rudyvdbrink/CitationDatabase huggingface dataset:
COVID-19: Are we dealing with a multisystem vasculopathy in disguise of a viral infection?
Journal of thrombosis and thrombolysis, 2020

After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic with unprecedented global response. With the expanding domain of presentations in COVID-19 patients, the full range of manifestations is yet to unfold. The classical clinical symptoms for SARS-CoV-2 affected patients are dry cough, high fever, dyspnoea, lethal pneumonia whereas many patients have also been found to be associated with a few additional signs and clinical manifestations of isolated vasculopathy. Albeit a deep and profound knowledge has been gained on the clinical features and management of COVID-19, less clear association has been provided on SARS-CoV-2 mediated direct or indirect vasculopathy and its possible correlation with disease prognosis. The accumulative evidences suggest that novel coronavirus, apart from its primary respiratory confinement, may also invade vascular endothelial cells of several systems including cerebral, cardio-pulmonary as well as renal microvasculature, modulating multiple visceral perfusion indices. Here we analyse the phylogenetic perspective of SARS-CoV-2 along with other strains of β-coronaviridae from a standpoint of vasculopathic derangements. Based on the existing case reports, literature and open data bases, we also analyse the differential pattern of vasculopathy related changes in COVID-19 positive patients. Besides, we debate the need of modulation in clinical approach from a hemodynamical point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV-2 affected patients.
Treatment options and long-term outcomes in pediatric spinal cord vascular malformations: a case report and review of the literature.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2020

A 16-month-old female was admitted for prolonged fever, gait ataxia, and neurogenic bowel and bladder. Neurological exam was significant for decreased sensory and motor functions in bilateral lower extremities. Initial MRI showed a thoracic spine hematoma and diagnostic angiogram revealed a large AVM and aneurysm. The patient underwent surgical resection of the hematoma and AVM, as well as clipping and later endovascular coiling of the aneurysm. Due to significant hemorrhage perioperatively, she developed spastic paraplegia improved by baclofen and onabotulinumtoxin A injections. The aims of this paper were to conduct a systematic review of the literature on pediatric spinal cord vascular malformations and analyze trends in treatment options and long-term neurological outcomes. PubMed searches were conducted using keywords "pediatric spinal vascular malformation" and "pediatric spinal AVM", yielding 34 results after abstract screening and cross-reference. Endovascular embolization was determined to have better long-term outcomes, with 10/19 (52.6%) patients with postoperative complications associated with open vascular surgeries. Open versus endovascular surgical decisions can be difficult with unique spinal AVM pathologies in pediatric patients. Important considerations such as size, location, neurological deficits, and risk of rupture are important factors to consider in treating these patients. We recommend endovascular treatment as a first-line approach due to lower risk of hemorrhage and postoperative deficits.
Inflammatory factors and amyloid β-induced microglial polarization promote inflammatory crosstalk with astrocytes.
Aging, 2020

The immunological responses are a key pathological factor in Alzheimer's disease (AD). We hypothesized that microglial polarization alters microglia-astrocyte immune interactions in AD. M1 and M2 microglia were isolated from primary rat microglia and were confirmed to secrete pro-inflammatory and anti-inflammatory factors, respectively. Primary rat astrocytes were co-cultured with M1 or M2 microglial medium. M1 microglial medium increased astrocyte production of pro-inflammatory factors (interleukin [IL]-1β, tumor necrosis factor α and IL-6), while M2 microglial medium enhanced astrocyte production of anti-inflammatory factors (IL-4 and IL-10). To analyze the crosstalk between microglia and astrocytes after microglial polarization specifically in AD, we co-cultured astrocytes with medium from microglia treated with amyloid-β (Aβ) alone or in combination with other inflammatory substances. Aβ alone and Aβ combined with lipopolysaccharide/interferon-γ induced pro-inflammatory activity in M1 microglia and astrocytes, whereas IL-4/IL-13 inhibited Aβ-induced pro-inflammatory activity. Nuclear factor κB p65 was upregulated in M1 microglia and pro-inflammatory astrocytes, while Stat6 was upregulated in M2 microglia and anti-inflammatory astrocytes. These results provide direct evidence that microglial polarization governs communication between microglia and astrocytes, and that AD debris alters this crosstalk.
Thapsigargin affects presenilin-2 but not presenilin-1 regulation in SK-N-BE cells.
Experimental biology and medicine (Maywood, N.J.), 2014

