rudyvdbrink/CitationDatabase huggingface dataset:
Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence.
Alcohol (Fayetteville, N.Y.), 2017

Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitinationhylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study.
Peri-hematoma corticospinal tract integrity in intracerebral hemorrhage patients: A diffusion-tensor imaging study.
Journal of the neurological sciences, 2021

The impact of perihematoma edema in Intracerebral Hemorrhage (ICH) on white matter integrity is uncertain. Fractional Anisotropy (FA), as measured with Diffusion Tensor Imaging (DTI), can be used to assess white matter microstructure. We tested the hypotheses that sections of the Corticospinal Tract (CST) passing through perihematoma edema would 1) have low FA relative to the contralateral CST and 2) would predict NIHSS motor score in ICH patients.
Peripheral blood gene expression of acute phase proteins in people with first episode psychosis.
Brain, behavior, and immunity, 2017

There is a growing interest in the association between schizophrenia and the activation of inflammatory system with signs of acute phase (AP) response. Majority of such studies had focused on C-reactive protein (CRP). The aims of the present study were (i) to examine the gene expression profiles of other acute phase proteins (APP), namely haptoglobin (HP), alpha-1 antitrypsin (A1T), and alpha-2 macroglobulin (A2M) in patients with first episode psychosis (FEP) over a period of three months and (ii) to explore the association between APP levels and severity of symptoms.
Highly specific and ultrasensitive plasma test detects Abeta(1-42) and Abeta(1-40) in Alzheimer's disease.
Scientific reports, 2021

Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms provide an insight in the treatment effects of Alzheimer's disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa 'Amyblood' assays that measure full length Abeta
Non-motor features in essential tremor.
Acta neurologica Scandinavica, 2012

Essential tremor (ET) is increasingly recognized to have several non-motor manifestations. The aim of this study was to determine the prevalence of non-motor manifestations in ET and its impact on the quality of life (QOL).
Light adaptation increases response latency of alpha ganglion cells via a threshold-like nonlinearity.
Neuroscience, 2014

Adaptation is an important process of sensory systems to adjust sensitivity to ensure the appropriate information encoding. Sensitivity and kinetics of retinal ganglion cell (RGC) responses have been studied extensively using a brief flash superimposed on different but steady backgrounds. However, it is still unclear if light adaptation exerts any effect on more complex response properties, such as response nonlinearity. In this study, we found that the latency of spike responses to a repeated flashing spot stimulation increased by 30 ms in the mouse ON α RGCs (An ON-type RGC is excited when a spot is turned on in the center of its receptive field). A single dimming event preceding the test flash on a steady adapting background could also produce similar effect in increasing latency of light responses. A simple computational model with a linear transformation of the light stimulus and a threshold-like nonlinearity could account for the experimental data. Moreover, the strength of the measured nonlinearity and the response latency were affected by the duration of light adaptation. The possible biological processes underlying this nonlinearity were explored. Voltage clamp recording revealed the presence of the increase in latency and threshold-like nonlinearity in the excitatory input of RGCs. However, no comparable nonlinearity was observed in the light responses of the ON cone bipolar cells. We further excluded GABAergic and glycinergic inhibition, N-methyl-D-aspartate receptor rectification and voltage-gated Na(+) channels as potential sources of this nonlinearity by pharmacological experiments. Our results indicate the bipolar cell terminals as the potential site of nonlinearity. Computational modeling constrained by experimental data supports that conclusion and suggests the voltage-sensitive Ca(++) channels and Ca(++)-dependent vesicle release in the bipolar cell terminals as mechanistic basis.
Vibration hotspots reveal longitudinal funneling of sound-evoked motion in the mammalian cochlea.
Nature communications, 2018

The micromechanical mechanisms that underpin tuning and dynamic range compression in the mammalian inner ear are fundamental to hearing, but poorly understood. Here, we present new, high-resolution optical measurements that directly map sound-evoked vibrations on to anatomical structures in the intact, living gerbil cochlea. The largest vibrations occur in a tightly delineated hotspot centering near the interface between the Deiters' and outer hair cells. Hotspot vibrations are less sharply tuned, but more nonlinear, than basilar membrane vibrations, and behave non-monotonically (exhibiting hyper-compression) near their characteristic frequency. Amplitude and phase differences between hotspot and basilar membrane responses depend on both frequency and measurement angle, and indicate that hotspot vibrations involve longitudinal motion. We hypothesize that structural coupling between the Deiters' and outer hair cells funnels sound-evoked motion into the hotspot region, under the control of the outer hair cells, to optimize cochlear tuning and compression.
Social withdrawal and gambling-like profile after lentiviral manipulation of DAT expression in the rat accumbens.
The international journal of neuropsychopharmacology, 2010

