rudyvdbrink/CitationDatabase huggingface dataset:
Characterization of a human keratinocyte HaCaT cell line model to study the regulation of CYP2S1.
Drug metabolism and disposition: the biological fate of chemicals, 2012

CYP2S1 is an extrahepatic cytochrome P450 (P450) that shows marked individuality in constitutive and inducible expression. CYP2S1 mRNA expression is increased in psoriasis and by treatments for psoriasis, including retinoids and UV radiation, although endogenous substrates remain poorly characterized. Because previous model systems have overexpressed modified CYP2S1 in bacteria, human HaCaT keratinocyte cells were screened for constitutive and regulatable CYP2S1 expression and CYP2S1 activity in HaCaT cells compared with a novel Chinese hamster ovary (CHO)-based cell line engineered to stably coexpress CYP2S1 and NADPH cytochrome P450 reductase. Constitutive mRNA expression for CYP2S1 and additional P450s, retinoid acid receptors (RARα, RARβ, RARγ), and retinoid X receptors (RXRα, RXRβ and RXRγ) was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis in HaCaT cells. Cells were then exposed to retinoids or to UV radiation (UVR), and changes in CYP2S1 mRNA abundance were further examined by qRT-PCR analysis. P450 expression in HaCaT cells was similar to human skin, with abundant CYP2S1 expression. RARα and RARγ (but not RARβ) and all RXR isoforms were also detectable. All-trans retinoic acid (atRA) induced CYPS1 mRNA expression more potently than 9-cis RA or 13-cis RA. P450-dependent atRA metabolism was demonstrated in HaCaT cells, with a very similar metabolite profile to that produced by our CYP2S1-expressing CHO cells. CYP2S1 mRNA expression was also induced by UVR, more potently than CYP1B1, a known UVR-inducible P450. Our results demonstrate regulatable and functional CYP2S1 expression in HaCaT cells, thus identifying a human cell line model with utility for further analysis of CYP2S1 regulation and substrate specificity.
Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress.
American journal of physiology. Endocrinology and metabolism, 2010

The type of free fatty acids (FFAs), saturated or unsaturated, is critical in the development of insulin resistance (IR), since the degree of saturation correlates with IR. We compared the effects of the saturated FFA palmitate, the unsaturated FFA oleate, and a mixture of each on the production of mitochondrial reactive oxygen species (mtROS), mitochondrial DNA (mtDNA) damage, mitochondrial function, apoptosis, and insulin-signaling pathway in skeletal muscle cells. Only palmitate caused a significant increase of mtROS production, which correlated with concomitant mtDNA damage, mitochondrial dysfunction, induction of JNK, apoptosis, and inhibition of insulin signaling. Blocking de novo synthesis of ceramide abolished the effects of palmitate on mtROS production, viability, and insulin signaling. Oleate alone did not cause mtROS generation and mtDNA damage, and its addition to palmitate prevented palmitate-induced mtDNA damage, increased total ATP levels and cell viability, and prevented palmitate-induced apoptosis and inhibition of insulin-stimulated Akt (Ser(473)) phosphorylation. The peroxisome proliferator activator receptor-γ coactivator 1α (PGC-1α) protein level and promoter activity were decreased at concentrations of palmitate ≥0.5 mM, whereas addition of oleate increased both PGC-1α level and promoter activity. Expression of the mitochondrial transcription factor (TFAM) was significantly diminished after palmitate but not oleate treatment. Addition of the ROS scavenger, N-acetylcystein (NAC), to palmitate restored both the expression and promoter activity of PGC-1α as well as TFAM expression. We propose that 1) mtROS generation is the initial event in the induction of mitochondrial dysfunction and consequent apoptosis and the inhibition of insulin signaling and that 2) oleate ameliorates palmitate-induced mitochondrial dysfunction and thus may contribute to the prevention of palmitate-induced IR.
The Therapeutic Effectiveness of Delayed Fetal Spinal Cord Tissue Transplantation on Respiratory Function Following Mid-Cervical Spinal Cord Injury.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2017

Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and γ-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.
Modelling mixing within the dead space of the lung improves predictions of functional residual capacity.
Respiratory physiology & neurobiology, 2017

