rudyvdbrink/CitationDatabase huggingface dataset:
Mitochondrial Superoxide Dismutase Specifies Early Neural Commitment by Modulating Mitochondrial Dynamics.
iScience, 2020

Studies revealing molecular mechanisms underlying neural specification have majorly focused on the role played by different transcription factors, but less on non-nuclear components. Earlier, we reported mitochondrial superoxide dismutase (SOD2) to be essential for self-renewal and pluripotency of mouse embryonic stem cells (mESCs). In the present study, we found SOD2 to be specifically required for neural lineage, but not the meso- or endoderm specification. Temporally, SOD2 regulated early neural genes, but not the matured genes, by modulating mitochondrial dynamics-specifically by enhancing the mitochondrial fusion protein Mitofusin 2 (MFN2). Bio-complementation strategy further confirmed SOD2 to enhance mitochondrial fusion process independent of its antioxidant activity. Over-expression of SOD2 along with OCT4, but neither alone, transdifferentiated mouse fibroblasts to neural progenitor-like colonies, conclusively proving the neurogenic potential of SOD2. In conclusion, our findings accredit a novel role for SOD2 in early neural lineage specification.
The association between selected genetic variants and individual differences in experimental pain.
Scandinavian journal of pain, 2021

The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain.
Absence of latitudinal gradient in oligoclonal bands prevalence in Argentina.
Multiple sclerosis and related disorders, 2020

Like MS prevalence, oligoclonal bands (OCB) frequency seems to follow a latitudinal gradient. Argentina is extensive, latitude-wise, and previous studies have not found an MS prevalence latitudinal gradient. Our aim is to describe OCB prevalence in MS, clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) patients included in the Argentinean MS and NMOSD registry (RelevarEM) and to investigate if it follows a latitudinal gradient.
Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region.
Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists, 2020

Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established.
Rules warp feature encoding in decision-making circuits.
PLoS biology, 2020

We have the capacity to follow arbitrary stimulus-response rules, meaning simple policies that guide our behavior. Rule identity is broadly encoded across decision-making circuits, but there are less data on how rules shape the computations that lead to choices. One idea is that rules could simplify these computations. When we follow a rule, there is no need to encode or compute information that is irrelevant to the current rule, which could reduce the metabolic or energetic demands of decision-making. However, it is not clear if the brain can actually take advantage of this computational simplicity. To test this idea, we recorded from neurons in 3 regions linked to decision-making, the orbitofrontal cortex (OFC), ventral striatum (VS), and dorsal striatum (DS), while macaques performed a rule-based decision-making task. Rule-based decisions were identified via modeling rules as the latent causes of decisions. This left us with a set of physically identical choices that maximized reward and information, but could not be explained by simple stimulus-response rules. Contrasting rule-based choices with these residual choices revealed that following rules (1) decreased the energetic cost of decision-making; and (2) expanded rule-relevant coding dimensions and compressed rule-irrelevant ones. Together, these results suggest that we use rules, in part, because they reduce the costs of decision-making through a distributed representational warping in decision-making circuits.
The removal of information from working memory.
Annals of the New York Academy of Sciences, 2018

What happens to goal-relevant information in working memory after it is no longer needed? Here, we review evidence for a selective removal process that operates on outdated information to limit working memory load and hence facilitates the maintenance of goal-relevant information. Removal alters the representations of irrelevant content so as to reduce access to it, thereby improving access to the remaining relevant content and also facilitating the encoding of new information. Both behavioral and neural evidence support the existence of a removal process that is separate from forgetting due to decay or interference. We discuss the potential mechanisms involved in removal and characterize the time course and duration of the process. In doing so, we propose the existence of two forms of removal: one is temporary, and reversible, which modifies working memory content without impacting content-to-context bindings, and another is permanent, which unbinds the content from its context in working memory (without necessarily impacting long-term forgetting). Finally, we discuss limitations on removal and prescribe conditions for evaluating evidence for or against this process.
Characterization of Human iPSC-derived Spinal Motor Neurons by Single-cell RNA Sequencing.
Neuroscience, 2020