Presenilin-1 (PS1) and presenilin-2 (PS2) are transmembrane proteins widely expressed in the central nervous system, which function as the catalytic subunits of γ-secretase, the enzyme that releases amyloid-β protein (Aβ) from ectodomain cleaved amyloid precursor protein (APP) by intramembrane proteolysis. Mutations in PS1, PS2, and Aβ protein precursor are involved in the etiology of familial Alzheimer's disease (FAD), while the cause of the sporadic form of AD (SAD) is still not known. However, since similar neuropathological changes have been observed in both FAD and SAD, a common pathway in the etiology of the disease has been suggested. Given that age-related deranged Ca(2+) regulation has been hypothesized to play a role in SAD pathogenesis via PS gene regulation and γ-secretase activity, we studied the in vitro regulation of PS1 and PS2 in the human neuron-like SK-N-BE cell line treated with the specific endoplasmic reticulum (ER) calcium ATPase inhibitor Thapsigargin (THG), to introduce intracellular Ca(2+) perturbations and mimic the altered Ca(2+) homeostasis observed in AD. Our results showed a consistent and significant down-regulation of PS2, while PS1 appeared to be unmodulated. These events were accompanied by oxidative stress and a number of morphological alterations suggestive of the induction of apoptotic machinery. The administration of the antioxidant N-acetylcysteine (NAC) did not revert the THG-induced effects reported, while treatment with the Ca(2+)-independent ER stressor Brefeldin A did not modulate basal PS1 and PS2 expression. Collectively, these results suggest that Ca(2+) fluctuation rather than ER stress and/or oxidative imbalance seems to play an essential role in PS2 regulation and confirm that, despite their strong homology, PS1 and PS2 could play different roles in AD.
Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP.
Molecular autism, 2020

Mutations in TSC2 are the most common cause of tuberous sclerosis (TSC), a disorder with a high incidence of autism and intellectual disability. TSC2 regulates mRNA translation required for group 1 metabotropic glutamate receptor-dependent synaptic long-term depression (mGluR-LTD) and behavior, but the identity of mRNAs responsive to mGluR-LTD signaling is largely unknown.
Nicotine' actions on energy balance: Friend or foe?
Pharmacology & therapeutics, 2021

Obesity has reached pandemic proportions and is associated with severe comorbidities, such as type 2 diabetes mellitus, hepatic and cardiovascular diseases, and certain cancer types. However, the therapeutic options to treat obesity are limited. Extensive epidemiological studies have shown a strong relationship between smoking and body weight, with non-smokers weighing more than smokers at any age. Increased body weight after smoking cessation is a major factor that interferes with their attempts to quit smoking. Numerous controlled studies in both humans and rodents have reported that nicotine, the main bioactive component of tobacco, exerts a marked anorectic action. Furthermore, nicotine is also known to modulate energy expenditure, by regulating the thermogenic activity of brown adipose tissue (BAT) and the browning of white adipose tissue (WAT), as well as glucose homeostasis. Many of these actions occur at central level, by controlling the activity of hypothalamic neuropeptide systems such as proopiomelanocortin (POMC), or energy sensors such as AMP-activated protein kinase (AMPK). However, direct impact of nicotine on metabolic tissues, such as BAT, WAT, liver and pancreas has also been described. Here, we review the actions of nicotine on energy balance. The relevance of this interaction is interesting, because considering the restricted efficiency of obesity treatments, a possible complementary approach may focus on compounds with known pharmacokinetic profile and pharmacological actions, such as nicotine or nicotinic acetylcholine receptors signaling.
Considerations and recent advances in neuroscience.
Biochemical Society transactions, 2009

Neuroscience is a rapidly developing area of science which has benefitted from the blurring of interdisciplinary boundaries. This was apparent in the range of papers presented at this year's Neuroscience Ireland Conference, held in Galway during August 2008. The event was attended by academics, postdoctoral and postgraduate researchers, scientists from industry and clinicians. The themes of this year's conference, neurodegeneration, neuroregeneration, pain, glial cell biology and psychopharmacology, were chosen for their reflection of areas of strength in neuroscience within Ireland. In addition to basic science, translational research also featured strongly.
Learned valuation during forage decision-making in cuttlefish.
Royal Society open science, 2020

Decision-making, when humans and other animals choose between two options, is not always based on the absolute values of the options but can also depend on their relative values. The present study examines whether decision-making by cuttlefish is dependent on relative values learned from previous experience. Cuttlefish preferred a larger quantity when making a choice between one or two shrimps (1 versus 2) during a two-alternative forced choice. However, after cuttlefish were primed under conditions where they were given a small reward for choosing one shrimp in a no shrimp versus one shrimp test (0 versus 1) six times in a row, they chose one shrimp significantly more frequently in the 1 versus 2 test. This reversed preference for a smaller quantity was not due to satiation at the time of decision-making, as cuttlefish fed a small shrimp six times without any choice test prior to the experiment still preferred two shrimps significantly more often in a subsequent 1 versus 2 test. This suggests that the preference of one shrimp in the quantity comparison test occurs via a process of learned valuation. Foraging preference in cuttlefish thus depends on the relative value of previous prey choices.
Activation in left primary visual cortex representing parafoveal visual field during reading Japanese texts.
Brain research, 2011