Routine estimation of functional residual capacity (FRC) in ventilated patients has been a long held goal, with many methods previously proposed, but none have been used in routine clinical practice. This paper proposes three models for determining FRC using the nitrous oxide concentration from the entire expired breath in order to improve the precision of the estimate. Of the three models proposed, a dead space with two mixing compartments provided the best results, reducing the mean limits of agreement with the FRC measured by whole body plethysmography by up to 41%. This moves away from traditional lung models, which do not account for mixing within the dead space. Compared to literature values for FRC, the results are similar to those obtained using helium dilution and better than the LUFU device (Dräger Medical, Lubeck, Germany), with significantly better limits of agreement compared to plethysmography.
Diagnosis and management of Alzheimer's disease: past, present and future ethical issues.
Progress in neurobiology, 2013

There is great interest in the ethical issues associated with Alzheimer's disease (AD) and related dementias given the prevalence of AD and the evolving neuroscience landscape in matters of diagnoses and therapeutics. Much of the ethics discussion arises in the tension between the principle of not doing harm (principle of non-maleficence) in this vulnerable population and the development of effective treatments (principle of beneficence). Autonomy and capacity issues are also numerous, wide-ranging, and concern (1) day to day affairs such as driving safely and spending money wisely, (2) life-time events such as designating a legal representative in case of incapacity, making a will, (3) consenting to treatment and diagnostic procedures, (4) participating in research. The latter issue is particularly thorny and illustrates well the complexity of tackling concerns related to capacity. The impetus to protect AD patients has partly led to ethics regulation and policies making research on inapt patients more difficult because of stringent requirements for signed informed consent or for showing the value of the research to this specific patient population. New issues are arising that relate to earlier diagnosis using biomarkers and (possibly soon) the use of drugs that modify disease progression. We here summarize and discuss the different ethical issues associated with AD from a historical perspective, with emphasis on diagnostic and treatments issues.
An update on conbercept to treat wet age-related macular degeneration.
Drugs of today (Barcelona, Spain : 1998), 2020

Wet age-related macular degeneration (w-AMD) represents the main cause of vision loss in the elderly in the western countries. The important role displayed by vascular endothelial growth factor (VEGF) in the pathogenesis of this disease has been largely demonstrated. For this reason, anti-VEGF drugs have been developed and currently are considered as the first-line treatment options in the management of w-AMD. Among the novel anti-VEGF agents studied, conbercept is a fusion protein composed of the combination between VEGF receptor domains with the Fc fragment of human immunoglobulin. It was already approved in China in 2014 for treating w-AMD. In this regard, the phase III PHOENIX trial has reported a good clinical efficacy and safety profile of conbercept for w-AMD, also by adopting a quarterly regimen. In this review, we will discuss its pharmacokinetics, pharmacodynamics, clinical efficacy, without neglecting also its safety and tolerability profile.
EEG synchronization measures are early outcome predictors in comatose patients after cardiac arrest.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2017

Outcome prognostication in comatose patients after cardiac arrest (CA) remains a major challenge. Here we investigated the prognostic value of combinations of linear and non-linear bivariate EEG synchronization measures.
Pitx2 cholinergic interneurons are the source of C bouton synapses on brainstem motor neurons.
Scientific reports, 2019

Cholinergic neuromodulation has been described throughout the brain and has been implicated in various functions including attention, food intake and response to stress. Cholinergic modulation is also thought to be important for regulating motor systems, as revealed by studies of large cholinergic synapses on spinal motor neurons, called C boutons, which seem to control motor neuron excitability in a task-dependent manner. C boutons on spinal motor neurons stem from spinal interneurons that express the transcription factor Pitx2. C boutons have also been identified on the motor neurons of specific cranial nuclei. However, the source and roles of cranial C boutons are less clear. Previous studies suggest that they originate from Pitx2+ and Pitx2- neurons, in contrast to spinal cord C boutons that originate solely from Pitx2 neurons. Here, we address this controversy using mouse genetics, and demonstrate that brainstem C boutons are Pitx2+ derived. We also identify new Pitx2 populations and map the cholinergic Pitx2 neurons of the mouse brain. Taken together, our data present important new information about the anatomical organization of cholinergic systems which impact motor systems of the brainstem. These findings will enable further analyses of the specific roles of cholinergic modulation in motor control.
Sequential congruency effects: disentangling priming and conflict adaptation.
Psychological research, 2012

