rudyvdbrink/CitationDatabase huggingface dataset:
Synaptophysin and caspase-3 expression on lumbar segments of spinal cord after sensorimotor restriction during early postnatal period and treadmill training.
Journal of exercise rehabilitation, 2018

The purpose of the current study was to investigate whether locomotor stimulation training could have beneficial effects on spinal cord plasticity consequent to sensorimotor restriction (SR). Male Wistar rats were exposed to SR from postnatal day 2 (P2) to P28. Control and experimental rats underwent locomotor stimulation training in a treadmill from P31 to P52. The intensity of the synaptophysin and caspase-3 immunoreaction was determined on ventral horn of spinal cord. The synaptophysin immunoreactivity was lower in the ventral horn of sensorimotor restricted rats compared to controls animals and was accompanied by an increased caspase-3 immunoreactivity. Those alterations were reversed at the end of the training period. Our results suggest that immobility affects the normal developmental process that spinal cord undergoes in early postnatal life influencing both pro-apoptotic and synapse markers. Also, we demonstrated that this phenomenon was reversed by 3 weeks of treadmill training.
County-level socioeconomic and crime risk factors for substantiated child abuse and neglect.
Child abuse & neglect, 2019

Rates of substantiated child abuse and neglect vary significantly across counties. Despite strong cross-sectional support for links between social-contextual characteristics and abuse and neglect, few longitudinal studies have tested relations between these risk factors and substantiated rates of abuse/neglect. The goal of this study was to identify county-level socioeconomic and crime factors associated with substantiated abuse/neglect rates over 13 years (2004-2016). Annual county-level data for Tennessee, obtained from the KIDS COUNT Data Center, included rates of substantiated child abuse and neglect, children's race and ethnicity, births to unmarried women, teen birth rate, children in families receiving Supplemental Nutrition Assistance Program (SNAP) benefits, and children in families receiving Temporary Assistance for Needy Families. Annual county-level crime report data, obtained from the Tennessee Incident Based Reporting System, included sexual offenses, non-sexual assaults, stalking incidents, thefts, property damage, and drug-related offenses. Bayesian spatio-temporal models indicated that substantiated child abuse and neglect rates were independently and positively associated with teen birth rates, percentages of births to unmarried mothers, drug-related offenses, and percentages of children receiving SNAP benefits. In contrast, substantiated child abuse and neglect rates were negatively associated with percentages of African-American youth. The findings highlighted distinct demographic, socioeconomic, and crime factors associated with substantiated child abuse and neglect rates and have the potential to enhance identification of high-risk counties that could benefit from targeted abuse and neglect prevention efforts.
Reporting outcomes in clinical trials for bipolar disorder: a commentary and suggestions for change.
Bipolar disorders, 2008

Newer outcome measures and statistical reporting that better translate efficacy data to evidence-based psychiatric care are needed when evaluating clinical trials for bipolar disorder. Using efficacy studies as illustrations, the authors review and recommend changes in the reporting of traditional clinical outcomes both in the acute and maintenance phases of bipolar disorder.
Association between high sensitivity C-reactive protein, heart rate variability and corrected QT interval in patients with chronic inflammatory arthritis.
European journal of internal medicine, 2013

The risk of sudden cardiac death is increased in chronic inflammatory arthritis, particularly rheumatoid arthritis (RA). To evaluate the putative effect of systemic inflammation on heart rate variability (HRV) and ventricular repolarization in chronic inflammatory arthritis, we analyzed in these patients the possible relationship among HRV parameters, QT interval, and high sensitivity C-reactive protein (hsCRP).
PKCε phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration.
BMC neuroscience, 2018

Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identified as a master switch that controls the nucleocytoplasmic trafficking of ATF2 and the survival of melanoma cells. It is of interest to assess the role of PKCε-ATF2 signaling in neurodegeneration.
A behavioural neuroscience perspective on the aetiology and treatment of anxiety disorders.
Behaviour research and therapy, 2014

Over the past decades, behaviour and cognitive psychology have produced fruitful and mutually converging theories from which hypotheses could be derived on the nature and origin of fear and anxiety disorders. Notwithstanding the emergence of effective treatments, there are still many questions that remain to be answered. Here, I will argue that the burgeoning field of behavioural neuroscience may advance our understanding of fear, anxiety disorders and its treatments. Decades of fear-conditioning research across species have begun to elucidate the neurobiological mechanisms underlying associative fear learning and memory. The fear-conditioning paradigm provides a well-controlled and fine-grained research platform to examine these processes. Although the traditional fear conditioning paradigm was originally designed to unveil general principles of fear (un)learning, it is well-suited to understand the transition from normal fear to pathological fear and the mechanisms of change. This paper presents 1) a selection of fear conditioning studies on the generalization and persistence of associative fear memory as intermediate phenotypes of fear and anxiety disorders, and 2) insights from neuroscience on the malleability of fear memory with the potential to provide a long-term cure for anxiety and related disorders.
Two-photon directed evolution of green fluorescent proteins.
Scientific reports, 2015

