rudyvdbrink/CitationDatabase huggingface dataset:
GluA1 subunit ubiquitination mediates amyloid-β-induced loss of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.
The Journal of biological chemistry, 2017

The accumulation of soluble amyloid-β (Aβ) peptides produces profound neuronal changes in the brain during the pathogenesis of Alzheimer's disease. Excessive levels of Aβ disrupt excitatory synaptic transmission by promoting the removal of synaptic AMPA receptors (AMPARs), dendritic spine loss, and synaptic depression. Recently, activity-dependent ubiquitination of the GluA1 subunit has been shown to regulate the intracellular sorting of AMPARs toward late endosomes for degradation. However, whether this ubiquitin signaling pathway mediates Aβ-induced loss of surface AMPARs is unknown. In this study, we demonstrate that acute exposure of cultured neurons to soluble Aβ oligomers induces AMPAR ubiquitination concomitant with the removal of AMPARs from the plasma membrane. Importantly, expression of the GluA1 ubiquitin-deficient mutants inhibited the adverse effects of Aβ on the surface expression of AMPARs in neurons. Furthermore, we revealed the cross-talk between GluA1 ubiquitination and phosphorylation, in particular phosphorylation at Ser-845, which is crucial for AMPAR recycling and is known to be dephosphorylated in the presence of Aβ. Our data showed that the GluA1 ubiquitin-deficient mutant enhances GluA1 phosphorylation on Ser-845. Conversely, the GluA1 S845D phosphomimetic mutant reduced binding with Nedd4-1 and hence the ubiquitination of AMPARs. Importantly, the GluA1 S845D mutant also prevented Aβ-induced removal of surface AMPARs. Taken together, these findings provide the first demonstration of the dynamic cross-modulation of GluA1 ubiquitination and phosphorylation, a process that is perturbed by Aβ, in regulating the membrane sorting decision that ultimately determines the number of AMPARs on the cell surface.
Interoceptive awareness selectively predicts timing accuracy in irregular contexts.
Behavioural brain research, 2020

Awareness of psychophysiological changes has been proposed to play a role in duration perception; however, evidence on whether interoceptive awareness affects timing is mixed, and it is not clear which task features favor the reliance on bodily changes to track time. Here we tested the hypothesis that interoceptive awareness is selectively involved in timing when the context does not provide reliable cues on elapsed time. We developed a novel paradigm assessing interval reproduction in two conditions: 1) with regularly spaced stimuli during the encoding/reproduction phase (regular condition), 2) with irregularly spaced stimuli during the encoding/reproduction phase (irregular condition). Interoceptive awareness was assessed using the "Self-Awareness Questionnaire", investigating the frequency of common bodily sensations. Interoceptive awareness predicted timing accuracy in the irregular, but not in the regular condition; also, the contribution was specifically due to awareness of visceral sensations rather than somatosensory sensations. Overall, results suggest that individual differences in interoception differently affect timing according to contextual features, consistently with evidence that different mechanisms mediate timing in different conditions.
Comparison of low-normal and high-normal IGF-1 target levels during growth hormone replacement therapy: A randomized clinical trial in adult growth hormone deficiency.
European journal of internal medicine, 2016

Current guidelines state that the goals of growth hormone (GH) therapy in adults should be an appropriate clinical response, avoidance of side effects, and an IGF-1 value within the age-adjusted reference range. There are no published studies on the target level for IGF-1 that offer specific guidance in this regard.
Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths.
The American journal of psychiatry, 2019

Childhood irritability is a common, impairing problem with changing age-related manifestations that predict long-term adverse outcomes. However, more investigation of overall and age-specific neural correlates is needed. Because youths with irritability exhibit exaggerated responses to frustrating stimuli, the authors used a frustration functional MRI (fMRI) paradigm to examine associations between irritability and neural activation and tested the moderating effect of age.
The Role of Intraoperative Cerebral Angiography in Transorbital Intracranial Penetrating Trauma: A Case Report and Literature Review.
World neurosurgery, 2017

Transorbital intracranial penetrating trauma with a retained intracranial foreign body is a rare event lacking a widely accepted diagnostic and therapeutic algorithm. Intraoperative catheter angiography (IOA) has been advocated by some authorities to rule out cerebrovascular injury before and/or after removal of the object, but no standard of care currently exists.
ABCA12 regulates insulin secretion from β-cells.
EMBO reports, 2020