Human induced pluripotent stem cells (iPSCs) offer the opportunity to generate specific cell types from healthy and diseased individuals, allowing the study of mechanisms of early human development, modelling a variety of human diseases, and facilitating the development of new therapeutics. Human iPSC-based applications are often limited by the variability among iPSC lines originating from a single donor, as well as the heterogeneity among specific cell types that can be derived from iPSCs. The ability to deeply phenotype different iPSC-derived cell types is therefore of primary importance to the successful and informative application of this technology. Here we describe a combination of motor neuron (MN) derivation and single-cell RNA sequencing approaches to generate and characterize specific MN subtypes obtained from human iPSCs. Our studies provide evidence for rapid and robust generation of MN progenitor cells that can give rise to a heterogenous population of MNs. Approximately 58% of human iPSC-derived MNs display molecular characteristics of lateral motor column MNs, with a number of molecularly distinct subpopulations present within this MN group. Roughly 19% of induced MNs resemble hypaxial motor column MNs, while ∼6% of induced MNs have features of median motor column MNs. The present study has the potential to improve our understanding of iPSC-derived MN subtype function and dysfunction, possibly leading to improved iPSC-based applications for the study of human MN biology and disease.
Detecting Cognitive Decline and Dementia in Santa Cruz, Galápagos Islands, Ecuador.
Cureus, 2020

Objective To assess the cognitive function, prevalence, and risk factors associated with cognitive decline and dementia in people above 65 years of age in Santa Cruz Island, Galápagos, Ecuador.  Methods This is a cross-sectional observational study that was carried out in adults over 65 years of age in Santa Cruz Island, Galápagos, Ecuador. The mini-mental state examination (MMSE) and ascertain dementia eight-item informant questionnaire (AD8)-validated Ecuador Spanish versions were used to assess cognition. Results There were a total of 80 participants, 55 (67%) women and 25 (31.2%) men. The majority of participants were Mestizos (85.3%), with the remainder classified as White (4.8%), Afro-Ecuadorians (2.4%), or Indigenous (3.6%). The prevalence of cognitive impairment is 30.0%-43.7%. The MMSE results showed that older age and lack of education are risk factors for cognitive decline (p < 0.01). There was high correlation between MMSE and AD8 scores. The AD8 showed that older age, widowhood, and living in Santa Rosa were risk factors for cognitive decline (p < 0.01). According to the AD8, the group with the highest education (six years or more) had the lowest risk of cognitive decline and dementia (p < 0.01).  Conclusions The main risk factors for cognitive decline and dementia in individuals above 65 years old in Santa Cruz Island, Galápagos, Ecuador are increased age, lack of education, and widowhood. The prevalence of cognitive impairment is similar to previous studies in Ecuador.
Effect of presynaptic membrane potential on electrical vs. chemical synaptic transmission.
Journal of neurophysiology, 2011

The growing realization that electrical coupling is present in the mammalian brain has sparked renewed interest in determining its functional significance and contrasting it with chemical transmission. One question of interest is whether the two types of transmission can be selectively regulated, e.g., if a cell makes both types of connections can electrical transmission occur in the absence of chemical transmission? We explore this issue in an experimentally advantageous preparation. B21, the neuron we study, is an Aplysia sensory neuron involved in feeding that makes electrical and chemical connections with other identified cells. Previously we demonstrated that chemical synaptic transmission is membrane potential dependent. It occurs when B21 is centrally depolarized prior to and during peripheral activation, but does not occur if B21 is peripherally activated at its resting membrane potential. In this article we study effects of membrane potential on electrical transmission. We demonstrate that maximal potentiation occurs in different voltage ranges for the two types of transmission, with potentiation of electrical transmission occurring at more hyperpolarized potentials (i.e., requiring less central depolarization). Furthermore, we describe a physiologically relevant type of stimulus that induces both spiking and an envelope of depolarization in the somatic region of B21. This depolarization does not induce functional chemical synaptic transmission but is comparable to the depolarization needed to maximally potentiate electrical transmission. In this study we therefore characterize a situation in which electrical and chemical transmission can be selectively controlled by membrane potential.
Garth J. Thomas, Physiological Psychologist: An Appraisal of His Contributions to Memory Research.
Annals of neurosciences, 2018

