rudyvdbrink/CitationDatabase huggingface dataset:
Altered bone development with impaired cartilage formation precedes neuromuscular symptoms in spinal muscular atrophy.
Human molecular genetics, 2020

Spinal muscular atrophy (SMA) is a fatal neurodegenerative disease of newborns and children caused by mutations or deletions of the survival of motoneuron gene 1 resulting in low levels of the SMN protein. While neuromuscular degeneration is the cardinal symptom of the disease, the reduction of the ubiquitously expressed SMN additionally elicits non-motoneuron symptoms. Impaired bone development is a key feature of SMA, but it is yet unknown whether this is an indirect functional consequence of muscle weakness or caused by bone-intrinsic mechanisms. Therefore, we radiologically examined SMA patients in a prospective, non-randomized cohort study characterizing bone size and bone mineral density (BMD) and performed equivalent measurements in pre-symptomatic SMA mice. BMD as well as lumbar vertebral body size were significantly reduced in SMA patients. This growth defect but not BMD reduction was confirmed in SMA mice by μCT before the onset of neuromuscular symptoms indicating that it is at least partially independent of neuromuscular degeneration. Interestingly, the number of chondroblasts in the hypertrophic zone of the growth plate was significantly reduced. This was underlined by RNAseq and expression data from developing SMA mice vertebral bodies, which revealed molecular changes related to cell division and cartilage remodeling. Together, these findings suggest a bone intrinsic defect in SMA. This phenotype may not be rescued by novel drugs that enhance SMN levels in the central nervous system only.
Brain structural basis of individual variability in dream recall frequency.
Brain imaging and behavior, 2019

Recent neuroimaging studies have indicated that inter-individual variability in dream recall frequency (DRF) is associated with both resting-state regional cerebral blood flow and task-induced brain activations. However, the brain structure underpinning this inter-individual variability in DRF remains unclear. The aim of the current study is to investigate the relationship between brain structural characteristics and DRF. We collected both T1-weighted and diffusion tensor magnetic resonance imaging data from 43 healthy volunteers. DRF was obtained from a two-week sleep diary with a subjective report of dream recall upon waking every morning. General linear model analysis was used to evaluate the relationship between brain structural characteristics (cortical volume and white matter integrity) and DRF. Not only the cortical volume of the medial portion of the right fusiform gyrus and parahippocampal gyrus but also the fractional anisotropy of white matter fibers connected to these regions were significantly negatively correlated with DRF, and these relationships were not modulated by a regular sleep. These findings provide direct evidence that brain structural characteristics are associated with inter-individual variability in DRF and may help us to better understand the structural mechanisms in the brain underlying dream recall.
Recent progress in translational engineered in vitro models of the central nervous system.
Brain : a journal of neurology, 2020

The complexity of the human brain poses a substantial challenge for the development of models of the CNS. Current animal models lack many essential human characteristics (in addition to raising operational challenges and ethical concerns), and conventional in vitro models, in turn, are limited in their capacity to provide information regarding many functional and systemic responses. Indeed, these challenges may underlie the notoriously low success rates of CNS drug development efforts. During the past 5 years, there has been a leap in the complexity and functionality of in vitro systems of the CNS, which have the potential to overcome many of the limitations of traditional model systems. The availability of human-derived induced pluripotent stem cell technology has further increased the translational potential of these systems. Yet, the adoption of state-of-the-art in vitro platforms within the CNS research community is limited. This may be attributable to the high costs or the immaturity of the systems. Nevertheless, the costs of fabrication have decreased, and there are tremendous ongoing efforts to improve the quality of cell differentiation. Herein, we aim to raise awareness of the capabilities and accessibility of advanced in vitro CNS technologies. We provide an overview of some of the main recent developments (since 2015) in in vitro CNS models. In particular, we focus on engineered in vitro models based on cell culture systems combined with microfluidic platforms (e.g. 'organ-on-a-chip' systems). We delve into the fundamental principles underlying these systems and review several applications of these platforms for the study of the CNS in health and disease. Our discussion further addresses the challenges that hinder the implementation of advanced in vitro platforms in personalized medicine or in large-scale industrial settings, and outlines the existing differentiation protocols and industrial cell sources. We conclude by providing practical guidelines for laboratories that are considering adopting organ-on-a-chip technologies.
[False memories and aging: age effects on predictive inferences].
Psychologie & neuropsychiatrie du vieillissement, 2008

