rudyvdbrink/CitationDatabase huggingface dataset:
Operation and plasticity of hippocampal CA3 circuits: implications for memory encoding.
Nature reviews. Neuroscience, 2017

The CA3 region of the hippocampus is important for rapid encoding of memory. Computational theories have proposed specific roles in hippocampal function and memory for the sparse inputs from the dentate gyrus to CA3 and for the extended local recurrent connectivity that gives rise to the CA3 autoassociative network. Recently, we have gained considerable new insight into the operation and plasticity of CA3 circuits, including the identification of novel forms of synaptic plasticity and their underlying mechanisms, and structural plasticity in the GABAergic control of CA3 circuits. In addition, experimental links between synaptic plasticity of CA3 circuits and memory are starting to emerge.
Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABA(A) receptors.
Journal of neurophysiology, 2011

Pain-related hyperactivity in the amygdala leads to deactivation of the medial prefrontal cortex (mPFC) and decision-making deficits. The mechanisms of pain-related inhibition of the mPFC are not yet known. Here, we used extracellular single-unit recordings of prelimbic mPFC neurons to determine the role of GABA(A) receptors and metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5, in pain-related activity changes of mPFC neurons. Background and evoked activity of mPFC neurons decreased after arthritis induction. To determine pain-related changes, the same neuron was recorded continuously before and after induction of arthritis in one knee joint by intra-articular injection of kaolin/carrageenan. Stereotaxic administration of a GABA(A) receptor antagonist {[R-(R*,S*)]-5-(6,8-dihydro-8-oxofuro[3,4-e]-1,3-benzodioxol-6-yl)-5,6,7,8-tetrahydro-6,6-dimethyl-1,3-dioxolo[4,5-g]isoquinolinium iodide (bicuculline)} into the mPFC by microdialysis reversed pain-related inhibition, whereas offsite injections into the adjacent anterior cingulate cortex had no or opposite effects on prelimbic mPFC neurons. A selective mGluR1/5 agonist [(S)-3,5-dihydroxyphenylglycine (DHPG)] inhibited background and evoked activity under normal conditions through a GABAergic mechanism, because the inhibitory effect was blocked with bicuculline. In the arthritis pain state, DHPG, alone or in the presence of bicuculline, had no effect. Consistent with the involvement of mGluR1 in pain-related inhibition of the mPFC, a selective mGluR1 antagonist [(S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid] reversed the pain-related decrease of background and evoked activity of mPFC neurons in arthritis, whereas a selective mGluR5 antagonist [2-methyl-6-(phenylethynyl)pyridine hydrochloride] had no effect. The mGluR antagonists had no effect under normal conditions. We interpret our data to suggest that pain-related inhibition of mPFC neurons in the arthritis model depends on mGluR1-mediated endogenous activation of GABA(A) receptors. Exogenous activation of mGluR1/5 produces GABAergic inhibition under normal conditions. Restoring normal activity in the mPFC may be a therapeutic strategy to improve cognitive deficits associated with persistent pain.
Long-term depression induced by endogenous cannabinoids produces neuroprotection via astroglial CB
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019

Ischemia not only activates cell death pathways but also triggers endogenous protective mechanisms. However, it is largely unknown what is the essence of the endogenous neuroprotective mechanisms induced by preconditioning. In this study we demonstrated that systemic injection of JZL195, a selective inhibitor of eCB clearance enzymes, induces in vivo long-term depression at CA3-CA1 synapses and at PrL-NAc synapses produces neuroprotection. JZL195-elicited long-term depression is blocked by AM281, the antagonist of cannabinoid 1 receptor (CB
Service user experiences of REFOCUS: a process evaluation of a pro-recovery complex intervention.
Social psychiatry and psychiatric epidemiology, 2016

Policy is increasingly focused on implementing a recovery-orientation within mental health services, yet the subjective experience of individuals receiving a pro-recovery intervention is under-studied. The aim of this study was to explore the service user experience of receiving a complex, pro-recovery intervention (REFOCUS), which aimed to encourage the use of recovery-supporting tools and support recovery-promoting relationships.
Postnatal and adult consequences of loss of huntingtin during development: Implications for Huntington's disease.
Neurobiology of disease, 2016

The mutation in huntingtin (mHtt) leads to a spectrum of impairments in the developing forebrain of Huntington's disease (HD) mouse models. Whether these developmental alterations are due to loss- or gain-of-function mechanisms and contribute to HD pathogenesis is unknown. We examined the role of selective loss of huntingtin (Htt) function during development on postnatal vulnerability to cell death. We employed mice expressing very low levels of Htt throughout embryonic life to postnatal day 21 (Hdh
Higher-level pattern features provide additional information to birds when recognizing and rejecting parasitic eggs.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2019