Directed evolution has been used extensively to improve the properties of a variety of fluorescent proteins (FPs). Evolutionary strategies, however, have not yet been used to improve the two-photon absorption (2PA) properties of a fluorescent protein, properties that are important for two-photon imaging in living tissues, including the brain. Here we demonstrate a technique for quantitatively screening the two-photon excited fluorescence (2PEF) efficiency and 2PA cross section of tens of thousands of mutant FPs expressed in E. coli colonies. We use this procedure to move EGFP through three rounds of two-photon directed evolution leading to new variants showing up to a 50% enhancement in peak 2PA cross section and brightness within the near-IR tissue transparency wavelength range.
Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65.
Scientific reports, 2015

Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Recent evidence suggests that HD is a consequence of multimodal, non-mutually exclusive mechanisms of pathogenesis that involve both HTT protein- and HTT RNA-triggered mechanisms. Here we provide further evidence for the role of expanded HTT (expHTT) RNA in HD by demonstrating that a fragment of expHTT is cytotoxic in the absence of any translation and that the extent of cytotoxicity is similar to the cytotoxicity of an expHTT protein fragment encoded by a transcript of similar length and with a similar repeat size. In addition, full-length (FL) expHTT is retained in the nucleus. Overexpression of the splicing factor muscleblind-like 1 (MBNL1) increases nuclear retention of expHTT and decreases the expression of expHTT protein in the cytosol. The splicing and nuclear export factor U2AF65 has the opposite effect, decreasing expHTT nuclear retention and increasing expression of expHTT protein. This suggests that MBNL1 and U2AF65 play a role in nuclear export of expHTT RNA.
Individual alpha frequency proximity associated with repetitive transcranial magnetic stimulation outcome: An independent replication study from the ICON-DB consortium.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2021

The aim of the current study was to attempt to replicate the finding that the individual alpha frequency (IAF) as well as the absolute difference between IAF and 10 Hz stimulation frequency (IAF-prox) is related to treatment outcome.
A unified framework for association and prediction from vertex-wise grey-matter structure.
Human brain mapping, 2020

The recent availability of large-scale neuroimaging cohorts facilitates deeper characterisation of the relationship between phenotypic and brain architecture variation in humans. Here, we investigate the association (previously coined morphometricity) of a phenotype with all 652,283 vertex-wise measures of cortical and subcortical morphology in a large data set from the UK Biobank (UKB; N = 9,497 for discovery, N = 4,323 for replication) and the Human Connectome Project (N = 1,110). We used a linear mixed model with the brain measures of individuals fitted as random effects with covariance relationships estimated from the imaging data. We tested 167 behavioural, cognitive, psychiatric or lifestyle phenotypes and found significant morphometricity for 58 phenotypes (spanning substance use, blood assay results, education or income level, diet, depression, and cognition domains), 23 of which replicated in the UKB replication set or the HCP. We then extended the model for a bivariate analysis to estimate grey-matter correlation between phenotypes, which revealed that body size (i.e., height, weight, BMI, waist and hip circumference, body fat percentage) could account for a substantial proportion of the morphometricity (confirmed using a conditional analysis), providing possible insight into previous MRI case-control results for psychiatric disorders where case status is associated with body mass index. Our LMM framework also allowed to predict some of the associated phenotypes from the vertex-wise measures, in two independent samples. Finally, we demonstrated additional new applications of our approach (a) region of interest (ROI) analysis that retain the vertex-wise complexity; (b) comparison of the information retained by different MRI processings.
The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study: prevalence and risk factors.
Atherosclerosis, 2012

The ongoing population-based Barcelona-Asymptomatic Intracranial Atherosclerosis (Barcelona-AsIA) study is a prospective study that plans to investigate the natural history of asymptomatic intracranial atherosclerosis (AsIA) in a Caucasian-Mediterranean population, which remains unknown until now. The present study aims to determine the prevalence of AsIA and associated risk factors in the final study cohort.
Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke.
Stroke, 2019