To study false memories in older adults, a lot of experiments used the DRM paradigm (Deese, Roediger et McDermott). Most of the time, the results showed that older adults make more false memories than young adults. To test this hypothesis with a more ecological material, we used a situation of text reading. When we read a text, we activate predictive inferences, which are anticipations of what will happen next. We constructed short texts inducing predictive inferences (represented by a target word not presented) to study false memories in young and older adults. For example, in the text <<Charlotte had her breakfast on the terrace when the bees beat about the bush of jam. She made a movement to move them away but one of them succeeds in being posed on its arm>>, the target word "sting" is not presented but represents the predictive inference. After the reading of the texts, we propose to the subjects a restitution task consisting in recalling texts with the first sentence as clue. Then, they made a recognition task composed of target words and lures; they had to say if they remembered having read these words in the texts. In these two tasks, the subjects tended to remember not presented target words, creating false memories. This effect was the same for the two age groups showing that, in an ecological situation like text reading, older persons make as many false memories as young adults.
Biomarkers of seizure response to vagus nerve stimulation: A scoping review.
Epilepsia, 2020

Although vagus nerve stimulation (VNS) is a common procedure, seizure outcomes are heterogeneous, with few available means to preoperatively identify the ideal surgical candidate. Here, we perform a scoping review of the literature to identify biomarkers of VNS response in patients with drug-resistant epilepsy. Several databases (Ovid MEDLINE, Ovid Embase, BIOSIS Previews, and Web of Science) were searched for all relevant articles that reported at least one biomarker of VNS response following implantation for intractable epilepsy. Patient demographics, seizure data, and details related to biomarkers were abstracted from all studies. From the 288 records screened, 28 articles reporting on 16 putative biomarkers were identified. These were grouped into four categories: network/connectomic-based biomarkers, electrophysiological signatures, structural findings on neuroimaging, and systemic assays. Differences in brain network organization, connectivity, and electrophysiological synchronicity demonstrated the most robust ability to identify VNS responders. Structural findings on neuroimaging yielded inconsistent associations with VNS responsiveness. With regard to systemic biomarkers, heart rate variability was shown to be an independent marker of VNS response, whereas inflammatory markers were not useful. There is an unmet need to preoperatively identify candidates who are likely to benefit from VNS. Several biomarkers demonstrate promise in predicting seizure responsiveness to VNS, particularly measures of brain network connectivity. Further efforts are required to validate existing biomarkers to inform clinical decision-making.
A polygenic score for age-at-first-birth predicts disinhibition.
Journal of child psychology and psychiatry, and allied disciplines, 2020

A recent genome-wide association study identified molecular-genetic associations with age-at-first-birth. However, the meaning of these genetic discoveries is unclear. Drawing on evidence linking early pregnancy with disinhibitory behavior, we tested the hypothesis that genetic discoveries for age-at-first-birth predict disinhibition.
No preference for direct versus averted gaze in autistic adults: a reinforced preferential looking paradigm.
Molecular autism, 2020

With the overarching objective to gain better insights into social attention in autistic adults, the present study addresses three outstanding issues about face processing in autism. First, do autistic adults display a preference for mouths over eyes; second, do they avoid direct gaze; third, is atypical visual exploration of faces in autism mediated by gender, social anxiety or alexithymia?
Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals.
Nature communications, 2020

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (N
Near-Term Decrease in Brain Volume following Mild Traumatic Injury Is Detectible in the Context of Preinjury Volumetric Stability: Neurobiologic Insights from Analysis of Historical Imaging Examinations.
AJNR. American journal of neuroradiology, 2018

Neurodegeneration after mild traumatic brain injury may manifest as decreasing regional brain volume that evolves from months to years following mild traumatic brain injury and is associated with worse clinical outcomes. We hypothesized that quantitative brain volume derived from CT of the head, performed for clinical indications during routine care, would change with time and provide insights into the putative neuroinflammatory response to mild traumatic brain injury.
Report of an inferior rectal nerve variant arising from the S3 ventral ramus.
Anatomy & cell biology, 2019

In surgical approaches to the perineum in general and anal region specifically, considering the possible variations of the inferior rectal nerve is important for the surgeon. Normally, the inferior rectal nerve originates as a branch of the pudendal nerve. However, during routine dissection, a variant of the inferior rectal nerve was found where it arose directly from the third sacral nerve ventral ramus (S3). Many cases have described the inferior rectal nerve arising independently from the sacral plexus, most commonly from the fourth sacral nerve root (S4); however, few cases have reported the inferior rectal nerve arising from S3. Herein, we describe a variant of the inferior rectal nerve in which the nerve arises independently from the sacral plexus.
Acute consequences of a unilateral VIIIth nerve transection on vestibulo-ocular and optokinetic reflexes in Xenopus laevis tadpoles.
Journal of neurology, 2020

