rudyvdbrink/CitationDatabase huggingface dataset:
Reducing proactive aggression through non-invasive brain stimulation.
Social cognitive and affective neuroscience, 2015

Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders.
Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse.
Twins Early Development Study: A Genetically Sensitive Investigation into Behavioral and Cognitive Development from Infancy to Emerging Adulthood.
Twin research and human genetics : the official journal of the International Society for Twin Studies, 2019

The Twins Early Development Study (TEDS) is a longitudinal twin study that recruited over 16,000 twin-pairs born between 1994 and 1996 in England and Wales through national birth records. More than 10,000 of these families are still engaged in the study. TEDS was and still is a representative sample of the population in England and Wales. Rich cognitive and emotional/behavioral data have been collected from the twins from infancy to emerging adulthood, with data collection at first contact and at ages 2, 3, 4, 7, 8, 9, 10, 12, 14, 16, 18 and 21, enabling longitudinal genetically sensitive analyses. Data have been collected from the twins themselves, from their parents and teachers, and from the UK National Pupil Database. Genotyped DNA data are available for 10,346 individuals (who are unrelated except for 3320 dizygotic co-twins). TEDS data have contributed to over 400 scientific papers involving more than 140 researchers in 50 research institutions. TEDS offers an outstanding resource for investigating cognitive and behavioral development across childhood and early adulthood and actively fosters scientific collaborations.
Thinking about multiple identities boosts children's flexible thinking.
Developmental science, 2020

Studies of children's developing social identification often focus on individual forms of identity. Yet, everyone has multiple potential identities. Here we investigated whether making children aware of their multifaceted identities-effectively seeing themselves from multiple angles-would promote their flexible thinking. In Experiment 1, 6- to 7-year-old children (N = 48) were assigned to either a Multiple-Identities condition where they were led to consider their multiple identities (e.g. friend, neighbor) or to a Physical-Traits condition where they considered their multiple physical attributes (e.g. legs, arms). Children in the Multiple-Identity condition subsequently expressed greater flexibility at problem-solving and categorization than children in the Physical-Traits condition. Experiment 2 (N = 72) replicated these findings with a new sample of 6- to 7-year-old children and demonstrated that a Multiple-Identity mindset must be self-relevant. Children who were led to think about another child's multiple identities did not express as much subsequent creative thinking as did children who thought about their own multiple identities. Experiment 3 (N = 76) showed that a Mmultiple-Identity framework may be particularly effective when the identities are presented via generic language suggesting that they are enduring traits (in this case, identities depicted as noun phrases rather than verbal phrases). These findings illustrate that something as simple as thinking about one's identity from multiple angles could serve as a tool to help reduce rigid thinking, which might increase open-mindedness in a society that is becoming increasingly diverse.
A possible universal role for mRNA secondary structure in bacterial translation revealed using a synthetic operon.
Nature communications, 2020

In bacteria, translation re-initiation is crucial for synthesizing proteins encoded by genes that are organized into operons. The mechanisms regulating translation re-initiation remain, however, poorly understood. We now describe the ribosome termination structure (RTS), a conserved and stable mRNA secondary structure localized immediately downstream of stop codons, and provide experimental evidence for its role in governing re-initiation efficiency in a synthetic Escherichia coli operon. We further report that RTSs are abundant, being associated with 18%-65% of genes in 128 analyzed bacterial genomes representing all phyla, and are selectively depleted when translation re-initiation is advantageous yet selectively enriched so as to insulate translation when re-initiation is deleterious. Our results support a potentially universal role for the RTS in controlling translation termination-insulation and re-initiation across bacteria.
Synergistic enhancing-memory effect of donepezil and S 47445, an AMPA positive allosteric modulator, in middle-aged and aged mice.
Psychopharmacology, 2018

Positive allosteric modulators of AMPA receptors (AMPA-PAMs) are described to facilitate cognitive processes in different memory-based models. Among them, S 47445 is a novel potent and selective AMPA-PAM. In order to assess its efficacy after repeated administration, S 47445 effect was evaluated in two aging-induced memory dysfunction tasks in old mice, one short-term working memory model evaluated in a radial maze task and one assessing contextual memory performance. S 47445 was shown to improve cognition in both models sensitive to aging. In fact, administration of S 47445 at 0.3 mg/kg (s.c.) reversed the age-induced deficits of the working memory model whatever the retention interval. Moreover, in the contextual task, S 47445 also reversed the age-induced deficit at all tested doses (from 0.03 to 0.3 mg/kg, p.o.). Since donepezil, an acetylcholinesterase inhibitor, induces only moderate symptomatic effects on memory in Alzheimer's disease patients, an alternative strategy for treatment of cognitive symptoms could be to act simultaneously on both glutamatergic AMPA receptors and cholinergic pathways by combining pharmacological treatments. The present study further examined such effects by assessing combinations of S 47445 and donepezil given orally during 9 days in aged C57/Bl6J mice using contextual memory task (CSD) and the working memory model of serial alternation task (AT). Interestingly, a significant synergistic memory-enhancing effect was observed with the combination of donepezil at 0.1 mg/kg with S 47445 at 0.1 mg/kg p.o. in the CSD or with S 47445 at 0.1 and 0.3 mg/kg in AT in comparison to compounds given alone and without any pharmacokinetic interaction.
Validation of the NIMH-ChEFS adolescent face stimulus set in an adolescent, parent, and health professional sample.
International journal of methods in psychiatric research, 2015

