rudyvdbrink/CitationDatabase huggingface dataset:
Ile258Met mutation of Brucella melitensis 7α-hydroxysteroid dehydrogenase significantly enhances catalytic efficiency, cofactor affinity, and thermostability.
Applied microbiology and biotechnology, 2021

NAD(H)-dependent 7α-hydroxysteroid dehydrogenase catalyzes the oxidation of chenodeoxycholic acid to 7-oxolithocholic acid. Here, we designed mutations of Ile258 adjacent to the catalytic pocket of Brucella melitensis 7α-hydroxysteroid dehydrogenase. The I258M variant gave a 4.7-fold higher k
Antineuroinflammatory Activities and Neurotoxicological Assessment of Curcumin Loaded Solid Lipid Nanoparticles on LPS-Stimulated BV-2 Microglia Cell Models.
Molecules (Basel, Switzerland), 2019

Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the blood⁻brain barrier and its rapid metabolism during circulation, which decreases its efficacy in treating chronic neuroinflammatory diseases in the central nervous system. The bioavailability and potential of curcumin can be improved by using a nanodelivery system, which includes solid lipid nanoparticles. Curcumin-loaded solid lipid nanoparticles (SLCN) were efficiently developed to have a particle size of about 86 nm and do not exhibit any toxicity in the endothelial brain cells. Furthermore, the curcumin-loaded solid lipid nanoparticles (SLCN) were studied to assess their efficacy in BV-2 microglial cells against LPS-induced neuroinflammation. The SLCN showed a higher inhibition of nitric oxide (NO) production compared to conventional curcumin in a dose-dependent manner. Similarly, the mRNA and proinflammatory cytokine levels were also reduced in a dose-dependent manner when compared to those with free curcumin. Thus, SLCN could be a potential delivery system for curcumin to treat microglia-mediated neuroinflammation.
Self-motion leads to mandatory cue fusion across sensory modalities.
Journal of neurophysiology, 2012

When perceiving properties of the world, we effortlessly combine multiple sensory cues into optimal estimates. Estimates derived from the individual cues are generally retained once the multisensory estimate is produced and discarded only if the cues stem from the same sensory modality (i.e., mandatory fusion). Does multisensory integration differ in that respect when the object of perception is one's own body, rather than an external variable? We quantified how humans combine visual and vestibular information for perceiving own-body rotations and specifically tested whether such idiothetic cues are subjected to mandatory fusion. Participants made extensive size comparisons between successive whole body rotations using only visual, only vestibular, and both senses together. Probabilistic descriptions of the subjects' perceptual estimates were compared with a Bayes-optimal integration model. Similarity between model predictions and experimental data echoed a statistically optimal mechanism of multisensory integration. Most importantly, size discrimination data for rotations composed of both stimuli was best accounted for by a model in which only the bimodal estimator is accessible for perceptual judgments as opposed to an independent or additive use of all three estimators (visual, vestibular, and bimodal). Indeed, subjects' thresholds for detecting two multisensory rotations as different from one another were, in pertinent cases, larger than those measured using either single-cue estimate alone. Rotations different in terms of the individual visual and vestibular inputs but quasi-identical in terms of the integrated bimodal estimate became perceptual metamers. This reveals an exceptional case of mandatory fusion of cues stemming from two different sensory modalities.
Spontaneous ocular positioning during visual imagery in patients with hemianopia and/or hemineglect.
Neuropsychologia, 2016

