rudyvdbrink/CitationDatabase huggingface dataset:
A novel approach to the human connectome: ultra-high resolution mapping of fiber tracts in the brain.
NeuroImage, 2011

Signal transmission between different brain regions requires connecting fiber tracts, the structural basis of the human connectome. In contrast to animal brains, where a multitude of tract tracing methods can be used, magnetic resonance (MR)-based diffusion imaging is presently the only promising approach to study fiber tracts between specific human brain regions. However, this procedure has various inherent restrictions caused by its relatively low spatial resolution. Here, we introduce 3D-polarized light imaging (3D-PLI) to map the three-dimensional course of fiber tracts in the human brain with a resolution at a submillimeter scale based on a voxel size of 100 μm isotropic or less. 3D-PLI demonstrates nerve fibers by utilizing their intrinsic birefringence of myelin sheaths surrounding axons. This optical method enables the demonstration of 3D fiber orientations in serial microtome sections of entire human brains. Examples for the feasibility of this novel approach are given here. 3D-PLI enables the study of brain regions of intense fiber crossing in unprecedented detail, and provides an independent evaluation of fiber tracts derived from diffusion imaging data.
Association between vestibulo-ocular reflex suppression, balance, gait, and fall risk in ageing and neurodegenerative disease: protocol of a one-year prospective follow-up study.
BMC neurology, 2015

Falls frequency increases with age and particularly in neurogeriatric cohorts. The interplay between eye movements and locomotion may contribute substantially to the occurrence of falls, but is hardly investigated. This paper provides an overview of current approaches to simultaneously measure eye and body movements, particularly for analyzing the association of vestibulo-ocular reflex (VOR) suppression, postural deficits and falls in neurogeriatric risk cohorts. Moreover, VOR suppression is measured during head-fixed target presentation and during gaze shifting while postural control is challenged. Using these approaches, we aim at identifying quantitative parameters of eye-head-coordination during postural balance and gait, as indicators of fall risk.
Pacifists and Revenge-Seekers in Response to Unambiguous Peer Provocation.
Journal of youth and adolescence, 2018

In order to better understand why some children retaliate when they feel provoked and others do not, the present study identified "pacifistically-oriented" children who made negative interpretations in response to unambiguous provocations, yet did not endorse revenge goals, and compared them to "revenge-seeking" children who also made negative interpretations but did endorse revenge goals. Groups were identified based on seventh graders' (N = 367; 54.77% male; 22.89% racial/ethnic minority) responses to hypothetical situations in which a peer excluded and insulted them. Comparing these groups revealed that Pacifists endorsed relationship-maintaining goals and emotion regulation goals more highly than Revenge-Seekers. Revenge-Seekers reported more anger and endorsed beliefs about negative reciprocity and aggression being legitimate more highly than Pacifists. Additionally, Revenge-Seekers were more disrespect sensitive than were Pacifists, based on a measure of vigilance for signs of disrespect and expectations that others would disrespect them. Together these findings point to social-cognitive and emotion-related processes that may inhibit revenge-seeking in unambiguous provocation situations, even when children interpret the peer's behavior quite negatively.
The posterior parietal cortex contributes to visuomotor processing for saccades in blindsight macaques.
Communications biology, 2021

Patients with damage to the primary visual cortex (V1) lose visual awareness, yet retain the ability to perform visuomotor tasks, which is called "blindsight." To understand the neural mechanisms underlying this residual visuomotor function, we studied a non-human primate model of blindsight with a unilateral lesion of V1 using various oculomotor tasks. Functional brain imaging by positron emission tomography showed a significant change after V1 lesion in saccade-related visuomotor activity in the intraparietal sulcus area in the ipsi- and contralesional posterior parietal cortex. Single unit recordings in the lateral bank of the intraparietal sulcus (lbIPS) showed visual responses to targets in the contralateral visual field on both hemispheres. Injection of muscimol into the ipsi- or contralesional lbIPSs significantly impaired saccades to targets in the V1 lesion-affected visual field, differently from previous reports in intact animals. These results indicate that the bilateral lbIPSs contribute to visuomotor function in blindsight.
Development of an Autism Subtyping Questionnaire Based on Social Behaviors.
Neuroscience bulletin, 2018

