rudyvdbrink/CitationDatabase huggingface dataset:
Binding site density enables paralog-specific activity of SLM2 and Sam68 proteins in Neurexin2 AS4 splicing control.
Nucleic acids research, 2017

SLM2 and Sam68 are splicing regulator paralogs that usually overlap in function, yet only SLM2 and not Sam68 controls the Neurexin2 AS4 exon important for brain function. Herein we find that SLM2 and Sam68 similarly bind to Neurexin2 pre-mRNA, both within the mouse cortex and in vitro. Protein domain-swap experiments identify a region including the STAR domain that differentiates SLM2 and Sam68 activity in splicing target selection, and confirm that this is not established via the variant amino acids involved in RNA contact. However, far fewer SLM2 and Sam68 RNA binding sites flank the Neurexin2 AS4 exon, compared with those flanking the Neurexin1 and Neurexin3 AS4 exons under joint control by both Sam68 and SLM2. Doubling binding site numbers switched paralog sensitivity, by placing the Neurexin2 AS4 exon under joint splicing control by both Sam68 and SLM2. Our data support a model where the density of shared RNA binding sites around a target exon, rather than different paralog-specific protein-RNA binding sites, controls functional target specificity between SLM2 and Sam68 on the Neurexin2 AS4 exon. Similar models might explain differential control by other splicing regulators within families of paralogs with indistinguishable RNA binding sites.
Early blindness alters the spatial organization of verbal working memory.
Cortex; a journal devoted to the study of the nervous system and behavior, 2016

Several studies suggest that serial order in working memory (WM) is grounded on space. For a list of ordered items held in WM, items at the beginning of the list are associated with the left side of space and items at the end of the list with the right side. This suggests that maintaining items in verbal WM is performed in strong analogy to writing these items down on a physical whiteboard for later consultation (The Mental Whiteboard Hypothesis). What drives this spatial mapping of ordered series in WM remains poorly understood. In the present study we tested whether visual experience is instrumental in establishing the link between serial order in WM and spatial processing. We tested early blind (EB), late blind (LB) and sighted individuals in an auditory WM task. Replicating previous studies, left-key responses were faster for early items in the list whereas later items facilitated right-key responses in the sighted group. The same effect was observed in LB individuals. In contrast, EB participants did not show any association between space and serial position in WM. These results suggest that early visual experience plays a critical role in linking ordered items in WM and spatial representations. The analogical spatial structure of WM may depend in part on the actual experience of using spatially organized devices (e.g., notes, whiteboards) to offload WM. These practices are largely precluded to EB individuals, who instead rely to mnemonic devices that are less spatially organized (e.g., recordings, vocal notes). The way we habitually organize information in the external world may bias the way we organize information in our WM.
Densely calcified atypical choroid plexus papilloma at the cerebellopontine angle in an adult.
Journal of neurological surgery reports, 2013

Choroid plexus papilloma is a rare benign tumor accounting for 0.5% of all intracranial tumors. The majority of choroid plexus papillomas occur during the first 2 years of life in the ventricular system. Moreover, dense calcification of the tumor is uncommon. We report an adult case of densely calcified, atypical choroid plexus papilloma that originated from the cerebellopontine angle without connection to the forth ventricle. Because the case involves a rare combination of four features-adult, dense calcification, atypical form, and cerebellopontine angle-each characteristic associated with the choroid plexus papilloma was discussed. The finding of calcification at the cerebellopontine angle in an adult should suggest the possible presence of choroid plexus papilloma.
Do EEG and Startle Reflex Modulation Vary with Self-Reported Aggression in Response to Violent Images?
Brain sciences, 2019

Increased violence and aggressive tendencies are a problem in much of the world and are often symptomatic of many other neurological and psychiatric conditions. Among clinicians, current methods of diagnosis of problem aggressive behaviour rely heavily on the use of self-report measures as described by the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) and International Classification of Diseases 10th revision (ICD-10). This approach does not place adequate emphasis on objective measures that are potentially sensitive to processes not feeding into subjective self-report. Numerous studies provide evidence that attitudes and affective content can be processed without leading to verbalised output. This exploratory study aimed to determine whether individuals in the normal population, grouped by self-reported aggression, differed in subjective versus objective affective processing. Participants (
Commentary: physician-scientist's frustrations fester.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009

