevant in the context of social stress and mechanisms of antidepressant action.
Microbeam radiation therapy - grid therapy and beyond: a clinical perspective.
The British journal of radiology, 2017

Microbeam irradiation is spatially fractionated radiation on a micrometer scale. Microbeam irradiation with therapeutic intent has become known as microbeam radiation therapy (MRT). The basic concept of MRT was developed in the 1980s, but it has not yet been tested in any human clinical trial, even though there is now a large number of animal studies demonstrating its marked therapeutic potential with an exceptional normal tissue sparing effect. Furthermore, MRT is conceptually similar to macroscopic grid based radiation therapy which has been used in clinical practice for decades. In this review, the potential clinical applications of MRT are analysed for both malignant and non-malignant diseases.
Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts.
American journal of human genetics, 2018

Infantile and childhood-onset cataracts form a heterogeneous group of disorders; among the many genetic causes, numerous pathogenic variants in additional genes associated with autosomal-recessive infantile cataracts remain to be discovered. We identified three consanguineous families affected by bilateral infantile cataracts. Using exome sequencing, we found homozygous loss-of-function variants in DNMBP: nonsense variant c.811C>T (p.Arg271
The pattern of cognitive symptoms predicts time to dementia onset.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2009

Few studies have examined whether cognitive symptom patterns differ by age and length of time before dementia onset. Our objective was to investigate whether different patterns of cognitive symptoms at ages 70, 75, and 79 years predict short-term (< or =5 years) and long-term (>5 years) dementia onset.
The new field of 'precision psychiatry'.
BMC medicine, 2017

Precision medicine is a new and important topic in psychiatry. Psychiatry has not yet benefited from the advanced diagnostic and therapeutic technologies that form an integral part of other clinical specialties. Thus, the vision of precision medicine as applied to psychiatry - 'precision psychiatry' - promises to be even more transformative than in other fields of medicine, which have already lessened the translational gap.
Breakthrough pain in patients with abdominal cancer pain.
The Clinical journal of pain, 2014

Characterization of breakthrough cancer pain (BTcP) in patients with abdominal cancer is lacking. The aim of this study was to assess the characteristics of BTcP in patients with abdominal cancer pain.