rudyvdbrink/CitationDatabase huggingface dataset:
Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice.
Science (New York, N.Y.), 2021

The integrated stress response (ISR) maintains proteostasis by modulating protein synthesis and is important in synaptic plasticity, learning, and memory. We developed a reporter, SPOTlight, for brainwide imaging of ISR state with cellular resolution. Unexpectedly, we found a class of neurons in mouse brain, striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Genetic and pharmacological manipulations revealed that ISR signaling was necessary in CINs for normal type 2 dopamine receptor (D2R) modulation. Inhibiting the ISR inverted the sign of D2R modulation of CIN firing and evoked dopamine release and altered skill learning. Thus, a noncanonical, steady-state mode of ISR activation is found in CINs, revealing a neuromodulatory role for the ISR in learning.
CSD-Induced Arterial Dilatation and Plasma Protein Extravasation Are Unaffected by Fremanezumab: Implications for CGRP's Role in Migraine with Aura.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019

Cortical spreading depression (CSD) is a wave of neuronal depolarization thought to underlie migraine aura. Calcitonin gene-related peptide (CGRP) is a potent vasodilator involved in migraine pathophysiology. Evidence for functional connectivity between CSD and CGRP has triggered scientific interest in the possibility that CGRP antagonism may disrupt vascular responses to CSD and the ensuing plasma protein extravasation (PPE). Using imaging tools that allow us to generate continuous, live, high-resolution views of spatial and temporal changes that affect arteries and veins in the dura and pia, we determined the extent to which CGRP contributes to the induction of arterial dilatation or PPE by CSD in female rats, and how these events are affected by the anti-CGRP monoclonal antibody (anti-CGRP-mAb) fremanezumab. We found that the CSD-induced brief dilatation and prolonged constriction of pial arteries, prolonged dilatation of dural arteries and PPE are all unaffected by fremanezumab, whereas the brief constriction and prolonged dilatation of pial veins are affected. In comparison, although CGRP infusion gave rise to the expected dilatation of dural arteries, which was effectively blocked by fremanezumab, it did not induce dilatation in pial arteries, pial veins, or dural veins. It also failed to induce PPE. Regardless of whether the nociceptors become active before or after the induction of arterial dilatation or PPE by CSD, the inability of fremanezumab to prevent them suggests that these events are not mediated by CGRP, a conclusion with important implications for our understanding of the mechanism of action of anti-CGRP-mAbs in migraine prevention.
Inflammatory bowel disease and restless leg syndrome.
Neurosciences (Riyadh, Saudi Arabia), 2020

Inflammatory bowel disease (IBD) has been associated with restless leg syndrome (RLS). This study aims to explore the prevalence, clinical predictors, and severity of RLS in IBD patients compared to controls.
Recent advances of HCI in decision-making tasks for optimized clinical workflows and precision medicine.
Journal of biomedical informatics, 2020

The ever-increasing amount of biomedical data is enabling new large-scale studies, even though ad hoc computational solutions are required. The most recent Machine Learning (ML) and Artificial Intelligence (AI) techniques have been achieving outstanding performance and an important impact in clinical research, aiming at precision medicine, as well as improving healthcare workflows. However, the inherent heterogeneity and uncertainty in the healthcare information sources pose new compelling challenges for clinicians in their decision-making tasks. Only the proper combination of AI and human intelligence capabilities, by explicitly taking into account effective and safe interaction paradigms, can permit the delivery of care that outperforms what either can do separately. Therefore, Human-Computer Interaction (HCI) plays a crucial role in the design of software oriented to decision-making in medicine. In this work, we systematically review and discuss several research fields strictly linked to HCI and clinical decision-making, by subdividing the articles into six themes, namely: Interfaces, Visualization, Electronic Health Records, Devices, Usability, and Clinical Decision Support Systems. However, these articles typically present overlaps among the themes, revealing that HCI inter-connects multiple topics. With the goal of focusing on HCI and design aspects, the articles under consideration were grouped into four clusters. The advances in AI can effectively support the physicians' cognitive processes, which certainly play a central role in decision-making tasks because the human mental behavior cannot be completely emulated and captured; the human mind might solve a complex problem even without a statistically significant amount of data by relying upon domain knowledge. For this reason, technology must focus on interactive solutions for supporting the physicians effectively in their daily activities, by exploiting their unique knowledge and evidence-based reasoning, as well as improving the various aspects highlighted in this review.
Killer Cell Immunoglobulin-like Receptor Variants Are Associated with Protection from Symptoms Associated with More Severe Course in Parkinson Disease.
Journal of immunology (Baltimore, Md. : 1950), 2020

Immune dysfunction plays a role in the development of Parkinson disease (PD). NK cells regulate immune functions and are modulated by killer cell immunoglobulin-like receptors (KIR). KIR are expressed on the surface of NK cells and interact with HLA class I ligands on the surface of all nucleated cells. We investigated
Spontaneous association of glial cells with regrowing neurites in mixed cultures of dissociated spiral ganglia.
Neuroscience, 2009

Evidence from developmental and regeneration studies of the cochlea and other tissues gives reason to hypothesize a role for nonneural cells in the growth and regeneration of cochlear spiral ganglion nerve fibers. We examined the spontaneous associations of regrowing neurites and nonneural cells in mixed cultures of dissociated newborn mouse spiral ganglia. After 7 days in vitro, nonneural cells formed a confluent layer in the culture well. Regrowing neurites grew atop this layer, forming non-uniform patterns that were similar to those formed by endogenously expressed laminin-1, entactin and integrin beta4, but not fibronectin or tenascin. In cultures grown for 42 h and maintained in three different growth media, all regrowing neurites were preferentially associated with spindle-shaped nonneural cells. The spindle-shaped cells incorporated bromodeoxyuridine in culture and were immunoreactive for the proteins S100, laminin-1, laminin-2, SRY-related high-mobility-group box 10 transcription factor (Sox10), neurotrophin receptor (P75) and connexin29 but negative for fibronectin and glial fibrillary acidic protein. These cells existed in the culture within a much larger, general population of fibronectin positive cells. Immunolabeling of fixed cochleas from neonatal mice localized Sox10, P75 and connexin29, to peripheral nerve bundles. The observed expressions of protein markers and the bipolar, spindle shape of the neurite-associated cells indicate that they are derived in vitro from the original Schwann or satellite cells in the ganglion or spiral lamina. The spontaneous and preferential association of neurites in culture with mitotic Schwann cells highlights the potential contribution neurite-Schwann cell interactions may have in promoting the growth and regrowth of damaged spiral ganglion neurons in the cochlea.
Association between poststroke epilepsy and death: A nationwide cohort study.
European stroke journal, 2016

Poststroke epilepsy (PSE) is the most common form of acquired epilepsy after middle age. The primary aim of this study was to study the impact of PSE on prognosis. A secondary aim was to validate recent findings from smaller studies on the risk of developing PSE on a nationwide scale.
Endothelins-1/3 and endothelin-A/B receptors expressing glial cells with special reference to activated microglia in experimentally induced cerebral ischemia in the adult rats.
Neuroscience, 2010

We reported previously that amoeboid microglial cells (AMC) in the developing brain exhibited endothelins (ETs) expression which diminished with advancing age and was undetected in microglia in the more mature brain. This study sought to explore if microglia in the adult would be induced to express ETs in altered conditions. By immunofluorescence microscopy, ETs and endothelin (ET)-B receptor were undetected in microglial cells in sham-operated and normal control rats. However, in adult rats subjected to middle cerebral artery occlusion (MCAO), lectin labeled activated microglia which occurred in large numbers in the marginal zones in the ischemic cortex at 3 days and 1 week intensely expressed ETs specifically endothelin (ET)-1 and ET-B receptor; ET-3 and ET-A receptor were absent in these cells. By RT-PCR and ELISA, ET-1 and -3 mRNA and protein expression level was progressively increased in the ischemic cerebral cortex after MCAO compared with the controls. ET-A and ET-B receptor mRNA and protein levels were concomitantly up-regulated. It is suggested that increased release of ET-1 following MCAO by massive activated microglia can exert an immediate constriction of local blood vessels bearing ET-A receptor. ET-1 may also interact with activated microglia endowed with ET-B receptor via an autocrine manner that may be linked to chemokines/cytokines production. ET-1, ET-3 and ET-B receptor were also localized in reactive astrocytes along with some oligodendrocytes. We conclude that activated microglia together with other glial cells in the marginal zone after MCAO are the main cellular source of ETs that may be involved in regulation of vascular constriction and glial chemokines/cytokines production. However, dissecting the role of individual component of the endothelin system in the various glial cells, notably activated microglia, would be vital in designing of an effective therapeutic strategy for clinical treatment of stroke in which microglial cells have been implicated.
Dopamine is Required for Activity-Dependent Amplification of Arc mRNA in Developing Postnatal Frontal Cortex.
Cerebral cortex (New York, N.Y. : 1991), 2017