Autism spectrum disorder can be differentiated into three subtypes (aloof, passive, and active-but-odd) based on social behaviors according to the Wing Subgroups Questionnaire (WSQ). However, the correlations between the scores on some individual items and the total score are poor. In the present study, we translated the WSQ into Chinese, modified it, validated it in autistic and typically-developing Chinese children, and renamed it the Beijing Autism Subtyping Questionnaire (BASQ). Our results demonstrated that the BASQ had improved validity and reliability, and differentiated autistic children into these three subtypes more precisely. We noted that the autistic symptoms tended to be severe in the aloof, moderate in the passive, and mild in the active-but-odd subtypes. The modified questionnaire may facilitate etiological studies and the selection of therapeutic regimes.
Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.
American journal of physiology. Regulatory, integrative and comparative physiology, 2017

Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are
Sex-differential DNA methylation and associated regulation networks in human brain implicated in the sex-biased risks of psychiatric disorders.
Molecular psychiatry, 2021

Many psychiatric disorders are characterized by a strong sex difference, but the mechanisms behind sex-bias are not fully understood. DNA methylation plays important roles in regulating gene expression, ultimately impacting sexually different characteristics of the human brain. Most previous literature focused on DNA methylation alone without considering the regulatory network and its contribution to sex-bias of psychiatric disorders. Since DNA methylation acts in a complex regulatory network to connect genetic and environmental factors with high-order brain functions, we investigated the regulatory networks associated with different DNA methylation and assessed their contribution to the risks of psychiatric disorders. We compiled data from 1408 postmortem brain samples in 3 collections to identify sex-differentially methylated positions (DMPs) and regions (DMRs). We identified and replicated thousands of DMPs and DMRs. The DMR genes were enriched in neuronal related pathways. We extended the regulatory networks related to sex-differential methylation and psychiatric disorders by integrating methylation quantitative trait loci (meQTLs), gene expression, and protein-protein interaction data. We observed significant enrichment of sex-associated genes in psychiatric disorder-associated gene sets. We prioritized 2080 genes that were sex-biased and associated with psychiatric disorders, such as NRXN1, NRXN2, NRXN3, FDE4A, and SHANK2. These genes are enriched in synapse-related pathways and signaling pathways, suggesting that sex-differential genes of these neuronal pathways may cause the sex-bias of psychiatric disorders.
A multidimensional precision medicine approach identifies an autism subtype characterized by dyslipidemia.
Nature medicine, 2020

The promise of precision medicine lies in data diversity. More than the sheer size of biomedical data, it is the layering of multiple data modalities, offering complementary perspectives, that is thought to enable the identification of patient subgroups with shared pathophysiology. In the present study, we use autism to test this notion. By combining healthcare claims, electronic health records, familial whole-exome sequences and neurodevelopmental gene expression patterns, we identified a subgroup of patients with dyslipidemia-associated autism.
Anticipatory and consummatory components of the experience of pleasure in schizophrenia: cross-cultural validation and extension.
Psychiatry research, 2010

This study examined anticipatory and consummatory pleasure in schizophrenia patients with and without negative symptoms. Negative symptom patients experienced less anticipatory pleasure than non-negative symptom patients; only one facet of consummatory pleasure was unaffected in negative schizophrenia. Greater pleasure deficits were correlated with more severe positive and negative symptoms.
Perspectives in regeneration and tissue engineering of peripheral nerves.
Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft, 2011

Peripheral nerve injury is a common casualty and although peripheral nerve fibers retain a considerable regeneration potential also in the adult, recovery is usually rather poor, especially in case of large nerve defects. The aim of this paper is to address the perspectives in regeneration and tissue engineering after peripheral nerve injury by reviewing the relevant experimental studies in animal models. After a brief overview of the morphological changes related to peripheral nerve injury and regeneration, the paper will address the evolution of peripheral nerve tissue engineering with special focus on transplantation strategies, from organs and tissues to cells and genes, that can be carried out, particularly in case of severe nerve lesions with substance loss. Finally, the need for integrated research which goes beyond therapeutic strategies based on single approaches is emphasized, and the importance of bringing together the various complimentary disciplines which can contribute to the definition of effective new strategies for regenerating the injured peripheral nerve is outlined.
When is "brainstem death" brain death? The case for ancillary testing in primary infratentorial brain lesion.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2018