Spontaneous eye movements during imagery are not random and can be used to study and reveal mental visualization processes (Fourtassi et al., 2013; Johansson et al. 2006). For example, we previously showed that during memory recall of French towns via imagery healthy individuals looks straight ahead when recalling Paris and their subsequent gaze positions are significantly correlated with the real GPS coordinates of the recalled towns. This correlation suggests that memory retrieval is done via depictive representations as it is never found when the towns are recalled using verbal fluency. In the present paper we added to this finding by showing that the mental image is spontaneously centered on the head or body midline. In order to investigate the capacities of visual imagery in patients, and by extension, the role of primary visual cortex and fronto-parietal cortex in spatial visual imagery, we recorded gaze positions during memory recall of French towns in an imagery task, a non-imagery task (verbal fluency), and a visually-guided task in five patients with left or right hemianopia and in four patients with hemineglect (two with left hemianopia and two without). The correlation between gaze position and real GPS coordinates of the recalled towns was significant in all hemianopic patients, but in patients with hemineglect this was only the case for towns located on the right half of the map of France. This suggests hemianopic patients can perform spatially consistent mental imagery despite direct or indirect unilateral lesions of the primary visual cortex. In contrast, the left-sided towns recalled by hemineglect patients, revealed that they have some spatial inconsistency or representational difficulty. Hemianopic patients positioned and maintained their gaze in their contralesional hemispace, suggesting that their mental map was not centered on their head or body midline. This contralesional gaze positioning appeared to be a general compensation strategy and was not observed in patients with neglect (with or without hemianopia). Instead, neglect patients positioned their gaze in their ipsilesional hemispace and only when performing the visual imagery task. These findings are discussed in the context of the role of occipital and fronto-parietal cortices in the neuroanatomical model of visual imagery developed by Kosslyn et al. (2006).
Gap junctions in the ventral hippocampal-medial prefrontal pathway are involved in anxiety regulation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Anxiety disorders are highly prevalent but little is known about their underlying mechanisms. Gap junctions exist in brain regions important for anxiety regulation, such as the ventral hippocampus (vHIP) and mPFC, but their functions in these areas have not been investigated. Using pharmacological blockade of neuronal gap junctions combined with electrophysiological recordings, we found that gap junctions play a role in theta rhythm in the vHIP and mPFC of adult mice. Bilateral infusion of neuronal gap junction blockers into the vHIP decreased anxiety-like behavior on the elevated plus maze and open field. Similar anxiolytic effects were observed with unilateral infusion of these drugs into the vHIP combined with contralateral infusion into the mPFC. No change in anxious behavior was observed with gap junction blockade in the unilateral vHIP alone or in the bilateral dorsal HIP. Since physical exercise is known to reduce anxiety, we examined the effects of long-term running on the expression of the neuronal gap junction protein connexin-36 among inhibitory interneurons and found a reduction in the vHIP. Despite this change, we observed no alteration in theta frequency or power in long-term runners. Collectively, these findings suggest that neuronal gap junctions in the vHIP-mPFC pathway are important for theta rhythm and anxiety regulation under sedentary conditions but that additional mechanisms are likely involved in running-induced reduction in anxiety.
Joint contact forces when minimizing the external knee adduction moment by gait modification: A computer simulation study.
The Knee, 2015

Gait modification is often used to reduce the external knee adduction moment (KAM) in human walking, but the relationship between KAM reduction and changes in medial knee joint contact force (JCF) is not well established. Our purpose was to examine the limiting case of KAM-based gait modification: reducing the KAM as much as possible, and the resulting effects on JCF.
The effect of bodily illusions on clinical pain: a systematic review and meta-analysis.
Pain, 2016

This systematic review and meta-analysis critically examined the evidence for bodily illusions to modulate pain. Six databases were searched; 2 independent reviewers completed study inclusion, risk of bias assessment, and data extraction. Included studies evaluated the effect of a bodily illusion on pain, comparing results with a control group/condition. Of the 2213 studies identified, 20 studies (21 experiments) were included. Risk of bias was high due to selection bias and lack of blinding. Consistent evidence of pain decrease was found for illusions of the existence of a body part (myoelectric/Sauerbruch prosthesis vs cosmetic/no prosthesis; standardized mean differences = -1.84, 95% CI = -2.67 to -1.00) and 4 to 6 weeks of mirror therapy (standardized mean differences = -1.11, 95% CI = -1.66 to -0.56). Bodily resizing illusions had consistent evidence of pain modulation (in the direction hypothesized). Pooled data found no effect on pain for 1 session of mirror therapy or for incongruent movement illusions (except for comparisons with congruent mirrored movements: incongruent movement illusion significantly increased the odds of experiencing pain). Conflicting results were found for virtual walking illusions (both active and inactive control comparisons). Single studies suggest no effect of resizing illusions on pain evoked by noxious stimuli, no effect of embodiment illusions, but a significant pain decrease with synchronous mirrored stroking in nonresponders to traditional mirror therapy. There is limited evidence to suggest that bodily illusions can alter pain, but some illusions, namely mirror therapy, bodily resizing, and use of functional prostheses show therapeutic promise.
Dynamics of ten-eleven translocation hydroxylase family proteins and 5-hydroxymethylcytosine in oligodendrocyte differentiation.
Glia, 2014