Loss of peripheral vestibular function provokes severe impairments of gaze and posture stabilization in humans and animals. However, relatively little is known about the extent of the instantaneous deficits. This is mostly due to the fact that in humans a spontaneous loss often goes unnoticed initially and targeted lesions in animals are performed under deep anesthesia, which prevents immediate evaluation of behavioral deficits. Here, we use isolated preparations of Xenopus laevis tadpoles with functionally intact vestibulo-ocular (VOR) and optokinetic reflexes (OKR) to evaluate the acute consequences of unilateral VIIIth nerve sections. Such in vitro preparations allow lesions to be performed in the absence of anesthetics with the advantage to instantly evaluate behavioral deficits. Eye movements, evoked by horizontal sinusoidal head/table rotation in darkness and in light, became reduced by 30% immediately after the lesion and were diminished by 50% at 1.5 h postlesion. In contrast, the sinusoidal horizontal OKR, evoked by large-field visual scene motion, remained unaltered instantaneously but was reduced by more than 50% from 1.5 h postlesion onwards. The further impairment of the VOR beyond the instantaneous effect, along with the delayed decrease of OKR performance, suggests that the immediate impact of the sensory loss is superseded by secondary consequences. These potentially involve homeostatic neuronal plasticity among shared VOR-OKR neuronal elements that are triggered by the ongoing asymmetric activity. Provided that this assumption is correct, a rehabilitative reduction of the vestibular asymmetry might restrict the extent of the secondary detrimental effect evoked by the principal peripheral impairment.
The transcription factor SoxD controls neuronal guidance in the Drosophila visual system.
Scientific reports, 2018

Precise control of neurite guidance during development is essential to ensure proper formation of neuronal networks and correct function of the central nervous system (CNS). How neuronal projections find their targets to generate appropriate synapses is not entirely understood. Although transcription factors are key molecules during neurogenesis, we do not know their entire function during the formation of networks in the CNS. Here, we used the Drosophila melanogaster optic lobe as a model for understanding neurite guidance during development. We assessed the function of Sox102F/SoxD, the unique Drosophila orthologue of the vertebrate SoxD family of transcription factors. SoxD is expressed in immature and mature neurons in the larval and adult lobula plate ganglia (one of the optic lobe neuropils), but is absent from glial cells, neural stem cells and progenitors of the lobula plate. SoxD RNAi knockdown in all neurons results in a reduction of the lobula plate neuropil, without affecting neuronal fate. This morphological defect is associated with an impaired optomotor response of adult flies. Moreover, knocking down SoxD only in T4/T5 neuronal types, which control motion vision, affects proper neurite guidance into the medulla and lobula. Our findings suggest that SoxD regulates neurite guidance, without affecting neuronal fate.
Children with poor adherence to antiepileptic drugs during the first 6 months of treatment are less likely to be seizure free after 4 years.
Evidence-based nursing, 2015

Implications for practice and research: Early adherence to antiepileptic medication is related to long-term seizure outcome. Interventions to enhance medication adherence may have a role in improving long-term seizure outcome in children with epilepsy. Further studies are needed with larger sample sizes to address the limitations of the study.
Input-Output Characteristics of Late Corticospinal Silent Period Induced by Transcranial Magnetic Stimulation.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 2015

Corticospinal silent period (SP) may be interrupted by a burst of muscle activity followed by a second (late) SP, generally assumed to be a continuation from the primary SP. Our objective was to characterize the input-output behavior of the late SP.
Drug-induced mitochondrial dysfunction in cardiac and skeletal muscle injury.
Expert opinion on drug safety, 2008

The list of clinically relevant molecules that affect skeletal and cardiac muscle mitochondria is gradually increasing, which strongly suggest that mitochondrial toxicity should be an important end point during the design and testing of novel pharmaceuticals.
Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions.
Genome biology, 2020

One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood.
Glia in Neurodegeneration: The Housekeeper, the Defender and the Perpetrator.
International journal of molecular sciences, 2020

Over the past decade, research has unveiled the intimate relationship between neuroinflammation and neurodegeneration. Microglia and astrocytes react to brain insult by setting up a multimodal inflammatory state and act as the primary defenders and executioners of neuroinflammatory structural and functional changes. Microglia and astrocytes also play critical roles in the maintenance of normal brain function. This intricate balance of homeostatic and neuroinflammatory functions can influence the onset and the course of neurodegenerative diseases. The emergent role of the microglial-astrocytic axis in neurodegenerative disease presents many druggable targets that may have broad therapeutic benefits across neurodegenerative disease. Here, we provide a brief review of the basal function of both microglia and astrocytes, how they are changed in disease states, the significant differences between mouse and human glia, and use of human induced pluripotent stem cells derived from patients to study cell autonomous changes in human astrocytes and microglia.
Phylogenetic analysis and epidemiological history of Hepatitis E virus 3f and 3c in swine and wild boar, Italy.
Heliyon, 2020