Dysregulation of lipid homeostasis is intimately associated with defects in insulin secretion, a key feature of type 2 diabetes. Here, we explore the role of the putative lipid transporter ABCA12 in regulating insulin secretion from β-cells. Mice with β-cell-specific deletion of Abca12 display impaired glucose-stimulated insulin secretion and eventual islet inflammation and β-cell death. ABCA12's action in the pancreas is independent of changes in the abundance of two other cholesterol transporters, ABCA1 and ABCG1, or of changes in cellular cholesterol or ceramide content. Instead, loss of ABCA12 results in defects in the genesis and fusion of insulin secretory granules and increases in the abundance of lipid rafts at the cell membrane. These changes are associated with dysregulation of the small GTPase CDC42 and with decreased actin polymerisation. Our findings establish a new, pleiotropic role for ABCA12 in regulating pancreatic lipid homeostasis and insulin secretion.
Ethyl nitrite is produced in the human stomach from dietary nitrate and ethanol, releasing nitric oxide at physiological pH: potential impact on gastric motility.
Free radical biology & medicine, 2015

Nitric oxide ((∙)NO), a ubiquitous molecule involved in a plethora of signaling pathways, is produced from dietary nitrate in the gut through the so-called nitrate-nitrite-NO pathway. In the stomach, nitrite derived from dietary nitrate triggers a network of chemical reactions targeting endogenous and exogenous biomolecules, thereby producing new compounds with physiological activity.
Language reorganization in early onset temporal lobe epilepsy.
Epilepsia, 2011

Behavioral and functional magnetic resonance imaging (fMRI) studies have consistently shown abnormalities of language function or cortical organization in patients with well-established temporal lobe epilepsy (TLE). However, whether these changes are present in new-onset TLE has not been studied to date. Studying such changes in new-onset TLE would provide valuable insight into the timing and factors that affect language deficits in TLE and may unmask fundamental differences in brain organization in persons who have TLE and those who do not.
Bigmelon: tools for analysing large DNA methylation datasets.
Bioinformatics (Oxford, England), 2019

The datasets generated by DNA methylation analyses are getting bigger. With the release of the HumanMethylationEPIC micro-array and datasets containing thousands of samples, analyses of these large datasets using R are becoming impractical due to large memory requirements. As a result there is an increasing need for computationally efficient methodologies to perform meaningful analysis on high dimensional data.
New evidence for chunk-based models in word segmentation.
Acta psychologica, 2014

There is large evidence that infants are able to exploit statistical cues to discover the words of their language. However, how they proceed to do so is the object of enduring debates. The prevalent position is that words are extracted from the prior computation of statistics, in particular the transitional probabilities between syllables. As an alternative, chunk-based models posit that the sensitivity to statistics results from other processes, whereby many potential chunks are considered as candidate words, then selected as a function of their relevance. These two classes of models have proven to be difficult to dissociate. We propose here a procedure, which leads to contrasted predictions regarding the influence of a first language, L1, on the segmentation of a second language, L2. Simulations run with PARSER (Perruchet & Vinter, 1998), a chunk-based model, predict that when the words of L1 become word-external transitions of L2, learning of L2 should be depleted until reaching below chance level, at least before extensive exposure to L2 reverses the effect. In the same condition, a transitional-probability based model predicts above-chance performance whatever the duration of exposure to L2. PARSER's predictions were confirmed by experimental data: Performance on a two-alternative forced choice test between words and part-words from L2 was significantly below chance even though part-words were less cohesive in terms of transitional probabilities than words.
Evolutionary differences in food preference rely on Gr64e, a receptor for glycerol.
Nature neuroscience, 2011

Very little is known about how stimuli that are typically not rich in sugars, such as beer, trigger attractive gustatory responses in Drosophila. We identified a member of the gustatory receptor family, Gr64e, as a receptor that is required for feeding preference for beer and other sources that have fermenting yeast. We found that Gr64e is required for neuronal and behavioral responses to glycerol, an abundant component of growing yeast and fermentation products. Ectopic expression of Gr64e in an olfactory neuron conferred responsiveness to glycerol. We also found that Drosophila species that are predicted to carry pseudogenes of Gr64e had reduced glycerol sensitivity. Our results provide insight into the molecular mechanisms of feeding acceptance of yeast products and raise the possibility that Gr64e contributes to specific evolutionary variations in appetitive selectivity across Drosophila species.
Sleep, circadian rhythms and health.
Interface focus, 2020