A growing problem of major proportions had been confronting biomedical scientists for many decades. Until solved, this long-neglected problem, the abject failure of the American health care system, presents a gigantic obstacle to the application of the discoveries flowing from neuropsychopharmacological research into deliverable medications utilized by medical practitioners. Although it is recognized that such advances could benefit all of society, both in the United States and globally, progress toward this important goal has not happened. As I noted 5 years ago, 'Unless steps are taken soon to undertake a comprehensive restoration of our system, the profound advances in bio-medical research so rapidly accruing today may never be effectively transformed into meaningful advances in health care for society.' I remain perplexed and frustrated by the reluctance of scientific research societies such as our ACNP to engage their energies and intellect into this most serious issue.
The effectiveness of guided internet-based cognitive behavioral therapy for social anxiety disorder in a routine care setting.
Internet interventions, 2018

Social anxiety disorder (SAD) is a common mental disorder with high persistence when untreated. As access to effective treatment is limited, guided internet-based cognitive behavioral therapy (ICBT) has been proposed as an effective alternative to face-to-face treatment. In this study, we examined the effectiveness of a 14-week therapist-guided ICBT program for patients with SAD undergoing routine care. From 2014 to 2017, 169 patients were included in the study, of which 145 started the treatment. The sample was all general practitioner-referred and had a lower educational level and higher rate of work absence compared to similar effectiveness studies. Regarding social anxiety symptoms, we identified significant within-group effect sizes (post-treatment:
Signaling through ERK1/2 controls myelin thickness during myelin repair in the adult central nervous system.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Oligodendrocytes, the myelin-forming cells of the CNS, exquisitely tailor the thickness of individual myelin sheaths to the diameter of their target axons to maximize the speed of action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries to the adult CNS, newly formed oligodendrocytes frequently generate new myelin sheaths. Following episodes of demyelination such as those that occur in patients with multiple sclerosis, however, the matching of myelin thickness to axon diameter fails leaving remyelinated axons with thin myelin sheaths potentially compromising function and leaving axons vulnerable to damage. How oligodendrocytes determine the appropriate thickness of myelin for an axon of defined size during repair is unknown and identifying the signals that regulate myelin thickness has obvious therapeutic implications. Here, we show that sustained activation of extracellular-regulated kinases 1 and 2 (ERK1/2) in oligodendrocyte lineage cells results in accelerated myelin repair after injury, and is sufficient for the generation of thick myelin sheaths around remyelinated axons in the adult mouse spinal cord. Our findings suggest a model where ERK1/2 MAP kinase signaling acts as a myelin thickness rheostat that instructs oligodendrocytes to generate axon-appropriate quantities of myelin.
Damage to the Ventromedial Prefrontal Cortex Impairs Learning from Observed Outcomes.
Cerebral cortex (New York, N.Y. : 1991), 2015

Individuals learn both from the outcomes of their own internally generated actions ("experiential learning") and from the observation of the consequences of externally generated actions ("observational learning"). While neuroscience research has focused principally on the neural mechanisms by which brain structures such as the ventromedial prefrontal cortex (vmPFC) support experiential learning, relatively less is known regarding how learning proceeds through passive observation. We explored the necessity of the vmPFC for observational learning by testing a group of patients with damage to the vmPFC as well as demographically matched normal comparison and brain-damaged comparison groups--and a single patient with bilateral dorsal prefrontal damage--using several value-learning tasks that required learning from direct experience, observational learning, or both. We found a specific impairment in observational learning in patients with vmPFC damage manifest in the reduced influence of previously observed rewards on current choices, despite a relatively intact capacity for experiential learning. The current study provides evidence that the vmPFC plays a critical role in observational learning, suggests that there are dissociable neural circuits for experiential and observational learning, and offers an important new extension of how the vmPFC contributes to learning and memory.
Limb-girdle muscular dystrophy type 2I: two Chinese families and a review in Asian patients.
The International journal of neuroscience, 2018

Limb-girdle muscular dystrophy type 2I (LGMD2I) is an autosomal recessive hereditary disorder caused by mutations in the fukutin-related protein (FKRP) gene. Although the features of the disorder in European patients have been summarized, Asian patients with LGMD2I have rarely been reported. Thus, the clinical differences in LGMD2I between Asian and European patients and the associated genetic changes remain unclear.
Direct Fit to Nature: An Evolutionary Perspective on Biological and Artificial Neural Networks.
Neuron, 2020

Evolution is a blind fitting process by which organisms become adapted to their environment. Does the brain use similar brute-force fitting processes to learn how to perceive and act upon the world? Recent advances in artificial neural networks have exposed the power of optimizing millions of synaptic weights over millions of observations to operate robustly in real-world contexts. These models do not learn simple, human-interpretable rules or representations of the world; rather, they use local computations to interpolate over task-relevant manifolds in a high-dimensional parameter space. Counterintuitively, similar to evolutionary processes, over-parameterized models can be simple and parsimonious, as they provide a versatile, robust solution for learning a diverse set of functions. This new family of direct-fit models present a radical challenge to many of the theoretical assumptions in psychology and neuroscience. At the same time, this shift in perspective establishes unexpected links with developmental and ecological psychology.
Factors that influence decisions by families to donate brain tissue for medical research.
Cell and tissue banking, 2009