The widely accepted concept of brain death (BD) comprises the demonstration of irreversible coma in combination with the loss of brainstem reflexes and irreversible apnea. In some countries the combined clinical finding of coma, apnea, and loss of all tested brainstem reflexes ("brainstem death") is sufficient for diagnosing BD irrespective of the primary location of brain lesion. The present article aims to substantiate the need for ancillary testing in patients with primary infratentorial brain lesions. Anatomically, the "brainstem-death" syndrome can theoretically occur without relevant lesion of the mesopontine tegmental reticular formation (MPT-RF). Thus, a brainstem lesion may cause an apneic total locked-in syndrome, a rare syndrome with preserved capability for consciousness, mimicking "brainstem death". Findings in animals and humans have shown that alpha- or alpha/theta- EEG patterns in case of isolated brainstem lesion indicate intactness of relevant parts of the MPT-RF. In such patients the presence of irreversible coma has to be doubted, and the potential capacity for some degree of consciousness cannot be excluded as long as the EEG activity persists. Consequently the demonstration of either ancillary finding, electro-cortical inactivity or, preferably, cerebral circulatory arrest, is mandatory for diagnosing BD in patients with a primary infratentorial brain lesion.
The high-mobility group I-Y transcription factor is involved in cerebral ischemia and modulates the expression of angiogenic proteins.
Neuroscience, 2014

The present study aims to identify transcription factors (TFs) contributing to angiogenesis, a mechanism involved in giving plasticity to the brain, as potential therapeutic targets after cerebral ischemia. The promoter sequences from candidate genes involved in angiogenesis were submitted to a comparative analysis by bioinformatics software. High-mobility group I-Y protein (HMGIY) TF characterization in a rat permanent focal cerebral ischemia model was performed by quantitative real time polymerase chain reaction and Western blot for the TF expression profile study. The TF functional study was carried out using a TF-TF interaction array and gene silencing by siRNA in rat brain microvascular endothelial cells. The results showed that the promoters shared a common TF binding site for HMGIY. The expression profile analysis in ischemic rat brain showed an increase in HMGIY mRNA in the acute phase and a progressive overexpression of protein over time post-ischemia. The interaction array analysis revealed that ischemia promotes the interaction of HMGIY with TFs involved in different cerebral plasticity processes. In vitro knockdown studies showed that angiopoietin 1 and vascular endothelial growth factor expression is controlled by HMGIY and that this TF is involved in cell survival in brain endothelial cells. These findings suggest that HMGIY is a potential therapeutic target that could promote brain repair functions after stroke.
Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat metabolism.
Cellular and molecular life sciences : CMLS, 2012

The LIM domain only 4 (LMO4) protein is expressed in the hypothalamus, but its function there is not known. Using mice with LMO4 ablated in postnatal glutamatergic neurons, including most neurons of the paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei where LMO4 is expressed, we asked whether LMO4 is required for metabolic homeostasis. LMO4 mutant mice exhibited early onset adiposity. These mice had reduced energy expenditure and impaired thermogenesis together with reduced sympathetic outflow to adipose tissues. The peptide hormone leptin, produced from adipocytes, activates Jak/Stat3 signaling at the hypothalamus to control food intake, energy expenditure, and fat metabolism. Intracerebroventricular infusion of leptin suppressed feeding similarly in LMO4 mutant and control mice. However, leptin-induced fat loss was impaired and activation of Stat3 in the VMH was blunted in these mice. Thus, our study identifies LMO4 as a novel modulator of leptin function in selective hypothalamic nuclei to regulate fat metabolism.
EBI2 regulates pro-inflammatory signalling and cytokine release in astrocytes.
Neuropharmacology, 2018

The endogenous oxysterol 7α, 25-dihydroxycholesterol (7α25HC) ligand activates the G protein-coupled receptor EBI2 to regulate T cell-dependant antibody response and B cell migration. We have demonstrated that EBI2 is expressed in human and mouse astrocytes, that 7α25HC induces intracellular signalling and astrocyte migration, and that EBI2 plays a role in the crosstalk between astrocytes and macrophages. Recently, we demonstrate that EBI2 regulates myelin development and inhibits LPC-induced demyelination. Here, we show that 7α25HC inhibits LPS- and IL17/TNF-induced pro-inflammatory cytokine release in astrocytes. We observe the following: 1. Human astrocytes treated with IL17/TNF increases the nuclear translocation of NFκB, which is attenuated by pre-treatment with 7α25HC; 2. IL17/TNF increases cell impedance in human astrocytes, which is also attenuated by pre-treatment with 7α25HC; 3. The EBI2 antagonist NIBR189 inhibits these effects of 7α25HC, supporting the role of EBI2; 4. in vivo data corroborate these in vitro findings, showing that EBI2 knock-out (KO) animals display enhanced pro-inflammatory cytokine in response to LPS challenge, in the brain. These results demonstrate a role for oxysterol/EBI2 signalling in attenuating the response of astrocytes to pro-inflammatory signals as well as limiting the levels of pro-inflammatory cytokines in the brain.
Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models.
Human reproduction (Oxford, England), 2010

