rudyvdbrink/CitationDatabase huggingface dataset:
CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies.
Molecular psychiatry, 2016

Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (CNS) is unknown. Here we show that CNS-derived HIV-1 strains possess polymorphisms within and surrounding the Sp transcription factor motifs in the long terminal repeat (LTR). These polymorphisms result in decreased ability of the transcription factor specificity protein 1 to bind CNS-derived LTRs, reducing the transcriptional activity of CNS-derived viruses. These mutations result in CNS-derived viruses being less responsive to activation by the HDACi panobinostat and romidepsin compared with lymphoid-derived viruses from the same subjects. Our findings suggest that HIV-1 strains residing in the CNS have unique transcriptional regulatory mechanisms, which impact the regulation of latency, the consideration of which is essential for the development of HIV-1 eradication strategies.
Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells.
ASN neuro, 2010

AD (Alzheimer's disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Aβs. Several reports have documented the bifunctional roles of Aβs in NSCs (neural stem cells), but the precise effects of G(M1) and Aβ on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Aβ-(1-40) on mouse NECs (neuroepithelial cells), which are known to be rich in NSCs. No change of cell number was detected in NECs cultured in the presence of either G(M1) or Aβ-(1-40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Aβ-(1-40). The exogenously added G(M1) and Aβ-(1-40) were confirmed to incorporate into NECs. The Ras-MAPK (mitogen-activated protein kinase) pathway, important for cell proliferation, was intact in NECs simultaneously treated with G(M1) and Aβ-(1-40), but caspase 3 was activated. NECs treated with G(M1) and Aβ-(1-40) were positive in the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, an indicator of cell death. It was found that G(M1) and Aβ-(1-40) interacted in the presence of cholesterol and sphingomyelin, components of cell surface microdomains. The cytotoxic effect was found also in NSCs prepared via neurospheres. These results indicate that Aβ-(1-40) and G(M1) co-operatively exert a cytotoxic effect on NSCs, likely via incorporation into NEC membranes, where they form a complex for the activation of cell death signalling.
Soft tissue rheology and its implications for elastography: Challenges and opportunities.
NMR in biomedicine, 2018

Magnetic resonance elastography and related shear wave ultrasound elastography techniques can be used to estimate the mechanical properties of soft tissues in vivo by using the relationships between wave propagation and the elastic properties of materials. These techniques have found numerous clinical and research applications, tracking changes in tissue properties as a result of disease or other interventions. Most dynamic elastography approaches estimate tissue elastic (or viscoelastic) properties from a simplified version of the equations for the propagation of acoustic waves through a homogeneous linear (visco)elastic medium. However, soft tissue rheology is complex and departs significantly from this idealized picture. In particular, soft tissues are nonlinearly viscoelastic, inhomogeneous and often anisotropic, and their apparent stiffness can vary with the current loading state. All of these features have implications for the reliability and reproducibility of elastography measurements, from data acquisition to analysis and interpretation. New developments in inversion algorithms for elastography are beginning to offer solutions to account for the complex rheology of tissues, including inhomogeneity and anisotropy. There remains considerable potential to further refine elastography to capture the full spectrum of tissue rheology, and thus to better understand the underlying tissue microstructural changes in a broad range of clinical disorders.
Diverse patterns of odor representation by neurons in the anterior piriform cortex of awake mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