Responding to the color of a word is slower and less accurate if the word refers to a different color (incongruent condition) than if it refers to the same color (congruent condition). This phenomenon, known as the Stroop effect, is modulated by sequential effects: it is bigger when the current trial is preceded by a congruent condition than by an incongruent one in the previous trial. Whether this phenomenon is due to priming mechanisms or to cognitive control is still debated. To disentangle the contribution of priming with respect to conflict adaptation mechanisms in determining sequential effects, two experiments were designed here with a four-alternative forced choice (4-AFC) Stroop task: in the first one only trials with complete alternations of features were used, while in the second experiment all possible types of repetitions were presented. Both response times (RTs) and errors were evaluated. Conflict adaptation effects on RTs were limited to congruent trials and were exclusively due to priming: they disappeared in the priming-free experiment and, in the second experiment, they occurred in sequences with feature repetitions but not in complete alternation sequences. Error results, instead, support the presence of conflict adaptation effects in incongruent trials. In priming-free sequences (experiment 1 and complete alternation sequences of experiment 2) with incongruent previous trials there was no error Stroop effect, while this effect was significant with congruent previous trials. These results indicate that cognitive control may modulate performance above and beyond priming effects.
Neurovascular Communication during CNS Development.
Developmental cell, 2018

A precise communication between the nervous and the vascular systems is crucial for proper formation and function of the central nervous system (CNS). Interestingly, this communication does not only occur by neural cells regulating the growth and properties of the vasculature, but new studies show that blood vessels actively control different neurodevelopmental processes. Here, we review the current knowledge on how neurons in particular influence growing blood vessels during CNS development and on how vessels participate in shaping the neural compartment. We also review the identified molecular mechanisms of this bidirectional communication.
Calcium channel kinetics of melanotrope cells in Xenopus laevis depend on environmental stimulation.
General and comparative endocrinology, 2008

We have tested the hypothesis that the type and kinetics of voltage-activated Ca(2+) channels in a neuroendocrine cell depend on the cell's long-term external input. For this purpose, the presence and kinetics of both low (LVA) and high-voltage-activated (HVA) L-type Ca(2+) channels have been assessed in melanotrope pituitary cells of the amphibian Xenopus laevis. The secretory activity of this cell type can readily be manipulated in vivo by changing the animal's environmental light condition, from a black to a white background. We here show that, compared to white background-adapted Xenopus, melanotropes from black background-adapted frogs have (1) a much larger size, as revealed by their 2.5 times larger membrane capacitance (P<0.001), (2) a 2 times higher HVA current density (P<0.05), (3) a clearly smaller Ca(2+)-dependent inactivation (10%; P<0.05), (4) L-type channels with 5 times slower activation and inactivation kinetics (P<0.05), and (5) slower kinetics of L-type channels that become faster and more similar to those in white-background adapted cells when the intracellular Ca(2+)-buffering capacity is reduced. Furthermore, white-adapted melanotropes possess LVA-type Ca(2+) channels, which are lacking from cells from black-adapted animals. The melanotrope calmodulin mRNA level does not differ between the two adaptation states. These results indicate that HVA L-type channel kinetics differ in relation to environmentally induced changes in cellular secretory state, probably mediated via intracellular Ca(2+)-buffering, whereas the occurrence of LVA Ca(2+) channels may depend on environmentally controlled channel gene expression.
Aspirin and Growth of Small Unruptured Intracranial Aneurysm: Results of a Prospective Cohort Study.
Stroke, 2020

The role of aspirin in unruptured intracranial aneurysm (UIA) growth remains largely unknown. We aim to identify whether aspirin is associated with a lower rate of UIA growth in patients with UIA <7 mm.
Modulation of neuronal dynamic range using two different adaptation mechanisms.
Neural regeneration research, 2017

The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents) in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms,
Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance.
Orphanet journal of rare diseases, 2019

Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA.
Novel compound heterozygous mutations in BCS1L gene causing Bjornstad syndrome in two siblings.
American journal of medical genetics. Part A, 2017

Bjornstad syndrome is a rare condition characterized by pili torti and sensorineural hearing loss associated with pathological variations in BCS1L. Mutations in this gene are also associated with the more severe complex III deficiency and GRACILE syndrome. We report the first Italian patients with Bjornstad syndrome, two siblings with pili torti and sensorineural hearing loss, in whom we detected two novel compound heterozygous mutations in BCS1L. A thorough clinical evaluation did not reveal any features consistent with complex III deficiency or GRACILE syndrome.
Strain differences in the effects of adrenalectomy on the midbrain dopamine system: implication for behavioral sensitization to cocaine.
Neuroscience, 2008

