rudyvdbrink/CitationDatabase huggingface dataset:
Adh1 and Adh1/4 knockout mice as possible rodent models for presymptomatic Parkinson's disease.
Behavioural brain research, 2012

Alcohol dehydrogenases (ADH) catalyze the reversible metabolism of many types of alcohols and aldehydes to prevent the possible toxic accumulation of these compounds. ADHs are of interest in Parkinson's disease (PD) since these compounds can be harmful to dopamine (DA) neurons. Genetic variants in ADH1C and ADH4 have been found to associate with PD and lack of Adh4 gene activity in a mouse model has recently been reported to induce changes in the DA system. Adh1 knockout (Adh1-/-) and Adh1/4 double knockout (Adh1/4-/-) mice were investigated for possible changes in DA system related activity, biochemical parameters and olfactory function compared to wild-type (WT) mice. Locomotor activity was tested at ∼7 (adult) and >15 months of age to mimic the late onset of PD. Adh1-/- and Adh1/4-/- mice displayed a significantly higher spontaneous locomotor activity than WT littermates. Both apomorphine and d-amphetamine increased total distance activity in Adh1-/- mice at both age intervals and in Adh1/4-/- mice at 7 months of age compared to WT mice. No significant changes were found regarding olfactory function, however biochemical data showed decreased 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratios in the olfactory bulb and decreased homovanillic acid (HVA)/DA ratios in the olfactory bulb, frontal cortex and striatum of Adh1/4-/- mice compared to WT mice. Our results suggest that lack of Adh1 alone or Adh1 and Adh4 together lead to changes in DA system related behavior, and that these knockout mice might be possible rodent models to study presymptomatic PD.
Psychiatry Today : Biology vs. Psychology.
Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry, 1995

This research addresses preferences and theoretical leanings of present-day psychiatrists along the continuum defined at one end by biology and at the other by psychology. A questionnaire was devised and sent to 5,702 randomly selected members of the American Psychiatric Association in 1990. The response rate was 307%. The results were analyzed for two groups: psychiatrists with fewer than 15 years of practice since residency and psychiatrists with more than 15 years of practice since graduation. Although the great majority of psychiatrists in both groups equally valued psychology and biology, the senior group attributed a greater importance to psychological methods, whereas the younger group stressed equally the importance of biology and psychology. This suggests that psychiatry has evolved over the years from a predominantly psychological practice to one with a more equal emphasis on psychology and biology. Recent advances in neuroscience may have shifted the pendulum toward a more balanced willingness of clinicians to consider the broad armamentarium of psychosocial and biological treatments. The results point to the need for further conceptualization into the relationship between biology and psychology and its incorporation into the psychiatric residency curriculum.
Intracellular recording of cardiomyocyte action potentials by nanobranched microelectrode array.
Biosensors & bioelectronics, 2020

Electrophysiological study that records the action potential of cardiomyocyte served as excellent tool to explore cardiology and neuroscience, disease investigation and pharmacological screening. Advances of micro/nanotechnologies promote the development of three-dimensional (3D) nanodevices to record high-quality intracellular recordings by various perforation approaches of cells, however, the complicated fabrication processes limited their large-scale manufacture. In this work, a unique nanobranched microelectrode array (NBMEA) platform is developed to achieve high-quality intracellular recording of cultured cardiomyocytes in a minimally invasive manner. The NBMEA is consisting of high aspect ratio conductive nanobranches fabricated on patterned microelectrodes combining hydrothermal growth and standard microfabrication. The 3D structure of nanobranches enables the electrode to form tight coupling with cardiomyocytes to achieve the low voltage cell electroporation and high-quality intracellular recording. The recorded intracellular action potentials of cardiomyocytes by NBMEA exhibited significant enhancement on amplitude (~5 mV), signal-to-noise ratio (SNR) (~67.47 dB), recording duration (up to 105 min), and recording yield (69.5 ± 17.8%). This NBMEA platform is a promising and powerful tool for electrophysiology that opens up new opportunities for high-quality and stable intracellular recording of cardiomyocytes.
Understanding the relationship between cognitive performance and function in daily life after traumatic brain injury.
Journal of neurology, neurosurgery, and psychiatry, 2020

Cognitive impairment is a key cause of disability after traumatic brain injury (TBI) but relationships with overall functioning in daily life are often modest. The aim is to examine cognition at different levels of function and identify domains associated with disability.
Processes regulating the initiation and postejaculatory resumption of copulatory behavior in male hamsters.
Behavioural processes, 2014