This note is a tribute to Garth J. Thomas (1916-2008), late Professor of Brain Research at the University of Rochester, New York. Thomas was an influential psychologist, albeit for his research in learning and memory, as much as for his work as editor of the
Antidepressant use and interpersonal violence perpetration: a protocol for a systematic review and meta-analysis.
BMJ open, 2021

There are conflicting perspectives as to whether antidepressant medication increases, decreases or has no effect on violence perpetration, impulsivity and aggressive behaviour. This is an important question given the widespread use of antidepressant medication and the significant medical, social, legal and health consequences of violence. We aim to: (1) systematically identify observational studies and randomised controlled trials that quantify the relationship between antidepressant use and interpersonal violence; (2) assess the quality of studies that quantify the relationship between antidepressant use and interpersonal violence and (3) estimate the pooled prevalence and measure of effect for the relationship between antidepressant use and interpersonal violence.
Changes in the intestinal mucosal proteome of turkeys (Meleagris gallopavo) infected with haemorrhagic enteritis virus.
Veterinary immunology and immunopathology, 2019

Haemorrhagic enteritis (HE) is a viral disease affecting intestinal integrity and barrier function in turkey (Meleagris gallopavo) and resulting in a significant economic loss. Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH-MS) was applied to identify crucial proteins involved in HE infection. A total of 938 proteins were identified and used to generate a reference library for SWATH-MS analysis. In total, 523 proteins were reliably quantified, and 64 proteins were found to be differentially expressed, including 49 up-regulated and 15 down-regulated proteins between healthy and HE-affected intestinal mucosa. Functional analysis suggested that these proteins were involved in the following categories of cellular pathways and metabolisms: 1) energy pathways; 2) intestine lipid and amino acid metabolism; 3) oxidative stress; 4) intestinal immune response. Major findings of this study demonstrated that natural HE infection is related to the changes in abundance of several proteins involved in cell-intrinsic immune defense against viral invasion, systemic inflammation, modulation of excessive inflammation, B and T cell development and function and antigen presentation. mRNA quantitative expression demonstrated that most of the proteins involved in innate immunity that were found to be differentially abundant were produced by intestinal mucosa, suggesting its direct involvement in immune defences against HE infection.
The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank.
Translational psychiatry, 2020

While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n = 2067), hallucinations (n = 6689), and any psychotic experience (delusions or hallucinations; n = 7803) in 157,366 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRS
Improving emotion regulation of social exclusion in depression-prone individuals: a tDCS study targeting right VLPFC.
Psychological medicine, 2020

Growing evidence has indicated that right ventrolateral prefrontal cortex (RVLPFC) is critical in down-regulating emotional responses to social exclusion, and that depression is accompanied by social emotional dysregulation associated with reduced lateral prefrontal engagement. This study used anodal transcranial direct current stimulation (tDCS) to examine whether stimulating RVLPFC could improve emotional down-regulation of social exclusion in individuals with high depressive mood (DM).
Collectibles and collections for comparative and evolutionary neurobiological research in Africa.
Annals of the New York Academy of Sciences, 2011

The scientific investigation of brains of different vertebrates, both extant and extinct, is of interest for several reasons: for translating medical research on rodent models into practice, for understanding the animals investigated in order to improve conservation and management strategies, and for understanding the evolution of the human brain. The African continent has vast resources that are incredibly valuable to this endeavor, including an enormous variety of extant species, as well as a rich fossil record covering human evolution and many aspects of vertebrate evolution. This paper briefly outlines the current situation in terms of collections in Africa, most of which are found in South Africa. It is hoped that these brief descriptions will increase international scientific interest in the available collections.
G6PD overexpression protects from oxidative stress and age-related hearing loss.
Aging cell, 2020

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL
The influence of horizontal convergence on slow oscillatory eye movements during visual fixation.
Investigative ophthalmology & visual science, 2013