At the core of human thought, for the majority of individuals in the developed nations at least, there is the tacit assumption that as a species we are unfettered by the demands imposed by our biology and that we can do what we want, at whatever time we choose, whereas in reality every aspect of our physiology and behaviour is constrained by a 24 h beat arising from deep within our evolution. Our daily circadian rhythms and sleep/wake cycle allow us to function optimally in a dynamic world, adjusting our biology to the demands imposed by the day/night cycle. The themes developed in this review focus upon the growing realization that we ignore the circadian and sleep systems at our peril, and this paper considers the mechanisms that generate and regulate circadian and sleep systems; what happens mechanistically when these systems collapse as a result of societal pressures and disease; how sleep disruption and stress are linked; why sleep disruption and mental illness invariably occur together; and how individuals and employers can attempt to mitigate some of the problems associated with working against our internal temporal biology. While some of the health costs of sleep disruption can be reduced, in the short-term at least, there will always be significant negative consequences associated with shift work and sleep loss. With this in mind, society needs to address this issue and decide when the consequences of sleep disruption are justified in the workplace.
Regeneration of the mammalian inner ear sensory epithelium.
Current opinion in otolaryngology & head and neck surgery, 2009

This review will focus on 'self-repair' of the mammalian inner ear sensory epithelium, including recruiting the in-situ proliferation and differentiation of endogenous cells at the damaged site and the autologous transplantation
From single gene analysis to single cell profiling: a new era for precision medicine.
Journal of experimental & clinical cancer research : CR, 2020

Molecular profiling of DNA and RNA has provided valuable new insights into the genetic basis of non-malignant and malignant disorders, as well as an increased understanding of basic mechanisms that regulate human disease. Recent technological advances have enabled the analyses of alterations in gene-based structure or function in a comprehensive, high-throughput fashion showing that each tumor type typically exhibits distinct constellations of genetic alterations targeting one or more key cellular pathways that regulate cell growth and proliferation, evasion of the immune system, and other aspects of cancer behavior. These advances have important implications for future research and clinical practice in areas as molecular diagnostics, the implementation of gene or pathway-directed targeted therapy, and the use of such information to drive drug discovery. The 1st international and 32nd Annual Conference of Italian Association of Cell Cultures (AICC) conference wanted to offer the opportunity to match technological solutions and clinical needs in the era of precision medicine.
Beyond Reading Modulation: Temporo-Parietal tDCS Alters Visuo-Spatial Attention and Motion Perception in Dyslexia.
Brain sciences, 2021

Dyslexia is a neurodevelopmental disorder with an atypical activation of posterior left-hemisphere brain reading networks (i.e., temporo-occipital and temporo-parietal regions) and multiple neuropsychological deficits. Transcranial direct current stimulation (tDCS) is a tool for manipulating neural activity and, in turn, neurocognitive processes. While studies have demonstrated the significant effects of tDCS on reading, neurocognitive changes beyond reading modulation have been poorly investigated. The present study aimed at examining whether tDCS on temporo-parietal regions affected not only reading, but also phonological skills, visuo-spatial working memory, visuo-spatial attention, and motion perception in a polarity-dependent way. In a within-subjects design, ten children and adolescents with dyslexia performed reading and neuropsychological tasks after 20 min of exposure to Left Anodal/Right Cathodal (LA/RC) and Right Anodal/Left Cathodal (RA/LC) tDCS. LA/RC tDCS compared to RA/LC tDCS improved text accuracy, word recognition speed, motion perception, and modified attentional focusing in our group of children and adolescents with dyslexia. Changes in text reading accuracy and word recognition speed-after LA/RC tDCS compared to RA/LC-were related to changes in motion perception and in visuo-spatial working memory, respectively. Our findings demonstrated that reading and domain-general neurocognitive functions in a group of children and adolescents with dyslexia change following tDCS and that they are polarity-dependent.
Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers.
Journal of psychosomatic research, 2019

Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the "bio depression score"). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P < .001), in serum (P = .02) and in the combined serum plus urine result (P < .001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.
Stress and consumption of alcohol in humans with a Type 1 family history of alcoholism in an experimental laboratory setting.
Pharmacology, biochemistry, and behavior, 2011

This paper investigates how stress interacts with alcohol consumption in subjects with a family history of alcoholism. One mechanism for increases in alcohol intake may be that stress alters the subjective effects produced by the drug.
Neurophysiological measures for users' training objective assessment during simulated robot-assisted laparoscopic surgery.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2016

Minimally invasive surgery can be performed with robotic assistance, as evolution of laparoscopic surgery. Robots for assisted surgery are far from being user friendly and require extensive training. To this end, ad-hoc devices and experimental set-ups are needed. The da Vinci system is one of the most diffused surgical robotics technology. The aim of the study was two-fold: i) to propose a neurophysiological measure by which objectively assess the learning progress of the users by means of a simulator of the da Vinci system, and ii) to demonstrate the advantages of cognitive assessment with respect to the standard methodologies for the evaluation of training efficiency.
Effect of Body Position on Pharyngeal Swallowing Pressures Using High-Resolution Manometry.
Dysphagia, 2018