Dysfunction of brain dopamine transporter (DAT) has been associated with sensation seeking and impulse-control disorders. We recently generated a new animal model by stereotaxical inoculation of lentiviral vectors, which allowed localized intra-accumbal delivery of modulators for DAT gene: GFP (green fluorescent protein) control, silencers (Sil), a regulatable enhancer (DAT+), or both (DAT+Sil). Wistar male rats were followed both for socio-emotional profiles and for propensity to seek risky, uncertain rewards. Elevated anxiety and affiliation towards an unfamiliar partner emerged in Sil rats. Interestingly, in DAT+Sil rats (and Sil rats to a lesser extent) levels of playful social interaction were markedly reduced compared to controls. These DAT+Sil rats displayed a marked 'gambling-like' profile (i.e. preference for a large/uncertain over a small/sure reward), which disappeared upon doxycycline-induced switch-off onto DAT enhancer, but consistently reappeared with doxycycline removal. MRI-guided 1H-MRS (at 4.7 T) examinations in vivo (under anaesthesia) revealed changes in the bioenergetic metabolites (phosphocreatine and total creatine) for DAT+Sil rats, indicating a functional up-regulation of dorsal striatum (Str) and conversely a down-regulation of ventral striatum (i.e. nucleus accumbens, NAc). A combined profile of (1) enhanced proneness to gambling and (2) strong social withdrawal is thus associated with altered DAT-induced balance within forebrain dopamine systems. In fact, risk of developing a gambling-prone, social-avoidant psychopathology might be associated with (1) dominant semi-automatic strategies and/or habits, developed within Str circuits, and (2) reduced NAc function, with poorer feedback adjustment on decisions by aversive experiences.
Brain-derived neurotrophic factor and glucocorticoids: reciprocal influence on the central nervous system.
Neuroscience, 2013

Brain-derived neurotrophic factor (BDNF) has multiple roles in the central nervous system (CNS), including maintaining cell survival and regulation of synaptic function. In CNS neurons, BDNF triggers activation of phospholipase Cγ (PLCγ), mitogen-activated protein/extracellular signal-regulated kinase (MAPK/ERK), and phosphoinositide 3-kinase (PI3K)/Akt pathways, influencing neuronal cells beneficially through these intracellular signaling cascades. There is evidence to suggest that decreased BDNF expression or function is related to the pathophysiology of brain diseases including psychiatric disorders. Additionally, glucocorticoids, which are critical stress hormones, also influence neuronal function in the CNS, and are putatively involved in the onset of depression when levels are abnormally high. In animal models of depression, changes in glucocorticoid levels, expression of glucocorticoid receptor (GR), and alterations in BDNF signaling are observed. Interestingly, several studies using in vivo and in vitro systems suggest that glucocorticoids interact with BDNF to ultimately affect CNS function. In the present review, we provide an overview of recent evidence concerning the interaction between BDNF and glucocorticoids.
Abnormal cortical activation during an auditory word comprehension task in benign childhood epilepsy with centrotemporal spikes: A magnetoencephalographic study.
Epilepsy & behavior : E&B, 2018

Benign childhood epilepsy with centrotemporal spikes (BECTS), also known as rolandic epilepsy, has recently been reported to be associated with variable degrees of cognitive dysfunction. Many studies reported poor language ability in children with BECTS compared with healthy control children. To elucidate the harmful effects of BECTS on language cognition, we studied the magnetoencephalographic activity elicited by an auditory language comprehension task.
The role of diffusion MRI in neuroscience.
NMR in biomedicine, 2019

Diffusion-weighted imaging has pushed the boundaries of neuroscience by allowing us to examine the white matter microstructure of the living human brain. By doing so, it has provided answers to fundamental neuroscientific questions, launching a new field of research that had been largely inaccessible. We briefly summarize key questions that have historically been raised in neuroscience concerning the brain's white matter. We then expand on the benefits of diffusion-weighted imaging and its contribution to the fields of brain anatomy, functional models and plasticity. In doing so, this review highlights the invaluable contribution of diffusion-weighted imaging in neuroscience, presents its limitations and proposes new challenges for future generations who may wish to exploit this powerful technology to gain novel insights.
The D50N mutation and syndromic deafness: altered Cx26 hemichannel properties caused by effects on the pore and intersubunit interactions.
The Journal of general physiology, 2013

