rudyvdbrink/CitationDatabase huggingface dataset:
Insight into the mechanism of cytotoxicity of membrane-permeant psoralenic Kv1.3 channel inhibitors by chemical dissection of a novel member of the family.
Redox biology, 2020

The potassium channel Kv1.3, involved in several important pathologies, is the target of a family of psoralen-based drugs whose mechanism of action is not fully understood. Here we provide evidence for a physical interaction of the mitochondria-located Kv1.3 (mtKv1.3) and Complex I of the respiratory chain and show that this proximity underlies the death-inducing ability of psoralenic Kv1.3 inhibitors. The effects of PAP-1-MHEG (PAP-1, a Kv1.3 inhibitor, with six monomeric ethylene glycol units attached to the phenyl ring of PAP-1), a more soluble novel derivative of PAP-1 and of its various portions on mitochondrial physiology indicate that the psoralenic moiety of PAP-1 bound to mtKv1.3 facilitates the diversion of electrons from Complex I to molecular oxygen. The resulting massive production of toxic Reactive Oxygen Species leads to death of cancer cells expressing Kv1.3. In vivo, PAP-1-MHEG significantly decreased melanoma volume. In summary, PAP-1-MHEG offers insights into the mechanisms of cytotoxicity of this family of compounds and may represent a valuable clinical tool.
Beneficial effects of DAAs on cardiac function and structure in hepatitis C patients with low-moderate liver fibrosis.
Journal of viral hepatitis, 2020

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.
Estimates of Geriatric Delirium Frequency in Noncardiac Surgeries and Its Evaluation Across the Years: A Systematic Review and Meta-analysis.
Journal of the American Medical Directors Association, 2021

Delirium is an acute neuropsychiatric syndrome associated with poor outcomes. Older adults undergoing surgery have a higher risk of manifesting perioperative delirium, particularly those having associated comorbidities. It remains unclear whether delirium frequency varies across surgical settings and if it has remained stable across the years. We conducted a systematic review to (1) determine the overall frequency of delirium in older people undergoing noncardiac surgery; (2) explore factors explaining the variability of the estimates; and (3) determine the changing of the estimates over the past 2 decades.
Seeing for ourselves: Insights into the development of moral behaviour from models of visual perception and misperception.
The Behavioral and brain sciences, 2018

Parallels from visual processing support Doris's cognitive architecture underlying moral agency. Unconscious visual processes change with conscious reflection. The sparse and partial representations of vision, its illusions, and hallucinations echo biases in moral reasoning and behaviour. Traditionally, unconscious moral processes are developed by teaching and reflection. Modern neuroscience could bypass reflection and directly influence unconscious processes, creating new dangers.
Sudden worsening after subdural haematoma surgery: will there be a corpus callosum injury?
BMJ case reports, 2014

We report a case of mild encephalopathy with a reversible splenial lesion (MERS) which occurred after chronic subdural haematoma (CSDH) surgery. The patient was admitted to our hospital for drowsiness and marked asthenia. The cerebral CT scan revealed a CSDH and surgery allowed to improve the symptoms, but after several days we observed a sudden worsening. The patient developed left-sided myoclonic seizures followed by left hemiplegia and worsening drowsiness. Electrolytes imbalance and inflammatory causes were excluded. The CT scan showed a right cerebral swelling and the subsequent MRI revealed a single lesion in the splenium of the corpus callosum, hyperintense on diffusion-weighted images. After osmotic therapy the patient improved and on day 10 of admission the MRI showed a complete resolution of the lesion. This is the first report that described an association between CSDH and MERS. Possible aetiopathogenetic mechanisms are discussed.
Neural repetition suppression effects in the human hippocampus.
Neurobiology of learning and memory, 2020

