rudyvdbrink/CitationDatabase huggingface dataset:
Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.
Journal of cellular physiology, 2018

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine.
Genetic control of circuit function: Vsx1 and Irx5 transcription factors regulate contrast adaptation in the mouse retina.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Transcriptional programs guide the specification of neural cell types in the developing nervous system. However, it is unclear whether such programs also control specific aspects of neural circuit function at maturity. In the mammalian retina, Vsx1 and Irx5 transcription factors are present in a subset of bipolar interneurons that convey signals from photoreceptors to ganglion cells. The biased expression of Vsx1 and Irx5 in hyperpolarizing OFF compared with depolarizing ON bipolar cells suggests that these transcription factors may selectively regulate signal processing in OFF circuits. To test this hypothesis, we generated mice lacking both Vsx1 and Irx5. Bipolar cells in these mice were morphologically normal, but the expression of cell-specific markers in some OFF but not ON bipolar cells was reduced or absent. To assess visual function in Vsx1(-/-)Irx5(-/-) retinas, we recorded light responses from ensembles of retinal ganglion cells (RGCs). We first identified functional RGC types in control mice and describe their response properties and adaptation to temporal contrast using a simple linear-nonlinear model. We found that space-time receptive fields of RGCs are unchanged in Vsx1(-/-)Irx5(-/-) mice compared with control retinas. In contrast, response threshold, gain, and range were lowered in a cell-type-specific manner in OFF but not ON RGCs in Vsx1(-/-)Irx5(-/-) retinas. Finally, we discovered that the ability to adapt to temporal contrast is greatly reduced in OFF RGCs in the double mutant, suggesting that Vsx1 and Irx5 control specific aspects of visual function in circuits of the mammalian retina.
Spiking resonances in models with the same slow resonant and fast amplifying currents but different subthreshold dynamic properties.
Journal of computational neuroscience, 2017

The generation of spiking resonances in neurons (preferred spiking responses to oscillatory inputs) requires the interplay of the intrinsic ionic currents that operate at the subthreshold voltage level and the spiking mechanisms. Combinations of the same types of ionic currents in different parameter regimes may give rise to different types of nonlinearities in the voltage equation (e.g., parabolic- and cubic-like), generating subthreshold (membrane potential) oscillations patterns with different properties. These nonlinearities are not apparent in the model equations, but can be uncovered by plotting the voltage nullclines in the phase-plane diagram. We investigate the spiking resonant properties of conductance-based models that are biophysically equivalent at the subthreshold level (same ionic currents), but dynamically different (parabolic- and cubic-like voltage nullclines). As a case study we consider a model having a persistent sodium and a hyperpolarization-activated (h-) currents, which exhibits subthreshold resonance in the theta frequency band. We unfold the concept of spiking resonance into evoked and output spiking resonance. The former focuses on the input frequencies that are able to generate spikes, while the latter focuses on the output spiking frequencies regardless of the input frequency that generated these spikes. A cell can exhibit one or both types of resonances. We also measure spiking phasonance, which is an extension of subthreshold phasonance (zero-phase-shift response to oscillatory inputs) to the spiking regime. The subthreshold resonant properties of both types of models are communicated to the spiking regime for low enough input amplitudes as the voltage response for the subthreshold resonant frequency band raises above threshold. For higher input amplitudes evoked spiking resonance is no longer present in these models, but output spiking resonance is present primarily in the parabolic-like model due to a cycle skipping mechanism (involving mixed-mode oscillations), while the cubic-like model shows a better 1:1 entrainment. We use dynamical systems tools to explain the underlying mechanisms and the mechanistic differences between the resonance types. Our results demonstrate that the effective time scales that operate at the subthreshold regime to generate intrinsic subthreshold oscillations, mixed-mode oscillations and subthreshold resonance do not necessarily determine the existence of a preferred spiking response to oscillatory inputs in the same frequency band. The results discussed in this paper highlight both the complexity of the suprathreshold responses to oscillatory inputs in neurons having resonant and amplifying currents with different time scales and the fact that the identity of the participating ionic currents is not enough to predict the resulting patterns, but additional dynamic information, captured by the geometric properties of the phase-space diagram, is needed.
Dual Specificity Phosphatases Support Axon Plasticity and Viability.
Molecular neurobiology, 2021