Mutations in the GJB2 gene, which encodes Cx26, are the most common cause of sensorineural deafness. In syndromic cases, such as keratitis-ichthyosis-deafness (KID) syndrome, in which deafness is accompanied by corneal inflammation and hyperkeratotic skin, aberrant hemichannel function has emerged as the leading contributing factor. We found that D50N, the most frequent mutation associated with KID syndrome, produces multiple aberrant hemichannel properties, including loss of inhibition by extracellular Ca(2+), decreased unitary conductance, increased open hemichannel current rectification and voltage-shifted activation. We demonstrate that D50 is a pore-lining residue and that negative charge at this position strongly influences open hemichannel properties. Examination of two putative intersubunit interactions involving D50 suggested by the Cx26 crystal structure, K61-D50 and Q48-D50, showed no evidence of a K61-D50 interaction in hemichannels. However, our data suggest that Q48 and D50 interact and disruption of this interaction shifts hemichannel activation positive along the voltage axis. Additional shifts in activation by extracellular Ca(2+) remained in the absence of a D50-Q48 interaction but required an Asp or Glu at position 50, suggesting a separate electrostatic mechanism that critically involves this position. In gap junction (GJ) channels, D50 substitutions produced loss of function, whereas K61 substitutions functioned as GJ channels but not as hemichannels. These data demonstrate that D50 exerts effects on Cx26 hemichannel and GJ channel function as a result of its dual role as a pore residue and a component of an intersubunit complex in the extracellular region of the hemichannel. Differences in the effects of substitutions in GJ channels and hemichannels suggest that perturbations in structure occur upon hemichannel docking that significantly impact function. Collectively, these data provide insight into Cx26 structure-function and the underlying bases for the phenotypes associated with KID syndrome patients carrying the D50N mutation.
Bidirectional regulation of the cAMP response element binding protein encodes spatial map alignment in prism-adapting barn owls.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

The barn owl midbrain contains mutually aligned maps of auditory and visual space. Throughout life, map alignment is maintained through the actions of an instructive signal that encodes the magnitude of auditory-visual mismatch. The intracellular signaling pathways activated by this signal are unknown. Here we tested the hypothesis that CREB (cAMP response element-binding protein) provides a cell-specific readout of instructive information. Owls were fitted with prismatic or control spectacles and provided rich auditory-visual experience: hunting live mice. CREB activation was analyzed within 30 min of hunting using phosphorylation state-specific CREB (pCREB) and CREB antibodies, confocal imaging, and immunofluorescence measurements at individual cell nuclei. In control owls or prism-adapted owls, which experience small instructive signals, the frequency distributions of pCREB/CREB values obtained for cell nuclei within the external nucleus of the inferior colliculus (ICX) were unimodal. In contrast, in owls adapting to prisms or readapting to normal conditions, the distributions were bimodal: certain cells had received a signal that positively regulated CREB and, by extension, transcription of CREB-dependent genes, whereas others received a signal that negatively regulated it. These changes were restricted to the subregion of the inferior colliculus that received optically displaced input, the rostral ICX, and were not evident in the caudal ICX or central nucleus. Finally, the topographic pattern of CREB regulation was patchy, not continuous, as expected from the actions of a topographically precise signal encoding discrete events. These results support a model in which the magnitude of CREB activation within individual cells provides a readout of the instructive signal that guides plasticity and learning.
Optogenetic stimulation of astrocytes in the posterior hypothalamus increases sleep at night in C57BL/6J mice.
The European journal of neuroscience, 2016

A distributed network of neurons regulates wake, non-rapid eye movement (NREM) sleep, and REM sleep. However, there are also glia in the brain, and there is growing evidence that neurons and astroglia communicate intimately to regulate behaviour. To identify the effect of optogenetic stimulation of astrocytes on sleep, the promoter for the astrocyte-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP) was used to direct the expression of channelrhodopsin-2 (ChR2) and the linked reporter gene, enhanced yellow fluorescent protein (EYFP), in astrocytes. rAAV-GFAP-ChR2 (H134R)-EYFP or rAAV-GFAP-EYFP was microinjected (750 nL) into the posterior hypothalamus (bilateral) of mice. Three weeks later baseline sleep was recorded (0 Hz) and 24 h later optogenetic stimulation applied during the first 6 h of the lights-off period. Mice with ChR2 were given 5, 10 or 30 Hz stimulation for 6 h (10-ms pulses; 1 mW; 1 min on 4 min off). At least 36 h elapsed between the stimulation periods (5, 10, 30 Hz) and although 0 Hz was always first, the order of the other three stimulation rates was randomised. In mice with ChR2 (n = 7), 10 Hz, but not 5 or 30 Hz stimulation increased both NREM and REM sleep during the 6-h period of stimulation. Delta power did not increase. In control mice (no ChR2; n = 5), 10 Hz stimulation had no effect. This study demonstrates that direct stimulation of astrocytes powerfully induces sleep during the active phase of the sleep-wake cycle and underlines the inclusion of astrocytes in network models of sleep-wake regulation.
The impact of surgery for lower urinary tract symptoms/benign prostatic enlargement on both erectile and ejaculatory function: a systematic review.
International journal of impotence research, 2019