The activity-regulated gene Arc/Arg3.1 encodes a postsynaptic protein crucially involved in glutamatergic synaptic plasticity. Genetic mutations in Arc pathway and altered Arc expression in human frontal cortex have been associated with schizophrenia. Although Arc expression has been reported to vary with age, what mechanisms regulate Arc mRNA levels in frontal cortex during postnatal development remains unclear. Using quantitative mRNA analysis of mouse frontal cortical tissues, we mapped the developmental profiles of Arc expression and found that its mRNA levels are sharply amplified near the end of the second postnatal week, when mouse pups open their eyes for the first time after birth. Surprisingly, electrical stimulation of the frontal cortex before eye-opening is not sufficient to drive the amplification of Arc mRNA. Instead, this amplification needs both electrical stimulation and dopamine D1-type receptor (D1R) activation. Furthermore, visual stimuli-driven amplification of Arc mRNA is also dependent on D1R activation and dopamine neurons located in the ventral midbrain. These results indicate that dopamine is required to drive activity-dependent amplification of Arc mRNA in the developing postnatal frontal cortex and suggest that joint electrical and dopaminergic activation is essential to establish the normal expression pattern of a schizophrenia-associated gene during frontal cortical development.
Neural correlates of a decision variable before learning to perform a match/non-match task.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

The lateral prefrontal cortex plays an important role in working memory and decision-making, although little is known about how neural correlates of these functions are shaped by learning. To understand the effect of learning on the neuronal representation of decision-making, we recorded single neurons from the lateral prefrontal cortex of monkeys before and after they were trained to judge whether two stimuli appeared at matching spatial locations. After training, and in agreement with previous studies, a population of neurons exhibited activity that was modulated depending on whether the second stimulus constituted a match or not, which had predictive ability for the monkey's choice. However, even before training, prefrontal neurons displayed modulation depending on the match or non-match status of a stimulus, with approximately equal percentages of neurons preferring a match or a non-match. The difference in firing rate and discriminability for match and non-match stimuli before training was of comparable magnitude as that after training. Changes observed after training involved an increase in the percentage of neurons exhibiting this effect, a greater proportion of neurons preferring non-match stimuli, and a greater percentage of neurons representing information about the first stimulus during the presentation of the second stimulus. Our results suggest that the neuronal activity representing some match/non-match judgments is present in the lateral prefrontal cortex even when subjects are not required to perform a comparison and before any training.
Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism.
Acta neuropathologica communications, 2018

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder that causes severe disability and death of young men. This disease is characterized by progressive muscle degeneration aggravated by sterile inflammation and is also associated with cognitive impairment and low bone density. Given that no current treatment can improve the long-term outcome, approaches with a strong translational potential are urgently needed. Duchenne muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory cells and inhibition of this receptor resulted in a significant attenuation of muscle and non-muscle symptoms in DMD
Distinct roles for innexin gap junctions and hemichannels in mechanosensation.
eLife, 2020

Mechanosensation is central to a wide range of functions, including tactile and pain perception, hearing, proprioception, and control of blood pressure, but identifying the molecules underlying mechanotransduction has proved challenging. In
Emotions amplify speaker-listener neural alignment.
Human brain mapping, 2019

Individuals often align their emotional states during conversation. Here, we reveal how such emotional alignment is reflected in synchronization of brain activity across speakers and listeners. Two "speaker" subjects told emotional and neutral autobiographical stories while their hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). The stories were recorded and played back to 16 "listener" subjects during fMRI. After scanning, both speakers and listeners rated the moment-to-moment valence and arousal of the stories. Time-varying similarity of the blood-oxygenation-level-dependent (BOLD) time series was quantified by intersubject phase synchronization (ISPS) between speaker-listener pairs. Telling and listening to the stories elicited similar emotions across speaker-listener pairs. Arousal was associated with increased speaker-listener neural synchronization in brain regions supporting attentional, auditory, somatosensory, and motor processing. Valence was associated with increased speaker-listener neural synchronization in brain regions involved in emotional processing, including amygdala, hippocampus, and temporal pole. Speaker-listener synchronization of subjective feelings of arousal was associated with increased neural synchronization in somatosensory and subcortical brain regions; synchronization of valence was associated with neural synchronization in parietal cortices and midline structures. We propose that emotion-dependent speaker-listener neural synchronization is associated with emotional contagion, thereby implying that listeners reproduce some aspects of the speaker's emotional state at the neural level.
Dopamine D5 receptors are localized at asymmetric synapses in the rat hippocampus.
Neuroscience, 2011