Slow oscillatory eye movements (SOMs) occur simultaneously with tremor, drifts, and microsaccades during visual fixation. In a previous study, the amplitude of SOM was found to be affected by the visual characteristics of the stimuli. This indicates a perceptual influence on the control of the movement. However, the frequency of SOM did not change. The aim of our study was to investigate how SOM is affected by extraocular muscle tension.
Novel drug delivery methods for improving efficacy of endometriosis treatments.
Expert opinion on drug delivery, 2021

Pharmacotherapy has a key role in the management of endometriosis. However, a significant proportion of patients gains only intermittent or limited benefits. In this regard, alternative and novel drug delivery methods are of paramount importance to improve efficacy and compliance of available treatments and develop alternative medical approaches.
Empirical Bayes evaluation of fused EEG-MEG source reconstruction: Application to auditory mismatch evoked responses.
NeuroImage, 2021

We here turn the general and theoretical question of the complementarity of EEG and MEG for source reconstruction, into a practical empirical one. Precisely, we address the challenge of evaluating multimodal data fusion on real data. For this purpose, we build on the flexibility of Parametric Empirical Bayes, namely for EEG-MEG data fusion, group level inference and formal hypothesis testing. The proposed approach follows a two-step procedure by first using unimodal or multimodal inference to derive a cortical solution at the group level; and second by using this solution as a prior model for single subject level inference based on either unimodal or multimodal data. Interestingly, for inference based on the same data (EEG, MEG or both), one can then formally compare, as alternative hypotheses, the relative plausibility of the two unimodal and the multimodal group priors. Using auditory data, we show that this approach enables to draw important conclusions, namely on (i) the superiority of multimodal inference, (ii) the greater spatial sensitivity of MEG compared to EEG, (iii) the ability of EEG data alone to source reconstruct temporal lobe activity, (iv) the usefulness of EEG to improve MEG based source reconstruction. Importantly, we largely reproduce those findings over two different experimental conditions. We here focused on Mismatch Negativity (MMN) responses for which generators have been extensively investigated with little homogeneity in the reported results. Our multimodal inference at the group level revealed spatio-temporal activity within the supratemporal plane with a precision which, to our knowledge, has never been achieved before with non-invasive recordings.
The escalation in ethanol consumption following chronic intermittent ethanol exposure is blunted in mice expressing ethanol-resistant GluN1 or GluN2A NMDA receptor subunits.
Psychopharmacology, 2021

N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels essential for glutamatergic transmission and plasticity. NMDARs are inhibited by acute ethanol and undergo brain region-specific adaptations after chronic alcohol exposure. In previous studies, we reported that knock-in mice expressing ethanol-insensitive GluN1 or GluN2A NMDAR subunits display altered behavioral responses to acute ethanol and genotype-dependent changes in drinking using protocols that do not produce dependence. A key unanswered question is whether the intrinsic ethanol sensitivity of NMDARs also plays a role in determining behavioral adaptations that accompany the development of dependence. To test this, we exposed mice to repeated cycles of chronic intermittent ethanol (CIE) vapor known to produce a robust escalation in ethanol consumption and preference. As expected, wild-type mice showed a significant increase from baseline in ethanol consumption and preference after each of the four weekly CIE cycles. In contrast, ethanol consumption in male GluN2A(A825W) mice was unchanged following cycles 1, 2, and 4 of CIE with a modest increase appearing after cycle 3. Wild-type and GluN2A(A825W) female mice did not show a clear or consistent escalation in ethanol consumption or preference following CIE treatment. In male GluN1(F639A) mice, the increase in ethanol consumption observed with their wild-type littermates was delayed until later cycles of exposure. These results suggest that the acute ethanol sensitivity of NMDARs especially those containing the GluN2A subunit may be a critical factor in the escalation of ethanol intake in alcohol dependence.
Identifying participants with knee osteoarthritis likely to benefit from physical therapy education and exercise: A hypothesis-generating study.
European journal of pain (London, England), 2021

The purpose of this investigation was to undertake a hypothesis-generating study to identify candidate variables that characterize people with knee osteoarthritis who are most likely to experience a positive response to exercise.