Studies using factor analysis have helped describe the organization of copulatory behavior in male rodents. However, the focus of these studies on a few traditional measures may have limited their results. To test this possibility, 74 sexually-experienced male hamsters were observed as they copulated with stimulus females. The measures collected exceeded the conventional ones in number, variety and independence. The factor analysis of these data revealed a structure with seven factors collectively accounting for 80% of the variance. Most resembled the factors in previous reports, reinforcing the contributions that the processes suggested by these factors make to the organization of male behavior. But several other factors were more novel, possibly reflecting the use of measures that were novel or revised for greater independence. The most interesting of these were two factors focusing on early steps in the progression leading to ejaculation. Importantly, both incorporated measures from each of the three copulatory series that were observed. Past work suggests that independent processes control the times required to initiate copulation and later resume it after an ejaculation. In contrast, these results suggest the existence of two processes, each of which contributes to both the initiation and reinitiation of copulation.
Founder effect of the TTTCA repeat insertions in SAMD12 causing BAFME1.
European journal of human genetics : EJHG, 2021

Benign adult familial myoclonic epilepsy type 1 (BAFME1) in several Japanese and Chinese families has recently been found to be caused by pentanucleotide repeat expansions in SAMD12. We identified a Thai family with six members affected with BAFME. Microsatellite studies suggested a linkage to the BAFME1 region on chromosome 8q24. Subsequently, long-read whole-genome sequencing showed the (TTTTA)
TET1 and 5-Hydroxymethylation Preserve the Stem Cell State of Mouse Trophoblast.
Stem cell reports, 2020

The ten-eleven translocation factor TET1 and its conferred epigenetic modification 5-hydroxymethylcytosine (5hmC) have important roles in maintaining the pluripotent state of embryonic stem cells (ESCs). We previously showed that TET1 is also essential to maintain the stem cell state of trophoblast stem cells (TSCs). Here, we establish an integrated panel of absolute 5hmC levels, genome-wide DNA methylation and hydroxymethylation patterns, transcriptomes, and TET1 chromatin occupancy in TSCs and differentiated trophoblast cells. We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. Hypoxia can slow down the global loss of 5hmC that occurs upon differentiation of TSCs. Notably, unlike in ESCs and epiblast cells, most TET1-bound regions overlap with active chromatin marks and TFAP2C binding sites and demarcate putative trophoblast enhancer regions. These chromatin modification and occupancy patterns are highly informative to identify novel candidate regulators of the TSC state.
Sensory Neurobiology: A New Crossroads Deep in the Cortex.
Current biology : CB, 2021

Self-generated movements elicit concomitant sensory responses that are beneficial to ignore. Combining state-of-the-art physiology, behavior, and anatomy, a new study discovers a neural crossroads in the deepest layer of auditory cortex where pre-lick ramping activity suppresses peri-lick sound responses across layers.
Causal role of lateral prefrontal cortex in mental effort and fatigue.
Human brain mapping, 2020

Dorsolateral prefrontal cortex (DLPFC) is well-known for its role in exerting mental work, however the contribution of DLPFC for deciding whether or not to engage in effort remains unknown. Here, we assessed the causal role of DLPFC in effort-based decision making. We disrupted functioning of DLPFC with noninvasive brain stimulation before participants repeatedly decided whether to exert mental effort in a working memory task. We found the same DLPFC subregion involved in mental effort exertion to influence also effort-based decisions: First, it enhanced effort discounting, suggesting that DLPFC may signal the capacity to successfully deal with effort demands. Second, a novel computational model integrating the costs of enduring effort into the effort-based decision process revealed that DLPFC disruption reduced fatigue after accumulated effort exertion, linking DLPFC activation with fatigue. Together, our findings indicate that in effort-based decisions DLPFC represents the capacity to exert mental effort and the updating of this information with enduring time-on-task, informing theoretical accounts on the role of DLPFC in the motivation to exert mental effort and the fatigue arising from it.
Real time large scale in vivo observations reveal intrinsic synchrony, plasticity and growth cone dynamics of midline crossing axons at the ventral floor plate of the zebrafish spinal cord.
Journal of integrative neuroscience, 2019

