rudyvdbrink/CitationDatabase huggingface dataset:
Immune epigenetic age in pregnancy and 1 year after birth: Associations with weight change.
American journal of reproductive immunology (New York, N.Y. : 1989), 2020

Epigenetic age indices are markers of biological aging determined from DNA methylation patterns. Accelerated epigenetic age predicts morbidity and mortality. Women tend to demonstrate slower blood epigenetic aging compared to men, possibly due to female-specific hormones and reproductive milestones. Pregnancy and the post-partum period are critical reproductive periods that have not been studied yet with respect to epigenetic aging. The purpose of this paper was to examine whether pregnancy itself and an important pregnancy-related variable, changes in body mass index (BMI) between pregnancy and the post-partum period, are associated with epigenetic aging.
Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior.
Proceedings of the National Academy of Sciences of the United States of America, 2021

Activity of sensory and motor cortices is essential for sensorimotor integration. In particular, coherence between these areas may indicate binding of critical functions like perception, motor planning, action, or sleep. Evidence is accumulating that cerebellar output modulates cortical activity and coherence, but how, when, and where it does so is unclear. We studied activity in and coherence between S1 and M1 cortices during whisker stimulation in the absence and presence of optogenetic Purkinje cell stimulation in crus 1 and 2 of awake mice, eliciting strong simple spike rate modulation. Without Purkinje cell stimulation, whisker stimulation triggers fast responses in S1 and M1 involving transient coherence in a broad spectrum. Simultaneous stimulation of Purkinje cells and whiskers affects amplitude and kinetics of sensory responses in S1 and M1 and alters the estimated S1-M1 coherence in theta and gamma bands, allowing bidirectional control dependent on behavioral context. These effects are absent when Purkinje cell activation is delayed by 20 ms. Focal stimulation of Purkinje cells revealed site specificity, with cells in medial crus 2 showing the most prominent and selective impact on estimated coherence, i.e., a strong suppression in the gamma but not the theta band. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1-M1 phase consistency predominantly via ventrolateral thalamus and M1. Our results indicate that activity of sensorimotor cortices can be dynamically and functionally modulated by specific cerebellar inputs, highlighting a widespread role of the cerebellum in coordinating sensorimotor behavior.
Click and Release: A Chemical Strategy toward Developing Gasotransmitter Prodrugs by Using an Intramolecular Diels-Alder Reaction.
Angewandte Chemie (International ed. in English), 2016

Prodrug strategies have been proven to be a very effective way of addressing delivery problems. Much of the chemistry in prodrug development relies on the ability to mask an appropriate functional group, which can be removed under appropriate conditions. However, developing organic prodrugs of gasotransmitters represent unique challenges. This is especially true with carbon monoxide, which does not have an easy "handle" for bioreversible derivatization. By taking advantage of an intramolecular Diels-Alder reaction, we have developed a prodrug strategy for preparations of organic CO prodrugs that are stable during synthesis and storage, and yet readily release CO with tunable release rates under near physiological conditions. The effectiveness of the CO prodrug system in delivering a sufficient quantity of CO for possible therapeutic applications has been studied using a cell culture anti-inflammatory assay and a colitis animal model. These studies fully demonstrate the proof of concept, and lay a strong foundation for further medicinal chemistry work in developing organic CO prodrugs.
Elite competitive swimmers exhibit higher motor cortical inhibition and superior sensorimotor skills in a water environment.
Behavioural brain research, 2020

Motor skill learning leads to task-related contextual behavioral changes that are underpinned by neuroplastic cortical reorganization. Short-term training induces environment-related contextual behavioral changes and neuroplastic changes in the primary motor cortex (M1). However, it is unclear whether environment-related contextual behavioral changes persist after long-term training and how cortical plastic changes are involved in behavior. To address these issues, we examined 14 elite competitive swimmers and 14 novices. We hypothesized that the sensorimotor skills of swimmers would be higher in a water environment than those of novices, and the recruitment of corticospinal and intracortical projections would be different between swimmers and novices. We assessed joint angle modulation performance as a behavioral measure and motor cortical excitation and inhibition using transcranial magnetic stimulation (TMS) at rest and during the tasks that were performed before, during, and after water immersion (WI). Motor cortical inhibition was measured with short-interval intracortical inhibition and long-interval intracortical inhibition by a paired-pulse TMS paradigm. We found that 1) the sensorimotor skills of swimmers who underwent long-term training in a water environment were superior and robustly unchanged compared with those of novices with respect to baseline on land, during WI, on land post-WI and 2) intracortical inhibition in water environments was increased in swimmers but was decreased in non-swimmers at rest compared to that on land; however, the latter alterations in intracortical inhibition in water environment were insufficient to account for the superior sensorimotor skills of swimmers. In conclusion, we demonstrate that environment-related contextual behavioral and neural changes occur even with long-term training experience.
Exploring hypotheses and rationale for causes of infantile colic.
Neurogastroenterology and motility, 2017

Infantile colic is a frequent problem in neonates and infants. This review addresses current management including the results for nutrient modifications; soy-based formulas; and prebiotics, probiotics, and synbiotics.
Voxelwise encoding models with non-spherical multivariate normal priors.
NeuroImage, 2019

Predictive models for neural or fMRI data are often fit using regression methods that employ priors on the model parameters. One widely used method is ridge regression, which employs a spherical multivariate normal prior that assumes equal and independent variance for all parameters. However, a spherical prior is not always optimal or appropriate. There are many cases where expert knowledge or hypotheses about the structure of the model parameters could be used to construct a better prior. In these cases, non-spherical multivariate normal priors can be employed using a generalized form of ridge known as Tikhonov regression. Yet Tikhonov regression is only rarely used in neuroscience. In this paper we discuss the theoretical basis for Tikhonov regression, demonstrate a computationally efficient method for its application, and show several examples of how Tikhonov regression can improve predictive models for fMRI data. We also show that many earlier studies have implicitly used Tikhonov regression by linearly transforming the regressors before performing ridge regression.
Psychostimulants, antidepressants and neurokinin-1 receptor antagonists ('motor disinhibitors') have overlapping, but distinct, effects on monoamine transmission: the involvement of L-type Ca2+ channels and implications for the treatment of ADHD.
Neuropharmacology, 2014

Both psychostimulants and antidepressants target monoamine transporters and, as a consequence, augment monoamine transmission. These two groups of drugs also increase motor activity in preclinical behavioural screens for antidepressants. Substance P-preferring receptor (NK1R) antagonists similarly increase both motor activity in these tests and monoamine transmission in the brain. In this article, the neurochemical and behavioural responses to these three groups of drugs are compared. It becomes evident that NK1R antagonists represent a distinct class of compounds ('motor disinhibitors') that differ substantially from both psychostimulants and antidepressants, especially during states of heightened arousal or stress. Also, all three groups of drugs influence the activation of voltage-gated Ca(v)1.2 and Ca(v)1.3 L-type channels (LTCCs) in the brain, albeit in different ways. This article discusses evidence that points to disruption of these functional interactions between NK1R and LTCCs as a contributing factor in the cognitive and behavioural abnormalities that are prominent features of Attention Deficit Hyperactivity Disorder (ADHD). Arising from this is the interesting possibility that the hyperactivity and impulsivity (as in ADHD) and psychomotor retardation (as in depression) reflect opposite poles of a behavioural continuum. A better understanding of this pharmacological network could help explain why psychostimulants augment motor behaviour during stress (e.g., in preclinical screens for antidepressants) and yet reduce locomotor activity and impulsivity in ADHD. This article is part of the Special Issue entitled 'CNS Stimulants'.
Unilateral peak nasal inspiratory flow, normal values in adult population.
Rhinology, 2012

Measurement of Peak Nasal Inspiratory Flow (PNIF) is a cheap, simple, easily performed method to assess nasal patency and it is suitable for serial measurements and for home use. The purpose of this study was to establish normative unilateral PNIF data for a healthy adult population and provide charts relating unilateral PNIF normal values with various explanatory variables.
Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats.
European journal of pharmacology, 2010

Present study investigated the role of agmatine in ethanol-induced anxiolysis and withdrawal anxiety using elevated plus maze (EPM) test in rats. The anxiolytic-like effect of ethanol was potentiated by pretreatment with imidazoline I(1)/I(2) receptor agonist agmatine (10-20 mg/kg, i.p.), imidazoline I(1) receptor agonists, moxonidine (0.25 mg/kg, i.p.) and clonidine (0.015 mg/kg, i.p.), imidazoline I(2) receptor agonist, 2-BFI (5 mg/kg, i.p.) as well as by the drugs known to increase endogenous agmatine levels in brain viz., L-arginine, an agmatine biosynthetic precursor (100 microg/rat, i.c.v.), ornithine decarboxylase inhibitor, DFMO (125 microg/rat, i.c.v.), diamine oxidase inhibitor, aminoguanidine (65 microg/rat, i.c.v.) and agmatinase inhibitor, arcaine (50 microg/rat, i.c.v.). Conversely, prior administration of I(1) receptor antagonist, efaroxan (1 mg/kg, i.p.), I(2) receptor antagonist, idazoxan (0.25mg/kg, i.p.) and arginine decarboxylase inhibitor, D-arginine (100 microg/rat, i.c.v.) blocked the anxiolytic-like effect of ethanol. Moreover, ethanol withdrawal anxiety was markedly attenuated by agmatine (10-20 mg/kg, i.p.), moxonidine (0.25 mg/kg, i.p.), clonidine (0.015 mg/kg, i.p.), 2-BFI (5 mg/kg, i.p.), L-arginine (100 microg/rat, i.c.v.), DFMO (125 microg/rat, i.c.v.), aminoguanidine (65 microg/rat, i.c.v.) and arcaine (50 microg/rat, i.c.v.). The anti-anxiety effect of agmatine in ethanol-withdrawn rats was completely blocked by efaroxan (1 mg/kg, i.p.) and idazoxan (0.25 mg/kg, i.p.). These results suggest that agmatine and imidazoline receptor system may be implicated in ethanol-induced anxiolysis and withdrawal anxiety and strongly support further investigation of agmatine in ethanol dependence mechanism. The data also project agmatine as a potential therapeutic target in overcoming alcohol withdrawal symptoms such as anxiety.
Comprehensive comparative analysis of methods and software for identifying viral integrations.
Briefings in bioinformatics, 2019

Many viruses are capable of integrating in the human genome, particularly viruses involved in tumorigenesis. Viral integrations can be considered genetic markers for discovering virus-caused cancers and inferring cancer cell development. Next-generation sequencing (NGS) technologies have been widely used to screen for viral integrations in cancer genomes, and a number of bioinformatics tools have been developed to detect viral integrations using NGS data. However, there has been no systematic comparison of the methods or software. In this study, we performed a comprehensive comparative analysis of the designs, performance, functionality and limitations among the existing methods and software for detecting viral integrations. We further compared the sensitivity, precision and runtime of integration detection of four representative tools. Our analyses showed that each of the existing software had its own merits; however, none of them were sufficient for parallel or accurate virome-wide detection. After carefully evaluating the limitations shared by the existing methods, we proposed strategies and directions for developing virome-wide integration detection.
Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.
European archives of psychiatry and clinical neuroscience, 2018

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.
Repeat-associated non-AUG (RAN) translation mechanisms are running into focus for GGGGCC-repeat associated ALS/FTD.
Progress in neurobiology, 2019

Many human diseases are associated with the expansion of repeat sequences within the genes. It has become clear that expressed disease transcripts bearing such long repeats can undergo translation, even in the absence of a canonical AUG start codon. Termed "RAN translation" for repeat associated non-AUG translation, this process is becoming increasingly prominent as a contributor to these disorders. Here we discuss mechanisms and variables that impact translation of the repeat sequences associated with the C9orf72 gene. Expansions of a G4C2 repeat within intron 1 of this gene are associated with the motor neuron disease ALS and dementia FTD, which comprise a clinical and pathological spectrum. RAN translation of G4C2 repeat expansions has been studied in cells in culture (ex vivo) and in the fly in vivo. Cellular states that lead to RAN translation, like stress, may be critical contributors to disease progression. Greater elucidation of the mechanisms that impact this process and the factors contributing will lead to greater understanding of the repeat expansion diseases, to the potential development of novel approaches to therapeutics, and to a greater understanding of how these players impact biological processes in the absence of disease.
Functional bimodality in the brain networks of preterm and term human newborns.
Cerebral cortex (New York, N.Y. : 1991), 2014

The spontaneous brain activity exhibits long-range spatial correlations detected using functional magnetic resonance imaging (fMRI) signals in newborns when (1) long neuronal pathways are still developing, and (2) the electrical brain activity consists of developmentally unique, intermittent events believed to guide activity-dependent brain wiring. We studied this spontaneous electrical brain activity using multichannel electroencephalography (EEG) of premature and fullterm babies during sleep to assess the development of spatial integration during last months of gestation. Correlations of frequency-specific amplitudes were found to follow a robust bimodality: During low amplitudes (low mode), brain activity exhibited very weak spatial correlations. In contrast, the developmentally essential high-amplitude events (high mode) showed strong spatial correlations. There were no clear spatial patterns in the early preterm, but clear frontal and parieto-occipital modules at term age. A significant fronto-occipital gradient was also seen in the development of the graph measure clustering coefficient. Strikingly, no bimodality was found in the fMRI recordings of the fullterm babies, suggesting that early EEG activity and fMRI signal reflect different mechanisms of spatial coordination. The results are compatible with the idea that early developing human brain exhibits intermittent long-range spatial connections that likely provide the endogenous guidance for early activity-dependent development of brain networks.
Anxiety in Parkinson's disease: Symptom dimensions and overlap with depression and autonomic failure.
Parkinsonism & related disorders, 2015

Anxiety disorders are highly prevalent in patients with Parkinson's disease (PD) and have a major impact on wellbeing. They nevertheless receive limited scientific attention. This study aimed to establish the symptom dimensions of anxiety in PD, and their relationship with depression, autonomic failure and motor symptoms.
Insular Epilepsy: Semiology and Noninvasive Investigations.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 2017

In this review, authors discuss the semiology and noninvasive investigations of insular epilepsy, an underrecognized type of epilepsy, which may mimic other focal epilepsies. In line with the various functions of the insula and its widespread network of connections, insular epilepsy may feature a variety of early ictal manifestations from somatosensory, visceral, olfactory, gustatory, or vestibular manifestations. Depending on propagation pathways, insular seizures may also include altered consciousness, dystonic posturing, complex motor behaviors, and even autonomic features. Considering the variability in seizure semiology, recognition of insular epilepsy may be challenging and confirmation by noninvasive tests is warranted although few studies have assessed their value. Detection of an insular lesion on MRI greatly facilitates the diagnosis. Scalp EEG findings in frontocentral and/or temporal derivations will generally allow lateralization of the seizure focus. Ictal single-photon computed tomography has moderate sensitivity, whereas positron emission tomography has lower sensitivity. Among newer techniques, magnetoencephalography is highly beneficial, whereas proton magnetic resonance spectroscopy currently has limited value.
Spontaneous listeriosis in grey mouse lemurs (Microcebus murinus), but not in Goodman's mouse lemurs (Microcebus lehilahytsara) of the same colony.
Veterinary microbiology, 2017

Listeriosis is a zoonotic infection with the gram positive, facultative intracellular bacterium Listeria (L.) monocytogenes. Infections mainly occur in ruminants, but also in other species, including humans. Case fatality rate usually is high. The incidence of listeriosis in captive non-human primates is very low. We report the first spontaneous, fatal, and likely food-born outbreak of listeriosis in a population of captive grey mouse lemurs (Microcebus murinus). Conspicuously, none of the closely related Goodman's mouse lemurs (Microcebus lehilahytsara) in the same facility were affected.
Comparing the phenomenological qualities of stimulus-independent thought, stimulus-dependent thought and dreams using experience sampling.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2021

Humans spend a considerable portion of their lives engaged in 'stimulus-independent thoughts' (SIT), or mental activity that occurs independently of input from the immediate external environment. Although such SITs are, by definition, different from thoughts that are driven by stimuli in one's external environment (i.e. stimulus-dependent thoughts; SDTs), at times, the phenomenology of these two types of thought appears to be deceptively similar. But how similar are they? We address this question by comparing the content of two types of SIT (dreaming and waking SITs) with the content of SDTs. In this 7 day, smartphone-based experience-sampling procedure, participants were intermittently probed during the day and night to indicate whether their current thoughts were stimulus dependent or stimulus independent. They then responded to content-based items indexing the qualitative aspects of their experience (e.g. My thoughts were jumping from topic to topic). Results indicate substantial distinctiveness between these three types of thought: significant differences between at least two of the three mental states were found across every measured variable. Implications are discussed. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.
Intermolecular Interaction between Anchoring Subunits Specify Subcellular Targeting and Function of RGS Proteins in Retina ON-Bipolar Neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016

In vertebrate retina, light responses generated by the rod photoreceptors are transmitted to the second-order neurons, the ON-bipolar cells (ON-BC), and this communication is indispensible for vision in dim light. In ON-BCs, synaptic transmission is initiated by the metabotropic glutamate receptor, mGluR6, that signals via the G-protein Go to control opening of the effector ion channel, TRPM1. A key role in this process belongs to the GTPase Activating Protein (GAP) complex that catalyzes Go inactivation upon light-induced suppression of glutamate release in rod photoreceptors, thereby driving ON-BC depolarization to changes in synaptic input. The GAP complex has a striking molecular complexity. It contains two Regulator of G-protein Signaling (RGS) proteins RGS7 and RGS11 that directly act on Go and two adaptor subunits: RGS Anchor Protein (R9AP) and the orphan receptor, GPR179. Here we examined the organizational principles of the GAP complex in ON-BCs. Biochemical experiments revealed that RGS7 binds to a conserved site in GPR179 and that RGS11 in vivo forms a complex only with R9AP. R9AP and GPR179 are further integrated via direct protein-protein interactions involving their cytoplasmic domains. Elimination of GPR179 prevents postsynaptic accumulation of R9AP. Furthermore, concurrent knock-out of both R9AP and RGS7 does not reconfigure the GAP complex and completely abolishes synaptic transmission, resulting in a novel mouse model of night blindness. Based on these results, we propose a model of hierarchical assembly and function of the GAP complex that supports ON-BCs visual signaling.