Despite a recent explosion of research on pattern recognition, in both neuroscience and computer vision, we lack a basic understanding of how most animals perceive and respond to patterns in the wild. Avian brood parasites and their hosts provide an ideal study system for investigating the mechanisms of pattern recognition. The cuckoo finch, Anomalospiza imberbis, and its host the tawny-flanked prinia, Prinia subflava, lay highly polymorphic eggs with a great deal of variation in colour and patterning, with the cuckoo finch capable of close egg mimicry. Behavioural experiments in Zambia have previously shown that prinias use colour and multiple 'low-level' (occurring in early stages of visual processing) pattern attributes, derived from spatial frequency analysis, when rejecting foreign eggs. Here, we explore the extent to which host birds might also use 'higher-level' pattern attributes, derived from a feature detection algorithm, to make rejection decisions. Using a SIFT-based pattern recognition algorithm, NaturePatternMatch, we show that hosts are more likely to reject a foreign egg if its higher-level pattern features-which capture information about the shape and orientation of markings-differ from those of the host eggs. A revised statistical model explains about 37% variance in egg rejection behaviour, and differences in colour, low-level and higher-level pattern features all predict rejection, accounting for 42, 44 and 14% of the explained variance, respectively. Thus, higher-level pattern features provide a small but measurable improvement to the original model and may be especially useful when colour and low-level pattern features provide hosts with little information. Understanding the relative importance of low- and higher-level pattern features is a valuable goal for future work on animal coloration, especially in the contexts of mimicry, camouflage and individual recognition. This article is part of the theme issue 'The coevolutionary biology of brood parasitism: from mechanism to pattern'.
PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery.
Cell reports, 2016

Roux-en-Y gastric bypass (RYGB) is a weight-reduction procedure resulting in rapid resolution of type 2 diabetes (T2D). The role of pancreatic islet function in this restoration of normoglycemia has not been fully elucidated. Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrate that RYGB restores normal glucose regulation of glucagon and insulin secretion and normalizes islet morphology. Culture of isolated islets with serum from RYGB animals mimicked these effects, implicating a humoral factor. These latter effects were reversed following neutralization of the gut hormone peptide tyrosine tyrosine (PYY) but persisted in the presence of a glucagon-like peptide-1 (GLP-1) receptor antagonist. The effects of RYGB on secretion were replicated by chronic exposure of diabetic rat islets to PYY in vitro. These findings indicate that the mechanism underlying T2D remission may be mediated by PYY and suggest that drugs promoting PYY release or action may restore pancreatic islet function in T2D.
Combining risk communication strategies to simultaneously convey the risks of four diseases associated with physical inactivity to socio-demographically diverse populations.
Journal of behavioral medicine, 2018

A single risk factor can increase the risk of developing multiple diseases, but most risk communication research has been conducted in the context of a single disease. We explored which combination of three recommended risk communication strategies is most effective in simultaneously conveying risk estimates of four diseases associated with physical inactivity: colon cancer, stroke, diabetes, and heart disease. Participants (N = 1161, 50% no college experience, 50% racial/ethnic minority) were shown hypothetical risk estimates for each of the four diseases. All four diseases were placed at varying heights on 1 of 12 vertical bar charts (i.e., "risk ladders") to indicate their respective probabilities. The risk ladders varied in a 2 (risk reduction information: present/absent) × 2 (numerical format: words/words and numbers) × 3 (social comparison information: none/somewhat higher than average/much higher than average) full factorial design. Participants were randomly assigned to view one of the risk ladders and then completed a questionnaire assessing message comprehension, message acceptance, physical activity-related risk and efficacy beliefs, and physical activity intentions. Higher message acceptance was found among (1) people who received risk reduction information versus those who did not (p = .01), and (2) people who did not receive social comparison information versus those told that they were at higher than average risk (p = .03). Further, absolute cognitive perceived risk of developing "any of the diseases shown in the picture" was higher among people who did not receive social comparison information (p = .03). No other main effects and only very few interactions with demographic variables were found. Combining recommended risk communication strategies did not improve or impair key cognitive or affective precursors of health behavior change. It might not be necessary to provide people with extensive information when communicating risk estimates of multiple diseases.
Detection of Osmotic Shock-Induced Extracellular Nucleotide Release with a Genetically Encoded Fluorescent Sensor of ADP and ATP.
Sensors (Basel, Switzerland), 2019