In peripheral neuropathies, axonal degeneration (AxD) impairs the prognosis for recovery. Here, we describe a role for dual specificity phosphatases (DUSPs; MAP kinase phosphatases, MKPs), in supporting autonomous axon plasticity and viability. Both DUSPs 1 and 4 were identified within intact or axotomized sensory neurons. Knockdown of DUSP 1 or 4 independently or combined impaired neurite outgrowth in adult dissociated sensory neurons. Furthermore, adult sensory neurons with DUSP knockdown were rendered sensitive to axonopathy in vitro following exposure to low, subtoxic TrpV1 (transient receptor potential cation channel subfamily V member 1) activation by capsaicin, an intervention normally supportive of growth. This was not prevented by concurrent DLK (dual leucine zipper kinase) knockdown. Ex vivo neurofilament dissolution was heightened by DUSP inhibition within explanted nerves. In vivo DUSP knockdown or inhibition was associated with more rapid loss of motor axon excitability. The addition of SARM1 (sterile alpha and TIR motif containing 1) siRNA abrogated DUSP1 and 4 mediated loss of excitability. DUSP knockdown accelerated neurofilament breakdown and there was earlier morphological evidence of myelinated axon degeneration distal to axotomy. Taken together, the findings identify a key role for DUSPs in supporting axon plasticity and survival.
Treating Sleep Problems in Patients with Schizophrenia.
Behavioural and cognitive psychotherapy, 2016

Sleep disturbance is increasingly recognized as a major problem for patients with schizophrenia but it is rarely the direct focus of treatment. The main recommended treatment for insomnia is cognitive behavioural therapy, which we have been evaluating for patients with current delusions and hallucinations in the context of non-affective psychosis.
Practice induces a qualitative change in the memory representation for visuomotor learning.
Journal of neurophysiology, 2019

Adaptation of our movements to changes in the environment is known to be supported by multiple learning processes that operate in parallel. One is an implicit recalibration process driven by sensory-prediction errors; the other process counters the perturbation through more deliberate compensation. Prior experience is known to enable adaptation to occur more rapidly, a phenomenon known as "savings," but exactly how experience alters each underlying learning process remains unclear. We measured the relative contributions of implicit recalibration and deliberate compensation to savings across 2 days of practice adapting to a visuomotor rotation. The rate of implicit recalibration showed no improvement with repeated practice. Instead, practice led to deliberate compensation being expressed even when preparation time was very limited. This qualitative change is consistent with the proposal that practice establishes a cached association linking target locations to appropriate motor output, facilitating a transition from deliberate to automatic action selection.
Sex matters: n-back modulates emotional mismatch negativity.
Neuroreport, 2013

This work investigates the impact of task load on irrelevant emotional voice processing between the sexes. The working memory task was manipulated by asking participants to evaluate the position of a visual stimulus (0-back) and compare the position of the current stimulus with the one or two trials before (1-back and 2-back). We recorded auditory event-related potentials while presenting the emotionally spoken syllables 'dada' and acoustically matched nonvocal sounds to healthy adults. Women, not men, showed larger amplitudes of emotional mismatch negativity (MMN), presumed to reflect preattentive auditory change detection, during the 1-back task than the 0-back and 2-back tasks. Among women only weaker emotional MMN amplitudes were associated with a higher 2-back accuracy. Neither task difficulty nor sex had any effect on MMN when responding to nonvocal sounds. Our findings suggest that there are sex differences in preattentive emotional voice processing under varying levels of task load.
Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated.
eLife, 2017

The mouse olfactory sensory neuron (OSN) repertoire is composed of 10 million cells and each expresses one olfactory receptor (OR) gene from a pool of over 1000. Thus, the nose is sub-stratified into more than a thousand OSN subtypes. Here, we employ and validate an RNA-sequencing-based method to quantify the abundance of all OSN subtypes in parallel, and investigate the genetic and environmental factors that contribute to neuronal diversity. We find that the OSN subtype distribution is stereotyped in genetically identical mice, but varies extensively between different strains. Further, we identify
Basin entropy: a new tool to analyze uncertainty in dynamical systems.
Scientific reports, 2016

In nonlinear dynamics, basins of attraction link a given set of initial conditions to its corresponding final states. This notion appears in a broad range of applications where several outcomes are possible, which is a common situation in neuroscience, economy, astronomy, ecology and many other disciplines. Depending on the nature of the basins, prediction can be difficult even in systems that evolve under deterministic rules. From this respect, a proper classification of this unpredictability is clearly required. To address this issue, we introduce the basin entropy, a measure to quantify this uncertainty. Its application is illustrated with several paradigmatic examples that allow us to identify the ingredients that hinder the prediction of the final state. The basin entropy provides an efficient method to probe the behavior of a system when different parameters are varied. Additionally, we provide a sufficient condition for the existence of fractal basin boundaries: when the basin entropy of the boundaries is larger than log2, the basin is fractal.
Risk of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patient Treated With Natalizumab: A Systematic Review.
Cureus, 2021

Natalizumab, a monoclonal antibody acting on alpha4 integrin receptors, is frequently used to treat multiple sclerosis patients. The biggest downside is the risk of development of progressive multifocal leukoencephalopathy, an immune-related condition affecting mainly the central nervous system. The presence of the John Cunningham virus (JCV) and its reactivation is an important factor in the development of progressive multifocal leukoencephalopathy (PML). This study highlights its different proposed mechanism and risk factors strongly related to natalizumab-induced progressive multifocal leukoencephalopathy. The pieces of literature will also be reviewed to look for a relation between the JCV and natalizumab-induced progressive multifocal leukoencephalopathy in multiple sclerosis treated patients. The articles were searched from three databases and reviewed systematically. The inclusion criteria for this study were patients aged 20-50 years, English language paper, full-text availability, and human studies, whereas articles on patients with AIDS and cancer-related disease prior to natalizumab treatment were excluded. Out of 6531 articles identified after applying the search strategy on three main databases PubMed, Google Scholar, and ResearchGate, a total of 32 articles were finalized for the review. This study follows the guidelines listed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist 2009. The data collected from these finalized articles were pertaining to the risk factor related to natalizumab induced progressive multifocal leukoencephalopathy and the mechanism related to its pathogenesis.  Natalizumab is known to have the potential to cause progressive multifocal leukoencephalopathy in treated patients; here, we evaluate a close relationship of its related risk factors. The articles studied exhibit a close relationship between the length of natalizumab treatment and the presence of the JCV before infusion of natalizumab. From our analysis, it seems that the mechanism related to natalizumab-induced PML is strongly related to antigen-specific T cells and its effects. The frequency of monitoring and vigilance on the management of patients treated with natalizumab will help detect progressive multifocal leukoencephalopathy.
CAPS facilitates filling of the rapidly releasable pool of large dense-core vesicles.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Calcium-activator protein for secretion (CAPS) is a cytosolic protein that associates with large dense-core vesicles and is involved in their secretion. Mammals express two CAPS isoforms, which share a similar domain structure including a Munc13 homology domain that is believed to be involved in the priming of secretory vesicles. A variety of studies designed to perturb CAPS function indicate that CAPS is involved in the secretion of large dense-core vesicles, but where in the secretory pathway CAPS acts is still under debate. Mice in which one allele of the CAPS-1 gene is deleted exhibit a deficit in catecholamine secretion from chromaffin cells. We have examined catecholamine secretion from chromaffin cells in which both CAPS genes were deleted and show that the deletion of both CAPS isoforms causes a strong reduction in the pool of rapidly releasable chromaffin granules and of sustained release during ongoing stimulation. We conclude that CAPS is required for the adequate refilling and/or maintenance of a rapidly releasable granule pool.
Psychobiology of PTSD in the acute aftermath of trauma: Integrating research on coping, HPA function and sympathetic nervous system activity.
Asian journal of psychiatry, 2013

Research on the psychobiological sequelae of trauma has typically focused on long-term alterations in individuals with chronic posttraumatic stress disorder (PTSD). Far less is known about the nature and course of psychobiological risk factors for PTSD during the acute aftermath of trauma. In this review, we summarize data from prospective studies focusing on the relationships among sympathetic nervous system activity, hypothalamic-pituitary-adrenal function, coping strategies and PTSD symptoms during the early recovery (or non-recovery) phase. Findings from pertinent studies are integrated to inform psychobiological profiles of PTSD-risk in children and adults in the context of existing models of PTSD-onset and maintenance. Data regarding bidirectional relations between coping strategies and stress hormones is reviewed. Limitations of existing literature and recommendations for future research are discussed.
The CONECSI trial: results of a randomized controlled trial of a multidisciplinary cognitive behavioral program for coping with chronic neuropathic pain after spinal cord injury.
Pain, 2012