The mammalian piriform cortex receives direct synaptic input from the olfactory bulb and is likely the locus for the formation of odor percept. It remains unclear how individual cortical neurons encode olfactory information in unanesthetized animals. By single-cell recordings from head-restrained awake mice, we studied the odor response profiles of individual neurons in the anterior piriform cortex (aPCX). Neurons were juxtacellularly labeled, and their cell types were determined by their morphology and neurotransmitter phenotypes. We found a considerable level of variability in selectivity patterns among pyramidal neurons (PNs). Approximately one-quarter of PNs were broadly activated by structurally dissimilar odorants, whereas the excitations to the rest of PNs were highly selective. Broad inhibition was only observed from a subpopulation of PNs. GABAergic neurons displayed nonselective excitatory responses to test odorants and rarely exhibited inhibition. In contrast, non-GABAergic nonpyramidal neurons in the deep layer tended to be strongly inhibited by multiple different odorants. Our findings suggest that odor representation is accomplished by both broadly tuned and narrow-tuned PNs in the aPCX of awake animals. In addition, various types of interneurons may play different roles in the intracortical processing of olfactory information.
Differential modulation of the oligodendrocyte transcriptome by sonic hedgehog and bone morphogenetic protein 4 via opposing effects on histone acetylation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is regulated by the interplay between extrinsic signals and intrinsic epigenetic determinants. In this study, we analyze the effect that the extracellular ligands sonic hedgehog (Shh) and bone morphogenetic protein 4 (BMP4), have on histone acetylation and gene expression in cultured OPCs. Shh treatment favored the progression toward oligodendrocytes by decreasing histone acetylation and inducing peripheral chromatin condensation. BMP4 treatment, in contrast, inhibited the progression toward oligodendrocytes and favored astrogliogenesis by favoring global histone acetylation and retaining euchromatin. Pharmacological treatment or silencing of histone deacetylase 1 (Hdac1) or histone deacetylase 2 (Hdac2) in OPCs did not affect BMP4-dependent astrogliogenesis, while it prevented Shh-induced oligodendrocyte differentiation and favored the expression of astrocytic genes. Transcriptional profiling of treated OPCs, revealed that BMP4-inhibition of oligodendrocyte differentiation was accompanied by increased levels of Wnt (Tbx3) and Notch-target genes (Jag1, Hes1, Hes5, Hey1, and Hey2), decreased recruitment of Hdac and increased histone acetylation at these loci. Similar upregulation of Notch-target genes and increased histone acetylation were observed in the corpus callosum of mice infused with BMP4 during cuprizone-induced demyelination. We conclude that Shh and Bmp4 differentially regulate histone acetylation and chromatin structure in OPCs and that BMP4 acts as a potent inducer of gene expression, including Notch and Wnt target genes, thereby enhancing the crosstalk among signaling pathways that are known to inhibit myelination and repair.
Does sleep restore the topology of functional brain networks?
Human brain mapping, 2013

Previous studies have shown that healthy anatomical as well as functional brain networks have small-world properties and become less optimal with brain disease. During sleep, the functional brain network becomes more small-world-like. Here we test the hypothesis that the functional brain network during wakefulness becomes less optimal after sleep deprivation (SD). Electroencephalography (EEG) was recorded five times a day after a night of SD and after a night of normal sleep in eight young healthy subjects, both during eyes-closed and eyes-open resting state. Overall synchronization was determined with the synchronization likelihood (SL) and the phase lag index (PLI). From these coupling strength matrices the normalized clustering coefficient C (a measurement of local clustering) and path length L (a measurement of global integration) were computed. Both measures were normalized by dividing them by their corresponding C-s and L-s values of random control networks. SD reduced alpha band C/C-s and L/L-s and theta band C/C-s during eyes-closed resting state. In contrast, SD increased gamma-band C/C-s and L/L-s during eyes-open resting state. Functional relevance of these changes in network properties was suggested by their association with sleep deprivation-induced performance deficits on a sustained attention simple reaction time task. The findings indicate that SD results in a more random network of alpha-coupling and a more ordered network of gamma-coupling. The present study shows that SD induces frequency-specific changes in the functional network topology of the brain, supporting the idea that sleep plays a role in the maintenance of an optimal functional network.
Proper Emotion Recognition, Dysfunctional Emotion Regulation.
Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie, 2018

A considerable number of adolescents exhibit severe self-regulation deficits in affect and behavior, which are referred to as affective dysregulation (AD). AD may be conceptualized as a dimensional trait that, in its extreme form, resembles the diagnostic categories of severe mood dysregulation (SMD) or disruptive mood dysregulation disorder (DMDD). Assuming a shared pathway of psychopathology in AD and SMD, similar underlying dysfunctional mechanisms in emotion processing, particularly emotion recognition (RECOG) and regulation (REGUL), may be postulated.
Glia instruct developmental neuronal remodeling through TGF-β signaling.
Nature neuroscience, 2011

We found that glia secrete myoglianin, a TGF-β ligand, to instruct developmental neural remodeling in Drosophila. Glial myoglianin upregulated neuronal expression of an ecdysone nuclear receptor that triggered neurite remodeling following the late-larval ecdysone peak. Thus glia orchestrate developmental neural remodeling not only by engulfment of unwanted neurites but also by enabling neuron remodeling.
Electrical Stimulation of Visual Cortex Can Immediately Improve Spatial Vision.
Current biology : CB, 2016