Attention to faces is a fundamental psychological process in humans, with atypical attention to faces noted across several clinical disorders. Although many clinical disorders onset in adolescence, there is a lack of well-validated stimulus sets containing adolescent faces available for experimental use. Further, the images comprising most available sets are not controlled for high- and low-level visual properties. Here, we present a cross-site validation of the National Institute of Mental Health Child Emotional Faces Picture Set (NIMH-ChEFS), comprised of 257 photographs of adolescent faces displaying angry, fearful, happy, sad, and neutral expressions. All of the direct facial images from the NIMH-ChEFS set were adjusted in terms of location of facial features and standardized for luminance, size, and smoothness. Although overall agreement between raters in this study and the original development-site raters was high (89.52%), this differed by group such that agreement was lower for adolescents relative to mental health professionals in the current study. These results suggest that future research using this face set or others of adolescent/child faces should base comparisons on similarly-aged validation data. Copyright © 2015 John Wiley & Sons, Ltd.
Conserved genes act as modifiers of invertebrate SMN loss of function defects.
PLoS genetics, 2010

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species.
Axon microdissection and transcriptome profiling reveals the in vivo RNA content of fully differentiated myelinated motor axons.
RNA (New York, N.Y.), 2020

Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in the maintenance of the axoplasm in a steady state. Recent studies have begun to identify the mRNAs localized in axons, which could be translated locally under different conditions. Despite that by now hundreds or thousands of mRNAs have been shown to be localized into the axonal compartment of cultured neurons in vitro, knowledge of which mRNAs are localized in mature myelinated axons is quite limited. With the purpose of characterizing the transcriptome of mature myelinated motor axons of peripheral nervous systems, we modified the axon microdissection method devised by Koenig, enabling the isolation of the axoplasm RNA to perform RNA-seq analysis. The transcriptome analysis indicates that the number of RNAs detected in mature axons is lower in comparison with in vitro data, depleted of glial markers, and enriched in neuronal markers. The mature myelinated axons are enriched for mRNAs related to cytoskeleton, translation, and oxidative phosphorylation. Moreover, it was possible to define core genes present in axons when comparing our data with transcriptomic data of axons grown in different conditions. This work provides evidence that axon microdissection is a valuable method to obtain genome-wide data from mature and myelinated axons of the peripheral nervous system, and could be especially useful for the study of axonal involvement in neurodegenerative pathologies of motor neurons such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMA).
Physician-Training Stress and Accelerated Cellular Aging.
Biological psychiatry, 2019

Stress is a key precipitant for many common diseases, but established biological markers to track stress and guide investigations into mechanisms linking stress and disease are lacking. Cross-sectional studies have identified correlations between stress and telomere attrition, but no large, longitudinal studies examining the impacts of chronic stress on telomere length exist. Residency training for physicians is a well-established stressful experience and can be used as a prospective stress model.
Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery.
European journal of medicinal chemistry, 2015

1,3-Thiazole is one of the most important scaffolds in heterocyclic chemistry and drug design and discovery. It is widely found in diverse pharmacologically active substances and in some naturally-occurring compounds. Thiazole is a versatile building-block for lead generation, and is easily access of diverse derivatives for subsequent lead optimization. In the recent years, many thiazole derivatives have been synthesized and subjected to varied biological activities. In this article we intended to review the most important biological effects of thiazole-based compounds and highlight their roles in new leads identification and drug discovery. This article is also intended to help researches for finding potential future directions on the development of more potent and specific analogs of thiazole-based compounds for various biological targets.
Network-Level Dysconnectivity in Drug-Naïve First-Episode Psychosis: Dissociating Transdiagnostic and Diagnosis-Specific Alterations.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017

The neuroimaging literature provides compelling evidence for functional dysconnectivity in people with psychosis. However, it is likely that at least some of the observed alterations represent secondary effects of illness chronicity and/or antipsychotic medication. In addition, the extent to which these alterations are specific to psychosis or represent a transdiagnostic feature of psychiatric illness remains unclear. The aim of this study was therefore to examine the diagnostic specificity of functional dysconnectivity in drug-naïve first-episode psychosis (FEP). We used resting-state functional magnetic resonance imaging and functional connectivity analysis to estimate network-level connectivity in 50 patients with FEP, 50 patients with major depressive disorder (MDD), 50 patients with post-traumatic stress disorder (PTSD), and 122 healthy controls (HCs). The FEP, MDD, and PTSD groups showed reductions in intranetwork connectivity of the default mode network relative to the HC group (p<0.05 corrected); therefore, intranetwork alterations were expressed across the three diagnostic groups. In addition, the FEP group showed heightened internetwork connectivity between the default mode network, particularly the anterior cingulate cortex, and the central executive network relative to the MDD, PTSD, and HC groups (p<0.05 corrected); therefore, internetwork alterations were specific to the FEP. These findings suggest that network-level alterations are present in individuals with a first episode of psychosis who have not been exposed to antipsychotic medication. In addition, they suggest a dissociation between aberrant internetwork connectivity as a distinctive feature of psychosis and aberrant intranetwork connectivity as a transdiagnostic feature of psychiatric illness.
Intellectual disability in Indigenous Australians: issues and challenges.
Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 2015