The ten-eleven translocation (TET) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and TET proteins in the brain, little is known about their role in oligodendrocytes (OLs). Here, we analyzed TET expression during OL development in vivo and in vitro, and found that three TET family members possess unique subcellular and temporal expression patterns. Furthermore, the level of 5hmC exhibits dynamic changes during OL maturation, which implies that 5hmC modification may play a role in the expression of critical genes necessary for OL maturation. siRNA-mediated silencing of the TET family proteins in OLs demonstrated that each of the TET proteins is required for OL differentiation. However, based on their unique domain structures, we speculate that the three TET members may function by different mechanisms. In summary, we have established the temporal expression of TET proteins and the dynamic level of 5hmC during OL development and demonstrate that all three TET members are necessary for OL differentiation.
Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain.
Proceedings of the National Academy of Sciences of the United States of America, 2016

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.
Neuronal nitric oxide synthase localizes to utrophin expressing intercalated discs and stabilizes their structural integrity.
Neuromuscular disorders : NMD, 2015

The neuronal nitric-oxide synthase (nNOS) splice variant nNOSµ is essential for skeletal muscle function. Its localization is dependent on dystrophin, which stabilizes the dystrophin glycoprotein complex (DGC) at the sarcolemma of skeletal muscle fibers. In Duchenne muscular dystrophy (DMD) dystrophin is absent and sarcolemmal nNOS is lost. This leads to functional ischemia due to a decrease in contraction-induced vasodilation. In cardiomyocytes, nNOSµ is believed to be the predominant NOS isoform. However, the association of nNOS with the DGC in the heart is unclear. Here, we report nNOS localization at the intercalated discs (IDs) of cardiomyocytes, where utrophin is highly expressed. In mdx, mdx:utr, nNOSµ knock-out (KO), and mdx:nNOSµ KO mice, we observed a gradual reduction of nNOS at IDs and disrupted ID morphology, compared to wild-type. In mdx:nNOSµ KO mice, but not in mdx or nNOSµ KO mice, we also observed an early development of cardiac fibrosis. These findings suggest that nNOS localization in the heart may not depend exclusively on the presence of dystrophin. Additionally, the β1 subunit of soluble guanylyl cyclase (sGC), responsible for the production of cGMP through nitric oxide (NO) signaling, was also detected at the IDs. Together, our results suggest a new role of nNOS at the IDs for the cGMP-dependent NO pathway and the maintenance of ID morphology.
The function of α-synuclein.
Neuron, 2013

Human genetics has indicated a causal role for the protein α-synuclein in the pathogenesis of familial Parkinson's disease (PD), and the aggregation of synuclein in essentially all patients with PD suggests a central role for this protein in the sporadic disorder. Indeed, the accumulation of misfolded α-synuclein now defines multiple forms of neural degeneration. Like many of the proteins that accumulate in other neurodegenerative disorders, however, the normal function of synuclein remains poorly understood. In this article, we review the role of synuclein at the nerve terminal and in membrane remodeling. We also consider the prion-like propagation of misfolded synuclein as a mechanism for the spread of degeneration through the neuraxis.
Structural Network Disorganization in Subjects at Clinical High Risk for Psychosis.
Schizophrenia bulletin, 2017

Previous network studies in chronic schizophrenia patients revealed impaired structural organization of the brain's rich-club members, a set of highly interconnected hub regions that play an important integrative role for global brain communication. Moreover, impaired rich-club connectivity has also been found in unaffected siblings of schizophrenia patients, suggesting that abnormal rich-club connectivity is related to familiar, possibly reflecting genetic, vulnerability for schizophrenia. However, no study has yet investigated whether structural rich-club organization is also impaired in individuals with a clinical risk syndrome for psychosis. Diffusion tensor imaging and probabilistic tractography was used to construct structural whole-brain networks in 24 healthy controls and 24 subjects with an at-risk mental state (ARMS). Graph theory was applied to quantify the structural rich-club organization and global network properties. ARMS subjects revealed a significantly altered structural rich-club organization compared with the control group. The disruption of rich-club organization was associated with the severity of negative psychotic symptoms and led to an elevated level of modularity in ARMS subjects. This study shows that abnormal structural rich-club organization is already evident in clinical high-risk subjects for psychosis and further demonstrates the impact of rich-club disorganization on global network communication. Together with previous evidence in chronic schizophrenia patients and unaffected siblings, our findings suggest that abnormal structural rich-club organization may reflect an endophenotypic marker of psychosis.
Neurological Deficits in Obstructive Sleep Apnea.
Current treatment options in neurology, 2017

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder characterized by repetitive episodes of complete or partial obstruction of the upper airway. The prevalence of this disorder is strictly dependent on its gravity. At ≥15 events/h apnea-hypopnea index (AHI), it ranges from 6 to 17% in the general population, with higher rates in men and increasing with age. The hypoxia induced by OSA severely affects the structure and function of blood vessels, culminating in mortality and morbidity. Its negative impact influences also cognitive functioning. Recent papers showed the relationship between OSA and some neurological disorders, such as neurodegenerative diseases, stroke, epilepsy, and headache. OSA may accelerate the onset of mild cognitive impairment and Alzheimer's disease (AD) and might also represent an independent risk factor for Parkinson's disease (PD). OSA is also frequent in multisystem atrophy. In the early stages of AD, continuous positive airway pressure (CPAP) treatment might slow down the progression of the disease, thus highlighting the potential importance of OSA screening and a timely intervention in these patients. Moreover, CPAP is effective in reducing daytime sleepiness in PD. OSA may induce seizures by means of sleep disruption and deprivation, as well as cerebral hypoxemia with consequent oxidative stress. It has been demonstrated that CPAP treatment is efficacious in controlling epileptic seizures. OSA can represent a risk factor for stroke and death, mainly related to the endothelial dysfunction, with the formation of atherosclerosis caused by hypoxia through oxidative stress. CPAP treatment in patients with OSA and stroke, if delivered in the early stages, is able to increase the magnitude of neurologic improvement after the vascular accident. There is a strong association between OSA and headache. In particular, there is a "sleep apnea headache" described as a recurrent morning headache, with resolution after effective treatment of sleep apnea. This review clearly shows the importance of taking a sleep history in neurological patients and considering the diagnosis and specific treatment of OSA in these patients.
Working memory training and perceptual discrimination training impact overlapping and distinct neurocognitive processes: Evidence from event-related potentials and transfer of training gains.
Cognition, 2019

There is emerging evidence that working memory (WM) can potentially be enhanced via targeted training protocols. However, the differential effects of targeted training of WM vs. training of general attentional processes on distinct neurocognitive mechanisms is not well understood. In the present study, we compared adaptive n-back WM training to an adaptive visual search training task that targeted perceptual discrimination, in the absence of demands on WM. The search task was closely matched to the n-back task on difficulty and participant engagement. The training duration for both protocols was 20 sessions over approximately 4 weeks. Before and after training, young adult participants were tested on a battery of cognitive tasks to examine transfer of training gains to untrained tests of WM, processing speed, cognitive control, and fluid intelligence. Event-related brain potential (ERP) measures obtained during a Letter 3-Back task and a Search task were examined to determine the neural processes that were affected by each training protocol. Both groups improved on measures of cognitive control and fluid intelligence at post- compared to pretest. However, n-back training resulted in more pronounced transfer effects to tasks involving WM compared to search training. With respect to ERPs, both groups exhibited enhancement of P3 amplitude following training, but distinct changes in neural responses were also observed for the two training protocols. The search training group exhibited earlier ERP latencies at post- compared to pretest on the Search task, indicating generalized improvement in processing speed. The n-back group exhibited a pronounced enhancement and earlier latency of the N2 ERP component on the Letter 3-back task, following training. Given the theoretical underpinnings of the N2, this finding was interpreted as an enhancement of conflict monitoring and sequential mismatch identification. The findings provide evidence that n-back training enhances distinct neural processes underlying executive aspects of WM.
Imbalance between firing homeostasis and synaptic plasticity drives early-phase Alzheimer's disease.
Nature neuroscience, 2018

During recent years, the preclinical stage of Alzheimer's disease (AD) has become a major focus of research. Continued failures in clinical trials and the realization that early intervention may offer better therapeutic outcome triggered a conceptual shift from late-stage AD pathology to early-stage pathophysiology. While much effort has been directed at understanding the factors initiating AD, little is known about the principle basis underlying the disease progression at its early stages. In this Perspective, we suggest a hypothesis to explain the transition from 'silent' signatures of aberrant neural circuit activity to clinically evident memory impairments. Namely, we propose that failures in firing homeostasis and imbalance between firing stability and synaptic plasticity in cortico-hippocampal circuits represent the driving force of early disease progression. We analyze the main types of possible homeostatic failures and provide the essential conceptual framework for examining the causal link between dysregulation of firing homeostasis, aberrant neural circuit activity and memory-related plasticity impairments associated with early AD.