Functional studies indicate that the dopamine D5 receptor is involved in synaptic transmission in the hippocampus. However, previous anatomical studies have detected D5 receptor labelling primarily on the soma and main dendrites of CA1 pyramidal cells and on dendritic spines in monkey but not in rats. In order to get a better understanding of putative dopamine function in the hippocampus, we quantified the D5 receptor immunoreactivity on the pyramidal cell somas and on spines and dendrites in stratum radiatum and stratum oriens in the hippocampal CA1 region of rats by quantitative immunofluorescence and immunogold electron microscopy. The quantitative immunogold results revealed a higher labelling density on dendritic spines, notably at their synaptic membranes, compared to pyramidal cell somas and dendrites. Hence, dopamine could have effects on spines as well as on somas and dendrites. The labelling density was similar on spines in stratum oriens and stratum radiatum, but the presence of labelling varied between the spines within each stratum, indicating that the effect of dopamine could be diverse between different spines.
Implications of Long Non-Coding RNAs in Age-Altered Proteostasis.
Aging and disease, 2020

This review aims to summarize the current knowledge on how lncRNAs are influencing aging and cancer metabolism. Recent research has shown that senescent cells re-enter cell-cycle depending on intrinsic or extrinsic factors, thus restoring tissue homeostasis in response to age-related diseases (ARDs). Furthermore, maintaining proteostasis or cellular protein homeostasis requires a correct quality control (QC) of protein synthesis, folding, conformational stability, and degradation. Long non-coding RNAs (lncRNAs), transcripts longer than 200 nucleotides, regulate gene expression through RNA-binding protein (RBP) interaction. Their association is linked to aging, an event of proteostasis collapse. The current review examines approaches that lead to recognition of senescence-associated lncRNAs, current methodologies, potential challenges that arise from studying these molecules, and their crucial implications in clinical practice.
Rostral anterior cingulate glutamate predicts response to subcallosal deep brain stimulation for resistant depression.
Journal of affective disorders, 2020

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) provided benefit for treatment-resistant depression (TRD) in open-label studies but failed in a recent randomized sham-controlled trial. Informed patient selection, based on reliable biomarkers, is needed to optimize outcome. We investigated if rostral anterior cingulate (rACC) glutamate/glutamine concentration could serve as a potential biomarker of response.
Epithelial downgrowth after cataract surgery: an atypical presentation with scleral thinning and massive seeding in anterior chamber.
European journal of ophthalmology, 2016

To report an atypical presentation of epithelial downgrowth (ED) after clear cornea cataract extraction, characterized by mixed clinical expression of both cystic and diffuse form and massive epithelial debris seeding in anterior chamber, associated with scleral involvement.
Sexually selected skin colour is heritable and related to fecundity in a non-human primate.
Proceedings. Biological sciences, 2014

Sexual selection promotes the prevalence of heritable traits that increase an individual's reproductive rate. Despite theoretically strong directional selection, sexually selected traits can show inter-individual variation. Here, we investigate whether red skin ornamentation, a rare example of a male mammalian trait involved in mate attraction, influences fecundity and is heritable in rhesus macaques (Macaca mulatta), and explore the mechanisms that are involved in maintaining trait variation. Interestingly, the trait is expressed by and is attractive to both sexes. We collected facial images of 266 free-ranging individuals and modelled skin redness and darkness to rhesus macaque vision. We used 20 years of genetic parentage data to calculate selection gradients on the trait and perform heritability analyses. Results show that males who were both darkly coloured and high-ranking enjoyed higher fecundity. Female skin redness was positively linked to fecundity, although it remains unclear whether this influences male selectiveness. Heritability explained 10-15% of the variation in redness and darkness, and up to 30% for skin darkness when sexes are considered separately, suggesting sex-influenced inheritance. Our results suggest that inter-individual variation is maintained through condition-dependence, with an added effect of balancing selection on male skin darkness, providing rare evidence for a mammalian trait selected through inter-sexual selection.
The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing-Remitting Multiple Sclerosis Mouse Model.
Cells, 2020

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellular signaling molecule. A direct correlation between increased amount of S100B and demyelination and inflammatory processes has been demonstrated. The aim of this study is to investigate the possible role of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of disease progression in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the central nervous system, we observed that pentamidine is able to delay the acute phase of the disease and to inhibit remission, resulting in an amelioration of clinical score when compared with untreated relapsing-remitting experimental autoimmune encephalomyelitis mice. Moreover, we observed a significant reduction of proinflammatory cytokines expression levels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxide synthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modify the neuropathology of the disease, reducing immune infiltrates and partially protecting the brain from the damage. Overall, our results indicate that pentamidine targeting the S100B protein is a novel potential drug to be considered for multiple sclerosis treatment.