Ectopic pregnancy, a worldwide health problem, is potentially life-threatening and occurs in approximately 1.5-2% of all pregnancies in the western world; however, the precise mechanisms underlying the initiation and development of tubal ectopic pregnancy are unknown. Tubal abnormalities and dysfunction, such as altered contractility or abnormal ciliary activity, have been speculated to lead to tubal ectopic pregnancy. To elucidate the cellular and molecular mechanisms of the tubal transport process, several knockout (KO) mouse models have been developed. This review summarizes what has been learned from studies of the Fallopian tube in caspase-1, cannabinoid receptor and Dicer1 KO mice. Our understanding of the mechanisms which contribute to tubal ectopic pregnancy in humans may be enhanced through further study of these KO mouse models.
Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

The impact of activity on neuronal circuitry is complex, involving both functional and structural changes whose interaction is largely unknown. We have used optical imaging of mouse visual cortex responses and two-photon imaging of superficial layer spines on layer 5 neurons to monitor network function and synaptic structural dynamics in the mouse visual cortex in vivo. Total lack of vision due to dark-rearing from birth dampens visual responses and shifts spine dynamics and morphologies toward an immature state. The effects of vision after dark rearing are strongly dependent on the timing of exposure: over a period of days, functional and structural changes are temporally related such that light stabilizes spines while increasing visually driven activity. The effects of long-term light exposure can be partially mimicked by experimentally enhancing inhibitory signaling in the darkness. Brief light exposure, however, results in a rapid, transient, NMDA-dependent increase of cortical responses, accompanied by increased dynamics of dendritic spines. These findings indicate that visual experience induces rapid reorganization of cortical circuitry followed by a period of stabilization, and demonstrate a close relationship between dynamic changes at single synapses and cortical network function.
Heparin-binding EGF-like growth factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas.
Molecular and cellular neurosciences, 2015

Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, heparin-binding EGF-like growth factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF not only stimulated MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas.
Human auditory cortex is sensitive to the perceived clarity of speech.
NeuroImage, 2012

Feedback connections among auditory cortical regions may play an important functional role in processing naturalistic speech, which is typically considered a problem solved through serial feed-forward processing stages. Here, we used fMRI to investigate whether activity within primary auditory cortex (PAC) is sensitive to the perceived clarity of degraded sentences. A region-of-interest analysis using probabilistic cytoarchitectonic maps of PAC revealed a modulation of activity, in the most primary-like subregion (area Te1.0), related to the intelligibility of naturalistic speech stimuli that cannot be driven by stimulus differences. Importantly, this effect was unique to those conditions accompanied by a perceptual increase in clarity. Connectivity analyses suggested sources of input to PAC are higher-order temporal, frontal and motor regions. These findings are incompatible with feed-forward models of speech perception, and suggest that this problem belongs amongst modern perceptual frameworks in which the brain actively predicts sensory input, rather than just passively receiving it.
Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease.
Cell, 2014

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and sporadic Parkinson's disease (PD). Elevated LRRK2 kinase activity and neurodegeneration are linked, but the phosphosubstrate that connects LRRK2 kinase activity to neurodegeneration is not known. Here, we show that ribosomal protein s15 is a key pathogenic LRRK2 substrate in Drosophila and human neuron PD models. Phosphodeficient s15 carrying a threonine 136 to alanine substitution rescues dopamine neuron degeneration and age-related locomotor deficits in G2019S LRRK2 transgenic Drosophila and substantially reduces G2019S LRRK2-mediated neurite loss and cell death in human dopamine and cortical neurons. Remarkably, pathogenic LRRK2 stimulates both cap-dependent and cap-independent mRNA translation and induces a bulk increase in protein synthesis in Drosophila, which can be prevented by phosphodeficient T136A s15. These results reveal a novel mechanism of PD pathogenesis linked to elevated LRRK2 kinase activity and aberrant protein synthesis in vivo.