How axons are wiring the vertebrate spinal cord has in particular been studied at the ventral floor plate using fixed samples or looking at single growing axons with various microscopy techniques. Thereby may remain hidden important live organismal scale information concerning dynamics and concurrent timing of the many axons simultaneously crossing the floor plate. Here then, applying light-sheet microscopy, axonal growth and guidance at the floor plate are followed in vivo in real time at high resolution along several hundred micrometers of the zebrafish spinal cord by using an interneuron expressing GFP as a model axon. The commissural axons are observed crossing the ventral floor plate midline perpendicularly at about 20 microns/h and in a manner dependent on the Robo3 receptor. Commissural growth rate reaches a minimum at the midline, confirming previous observations. Ipsilateral axons extend concurrently, at three to six times higher growth rates. At guidance points, commissural axons are seen to decrease their growth rate and growth cones increase in size. Commissural filopodia appear to interact with the nascent neural network, and thereby trigger immediate plastic and reversible sinusoidal-shaped bending movements of neighboring commissural shafts. A simple protocol isolating single neuronal cells from the spinal cord is developed to facilitate further molecular characterization. The recordings show the strikingly stereotyped spatio-temporal control that governs midline crossing. The live observations give renewed perspective on the mechanisms of axonal guidance in the spinal cord that provide for a discussion of the current distinction between diffusible long-range versus substrate-bound short-range guidance cues.
Overlapping Neurobiological Substrates for Early-Life Stress and Resilience to Psychosis.
Biological psychiatry. Cognitive neuroscience and neuroimaging, 2021

Early-life stress, such as childhood maltreatment, is a well-known etiological factor in psychopathology, including psychosis. Exposure to early-life stress disrupts the neurodevelopment of widespread brain systems, including key components of the hypothalamic-pituitary-adrenal axis stress response, such as the amygdala, hippocampus, and medial prefrontal cortex, as well as key components of the brain's reward system, such as the nucleus accumbens and orbitofrontal cortex. These disruptions have a considerable impact on the function of emotion and reward circuitry, which play a central role in the emergence and severity of psychosis. While this overlap may provide insight into the pathophysiology of psychosis, it also provides unique opportunities to elucidate neurobiological substrates that may promote resilience to psychosis. In this review, we discuss the hypothalamic-pituitary-adrenal axis stress response, discuss the disruption in the neurodevelopment of emotion and reward processing associated with early stress exposures, and examine how this circuitry may contribute to resilience to psychotic disorders.
Working Memory Decline in Alzheimer's Disease Is Detected by Complexity Analysis of Multimodal EEG-fNIRS.
Entropy (Basel, Switzerland), 2020

Alzheimer's disease (AD) is characterized by working memory (WM) failures that can be assessed at early stages through administering clinical tests. Ecological neuroimaging, such as Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS), may be employed during these tests to support AD early diagnosis within clinical settings. Multimodal EEG-fNIRS could measure brain activity along with neurovascular coupling (NC) and detect their modifications associated with AD. Data analysis procedures based on signal complexity are suitable to estimate electrical and hemodynamic brain activity or their mutual information (NC) during non-structured experimental paradigms. In this study, sample entropy of whole-head EEG and frontal/prefrontal cortex fNIRS was evaluated to assess brain activity in early AD and healthy controls (HC) during WM tasks (i.e., Rey-Osterrieth complex figure and Raven's progressive matrices). Moreover, conditional entropy between EEG and fNIRS was evaluated as indicative of NC. The findings demonstrated the capability of complexity analysis of multimodal EEG-fNIRS to detect WM decline in AD. Furthermore, a multivariate data-driven analysis, performed on these entropy metrics and based on the General Linear Model, allowed classifying AD and HC with an AUC up to 0.88. EEG-fNIRS may represent a powerful tool for the clinical evaluation of WM decline in early AD.
Peripheral chemoreflex control of fetal heart rate decelerations overwhelms the baroreflex during brief umbilical cord occlusions in fetal sheep.
The Journal of physiology, 2020

The majority of intrapartum decelerations are widely believed to be mediated by the baroreflex secondary to brief umbilical cord occlusions (UCOs) but this remains unproven. We examined the responses to brief-UCOs in fetal sheep and compared these to a phenylephrine-stimulated baroreflex in a separate cohort. A further cohort was instrumented with near-infrared spectroscopy to measure cerebral oxygenation during UCO. The first 3-4 s of the brief-UCOs were consistent with a baroreflex, and associated with a minor fall in fetal heart rate (FHR). Thereafter, the remainder of the FHR decelerations were highly consistent with the peripheral chemoreflex. The baroreflex is not sufficient to produce deep, rapid decelerations characteristic of variable decelerations and it is therefore likely to be a minor contributor to intrapartum decelerations.
Filling in at partially deafferented visual cortex.
The British journal of ophthalmology, 2008