Whilst mainstream transplant literature provides valuable insights into the influences on families to donate organs and tissues for transplant, the relevance of these findings in relation to organ donation for research remain speculative. The present study aims to expand the research donation literature, by exploring factors that influence a family's decision to donate brain tissue to neuroscience research. The verbal responses of the senior available next-of-kin (NOK), to the question of brain donation for research, are analysed. The donation rate was high (54%) over the 5-year-period. NOK relationship to the deceased, and post mortem interval were the main factors associated with a positive donation. Parents were most likely to donate and this may result from a lifetime of decision-making on behalf of the deceased. Also, the longer the interval between death of the potential donor and the question being asked, the greater the likelihood of donation.
Alpha-Ca2+/calmodulin-dependent protein kinase II contributes to the developmental programming of anxiety in serotonin receptor 1A knock-out mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Mice lacking the serotonin receptor 1A [Htr1aknock-out (Htr1a(KO))] display increased innate and conditioned anxiety-related behavior. Expression of the receptor in the mouse forebrain during development is sufficient to restore normal anxiety-related behavior to knock-out mice, demonstrating a role for serotonin in the developmental programming of anxiety circuits. However, the precise developmental period as well as the signaling pathways and neural substrates involved in this phenomenon are unknown. Here, we show that pharmacological blockade of the receptor from postnatal day 13 (P13)-P34 is sufficient to reproduce the knock-out phenotype in adulthood, thus defining a role for serotonin in the maturation and refinement of anxiety circuits during a limited postnatal period. Furthermore, we identify increases in the phosphorylation of alpha-Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII) at threonine 286 in the hippocampus of young Htr1a(KO) mice under anxiety-provoking conditions. Increases in alphaCaMKII phosphorylation were most pronounced in the CA1 region of the hippocampus and were localized to the extrasynaptic compartment, consistent with a tissue-specific effect of the receptor. No changes in alphaCaMKII phosphorylation were found in adult knock-out mice, suggesting a transient role of alphaCaMKII as a downstream target of the receptor. Finally, the anxiety phenotype was abolished when knock-out mice were crossed to mice in which alphaCaMKII phosphorylation was compromised by the heterozygous mutation of threonine 286 into alanine. These findings suggest that modulation of alphaCaMKII function by serotonin during a restricted postnatal period contributes to the developmental programming of anxiety-related behavior.
Navigated transcranial magnetic stimulation for "somatotopic" tractography of the corticospinal tract.
Neurosurgery, 2014

Diffusion tensor imaging tractography provides 3-dimensional reconstruction of principal white matter tracts, but its spatial accuracy has been questioned. Navigated transcranial magnetic stimulation (nTMS) enables somatotopic mapping of the motor cortex.
Is tactile acuity altered in people with chronic pain? a systematic review and meta-analysis.
The journal of pain, 2014

Impaired tactile acuity in people with chronic pain conditions has been suggested to reflect altered cortical representation of the painful body part, and treatments that aim to improve tactile acuity in these conditions have shown clinical benefit. Whether abnormalities in tactile acuity are a consistent feature of chronic pain remains largely unknown. The aim of this review was to systematically evaluate the literature and use meta-analysis to establish whether tactile acuity is altered in people with chronic non-neuropathic pain. We systematically searched the literature for studies that investigated tactile acuity in people with chronic non-neuropathic pain and compared it to an appropriate control group. Sixteen studies, reporting data from 5 chronic pain conditions, were included. Data were available for 18 chronic pain populations (n = 484) and 15 control populations (n = 378). Our results suggest that tactile acuity is diminished in arthritis, complex regional pain syndrome, and chronic low back pain but not in burning mouth syndrome. The strength of the available evidence is weakened by somewhat inconsistent results and the high risk of bias observed in all of the included studies.
Automatic segmentation of the lateral geniculate nucleus: Application to control and glaucoma patients.
Journal of neuroscience methods, 2015

The lateral geniculate nucleus (LGN) is a key relay center of the visual system. Because the LGN morphology is affected by different diseases, it is of interest to analyze its morphology by segmentation. However, existing LGN segmentation methods are non-automatic, inefficient and prone to experimenters' bias.
The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review.
International journal of molecular sciences, 2018

Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are needed to successfully address those who did not respond, or partially respond, to available antidepressant pharmacotherapy. Research findings revealed that the opioid system is significantly involved in the regulation of mood and incentives salience and may be an appropriate target for novel therapeutic agents. The present study aimed to systematically review the current literature about the use of buprenorphine (BUP) for major depression, treatment-resistant depression (TRD), non-suicidal self-injury (NSSI) behavior, and suicidal behavior. We investigated Pubmed and Scopus databases using the following keywords: "buprenorphine AND depression", "buprenorphine AND treatment resistant depression", "buprenorphine AND suicid*", "buprenorphine AND refractory depression". Several evidence demonstrate that, at low doses, BUP is an efficacious, well-tolerated, and safe option in reducing depressive symptoms, serious suicidal ideation, and NSSI, even in patients with TRD. However, more studies are needed to evaluate the long-term effects, and relative efficacy of specific combinations (e.g., BUP + samidorphan (BUP/SAM), BUP + naloxone (BUP/NAL), BUP + naltrexone) over BUP monotherapy or adjunctive BUP treatment with standard antidepressants, as well as to obtain more uniform guidance about the optimal BUP dosing interval.
Unsupervised MRI Homogenization: Application to Pediatric Anterior Visual Pathway Segmentation.
Machine learning in medical imaging. MLMI (Workshop), 2020

Deep learning strategies have become ubiquitous optimization tools for medical image analysis. With the appropriate amount of data, these approaches outperform classic methodologies in a variety of image processing tasks. However, rare diseases and pediatric imaging often lack extensive data. Specially, MRI are uncommon because they require sedation in young children. Moreover, the lack of standardization in MRI protocols introduces a strong variability between different datasets. In this paper, we present a general deep learning architecture for MRI homogenization that also provides the segmentation map of an anatomical region of interest. Homogenization is achieved using an unsupervised architecture based on variational autoencoder with cycle generative adversarial networks, which learns a common space (i.e. a representation of the optimal imaging protocol) using an unpaired image-to-image translation network. The segmentation is simultaneously generated by a supervised learning strategy. We evaluated our method segmenting the challenging anterior visual pathway using three brain T1-weighted MRI datasets (variable protocols and vendors). Our method significantly outperformed a non-homogenized multi-protocol U-Net.
Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases.
Nature communications, 2019

Alterations in gut microbiota composition are associated with metabolic syndrome and chronic inflammatory diseases such as inflammatory bowel disease. One feature of inflammation-associated gut microbiotas is enrichment of motile bacteria, which can facilitate microbiota encroachment into the mucosa and activate pro-inflammatory gene expression. Here, we set out to investigate whether elicitation of mucosal anti-flagellin antibodies by direct administration of purified flagellin might serve as a general vaccine against subsequent development of chronic gut inflammation. We show, in mice, that repeated injection of flagellin elicits increases in fecal anti-flagellin IgA and alterations in microbiota composition, reduces fecal flagellin concentration, prevents microbiota encroachment, protects against IL-10 deficiency-induced colitis, and ameliorates diet-induced obesity. Flagellin's impact on the microbiota is B-lymphocyte dependent and, in humans, obese subjects exhibit increased levels of fecal flagellin and reduced levels of fecal flagellin-specific IgA, relative to normal weight subjects. Thus, administration of flagellin, and perhaps other pathobiont antigens, may confer some protection against chronic inflammatory diseases.
Defective glutamate and K+ clearance by cortical astrocytes in familial hemiplegic migraine type 2.
EMBO molecular medicine, 2016

Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 2: FHM2) is caused by loss-of-function mutations in α2 Na(+),K(+) ATPase (α2 NKA), an isoform almost exclusively expressed in astrocytes in adult brain. Cortical spreading depression (CSD), the phenomenon that underlies migraine aura and activates migraine headache mechanisms, is facilitated in heterozygous FHM2-knockin mice with reduced expression of α2 NKA The mechanisms underlying an increased susceptibility to CSD in FHM2 are unknown. Here, we show reduced rates of glutamate and K(+) clearance by cortical astrocytes during neuronal activity and reduced density of GLT-1a glutamate transporters in cortical perisynaptic astrocytic processes in heterozygous FHM2-knockin mice, demonstrating key physiological roles of α2 NKA and supporting tight coupling with GLT-1a. Using ceftriaxone treatment of FHM2 mutants and partial inhibition of glutamate transporters in wild-type mice, we obtain evidence that defective glutamate clearance can account for most of the facilitation of CSD initiation in FHM2-knockin mice, pointing to excessive glutamatergic transmission as a key mechanism underlying the vulnerability to CSD ignition in migraine.