The effect of body position and gravitational pull on the complex pressure-driven process of pharyngeal swallowing remains unknown. Using high-resolution manometry (HRM), this study aims to identify positional adaptations of pharyngeal physiology by evaluating swallowing pressure patterns in a series of inverted body positions. Ten healthy adults each underwent swallowing tasks with pharyngeal HRM at six body positions using an inversion table (0°[upright], 45°, 90°[supine], 110°, 135°, and 180°[fully inverted]). Repeated measures ANOVA was used to assess impact of position on pressure parameters, and pharyngeal-UES pressure gradients translate. Velopharyngeal pressures varied by position (P < 0.001), with significantly higher pressures generated with inversion ≥90°, compared with upright and 45°. Change in position did not significantly affect common mesopharyngeal pressures or swallowing pressure durations. UES valving mechanisms were preserved during inversion, with subtle variations observed in integral pressures (P = 0.011). Pharyngeal-UES pressure gradients changed with position (P < 0.01), increasing with inversion > 90° compared to upright and 45°. Mechanisms of deglutition may differ with position and relative direction of gravity, particularly when at > 45° inclination. Increased palatal pressure is generated in the upside-down position to achieve nasopharyngeal closure and prevent regurgitation. While other classically measured pressures may not consistently differ with positioning, many individuals exhibit adaptations in pressure gradients when inverted, likely due to a combination of changes in pharyngeal driving force and UES opening mechanisms. Identification of these changes, relative to position, further builds on our understanding of the adaptability of the pharyngeal swallowing system.
Social stress is lethal in the mdx model of Duchenne muscular dystrophy.
EBioMedicine, 2020

Duchenne muscular dystrophy (DMD) is caused by the loss of dystrophin. Severe and ultimately lethal, DMD progresses relatively slowly in that patients become wheelchair bound only around age twelve with a survival expectancy reaching the third decade of life.
There Is a "U" in Clutter: Evidence for Robust Sparse Codes Underlying Clutter Tolerance in Human Vision.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

The ability to recognize objects in clutter is crucial for human vision, yet the underlying neural computations remain poorly understood. Previous single-unit electrophysiology recordings in inferotemporal cortex in monkeys and fMRI studies of object-selective cortex in humans have shown that the responses to pairs of objects can sometimes be well described as a weighted average of the responses to the constituent objects. Yet, from a computational standpoint, it is not clear how the challenge of object recognition in clutter can be solved if downstream areas must disentangle the identity of an unknown number of individual objects from the confounded average neuronal responses. An alternative idea is that recognition is based on a subpopulation of neurons that are robust to clutter, i.e., that do not show response averaging, but rather robust object-selective responses in the presence of clutter. Here we show that simulations using the HMAX model of object recognition in cortex can fit the aforementioned single-unit and fMRI data, showing that the averaging-like responses can be understood as the result of responses of object-selective neurons to suboptimal stimuli. Moreover, the model shows how object recognition can be achieved by a sparse readout of neurons whose selectivity is robust to clutter. Finally, the model provides a novel prediction about human object recognition performance, namely, that target recognition ability should show a U-shaped dependency on the similarity of simultaneously presented clutter objects. This prediction is confirmed experimentally, supporting a simple, unifying model of how the brain performs object recognition in clutter.
The role of serotonin in reward, punishment and behavioural inhibition in humans: insights from studies with acute tryptophan depletion.
Neuroscience and biobehavioral reviews, 2014

Deakin and Graeff proposed that forebrain 5-hydroxytryptamine (5-HT) projections are activated by aversive events and mediate anticipatory coping responses including avoidance learning and suppression of the fight-flight escape/panic response. Other theories proposed 5-HT mediates aspects of behavioural inhibition or reward. Most of the evidence comes from rodent studies. We review 36 experimental studies in humans in which the technique of acute tryptophan depletion (ATD) was used to explicitly address the role of 5-HT in response inhibition, punishment and reward. ATD did not cause disinhibition of responding in the absence of rewards or punishments (9 studies). A major role for 5-HT in reward processing is unlikely but further tests are warranted by some ATD findings. Remarkably, ATD lessened the ability of punishments (losing points or notional money) to restrain behaviour without affecting reward processing in 7 studies. Two of these studies strongly indicate that ATD blocks 5-HT mediated aversively conditioned Pavlovian inhibition and this can explain a number of the behavioural effects of ATD.