Purinergic signals, such as extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP), mediate intercellular communication and stress responses throughout mammalian tissues, but the dynamics of their release and clearance are still not well understood. Although physiochemical methods provide important insight into physiology, genetically encoded optical sensors have proven particularly powerful in the quantification of signaling in live specimens. Indeed, genetically encoded luminescent and fluorescent sensors provide new insights into ATP-mediated purinergic signaling. However, new tools to detect extracellular ADP are still required. To this end, in this study, we use protein engineering to generate a new genetically encoded sensor that employs a high-affinity bacterial ADP-binding protein and reports a change in occupancy with a change in the Förster-type resonance energy transfer (FRET) between cyan and yellow fluorescent proteins. We characterize the sensor in both protein solution studies, as well as live-cell microscopy. This new sensor responds to nanomolar and micromolar concentrations of ADP and ATP in solution, respectively, and in principle it is the first fully-genetically encoded sensor with sufficiently high affinity for ADP to detect low levels of extracellular ADP. Furthermore, we demonstrate that tethering the sensor to the cell surface enables the detection of physiologically relevant nucleotide release induced by hypoosmotic shock as a model of tissue edema. Thus, we provide a new tool to study purinergic signaling that can be used across genetically tractable model systems.
Arrhythmogenic right ventricular cardiomyopathy: implications of next-generation sequencing in appropriate diagnosis.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2017

To evaluate potential differences in the genetic profile of cases with 'definite', 'borderline', and 'possible' arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype by 2010 task force criteria using a custom genetic panel after whole-exome analysis.
CT and MRI-based door-needle-times for acute stroke patients a quasi-randomized clinical trial.
Clinical neurology and neurosurgery, 2017

Door-Needle-times (DNT) of 20min are feasible when Computer Tomography (CT) is used for first-line brain-imaging to assess stroke-patients' eligibility for intravenous-tissue-Plasminogen-Activator (iv-tPA), but the more time-consuming Magnetic Resonance Imaging (MRI)-based-evaluation is superior in detecting acute ischaemia.
What explains the link between childhood ADHD and adolescent depression? Investigating the role of peer relationships and academic attainment.
European child & adolescent psychiatry, 2020

There is increasing evidence that childhood Attention-Deficit Hyperactivity Disorder (ADHD) elevates risk of later depression, but the mechanisms behind this association are unclear. We investigated the relationship between childhood ADHD symptoms and late-adolescent depressive symptoms in a population cohort, and examined whether academic attainment and peer problems mediated this association. ALSPAC (Avon Longitudinal Study of Parents and Children) is an ongoing prospective longitudinal population-based UK cohort that has collected data since September 1990. 2950 individuals with data on parent-reported ADHD symptoms in childhood (7.5 years) and self-reported depressive symptoms in late adolescence (17.5 years) were included in analyses. 2161 individuals with additional data at age 16 years on parent-reported peer problems as an indicator of peer relationships and formal examination results (General Certificate of Secondary Education; GCSE) as an indicator of academic attainment were included in mediation analyses. Childhood ADHD symptoms were associated with higher depressive symptoms (b = 0.49, SE = 0.11, p < 0.001) and an increased odds of clinically significant depressive symptoms in adolescence (OR = 1.27, 95% CI 1.15-1.41, p < 0.001). The association with depressive symptoms was mediated in part by peer problems and academic attainment which accounted for 14.68% and 20.13% of the total effect, respectively. Childhood ADHD is associated with increased risk of later depression. The relationship is mediated in part by peer relationships and academic attainment. This highlights peer relationships and academic attainment as potential targets of depression prevention and intervention in those with ADHD. Future research should investigate which aspects of peer relationships are important in conferring later risk for depression.
In vitro evaluation of a 'stealth' adenoviral vector for targeted gene delivery to adult mammalian neurones.
The journal of gene medicine, 2009

Polymer coating of adenovirus type 5 (Ad5) particles produces a 'stealth' Ad5 (sAd5) that confers protection from immune recognition, blocks receptor-mediated uptake, and favours uptake into pinocytic cells.
Social status alters defeat-induced neural activation in Syrian hamsters.
Neuroscience, 2012

Although exposure to social stress leads to increased depression-like and anxiety-like behavior, some individuals are more vulnerable than others to these stress-induced changes in behavior. Prior social experience is one factor that can modulate how individuals respond to stressful events. In this study, we investigated whether experience-dependent resistance to the behavioral consequences of social defeat was associated with a specific pattern of neural activation. We paired weight-matched male Syrian hamsters in daily aggressive encounters for 2 weeks, during which they formed a stable dominance relationship. We also included control animals that were exposed to an empty cage each day for 2 weeks. Twenty-four hours after the final pairing or empty cage exposure, half of the subjects were socially defeated in 3, 5-min encounters, whereas the others were not socially defeated. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains after social defeat and processed the tissue for c-Fos immunoreactivity. We found that dominants were more likely than subordinates to counter-attack the resident aggressor during social defeat, and they showed less submissive and defensive behavior at conditioned defeat testing compared with subordinates. Also, social status was associated with distinct patterns of defeat-induced neural activation in select brain regions, including the amygdala, prefrontal cortex, hypothalamus, and lateral septum. Our results indicate that social status is an important form of prior experience that predicts both initial coping style and the degree of resistance to social defeat. Further, the differences in defeat-induced neural activation suggest possible brain regions that may control resistance to conditioned defeat in dominant individuals.
Fast construction of voxel-level functional connectivity graphs.
BMC neuroscience, 2014

Graph-based analysis of fMRI data has recently emerged as a promising approach to study brain networks. Based on the assessment of synchronous fMRI activity at separate brain sites, functional connectivity graphs are constructed and analyzed using graph-theoretical concepts. Most previous studies investigated region-level graphs, which are computationally inexpensive, but bring along the problem of choosing sensible regions and involve blurring of more detailed information. In contrast, voxel-level graphs provide the finest granularity attainable from the data, enabling analyses at superior spatial resolution. They are, however, associated with considerable computational demands, which can render high-resolution analyses infeasible. In response, many existing studies investigating functional connectivity at the voxel-level reduced the computational burden by sacrificing spatial resolution.
Relating pessimistic memory predictions to Alzheimer's disease brain structure.
Cortex; a journal devoted to the study of the nervous system and behavior, 2016

Patients with Alzheimer's disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory retrieval and investigated the neural correlates of pessimistic predictions for successfully retrieved memories in AD patients. AD patients and healthy older (HO) participants provided predictive judgments on their recognition performance before retrieval of famous (semantic) and recently learned (episodic) names. Correlations between gray matter volume (GMV) in T1 images and behavioral scores were examined with multivariate (partial least square - PLS) and univariate (general linear model - GLM) analyses in AD patients. AD patients showed a significant proportion of successful name recognition preceded by pessimistic prediction in episodic memory. PLS revealed that the behavioral pattern in AD patients was related with a mainly right lateralized pattern of GMV decrease including medial temporal lobe and posterior cingulate cortex (PCC), but also right ventrolateral prefrontal cortex (VLPFC). GLM further confirmed that pessimistic prediction negatively correlated with GMV in VLPFC. Thus, impaired monitoring processes (possibly influenced by inaccurate beliefs) allowing inferences about one's own memory performance are primarily related to decrease GMV in VLPFC in AD patients.
Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families.
International journal of molecular sciences, 2021

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of
Role of central glucagon-like peptide-1 in hypothalamo-pituitary-adrenocortical facilitation following chronic stress.
Experimental neurology, 2008

Central glucagon-like peptide-1 (GLP-1) regulates food intake, glucose homeostasis, and behavioral and neuroendocrine responses to acute stress. Given its pronounced role in acute stress regulation, the GLP-1 system is a prime candidate for mediating the prolonged drive of the hypothalamo-pituitary-adrenocortical axis by chronic stress. To test this hypothesis, we evaluated the necessity and sufficiency of GLP-1 for production of chronic stress-induced changes in HPA axis function. Exogenous GLP-1 or the GLP-1 receptor antagonist, dHG-exendin, were delivered into the 3rd ventricle of control animals or animals exposed to chronic variable stress (CVS) for 7 days. Animals in the CVS groups received GLP-1 or dHG-exendin immediately prior to each stress exposure. Prior to and at the end of the 7-day trial, chronically-stressed animals were subjected to a novel stressor to test for HPA axis facilitation. Neither GLP-1 nor dHG-exendin affected CVS-associated increases in adrenal weight or decreases in basal plasma glucose levels. In addition, neither exogenous GLP-1 nor dHG-exendin altered any index of HPA axis activity in unstressed rats. However, GLP-1 enhanced CVS-induced facilitation of corticosterone (but not ACTH) response to an acute stress, whereas dHG-exendin inhibited facilitation. In addition, GLP-1 decreased body weight in chronically-stressed animals. dHG-exendin increased food intake and body weight in unstressed animals, consistent with a tonic role for GLP-1 in body weight regulation. Overall, our data suggest that brain GLP-1 modulates HPA axis activity within the context of chronic stress, perhaps at the level of the adrenal gland.