Neurons in the temporal lobe cortex exhibit reduced responses when a stimulus or a stimulus feature is repeated. This phenomenon, termed "repetition suppression", is the basis for many functional imaging studies that have used Blood Oxygenation Level Dependent (BOLD) activity differences between novel and repeated items as an index of neural selectivity in hippocampal subfields. However, it is not clear how hippocampal neural activity changes across repeated exposure to a stimulus. Here, we used direct intracranial electroencephalography (iEEG) recordings of hippocampal activity to examine whether neural activity in the human hippocampus is modulated across successive repetitions of an item. Time-frequency analyses revealed that high-frequency activity, which is thought to include gamma oscillations and possible correlates of multi-unit activity, declined monotonically across successive presentations of an item. In contrast, low-frequency oscillations in the alpha and beta bands monotonically increased across successive presentations of an object. These results provide support for the assumption that, at least under some circumstances, repetition suppression (as measured by declines in high-frequency activity) can be observed in the hippocampus, and these effects are accompanied by increases in low-frequency oscillations as well.
Targeting apoptosis and autophagy following spinal cord injury: Therapeutic approaches to polyphenols and candidate phytochemicals.
Pharmacological research, 2020

Spinal cord injury (SCI) is a neurological disorder associated with the loss of sensory and motor function. Understanding the precise dysregulated signaling pathways, especially apoptosis and autophagy following SCI, is of vital importance in developing innovative therapeutic targets and treatments. The present study lies in the fact that it reveals the precise dysregulated signaling mediators of apoptotic and autophagic pathways following SCI and also examines the effects of polyphenols and other candidate phytochemicals. It provides new insights to develop new treatments for post-SCI complications. Accordingly, a comprehensive review was conducted using electronic databases including, Scopus, Web of Science, PubMed, and Medline, along with the authors' expertise in apoptosis and autophagy as well as their knowledge about the effects of polyphenols and other phytochemicals on SCI pathogenesis. The primary mechanical injury to spinal cord is followed by a secondary cascade of apoptosis and autophagy that play critical roles during SCI. In terms of pharmacological mechanisms, caspases, Bax/Bcl-2, TNF-α, and JAK/STAT in apoptosis along with LC3 and Beclin-1 in autophagy have shown a close interconnection with the inflammatory pathways mainly glutamatergic, PI3K/Akt/mTOR, ERK/MAPK, and other cross-linked mediators. Besides, apoptotic pathways have been shown to regulate autophagy mediators and vice versa. Prevailing evidence has highlighted the importance of modulating these signaling mediators/pathways by polyphenols and other candidate phytochemicals post-SCI. The present review provides dysregulated signaling mediators and therapeutic targets of apoptotic and autophagic pathways following SCI, focusing on the modulatory effects of polyphenols and other potential phytochemical candidates.
Correction: Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018

This article was originally published under NPG's License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the paper have been modified accordingly.
Enhancing biocompatibility and neuronal anti-inflammatory activity of polymyxin B through conjugation with gellan gum.
International journal of biological macromolecules, 2020

Polymyxins, as strong antibiotics with high liposaccharide deactivation abilities, are rarely used as neuronal anti-inflammatory agent because of their high cytotoxicity. In this study, polymyxin B (PMB) was conjugated with deacylated gellan gum for the sustained release of PMB to reduce its cytotoxicity at high concentration without affecting the antibacterial and liposaccharide binding activities. For the conjugate of original PMB/GN ratio of 1.0 (GPC), the conjugating rate was 96.40%, and the releasing ratio of PMB was 30.12% within 60 h. The FT-IR spectra of GPC indicated that the amino groups of PMB were covalently bonded with the COOH groups of gellan and other PMB molecules. Most GPCs were micelle shaped regardless of whether they were under dry conditions or in an aqueous solution. The inhibition zones of PMB against Escherichia coli and Pseudomonas aeruginosa were small, but the half maximal inhibitory concentration value against BV-2 cells increased from 15.63 μg/mL to 2000.00 μg/mL after conjugation. GPC can also effectively depress the liposaccharide-stimulated overexpression of cytotoxic nitric oxide by BV-2 cells. This study revealed the possibility of using polymyxins for neuronal anti-inflammation and that this gellan/PMB conjugate can potentially be applied to wound healing and implants.
Female Residents with Psychopathy in a High-Security Italian Hospital.
The journal of the American Academy of Psychiatry and the Law, 2018