Activation in the left primary visual cortex (V1) representing the parafoveal field during text reading has been interpreted as attentional modulation in the process of deciding saccadic target for reading ahead. Kanji words serve the main cue to decide the goal of saccades in Japanese. We aimed to determine the exact location of this modulation in the V1 and to determine whether the area of the modulation changes according to the location where the next Kanji word appears or it is fixed on a certain region in V1. Using functional magnetic resonance imaging, we determined the area in V1 representing each eccentricity on the horizontal meridian of the visual field for each participant. Then we investigated brain activation while they were reading two sets of Japanese texts that scrolled leftward as the participants. In set 1, the distance between the heads of adjacent Kanji words was about 3°. In set 2, the distance was about 5°. From the results of these experiments, we obtained activation amplitude of the area corresponding to each eccentricity. We recorded eye movements simultaneously with the acquisition of fMRI data. The maximum peak of the activation was found in the region representing about 4.5° of eccentricity on the horizontal meridian in the left V1 for each participant. The activation pattern did not essentially differ between the two text conditions, although the location of the saccades made for reading next section of the text corresponds to the head of the next Kanji word. The activation modulation during reading Japanese texts occurs in the parafoveal V1 of the left hemisphere. The attentional modulation did not change with the distance to the next goal of saccade but was fixed on the area representing about 4.5° of eccentricity.
Clinical features of anti-leucine-rich glioma-inactivated 1 encephalitis in northeast China.
Clinical neurology and neurosurgery, 2021

To examine the clinical characteristics, laboratory tests, imaging and electroencephalography presentation, treatment, and prognosis of anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis and improve the awareness of this disease.
Reelin-Nrp1 Interaction Regulates Neocortical Dendrite Development in a Context-Specific Manner.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Reelin plays versatile roles in neocortical development. The C-terminal region (CTR) of Reelin is required for the correct formation of the superficial structure of the neocortex; however, the mechanisms by which this position-specific effect occurs remain largely unknown. In this study, we demonstrate that Reelin with an intact CTR binds to neuropilin-1 (Nrp1), a transmembrane protein. Both male and female mice were used. Nrp1 is localized with very-low-density lipoprotein receptor (VLDLR), a canonical Reelin receptor, in the superficial layers of the developing neocortex. It forms a complex with VLDLR, and this interaction is modulated by the alternative splicing of VLDLR. Reelin with an intact CTR binds more strongly to the VLDLR/Nrp1 complex than to VLDLR alone. Knockdown of Nrp1 in neurons leads to the accumulation of Dab1 protein. Since the degradation of Dab1 is induced by Reelin signaling, it is suggested that Nrp1 augments Reelin signaling. The interaction between Reelin and Nrp1 is required for normal dendritic development in superficial-layer neurons. All of these characteristics of Reelin are abrogated by proteolytic processing of the six C-terminal amino acid residues of Reelin (0.17% of the whole protein). Therefore, Nrp1 is a coreceptor molecule for Reelin and, together with the proteolytic processing of Reelin, can account for context-specific Reelin function in brain development.
Age-related cognitive decline as a function of daytime testing.
Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition, 2017

The current study investigates the effects of age, cognitive load, optimal time-of-day testing, and irrelevant background noise suppression on mental processing. One hundred and seventy-eight young (M = 22.97 years) and 114 old adults (M = 56.38 years) were assessed for implicit learning and speed of information processing under irrelevant sound interference early during daytime (7AM-2.30PM) or in the afternoons (3PM-midnight). No direct effect of irrelevant speech effect was found on implicit learning. An optimal time of testing per age group was identified according to the ability to suppress irrelevant auditory information. If no semantic meaning was derived from the sound conditions, irrelevant sound was easily inhibited leaving no room for declined cognitive performance. This suggests an intact phonological inhibition in older adults and a further circumvention of the phonological loop. However, when difficulty was increased, a widened performance gap between young and old people could be observed. Education modulated difficult performance irrespective of age. With increasing age, task demand fulfillment becomes a function of a limited time mechanism. If extraneous time is not adapted to cognitive skills and performance, higher order processing cannot be reached, rendering older adults slower than their younger counterparts.
Gut-brain axis: A matter of concern in neuropsychiatric disorders…!
Progress in neuro-psychopharmacology & biological psychiatry, 2021