Perceptual visual filling in at the corresponding area of toxoplasmic retinochoroiditis scotomas in the fellow eye was studied in 14 patients. Targets were programmed to appear inside the scotoma corresponding area in the fellow eye, and at two control points.
The effect of healthy aging on change detection and sensitivity to predictable structure in crowded acoustic scenes.
Hearing research, 2021

The auditory system plays a critical role in supporting our ability to detect abrupt changes in our surroundings. Here we study how this capacity is affected in the course of healthy ageing. Artifical acoustic 'scenes', populated by multiple concurrent streams of pure tones ('sources') were used to capture the challenges of listening in complex acoustic environments. Two scene conditions were included: REG scenes consisted of sources characterized by a regular temporal structure. Matched RAND scenes contained sources which were temporally random. Changes, manifested as the abrupt disappearance of one of the sources, were introduced to a subset of the trials and participants ('young' group N = 41, age 20-38 years; 'older' group N = 41, age 60-82 years) were instructed to monitor the scenes for these events. Previous work demonstrated that young listeners exhibit better change detection performance in REG scenes, reflecting sensitivity to temporal structure. Here we sought to determine: (1) Whether 'baseline' change detection ability (i.e. in RAND scenes) is affected by age. (2) Whether aging affects listeners' sensitivity to temporal regularity. (3) How change detection capacity relates to listeners' hearing and cognitive profile (a battery of tests that capture hearing and cognitive abilities hypothesized to be affected by aging). The results demonstrated that healthy aging is associated with reduced sensitivity to abrupt scene changes in RAND scenes but that performance does not correlate with age or standard audiological measures such as pure tone audiometry or speech in noise performance. Remarkably older listeners' change detection performance improved substantially (up to the level exhibited by young listeners) in REG relative to RAND scenes. This suggests that the ability to extract and track the regularity associated with scene sources, even in crowded acoustic environments, is relatively preserved in older listeners.
Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome.
World journal of stem cells, 2020

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a "cytokine storm", as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a "living anti-inflammatory", which can "rebalance" the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.
Evaluation of a structured skills training group for adolescents with attention deficit/hyperactivity disorder (ADHD) - study protocol of a randomised controlled trial.
BMC psychiatry, 2019

Attention deficit/hyperactivity disorder (ADHD) has a negative impact on several domains of life. However, there is a shortage of evidence-based non-pharmacological treatments for adolescents with ADHD. A structured skills training group (SSTG) based on dialectical behaviour therapy (DBT) has been used in adult patients with ADHD with some promising results, although the treatment has not yet been adapted or evaluated for adolescents with ADHD. This study protocol describes how this treatment was adapted for an adolescent population and how the efficacy of the SSTG will be evaluated using a randomised controlled trial (RCT) design.
Sex Differences in the Epilepsies and Associated Comorbidities: Implications for Use and Development of Pharmacotherapies.
Pharmacological reviews, 2020

The epilepsies are common neurologic disorders characterized by spontaneous recurrent seizures. Boys, girls, men, and women of all ages are affected by epilepsy and, in many cases, by associated comorbidities as well. The primary courses of treatment are pharmacological, dietary, and/or surgical, depending on several factors, including the areas of the brain affected and the severity of the epilepsy. There is a growing appreciation that sex differences in underlying brain function and in the neurobiology of epilepsy are important factors that should be accounted for in the design and development of new therapies. In this review, we discuss the current knowledge on sex differences in epilepsy and associated comorbidities, with emphasis on those aspects most informative for the development of new pharmacotherapies. Particular focus is placed on sex differences in the prevalence and presentation of various focal and generalized epilepsies; psychiatric, cognitive, and physiologic comorbidities; catamenial epilepsy in women; sex differences in brain development; the neural actions of sex and stress hormones and their metabolites; and cellular mechanisms, including brain-derived neurotrophic factor signaling and neuronal-glial interactions. Further attention placed on potential sex differences in epilepsies, comorbidities, and drug effects will enhance therapeutic options and efficacy for all patients with epilepsy. SIGNIFICANCE STATEMENT: Epilepsy is a common neurological disorder that often presents together with various comorbidities. The features of epilepsy and seizure activity as well as comorbid afflictions can vary between men and women. In this review, we discuss sex differences in types of epilepsies, associated comorbidities, pathophysiological mechanisms, and antiepileptic drug efficacy in both clinical patient populations and preclinical animal models.