Hepatitis E virus (HEV) genotype 3 has a worldwide distribution. The food-borne transmission of HEV associated with the consumption of products derived from domestic pig, wild boar has been reported in various countries. In this study the genetic diversity, evolutionary rates of HEV 3f, 3c among swine and wild boar in Italy were estimated.
Opioid and neuroHIV Comorbidity - Current and Future Perspectives.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2020

With the current national opioid crisis, it is critical to examine the mechanisms underlying pathophysiologic interactions between human immunodeficiency virus (HIV) and opioids in the central nervous system (CNS). Recent advances in experimental models, methodology, and our understanding of disease processes at the molecular and cellular levels reveal opioid-HIV interactions with increasing clarity. However, despite the substantial new insight, the unique impact of opioids on the severity, progression, and prognosis of neuroHIV and HIV-associated neurocognitive disorders (HAND) are not fully understood. In this review, we explore, in detail, what is currently known about mechanisms underlying opioid interactions with HIV, with emphasis on individual HIV-1-expressed gene products at the molecular, cellular and systems levels. Furthermore, we review preclinical and clinical studies with a focus on key considerations when addressing questions of whether opioid-HIV interactive pathogenesis results in unique structural or functional deficits not seen with either disease alone. These considerations include, understanding the combined consequences of HIV-1 genetic variants, host variants, and μ-opioid receptor (MOR) and HIV chemokine co-receptor interactions on the comorbidity. Lastly, we present topics that need to be considered in the future to better understand the unique contributions of opioids to the pathophysiology of neuroHIV. Graphical Abstract Blood-brain barrier and the neurovascular unit. With HIV and opiate co-exposure (represented below the dotted line), there is breakdown of tight junction proteins and increased leakage of paracellular compounds into the brain. Despite this, opiate exposure selectively increases the expression of some efflux transporters, thereby restricting brain penetration of specific drugs.
Hypoxia-inducible Factor 2α Exerts Neuroprotective Effects by Promoting Angiogenesis via the VEGF/Notch Pathway after Intracerebral Hemorrhage Injury in Rats.
Neuroscience, 2020

Angiogenesis after intracerebral hemorrhage (ICH) injury can effectively alleviate brain damage and improve neurological function. Hypoxia-inducible factor 2α (HIF-2α) is an important angiogenic regulator and exhibits protective effects in several neurological diseases; however, its role in ICH has not yet been reported. Hence, in the present study, we explored whether HIF-2α reduces ICH injury by promoting angiogenesis. In addition, we explored the role of the vascular endothelial growth factor (VEGF)/Notch pathway in HIF-2α-mediated angiogenesis. We injected 50 μL of autologous blood taken from the femoral artery into the right striatum of healthy male adult Sprague-Dawley rats to create an autologous-blood-induced rat model of ICH. Lentiviral vectors were injected to both overexpress and knock down HIF-2α expression. VEGF receptor 2 (VEGFR2) and Notch-specific inhibitors were injected intraperitoneally to block VEGFR2- and Notch-mediated signaling after lentiviral injections. Our data showed that HIF-2α overexpression reduced neurological-damage scores and brain-water content, suggesting it had a protective effect on ICH injury. In addition, overexpression of HIF-2α promoted angiogenesis, increased focal cerebral blood flow (CBF), and reduced neuronal damage, whereas HIF-2α knockdown resulted in the opposite effects. Furthermore, we found that HIF-2α-mediated angiogenesis was blocked by a Notch-specific inhibitor. Likewise, the HIF-2α-mediated increase in phospho-VEGFR-2, cleaved-Notch1 and Notch1 expression was reversed via a VEGFR2-specific inhibitor. Taken together, our results indicate that HIF-2α promotes angiogenesis via the VEGF/Notch pathway to attenuate ICH injury. Moreover, our findings may contribute to the development of a novel strategy for alleviating ICH injury via HIF-2α-mediated upregulation of angiogenesis.
Oxytocin Shapes Spontaneous Activity Patterns in the Developing Visual Cortex by Activating Somatostatin Interneurons.
Current biology : CB, 2021

Spontaneous network activity shapes emerging neuronal circuits during early brain development prior to sensory perception. However, how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin differentially shapes spontaneous activity patterns across sensory cortices. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in the primary visual cortex (V1), but it did not affect the frequency of spontaneous network events in the somatosensory cortex (S1). Patch-clamp recordings in slices and RNAscope showed that oxytocin affects S1 excitatory and inhibitory neurons similarly, whereas in V1, oxytocin targets only inhibitory neurons. Somatostatin-positive (SST