Before its closure on April 1, 2015, the Castiglione delle Stiviere was the only maximum-security hospital in Italy that admitted women. In this context, the investigators examined factors related to psychopathy that were thought to be gender specific. Several prior investigations have reported a significant correlation between psychopathy and borderline personality disorder, a disorder thought to represent the phenotypical expression of psychopathy in women. The purpose of this research was to identify psychopathological and phenotypical gender-specific factors that are associated with psychopathy in women. The data appear consistent with that found in the recent international literature and also highlight the different phenotypical manifestation of psychopathy in the two genders. Whereas in males psychopathy is associated with antisocial personality disorder, in females psychopathy is associated with borderline personality disorder.
Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020

The most common chemogenetic neuromodulatory system, designer receptors exclusively activated by designer drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is insensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug, particularly in experiments using nonhuman primates. We investigated working memory performance after injections of three DREADD actuators, clozapine, olanzapine, and deschloroclozapine, in four male rhesus monkeys tested in a spatial delayed response task before any DREADD transduction took place. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from vehicle in any of the four subjects. 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after 0.1 mg/kg olanzapine and two were impaired after 0.3 mg/kg deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs in the specific tasks under study to confirm that effects following DREADD receptor transduction are not owing to the actuator drug itself. They also suggest that off-target effects of DREADD actuators may limit translational applications of chemogenetic neuromodulation.
Zn, Cu, and Fe Concentrations in Dehydrated Herbs (Thyme, Rosemary, Cloves, Oregano, and Basil) and the Correlation with the Microbial Counts of 
Foods (Basel, Switzerland), 2020

Zn, Cu, and Fe concentrations were measured in dehydrated herbs (thyme, rosemary, cloves, oregano, and basil) marketed in bulk or packaged in glass or polyethylene terephthalate (PET). Microbial counts of
Solutes as controllers of endomembrane dynamics.
Nature reviews. Molecular cell biology, 2021

Membrane dynamics, such as those associated with intracellular traffic, require controlled deformation of the membrane. There is now evidence that the regulation of the luminal fluid composition — via solute fluxes — prominently impacts dynamic properties of endomembranes by modulating their tension. This has important consequences for the function of the endo-lysosomal system.
GRIN database: A unified and manually curated repertoire of GRIN variants.
Human mutation, 2021

Glutamatergic neurotransmission is crucial for brain development, wiring neuronal function, and synaptic plasticity mechanisms. Recent genetic studies showed the existence of autosomal dominant de novo GRIN gene variants associated with GRIN-related disorders (GRDs), a rare pediatric neurological disorder caused by N-methyl- d-aspartate receptor (NMDAR) dysfunction. Notwithstanding, GRIN variants identification is exponentially growing and their clinical, genetic, and functional annotations remain highly fragmented, representing a bottleneck in GRD patient's stratification. To shorten the gap between GRIN variant identification and patient stratification, we present the GRIN database (GRINdb), a publicly available, nonredundant, updated, and curated database gathering all available genetic, functional, and clinical data from more than 4000 GRIN variants. The manually curated GRINdb outputs on a web server, allowing query and retrieval of reported GRIN variants, and thus representing a fast and reliable bioinformatics resource for molecular clinical advice. Furthermore, the comprehensive mapping of GRIN variants' genetic and clinical information along NMDAR structure revealed important differences in GRIN variants' pathogenicity and clinical phenotypes, shedding light on GRIN-specific fingerprints. Overall, the GRINdb and web server is a resource for molecular stratification of GRIN variants, delivering clinical and investigational insights into GRDs. GRINdb is accessible at http://lmc.uab.es/grindb.
Brain-wide, scale-wide physiology underlying behavioral flexibility in zebrafish.
Current opinion in neurobiology, 2020

The brain is tasked with choosing actions that maximize an animal's chances of survival and reproduction. These choices must be flexible and informed by the current state of the environment, the needs of the body, and the outcomes of past actions. This information is physiologically encoded and processed across different brain regions on a wide range of spatial scales, from molecules in single synapses to networks of brain areas. Uncovering these spatially distributed neural interactions underlying behavior requires investigations that span a similar range of spatial scales. Larval zebrafish, given their small size, transparency, and ease of genetic access, are a good model organism for such investigations, allowing the use of modern microscopy, molecular biology, and computational techniques. These approaches are yielding new insights into the mechanistic basis of behavioral states, which we review here and compare to related studies in mammalian species.
Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases.
Human molecular genetics, 2020

The role of Discoidin Domain Receptors (DDRs) is poorly understood in neurodegeneration. DDRs are upregulated in Alzheimer's and Parkinson's disease (PD), and DDRs knockdown reduces neurotoxic protein levels. Here we show that potent and preferential DDR1 inhibitors reduce neurotoxic protein levels in vitro and in vivo. Partial or complete deletion or inhibition of DDR1 in a mouse model challenged with α-synuclein increases autophagy and reduces inflammation and neurotoxic proteins. Significant changes of cerebrospinal fluid microRNAs that control inflammation, neuronal injury, autophagy and vesicular transport genes are observed in PD with and without dementia and Lewy body dementia, but these changes are attenuated or reversed after treatment with the DDR1 inhibitor, nilotinib. Collectively, these data demonstrate that DDR1 regulates autophagy and reduces neurotoxic proteins and inflammation and is a therapeutic target in neurodegeneration.
It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Early-life stress (ELS) is associated with increased vulnerability to mental disorders. The basolateral amygdala (BLA) plays a critical role in fear conditioning and is extremely sensitive to ELS. Using a naturalistic rodent model of ELS, the limited bedding paradigm (LB) between postnatal days 1-10, we previously documented that LB male, but not female preweaning rat pups display increased BLA neuron spine density paralleled with enhanced evoked synaptic responses and altered BLA functional connectivity. Since ELS effects are often sexually dimorphic and amygdala processes exhibit hemispheric asymmetry, we investigated changes in synaptic plasticity and neuronal excitability of BLA neurons
Involvement of hippocampal agmatine in β
Neurotoxicology, 2020

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by abnormal accumulation of extracellular β-amyloid (Aβ) plaques and neuronal damage. The present study investigated the effect of chronic intra-hippocampal agmatine administration on β-Amyloid (Aβ) induced memory impairment in mice. Aβ
Selective neural sensitivity to familial threat in adolescents with weak family bonds.
Social neuroscience, 2019

Familial stressors, such as weak familial connectedness, are associated with the development of maladaptive threat processing, yet little is known regarding how weak familial bonds impinge on biological mechanisms of threat processing. The present study leveraged multivoxel pattern analysis of fMRI data to compare the neural encoding of familial and nonfamilial threatening and non-threatening stimuli in adolescents who endorsed varying levels of connectedness to their families. Adolescents (N = 22, Mage = 14.38 years) reporting lower family connectedness 1 year earlier showed elevated sensitivity to familial threat, but not to nonfamilial threat in a neural network associated with threat processing, comprising left and right amygdala, and right inferior and middle temporal gyri. Results suggest that a learning history about one's social environment may shape neural mechanisms of threat processing by sensitizing them to risk-relevant stimuli. Such findings advance our understanding of how familial stressors contribute to disordered threat processing in adolescence.
Effects of sub-concussion on neuropsychological performance and its potential mechanisms: A narrative review.
Brain research bulletin, 2020

Concussion and mild traumatic brain injury (mTBI) are recognised as serious medical events that are relatively common in contact sports. Recently, the seemingly non-injurious phenomenon of sub-concussion has gained interest among neuroscience researchers and early studies are showing that there may be some acute and chronic effects on brain health and function with repeated sub-concussive events of the type seen in soccer, where players strike the ball with the head, and collision sports like the rugby codes. The aim of this narrative review is to describe sub-concussion and the current understanding of short and long term effects of repeated minor impacts that have been found to occur in human and animal models. Here, potential mechanisms for cognitive dysfunction following sub-concussion and recommend directions for future research are discussed. The Potential mechanisms of injuries resulting from sub-concussion such as changes in blood brain barrier integrity, neuroinflammation, cognitive impairment, and oxidative stress damage, among other changes in central nervous system function vary considerably making understanding of the underlying causative mechanism challenging for researchers. Some evidence suggests a link between impaired cerebrovascular function and cognitive impairment which poses a potential mechanism linking the two. It is hoped that this review helps guide researchers toward a potential direction of investigations.