Many people with spinal cord injury (SCI) rate chronic neuropathic pain as one of the most difficult problems to manage. The aim of the CONECSI (COping with NEuropathiC Spinal cord Injury pain) trial was to evaluate a multidisciplinary cognitive behavioral treatment program for persons with chronic neuropathic pain after SCI. The intervention consisted of educational, cognitive, and behavioral elements. A total of 61 people were randomized to either the intervention group or the waiting list control group in 4 Dutch rehabilitation centers. Primary outcomes were pain intensity and pain-related disability (Chronic Pain Grade questionnaire), and secondary outcomes were mood (Hospital Anxiety and Depression Scale), participation in activities (Utrecht Activities List), and life satisfaction (Life Satisfaction Questionnaire). Measurements were performed at baseline, and at 3, and 6 months follow-up. The primary statistical technique was random coefficient analysis. The analyses showed significant changes over time on both primary (t1-t2), and 2 out of 4 secondary outcomes (both t1-t2 and t1-t3). Significant intervention effects (Time*Group interactions) were found for anxiety and participation in activities, but not for the primary outcomes. Subsequent paired t tests showed significant changes in the intervention group that were not seen in the control group: decrease of pain intensity, pain-related disability, anxiety, and increase of participation in activities. This study implies that a multidisciplinary cognitive behavioral program might have beneficial effects on people with chronic neuropathic SCI pain.
Reference values for CSF outflow resistance and intracranial pressure in healthy elderly.
Neurology, 2011

The intracranial pressure (ICP) and CSF outflow resistance (R(out)) are essential to describe the dynamics of the CSF system. R(out) affects ICP, pulse amplitudes, CSF absorption, and the compliance of the system. The objective of this study was to determine the reference values in healthy elderly subjects.
Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations.
Journal of Alzheimer's disease : JAD, 2016

Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD).
Hemichorea as Presentation of Acute Cortical Ischemic Stroke. Case Series and Review of the Literature.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2020

Hemichorea and other hyperkinetic movement disorders are a rare presentation of stroke, usually secondary to deep infarctions affecting the basal ganglia and the thalamus. Chorea can also result from lesions limited to the cortex, as shown in recent reports. Still, the pathophysiology of this form of cortical stroke-related chorea remains unknown. We report 4 cases of acute ischemic cortical strokes presenting as hemichorea, with the infarction being limited to the parietal and insular cortex in perfusion computed tomography scans and magnetic resonance imaging. These cases suggest potential dysfunction of pathways connecting these cortical regions with the basal ganglia.
Mycosporine-like amino acids are multifunctional molecules in sea hares and their marine community.
Proceedings of the National Academy of Sciences of the United States of America, 2011

Molecules of keystone significance are relatively rare, yet mediate a variety of interactions between organisms. They influence the distribution and abundance of species, the transfer of energy across multiple trophic levels, and thus they play significant roles in structuring ecosystems. Despite their potential importance in facilitating our understanding of ecological systems, only three molecules thus far have been proposed as molecules of keystone significance: saxitoxin and dimethyl sulfide in marine communities and tetrodotoxin in riparian communities. In the course of studying the neuroecology of chemical defenses, we identified three mycosporine-like amino acids (MAAs)--N-ethanol palythine (= asterina-330), N-isopropanol palythine (= aplysiapalythine A), and N-ethyl palythine (= aplysiapalythine B)--as intraspecific alarm cues for sea hares (Aplysia californica). These alarm cues are released in the ink secretion of sea hares and cause avoidance behaviors in neighboring conspecifics. Further, we show that these three bioactive MAAs, two [aplysiapalythine A (APA) and -B (APB)] being previously unknown molecules, are present in the algal diet of sea hares and are concentrated in their defensive secretion as well as in their skin. MAAs are known to be produced by algae, fungi, and cyanobacteria and are acquired by many aquatic animals through trophic interactions. MAAs are widely used as sunscreens, among other uses, but sea hares modify their function to serve a previously undocumented role, as intraspecific chemical cues. Our findings highlight the multifunctionality of MAAs and their role in ecological connectivity, suggesting that they may function as molecules of keystone significance in marine ecosystems.