Literature on Indigenous Australians (Aboriginal and Torres Strait Islander people) and intellectual disability (ID) is summarized in order to identify current state of knowledge, gaps, and areas for further research.
Fatiguing Neuromuscular Electrical Stimulation Decreases the Sense of Effort During Subsequent Voluntary Contractions in Men.
Neuroscience, 2020

As voluntary muscle fatigue increases, the perception of the effort required to produce a particular level of force also increases. This occurs because we produce greater neural outputs from the brain to compensate for the fatigue-induced loss of force. Muscle fatigue can also be generated following bouts of neuromuscular electrical stimulation (NMES), a technique widely used for rehabilitation and training purposes. Yet the effects of NMES-induced fatigue on the perception of effort have never been tested. In this study, we thus evaluated how electrically evoked fatigue would affect the sense of effort. For this purpose, we used two psychophysical tasks intended to assess effort perception: (i) a bilateral matching task in which subjects were asked to contract the elbow flexors of their reference and indicator arms with similar amounts of effort and (ii) a unilateral matching task in which they produced controlled levels of isometric force with their indicator arm and rated their perceived effort using the Borg CR10 scale. These tasks were performed before and after the biceps brachii of the indicator arm was submitted to a fatiguing NMES program that generated maximal force losses of 10-15%. Contrary to voluntary muscle fatigue, the sense of effort decreased post-NMES in both tasks despite increased neural outputs to the elbow flexors of the fatigued indicator arm. This shows that the relationship between motor command magnitude and effort perception was completely modified by NMES. It is proposed that NMES alters the sensory structures responsible for effort signal integration.
Neural correlates of prospection impairments in schizophrenia: Evidence from voxel-based morphometry analysis.
Psychiatry research. Neuroimaging, 2019

Prospection, which has a close relationship with motivation and goal-directed behavior, could be a potential target for alleviating negative symptoms. The present study aimed to examine the structural neural correlates of prospection impairments and the involvement of working memory in prospection in schizophrenia patients. Thirty-seven patients with schizophrenia and 28 healthy controls were recruited and all of them completed a prospection task. Working memory was assessed with the Letter Number Span test. In addition, all participants underwent a structural MRI scan. Voxel-based morphometry (VBM) analysis was used to measure grey matter (GM) volume. We found that in schizophrenia patients, GM loss in the right lateral prefrontal cortex (PFC) and the right ventral medial PFC was correlated with decreased internal details in the prospection task. Moreover, GM volume of the right lateral PFC was found to mediate the relationship between working memory and internal details in these patients. In conclusion, GM loss in the PFC is associated with prospection impairments in schizophrenia patients. Working memory deficits may partially account for prospection impairments in schizophrenia patients.
Cognition and diabetes: a lifespan perspective.
The Lancet. Neurology, 2008

Diabetes mellitus is associated with cognitive dysfunction and abnormalities that can be seen with brain imaging. Recent studies provide important new insights into the nature and severity of these cerebral complications that help to explain why some patients with diabetes have clinically relevant neurocognitive morbidity, whereas most are apparently unaffected. This Personal View investigates the hypothesis that clinically relevant diabetes-related cognitive decrements mainly occur at two crucial periods in life: when the brain is developing in childhood, and when the brain undergoes neurodegenerative changes associated with ageing. Outside of these periods cognitive decrements mainly occur in patients with notable diabetes-related comorbidities, in particular microvascular or macrovascular complications. The identification of crucial periods and conditions for the development of diabetes-related cognitive decrements helps to draw the attention of physicians to individuals at risk and can direct future studies into the mechanisms that underlie these conditions.
Genetic basis in motor skill and hand preference for tool use in chimpanzees (Pan troglodytes).
Proceedings. Biological sciences, 2015

Chimpanzees are well known for their tool using abilities. Numerous studies have documented variability in tool use among chimpanzees and the role that social learning and other factors play in their development. There are also findings on hand use in both captive and wild chimpanzees; however, less understood are the potential roles of genetic and non-genetic mechanisms in determining individual differences in tool use skill and laterality. Here, we examined heritability in tool use skill and handedness for a probing task in a sample of 243 captive chimpanzees. Quantitative genetic analysis, based on the extant pedigrees, showed that overall both tool use skill and handedness were significantly heritable. Significant heritability in motor skill was evident in two genetically distinct populations of apes, and between two cohorts that received different early social rearing experiences. We further found that motor skill decreased with age and that males were more commonly left-handed than females. Collectively, these data suggest that though non-genetic factors do influence tool use performance and handedness in chimpanzees, genetic factors also play a significant role, as has been reported in humans.