We can improve human vision by correcting the optics of our lenses [1-3]. However, after the eye transduces the light, visual cortex has its own limitations that are challenging to correct [4]. Overcoming these limitations has typically involved innovative training regimes that improve vision across many days [5, 6]. In the present study, we wanted to determine whether it is possible to immediately improve the precision of spatial vision with noninvasive direct-current stimulation. Previous work suggested that visual processing could be modulated with such stimulation [7-9]. However, the short duration and variability of such effects made it seem unlikely that spatial vision could be improved for more than several minutes [7, 10]. Here we show that visual acuity in the parafoveal belt can be immediately improved by delivering noninvasive direct current to visual cortex. Twenty minutes of anodal stimulation improved subjects' vernier acuity by approximately 15% and increased the amplitude of the earliest visually evoked potentials in lockstep with the behavioral effects. When we reversed the orientation of the electric field, we impaired resolution and reduced the amplitude of visually evoked potentials. Next, we found that anodal stimulation improved acuity enough to be measurable with the relatively coarse Snellen test and that subjects with the poorest acuity benefited the most from stimulation. Finally, we found that stimulation-induced acuity improvements were accompanied by changes in contrast sensitivity at high spatial frequencies.
Ultrafast Glutamate Biosensor Recordings in Brain Slices Reveal Complex Single Exocytosis Transients.
ACS chemical neuroscience, 2019

Neuronal communication relies on vesicular neurotransmitter release from signaling neurons and detection of these molecules by neighboring neurons. Glutamate, the main excitatory neurotransmitter in the mammalian brain, is involved in nearly all brain functions. However, glutamate has suffered from detection schemes that lack temporal and spatial resolution allowed by electrochemistry. Here we show an amperometric, novel, ultrafast enzyme-based nanoparticle modified sensor, measuring random bursts of hundreds to thousands of rapid spontaneous glutamate exocytotic release events at approximately 30 Hz frequency in the nucleus accumbens of rodent brain slices. Characterizing these single submillisecond exocytosis events revealed a great diversity in spike shape characteristics and size of quantal release, suggesting variability in fusion pore dynamics controlling the glutamate release by cells in this brain region. Hence, this novel biosensor allows recording of rapid single glutamate exocytosis events in the brain tissue and offers insight on regulatory aspects of exocytotic glutamate release, which is critical to understanding of brain glutamate function and dysfunction.
Cloning and functional expression of a human orthologue of rat vanilloid receptor-1.
Pain, 2000

Capsaicin, resiniferatoxin, protons or heat have been shown to activate an ion channel, termed the rat vanilloid receptor-1 (rVR1), originally isolated by expression cloning for a capsaicin sensitive phenotype. Here we describe the cloning of a human vanilloid receptor-1 (hVR1) cDNA containing a 2517 bp open reading frame that encodes a protein with 92% homology to the rat vanilloid receptor-1. Oocytes or mammalian cells expressing this cDNA respond to capsaicin, pH and temperature by generating inward membrane currents. Mammalian cells transfected with human VR1 respond to capsaicin with an increase in intracellular calcium. The human VR1 has a chromosomal location of 17p13 and is expressed in human dorsal root ganglia and also at low levels throughout a wide range of CNS and peripheral tissues. Together the sequence homology, similar expression profile and functional properties confirm that the cloned cDNA represents the human orthologue of rat VR1.
Multiple sclerosis: distribution of inflammatory cells in newly forming lesions.
Annals of neurology, 2009