We performed a systematic review of studies evaluating the impact of surgery for lower urinary tract symptoms suggestive of benign prostate enlargement (LUTS/BPE) on both erectile and ejaculatory functions. In June 2018, we searched for randomized controlled trials (RCTs) published between 1998 and 2018 in which both functions were assessed using questionnaires. Overall, 15 studies were identified. Pre-operatively, mean International Index of Erectile Function -5 (IIEF-5) and mean IIEF-Erectile Function (EF) scores ranged from 13.3 to 20.8, and from 13.7 to 22.3, respectively. At follow-up evaluations, mean IIEF-5 and mean IIEF-EF scores did not significantly vary (13.4 to 20.7 and 14.4 to 24.3, respectively). Mean baseline Male Sexual Health Questionnaire- Ejaculatory Disease function score at baseline and follow-up evaluations ranged from 8.7 to 10.6, and from 4.9 to 11.9, respectively. Ejaculatory function significantly worsened in three studies after transurethral resection of the prostate and significantly improved in 2 studies after prostate urethral lift implant. In conclusions, available RCTs evaluating both erectile and ejaculatory functions after surgical procedures for LUTS/BPE fail to demonstrate significant variations in terms of erectile function scores while providing significant variations of ejaculatory function scores that are heterogeneous depending on the procedure adopted.
Optic nerve sheath diameter ultrasonography at admission as a predictor of intracranial hypertension in traumatic brain injured patients: a prospective observational study.
Journal of neurosurgery, 2020

Intracranial hypertension and impaired cerebral autoregulation are common causes of secondary injuries in patients with traumatic brain injury (TBI). The primary outcome of this study was to assess whether a noninvasive method to estimate intracranial pressure (ICP) based on the ultrasonography of the optic nerve sheath diameter (ONSD) measured at the time of neurocritical care unit (NCCU) admission is correlated with the mean ICP during NCCU stay. Secondary outcomes were to assess whether ONSD is correlated with the dose of ICP > 20 mm Hg and impaired autoregulation during NCCU stay and with instantaneous ICP and whether ONSD is associated with NCCU mortality.
A specialized molecular motion opens the Hv1 voltage-gated proton channel.
Nature structural & molecular biology, 2015

The Hv1 proton channel is unique among voltage-gated channels for containing the pore and gate within its voltage-sensing domain. Pore opening has been proposed to include assembly of the selectivity filter between an arginine (R3) of segment S4 and an aspartate (D1) of segment S1. We determined whether gating involves motion of S1, using Ciona intestinalis Hv1. We found that channel opening is concomitant with solution access to the pore-lining face of S1, from the cytoplasm to deep inside the pore. Voltage- and patch-clamp fluorometry showed that this involves a motion of S1 relative to its surroundings. S1 motion and the S4 motion that precedes it are each influenced by residues on the other helix, thus suggesting a dynamic interaction between S1 and S4. Our findings suggest that the S1 of Hv1 has specialized to function as part of the channel's gate.
Presynaptic inhibition of spinal sensory feedback ensures smooth movement.
Nature, 2014

The precision of skilled movement depends on sensory feedback and its refinement by local inhibitory microcircuits. One specialized set of spinal GABAergic interneurons forms axo-axonic contacts with the central terminals of sensory afferents, exerting presynaptic inhibitory control over sensory-motor transmission. The inability to achieve selective access to the GABAergic neurons responsible for this unorthodox inhibitory mechanism has left unresolved the contribution of presynaptic inhibition to motor behaviour. We used Gad2 as a genetic entry point to manipulate the interneurons that contact sensory terminals, and show that activation of these interneurons in mice elicits the defining physiological characteristics of presynaptic inhibition. Selective genetic ablation of Gad2-expressing interneurons severely perturbs goal-directed reaching movements, uncovering a pronounced and stereotypic forelimb motor oscillation, the core features of which are captured by modelling the consequences of sensory feedback at high gain. Our findings define the neural substrate of a genetically hardwired gain control system crucial for the smooth execution of movement.
Psychological treatments for people with epilepsy.
The Cochrane database of systematic reviews, 2017

Given the significant impact epilepsy can have on the health-related quality of life (HRQoL) of individuals with epilepsy and their families, there is great clinical interest in evidence-based psychological treatments, aimed at enhancing psychological well-being in people with epilepsy. A review of the current evidence was needed to assess the effects of psychological treatments for people with epilepsy on HRQoL outcomes, in order to inform future therapeutic recommendations and research designs.