The gut microbiota is composed of a large number of microbes, usually regarded as commensal bacteria. It has become gradually clear that gastrointestinal microbiota affects gut pathophysiology and the central nervous system (CNS) function by modulating the signaling pathways of the microbiota-gut-brain (MGB) axis. This bidirectional MGB axis communication primarily acts through neuroendocrine, neuroimmune, and autonomic nervous systems (ANS) mechanisms. Accumulating evidence reveals that gut microbiota interacts with the host brain, and its modulation may play a critical role in the pathology of neuropsychiatric disorders. Recently, neuroscience research has established the significance of gut microbiota in the development of brain systems that are essential to stress-related behaviors, including depression and anxiety. Application of modulators of the MGB, such as psychobiotics (e.g., probiotics), prebiotics, and specific diets, may be a promising therapeutic approach for neuropsychiatric disorders. The present review article primarily focuses on the relevant features of the disturbances of the MGB axis in the pathophysiology of neuropsychiatric disorders and its potential mechanisms.
Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer's Disease.
International journal of molecular sciences, 2020

People with Alzheimer's disease (AD) have significantly higher rates of subclinical and overt epileptiform activity. In animal models, oligomeric Aβ amyloid is able to induce neuronal hyperexcitability even in the early phases of the disease. Such aberrant activity subsequently leads to downstream accumulation of toxic proteins, and ultimately to further neurodegeneration and neuronal silencing mediated by concomitant tau accumulation. Several neurotransmitters participate in the initial hyperexcitable state, with increased synaptic glutamatergic tone and decreased GABAergic inhibition. These changes appear to activate excitotoxic pathways and, ultimately, cause reduced long-term potentiation, increased long-term depression, and increased GABAergic inhibitory remodelling at the network level. Brain hyperexcitability has therefore been identified as a potential target for therapeutic interventions aimed at enhancing cognition, and, possibly, disease modification in the longer term. Clinical trials are ongoing to evaluate the potential efficacy in targeting hyperexcitability in AD, with levetiracetam showing some encouraging effects. Newer compounds and techniques, such as gene editing via viral vectors or brain stimulation, also show promise. Diagnostic challenges include identifying best biomarkers for measuring sub-clinical epileptiform discharges. Determining the timing of any intervention is critical and future trials will need to carefully stratify participants with respect to the phase of disease pathology.
Afferents of the mouse linear nucleus.
Molecular brain, 2020

The linear nucleus (Li) was identified in 1978 from its projections to the cerebellum. However, there is no systematic study of its connections with other areas of the central nervous system possibly due to the challenge of injecting retrograde tracers into this nucleus. The present study examines its afferents from some nuclei involved in motor and cardiovascular control with anterograde tracer injections. BDA injections into the central amygdaloid nucleus result in labeled fibers to the ipsilateral Li. Bilateral projections with an ipsilateral dominance were observed after injections in a) jointly the paralemniscal nucleus, the noradrenergic group 7/ Köllike -Fuse nucleus/subcoeruleus nucleus, b) the gigantocellular reticular nucleus, c) and the solitary nucleus/the parvicellular/intermediate reticular nucleus. Retrogradely labeled neurons were observed in Li after BDA injections into all these nuclei except the central amygdaloid and the paralemniscal nuclei. Our results suggest that Li is involved in a variety of physiological functions apart from motor and balance control it may exert via its cerebellar projections.
Thermodynamics and Kinetics of Ion Permeation in Wild-Type and Mutated Open Active Conformation of the Human α7 Nicotinic Receptor.
Journal of chemical information and modeling, 2020

Molecular studies of human pentameric ligand-gated ion channels (LGICs) expressed in neurons and at neuromuscular junctions are of utmost importance in the development of therapeutic strategies for neurological disorders. We focus here on the nicotinic acetylcholine receptor nAChR-α7, a homopentameric channel widely expressed in the human brain, with a proven role in a wide spectrum of disorders including schizophrenia and Alzheimer's disease. By exploiting an all-atom structural model of the full (transmembrane and extracellular) protein in the open, agonist-bound conformation we recently developed, we evaluate the free energy and the mean first passage time of single-ion permeation using molecular dynamics simulations and the milestoning method with Voronoi tessellation. The results for the wild-type channel provide the first available mapping of the potential of mean force in the full-length α7 nAChR, reveal its expected cationic nature, and are in good agreement with simulation data for other channels of the LGIC family and with experimental data on nAChRs. We then investigate the role of a specific mutation directly related to ion selectivity in LGICs, the E-1' → A-1' substitution at the cytoplasmatic selectivity filter. We find that the mutation strongly affects sodium and chloride permeation in opposite directions, leading to a complete inversion of selectivity, at variance with the limited experimental results available that classify this mutant as cationic. We thus provide structural determinants for the observed cationic-to-anionic inversion, revealing a key role of the protonation state of residue rings far from the mutation, in the proximity of the hydrophobic channel gate.