Adrenalectomy (ADX) abolishes behavioral sensitization to cocaine in DBA/2, but not C57BL/6 inbred mice. The present study tests the hypothesis that this ADX effect on behavioral sensitization in the DBA/2 strain involves changes in midbrain dopamine systems that do not occur in the C57BL/6 strain. For that purpose, we have measured tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA and D1- and D2-like receptor binding in C57BL/6 and DBA/2 mice that were i) unoperated, ii) ADX or sham (SHAM) operated, or iii) ADX or SHAM operated and subjected to a cocaine sensitization regimen (15.0 mg/kg cocaine on nine consecutive days, followed by a 7.5 mg/kg challenge after a 5-day withdrawal). ADX prevented behavioral sensitization to cocaine in the DBA/2, but not the C57BL/6 strain [de Jong IEM, Oitzl MS, de Kloet ER (2007) Adrenalectomy prevents behavioural sensitisation of mice to cocaine in a genotype-dependent manner. Behav Brain Res 177:329-339]. Mice were killed under basal conditions, in the latter case 24 h after the cocaine challenge. ADX did not affect the dopaminergic markers in drug naïve mice. By contrast, strain-dependent neuroadaptations were found in the midbrain dopamine system of mice subjected to the sensitization regimen. In the DBA/2 strain, sensitization-resistant ADX mice were characterized by reduced D2 binding in the nucleus accumbens core and rostral caudate putamen. Furthermore, ADX prevented the increase in TH and DAT mRNA expression in the substantia nigra, and the decrease in D2 binding in the dorsomedial subdivision of the caudal caudate putamen associated with sensitization in SHAM mice. In the C57BL/6 strain ADX only marginally affected dopaminergic adaptations. These data suggest that adrenal hormones modulate behavioral sensitization to cocaine in a genotype-dependent fashion possibly through adaptations in pre- and post-synaptic components of the midbrain dopamine system. During cocaine sensitization, the DBA/2, but not the C57BL/6 strain, was susceptible to ADX in the dopamine system with respect to presynaptic TH and DAT and terminal D2 receptor expression.
Flying in silence: Echolocating bats cease vocalizing to avoid sonar jamming.
Proceedings of the National Academy of Sciences of the United States of America, 2008

Although it has been recognized that echolocating bats may experience jamming from the signals of conspecifics, research on this problem has focused exclusively on time-frequency adjustments in the emitted signals to minimize interference. Here, we report a surprising new strategy used by bats to avoid interference, namely silence. In a quantitative study of flight and vocal behavior of the big brown bat (Eptesicus fuscus), we discovered that the bat spends considerable time in silence when flying with conspecifics. Silent behavior, defined here as at least one bat in a pair ceasing vocalization for more than 0.2 s (200 ms), occurred as much as 76% of the time (mean of 40% across 7 pairs) when their separation was shorter than 1 m, but only 0.08% when a single bat flew alone. Spatial separation, heading direction, and similarity in call design of paired bats were related to the prevalence of this silent behavior. Our data suggest that the bat uses silence as a strategy to avoid interference from sonar vocalizations of its neighbor, while listening to conspecific-generated acoustic signals to guide orientation. Based on previous neurophysiological studies of the bat's auditory midbrain, we hypothesize that environmental sounds (including vocalizations produced by other bats) and active echolocation evoke neural activity in different populations of neurons. Our findings offer compelling evidence that the echolocating bat switches between active and passive sensing to cope with a complex acoustic environment, and these results hold broad implications for research on navigation and communication throughout the animal kingdom.
Magnetoencephalography of epilepsy with a microfabricated atomic magnetrode.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Magnetoencephalography has long held the promise of providing a noninvasive tool for localizing epileptic seizures in humans because of its high spatial resolution compared with the scalp EEG. Yet, this promise has been elusive, not because of a lack of sensitivity or spatial resolution but because the large size and immobility of present cryogenic (superconducting) technology prevent long-term telemetry required to capture these very infrequent epileptiform events. To circumvent this limitation, we used Micro-Electro-Mechanical Systems technology to construct a noncryogenic (room temperature) microfabricated atomic magnetometer ("magnetrode") based on laser spectroscopy of rubidium vapor and similar in size and flexibility to scalp EEG electrodes. We tested the magnetrode by measuring the magnetic signature of epileptiform discharges in a rat model of epilepsy. We were able to measure neuronal currents of single epileptic discharges and more subtle spontaneous brain activity with a high signal-to-noise ratio approaching that of present superconducting sensors. These measurements are a promising step toward the goal of high-resolution noninvasive telemetry of epileptic events in humans with seizure disorders.
Early-life stress induces the development of Alzheimer's disease pathology via angiopathy.
Experimental neurology, 2021

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is a major societal, scientific, and economic problem. Several early-life factors associated with an increased risk for the clinical diagnosis of AD have recently been identified. In the present study, we investigated the involvement of early-life stress in the pathogenesis of AD using heterozygous amyloid precursor protein (APP) mutant mice (App