CD4 T-cell-dependent macrophage activation directed against a myelin or oligodendrocyte antigen is generally thought to be the mechanism causing myelin destruction in multiple sclerosis (MS). However, areas within expanding MS lesions may exhibit prominent oligodendrocyte loss and apoptosis in the absence of infiltrating lymphocytes. The present study was designed to further investigate the inflammatory profile of different regions within rapidly expanding MS lesions.
Hyperlipidemic diet causes loss of olfactory sensory neurons, reduces olfactory discrimination, and disrupts odor-reversal learning.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Currently, 65% of Americans are overweight, which leads to well-supported cardiovascular and cognitive declines. Little, however, is known concerning obesity's impact on sensory systems. Because olfaction is linked with ingestive behavior to guide food choice, its potential dysfunction during obesity could evoke a positive feedback loop to perpetuate poor ingestive behaviors. To determine the effect of chronic energy imbalance and reveal any structural or functional changes associated with obesity, we induced long-term, diet-induced obesity by challenging mice to high-fat diets: (1) in an obesity-prone (C57BL/6J) and obesity-resistant (Kv1.3(-/-)) line of mice, and compared this with (2) late-onset, genetic-induced obesity in MC4R(-/-) mice in which diabetes secondarily precipitates after disruption of the hypothalamic axis. We report marked loss of olfactory sensory neurons and their axonal projections after exposure to a fatty diet, with a concomitant reduction in electro-olfactogram amplitude. Loss of olfactory neurons and associated circuitry is linked to changes in neuronal proliferation and normal apoptotic cycles. Using a computer-controlled, liquid-based olfactometer, mice maintained on fatty diets learn reward-reinforced behaviors more slowly, have deficits in reversal learning demonstrating behavioral inflexibility, and exhibit reduced olfactory discrimination. When obese mice are removed from their high-fat diet to regain normal body weight and fasting glucose, olfactory dysfunctions are retained. We conclude that chronic energy imbalance therefore presents long-lasting structural and functional changes in the operation of the sensory system designed to encode external and internal chemical information and leads to altered olfactory- and reward-driven behaviors.
Intradural Hemangioendothelioma of Lumbar Spine: Dilemmas and Differentials in Diagnosis.
World neurosurgery, 2019

Vascular tumors of the spine range from benign hemangiomas to malignant angiosarcomas. Hemangioendotheliomas of spine are tumors of intermediate-grade malignancy with rare occurrence in the intradural location. The imaging and histopathologic features may mimic other common lesions occurring at this location.
Magnetic Resonance Imaging Derived Biomarkers of IDH Mutation Status and Overall Survival in Grade III Astrocytomas.
Diagnostics (Basel, Switzerland), 2020

The evaluation of the isocitrate dehydrogenase (IDH) mutation status in the glioma decision-making process has diagnostic, prognostic and therapeutic implications. The aim of this study was to evaluate whether conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) can noninvasively predict the most common IDH mutational status (R132H) in GIII-astrocytomas and the overall survival (OS). Hence, twenty-two patients (9-F, 13-M) with a histological diagnosis of GIII-astrocytoma and evaluation of IDH-mutation status (12-wild type, 10-mutant) were retrospectively evaluated. Imaging studies were reviewed for the morphological feature and mean ADC values (ADCm). Statistics included a Fisher's exact test, Student's
Neurofeedback of SMR and Beta1 Frequencies: An Investigation of Learning Indices and Frequency-Specific Effects.
Neuroscience, 2018

Despite evidence that Sensorimotor Rhythm (SMR) and beta1 neurofeedback have distinct cognitive enhancement effects, it remains unclear whether their amplitudes can be independently enhanced. Furthermore, demands for top-down attention control, postural restraint and maintenance of cognitive set processes, all requiring low-beta frequencies, might masquerade as learning and confound interpretation. The feasibility of selectively enhancing SMR and beta1 amplitudes was investigated with the addition of a random frequency control condition that also requires the potentially confounding cognitive processes. A comprehensive approach to assessing neurofeedback learning was undertaken through the calculation of learning indices within- and across-session and pre-to-post baseline. Herein we provide the first demonstration of beta1 within-session amplitude learning that was not attributable to extraneous cognitive processes, for it was not found with random frequency training. On the other hand, within-session SMR learning might have been obscured by high interindividual variability and methodological limitations such as the type of feedback screen, the insufficient number of sessions, and the exclusion of simultaneous theta and high-beta inhibition. Interestingly, SMR and beta1 amplitude increased across sessions in the three groups suggesting unspecific effects of neurofeedback in the low beta frequency band. Moreover, there was no clear evidence of frequency specificity associated with either SMR or beta1 training. Some methodological limitations may underpin the divergent results with previous studies.
Effects of mild running on substantia nigra during early neurodegeneration.
Journal of sports sciences, 2018

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H
Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease.
Steroids, 2017

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline.