rudyvdbrink/CitationDatabase huggingface dataset:
Expression of cholinergic phenotype by embryonic ventral horn neurons transplanted into the spinal cord in the rat.
Restorative neurology and neuroscience, 1994

Solid grafts of E12 embryonic spinal ventral horn were transplanted into motoneuron-depleted adult lumbar spinal cord in the rat. A muscle was implanted parallel to the vertebral column with its nerve inserted into the lumbar cord at the site of transplantation so as to provide a target for innervation by the grafted neurons. Previous retrograde labelling studies have shown that modest numbers of grafted motoneuron-like cells participate in the muscle's reinnervation and these are often found outside the graft within the host spinal cord. However, Nissl stained sections show that larger numbers of neurons survive within tissue recognisable as being of graft origin. In this study we have examined the expression of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) by neurons within the graft. These enzymes are involved in cholinergic neurotransmission and are characteristic of motoneurons. Thirty-four to seventy days following transplantation the grafts contained numerous neurons with acetylcholinesterase (AChE) activity. Different patterns of AChE staining were observed which probably reflected the degree of differentiation and maturation within the graft. AChE positive neurons were found in isolation or in groups resembling developing motor pools. Most of the AChE-positive neurons appeared immature with scant cytoplasm. However, neurons could be found which appeared relatively mature with a regularly shaped nucleus, prominent nucleolus and Nissl bodies. The grafts contained few AChE-positive axons and no dense plexuses of varicose fibres around the neurons such as are found around motoneurons in the mature ventral horn. Comparisons between the size of AChE-positive neurons in the graft and the size of AChE-positive neurons in the developing ventral horn found that the size of grafted neurons to be intermediate between the sizes of spinal motoneurons at E19 and P0. Far fewer grafted neurons were found to be immunoreactive for choline acetyltransferase (ChAT) than histochemically reactive for AChE. This was consistent with our findings in the spinal cord during normal development where we found that fixation and staining procedures which labelled adult motoneurons failed to reliably demonstrate ChAT immunoreactivety in normal motoneurons prenatally, although AChE histochemical reactivity could be demonstrated as early as E16. We conclude that the grafts contain numbers of immature motoneurons which fail to proceed beyond a certain stage of development, perhaps because of a failure to form appropriate efferent and afferent connections.
Comparison of clinical outcomes and impact of SVR in American and Chinese patients with chronic hepatitis C.
JHEP reports : innovation in hepatology, 2020

Chronic HCV infection is an important cause of hepatocellular carcinoma (HCC) and liver failure in the US but limited data are available in China. We compared the incidence of clinical outcomes among adults with chronic HCV infection in the US and China and examined factors associated with outcomes.
Hitchhiking on vesicles: a way to harness age-related proteopathies?
The FEBS journal, 2020

Central to proteopathies and leading to most age-related neurodegenerative disorders is a failure in protein quality control (PQC). To harness the toxicity of misfolded and damaged disease proteins, such proteins are either refolded, degraded by temporal PQC, or sequestered by spatial PQC into specific, organelle-associated, compartments within the cell. Here, we discuss the impact of vesicle trafficking pathways in general, and syntaxin 5 in particular, as key players in spatial PQC directing misfolded proteins to the surface of vacuole and mitochondria, which facilitates their clearance and detoxification. Since boosting vesicle trafficking genetically can positively impact on spatial PQC and make cells less sensitive to misfolded disease proteins, we speculate that regulators of such trafficking might serve as therapeutic targets for age-related neurological disorders.
Intracranial Mass Lesions in Human Immunodeficiency Virus Patients in the Philippines: A Retrospective Cohort Study.
World neurosurgery, 2021

Central nervous system involvement is commonly seen in patients with human immunodeficiency virus (HIV) infection, with up to 2%-10% of patients presenting with intracranial mass lesions. The management of these lesions depends largely on their etiology and their relative frequency in the local population.
Effect of brexpiprazole on control of impulsivity in schizophrenia: A randomized functional magnetic resonance imaging study.
Psychiatry research. Neuroimaging, 2020

Impulsivity in schizophrenia is a risk factor for suicide, drug abuse, and other risk-taking behaviors. This exploratory, multicenter, randomized, double-blind, functional magnetic resonance imaging (fMRI) study assessed the effects of brexpiprazole on brain regions that control impulsive behavior. Thirty-eight outpatients with stable schizophrenia and impulsivity symptoms were randomized to 6 weeks of brexpiprazole 2 or 4 mg/day. The prespecified outcome measure was blood oxygen-level dependent (BOLD) activation in the right ventrolateral prefrontal cortex (VLPFC) during performance of tasks associated with inhibition/control of impulsivity: the go/no-go task and stop-signal task. Secondary objectives evaluated the efficacy, safety and tolerability of brexpiprazole. Over 6 weeks, patients receiving brexpiprazole had no statistically significant change in right VLPFC BOLD activation during the go/no-go task, but showed a significant decrease in right VLPFC BOLD activation during the stop-signal task. Brexpiprazole was also associated with significantly improved stop-signal reaction time (SSRT). No worsening of psychiatric symptoms, functioning, or impulsivity occurred in these patients. No unexpected safety or tolerability concerns were identified. In conclusion, brexpiprazole treatment among patients with schizophrenia and impulsivity was associated with decreased right VLPFC activation and decreased SSRT, supportive of a benefit of brexpiprazole on inhibition-related brain activation and behavior. ClinicalTrials.gov identifier: NCT02194933.
Customizable Recorder of Animal Kinesis (CRoAK): A multi-axis instrumented enclosure for measuring animal movements.
HardwareX, 2020

Accurately quantifying animal activity and movements is of fundamental importance in a broad range of disciplines, from biomedical research to behavioral ecology. In many instances, it is desirable to measure natural movements in controlled sensory environments in which the animals are not physically or chemically restrained, but their movements are nevertheless constrained to occur within a fixed volume. Here, we describe a novel device to quantify the movements of small animals in response to sensory stimulation. The device consists of an Arduino controlled inertial measurement unit that senses angular velocity (along three axes) of a suspended mesh enclosure that temporarily houses the animal subject. We validated the device by measuring the phonotaxis behavior of gravid female frogs in response to acoustic broadcasts of male mating calls. The system, as designed, proved effective at measuring natural movements made in response to acoustic stimulation.
Estimating and inferring the maximum degree of stimulus-locked time-varying brain connectivity networks.
Biometrics, 2021

Neuroscientists have enjoyed much success in understanding brain functions by constructing brain connectivity networks using data collected under highly controlled experimental settings. However, these experimental settings bear little resemblance to our real-life experience in day-to-day interactions with the surroundings. To address this issue, neuroscientists have been measuring brain activity under natural viewing experiments in which the subjects are given continuous stimuli, such as watching a movie or listening to a story. The main challenge with this approach is that the measured signal consists of both the stimulus-induced signal, as well as intrinsic-neural and nonneuronal signals. By exploiting the experimental design, we propose to estimate stimulus-locked brain networks by treating nonstimulus-induced signals as nuisance parameters. In many neuroscience applications, it is often important to identify brain regions that are connected to many other brain regions during cognitive process. We propose an inferential method to test whether the maximum degree of the estimated network is larger than a prespecific number. We prove that the type I error can be controlled and that the power increases to one asymptotically. Simulation studies are conducted to assess the performance of our method. Finally, we analyze a functional magnetic resonance imaging dataset obtained under the Sherlock Holmes movie stimuli.
Macroscopic, biochemical and hystological evaluation of topical anti-inflammatory activity of Casearia sylvestris (Flacourtiaceae) in mice.
Journal of ethnopharmacology, 2021

Inflammatory skin diseases presents high prevalence and lack of alternatives that can be used for self-care by the population. Casearia sylvestris is a plant used topically in different communities in Brazil, to treat wounds or promote cutaneous healing. To evaluate the topical anti-inflammatory activity for the crude hydroalcoholic extract of Casearia sylvestris (HCE-CS) in the models of single or multiple administration of chroton oil to induce ear edema in mice.
Shape coding in occipito-temporal cortex relies on object silhouette, curvature, and medial axis.
Journal of neurophysiology, 2020

Object recognition relies on different transformations of the retinal input, carried out by the visual system, that range from local contrast to object shape and category. While some of those transformations are thought to occur at specific stages of the visual hierarchy, the features they represent are correlated (e.g., object shape and identity) and selectivity for the same feature overlaps in many brain regions. This may be explained either by collinearity across representations or may instead reflect the coding of multiple dimensions by the same cortical population. Moreover, orthogonal and shared components may differently impact distinctive stages of the visual hierarchy. We recorded functional MRI activity while participants passively attended to object images and employed a statistical approach that partitioned orthogonal and shared object representations to reveal their relative impact on brain processing. Orthogonal shape representations (silhouette, curvature, and medial axis) independently explained distinct and overlapping clusters of selectivity in the occitotemporal and parietal cortex. Moreover, we show that the relevance of shared representations linearly increases moving from posterior to anterior regions. These results indicate that the visual cortex encodes shared relations between different features in a topographic fashion and that object shape is encoded along different dimensions, each representing orthogonal features.
scREAD: A Single-Cell RNA-Seq Database for Alzheimer's Disease.
iScience, 2020

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain and the most common form of dementia among the elderly. The single-cell RNA-sequencing (scRNA-Seq) and single-nucleus RNA-sequencing (snRNA-Seq) techniques are extremely useful for dissecting the function/dysfunction of highly heterogeneous cells in the brain at the single-cell level, and the corresponding data analyses can significantly improve our understanding of why particular cells are vulnerable in AD. We developed an integrated database named scREAD (single-cell RNA-Seq database for Alzheimer's disease), which is as far as we know the first database dedicated to the management of all the existing scRNA-Seq and snRNA-Seq data sets from the human postmortem brain tissue with AD and mouse models with AD pathology. scREAD provides comprehensive analysis results for 73 data sets from 10 brain regions, including control atlas construction, cell-type prediction, identification of differentially expressed genes, and identification of cell-type-specific regulons.
Potassium conductance dynamics confer robust spike-time precision in a neuromorphic model of the auditory brain stem.
Journal of neurophysiology, 2013

A fundamental question in neuroscience is how neurons perform precise operations despite inherent variability. This question also applies to neuromorphic engineering, where low-power microchips emulate the brain using large populations of diverse silicon neurons. Biological neurons in the auditory pathway display precise spike timing, critical for sound localization and interpretation of complex waveforms such as speech, even though they are a heterogeneous population. Silicon neurons are also heterogeneous, due to a key design constraint in neuromorphic engineering: smaller transistors offer lower power consumption and more neurons per unit area of silicon, but also more variability between transistors and thus between silicon neurons. Utilizing this variability in a neuromorphic model of the auditory brain stem with 1,080 silicon neurons, we found that a low-voltage-activated potassium conductance (g(KL)) enables precise spike timing via two mechanisms: statically reducing the resting membrane time constant and dynamically suppressing late synaptic inputs. The relative contribution of these two mechanisms is unknown because blocking g(KL) in vitro eliminates dynamic adaptation but also lengthens the membrane time constant. We replaced g(KL) with a static leak in silico to recover the short membrane time constant and found that silicon neurons could mimic the spike-time precision of their biological counterparts, but only over a narrow range of stimulus intensities and biophysical parameters. The dynamics of g(KL) were required for precise spike timing robust to stimulus variation across a heterogeneous population of silicon neurons, thus explaining how neural and neuromorphic systems may perform precise operations despite inherent variability.
Retinal microvasculature dysfunction is associated with Alzheimer's disease and mild cognitive impairment.
Alzheimer's research & therapy, 2020

The retina and brain share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in Alzheimer's disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography angiography (OCTA).
Optimizing intracellular signaling domains for CAR NK cells in HIV immunotherapy: a comprehensive review.
Drug discovery today, 2019

Natural killer (NK) cells are innate immune lymphocytes with a key role in host defense against HIV infection. Recent advances in chimeric antigen receptors (CARs) have made NK cells a prime target for expressing recombinant receptors capable of redirecting NK cytotoxic functions towards HIV-infected cells. In this review, we discuss the role of NK cells in HIV and the mechanisms of actions of HIV-targeting CAR strategies. Furthermore, we also review NK cells signal transduction and its application to CAR NK cell strategies to develop new combinations of CAR intracellular domains and to improve CAR NK signaling and cytotoxic functions.
Spatiotemporal structure of cell fate decisions in murine neural crest.
Science (New York, N.Y.), 2019

Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single-cell analysis, we show that mouse trunk neural crest cells become biased toward neuronal lineages when they delaminate from the neural tube, whereas cranial neural crest cells acquire ectomesenchyme potential dependent on activation of the transcription factor
Can an auditory illusion trick the brain into turning down tinnitus?
Medical hypotheses, 2014

Tinnitus, the phantom perception of sound with no external source, affects an estimated 10-15% of the adult population. Current treatments for this oftentimes distressing condition are of limited effectiveness. The "central gain" model proposes that tinnitus arises from an increase in the responsiveness, or gain, of neurons in central auditory pathways, triggered by damage to the auditory periphery. It has been suggested that tinnitus might be treated by compensating for the peripheral damage, thereby restoring normal levels of input to the central pathways, and hence reducing central gain. Unfortunately, when tinnitus originates with permanent damage to the auditory periphery, it may be impossible to compensate for this damage directly. However, we hypothesize that tinnitus may be treated by tricking the brain into believing that it temporarily receives normal levels of input at frequencies where peripheral damage has occurred. We identify an auditory illusion that seems capable, in principle, of achieving this objective. If effective, this approach would offer a safe, accessible, and non-invasive treatment for tinnitus.
Role of child neurologists and neurodevelopmentalists in the diagnosis of cerebral palsy: A survey study.
Neurology, 2020

To contextualize the role of child neurologists and neurodevelopmentalists (CNs/NDDs) in cerebral palsy (CP) care, we review the changing landscape of CP diagnosis and survey stakeholder CNs/NDDs regarding their roles in CP care.
Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer's Disease.
Neurotoxicity research, 2020

Alzheimer's disease (AD) is the most common cause of dementia. Mutations of presenilin (PSEN) genes that encode presenilin proteins have been found as the vital causal factors for early-onset familial AD (FAD). AD pathological features such as memory loss, synaptic dysfunction, and formation of plaques have been successfully mimicked in the transgenic mouse models that coexpress FAD-related presenilin and amyloid precursor protein (APP) variants. γ-Secretase (GS) is an enzyme that plays roles in catalyzing intramembranous APP proteolysis to release pathogenic amyloid beta (Aβ). It has been found that presenilins can play a role as the GS's catalytic subunit. FAD-related mutations in presenilins can modify the site of GS cleavage in a way that can elevate the production of longer and highly fibrillogenic Aβ. Presenilins can interact with β-catenin to generate presenilin complexes. Aforesaid interactions have also been studied to observe the mutational and physiological activities in the catenin signal transduction pathway. Along with APP, GS can catalyze intramembrane proteolysis of various substrates that play a vital role in synaptic function. PSEN mutations can cause FAD with autosomal dominant inheritance and early onset of the disease. In this article, we have reviewed the current progress in the analysis of PSENs and the correlation of PSEN mutations and AD pathogenesis.
IL-22-induced cell extrusion and IL-18-induced cell death prevent and cure rotavirus infection.
Science immunology, 2020

Bacterial flagellin can elicit production of TLR5-mediated IL-22 and NLRC4-mediated IL-18 cytokines that act in concert to cure and prevent rotavirus (RV) infection. This study investigated the mechanism by which these cytokines act to impede RV. Although IL-18 and IL-22 induce each other's expression, we found that IL-18 and IL-22 both impeded RV independently of one another and did so by distinct mechanisms that involved activation of their cognate receptors in intestinal epithelial cells (IEC). IL-22 drove IEC proliferation and migration toward villus tips, which resulted in increased extrusion of highly differentiated IEC that serve as the site of RV replication. In contrast, IL-18 induced cell death of RV-infected IEC thus directly interrupting the RV replication cycle, resulting in spewing of incompetent virus into the intestinal lumen and causing a rapid drop in the number of RV-infected IEC. Together, these actions resulted in rapid and complete expulsion of RV, even in hosts with severely compromised immune systems. These results suggest that a cocktail of IL-18 and IL-22 might be a means of treating viral infections that preferentially target short-lived epithelial cells.
Identification of nonlinear features in cortical and subcortical signals of Parkinson's Disease patients via a novel efficient measure.
NeuroImage, 2020

This study offers a novel and efficient measure based on a higher order version of autocorrelative signal memory that can identify nonlinearities in a single time series. The suggested method was applied to simultaneously recorded subthalamic nucleus (STN) local field potentials (LFP) and magnetoencephalography (MEG) from fourteen Parkinson's Disease (PD) patients who underwent surgery for deep brain stimulation. Recordings were obtained during rest for both OFF and ON dopaminergic medication states. We analyzed the bilateral LFP channels that had the maximum beta power in the OFF state and the cortical sources that had the maximum coherence with the selected LFP channels in the alpha band. Our findings revealed the inherent nonlinearity in the PD data as subcortical high beta (20-30 Hz) band and cortical alpha (8-12 Hz) band activities. While the former was discernible without medication (p=0.015), the latter was induced upon the dopaminergic medication (p<6.10
Corticospinal Pathways and Interactions Underpinning Dexterous Forelimb Movement of the Rodent.
Neuroscience, 2020

In 2013, Thomas Jessell published a paper with Andrew Miri and Eiman Azim that took on the task of examining corticospinal neuron function during movement (Miri et al., 2013). They took the view that a combination of approaches would be able to shed light on corticospinal function, and that this function must be considered in the context of corticospinal connectivity with spinal circuits. In this review, we will highlight recent developments in this area, along with new information regarding inputs and cross-connectivity of the corticospinal circuit with other circuits across the rodent central nervous system. The genetic and viral manipulations available in these animals have led to new insights into descending circuit interaction and function. As species differences exist in the circuitry profile that contributes to dexterous forelimb movements (Lemon, 2008; Yoshida and Isa, 2018), highlighting important advances in one model could help to compare and contrast with what is known about other models. We will focus on the circuitry underpinning dexterous forelimb movements, including some recent developments from systems besides the corticospinal tract, to build a more holistic understanding of sensorimotor circuits and their control of voluntary movement. The rodent corticospinal system is thus a central point of reference in this review, but not the only focus.