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
Neural oscillations associated with item and temporal order maintenance in working memory.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

The ability to retain information in working memory (WM) requires not only the active maintenance of information about specific items, but also the temporal order in which the items appeared. Although many studies have investigated the neural mechanisms of item maintenance, little is known about the neural mechanisms of temporal order maintenance in WM. Here, we used electroencephalography (EEG) to compare neural oscillations during WM tasks that required maintenance of item or temporal order information. Behavioral results revealed that accuracy and reaction times were comparable between the two conditions, suggesting that task difficulty was matched between the item and temporal order WM tasks. EEG analyses indicated that theta (5-7 Hz) oscillations over prefrontal sites were increased during temporal order maintenance, whereas alpha oscillations (9-12 Hz) over posterior parietal and lateral occipital sites were increased during item maintenance. The frontal theta enhancement was primarily evident in high performers on the order WM task, whereas the posterior alpha enhancement was primarily evident in high performers on the item WM task. These results support the idea that frontal theta and posterior alpha oscillations are differentially related to maintenance of item and temporal order information.
The association between dispositional mindfulness, psychological well-being, and perceived health in a Swedish population-based sample.
British journal of health psychology, 2011

There is increasing recognition of the links between mindfulness, decreased stress, and healthier psychological functioning. However, the majority of this research has been conducted in US samples and the mechanisms through which mindfulness decreases stress and increases well-being are not well understood. The aim of this study was to examine the relations between mindfulness and psychological functioning in a general population sample in Sweden.
Hemispheric dominance underlying the neural substrate for learned vocalizations develops with experience.
Scientific reports, 2015

Many aspects of song learning in songbirds resemble characteristics of speech acquisition in humans. Genetic, anatomical and behavioural parallels have most recently been extended with demonstrated similarities in hemispheric dominance between humans and songbirds: the avian higher order auditory cortex is left-lateralized for processing song memories in juvenile zebra finches that already have formed a memory of their fathers' song, just like Wernicke's area in the left hemisphere of the human brain is dominant for speech perception. However, it is unclear if hemispheric specialization is due to pre-existing functional asymmetry or the result of learning itself. Here we show that in juvenile male and female zebra finches that had never heard an adult song before, neuronal activation after initial exposure to a conspecific song is bilateral. Thus, like in humans, hemispheric dominance develops with vocal proficiency. A left-lateralized functional system that develops through auditory-vocal learning may be an evolutionary adaptation that could increase the efficiency of transferring information within one hemisphere, benefiting the production and perception of learned communication signals.
Neuritogenic activity of bi-functional bis-tryptoline triazole.
Bioorganic & medicinal chemistry, 2017

Alzheimer's disease (AD) is a common neurodegenerative disorder, one of the hallmarks of which is the deposition of aggregated β-amyloid peptides (Aβ40,42) as plaques in the brain. Oligomers of these peptides have been reported to be toxic and to inhibit neurite outgrowth, as evidenced by neurite dystrophy and significant loss of synaptic connectivity of neurons in the AD brain resulting in cognitive decline. These peptides also react with biological metal in the brain to generate free radicals, thereby aggravating neuronal cell injury and death. Herein, multifunctional triazole-based compounds acting on multiple targets, namely β-secretase (BACE1), β-amyloid peptides (Aβ) as well as those possessing metal chelation and antioxidant properties, were developed and evaluated for neuritogenic activity in P19-derived neurons. At the non-cytotoxic concentration (1nM), all multifunctional compounds significantly enhanced neurite outgrowth. New bis-tryptoline triazole (BTT) increased the neurite length and neurite number, by 93.25% and 136.09% over the control, respectively. This finding demonstrates the ability of multifunctional compounds targeting Aβ to enhance neurite outgrowth in addition to their neuroprotective action.
HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma.
Cancer cell, 2016

Medulloblastoma (MB) is a highly malignant pediatric brain tumor. Despite aggressive therapy, many patients succumb to the disease, and survivors experience severe side effects from treatment. MYC-driven MB has a particularly poor prognosis and would greatly benefit from more effective therapies. We used an animal model of MYC-driven MB to screen for drugs that decrease viability of tumor cells. Among the most effective compounds were histone deacetylase inhibitors (HDACIs). HDACIs potently inhibit survival of MYC-driven MB cells in vitro, in part by inducing expression of the FOXO1 tumor suppressor gene. HDACIs also synergize with phosphatidylinositol 3-kinase inhibitors to inhibit tumor growth in vivo. These studies identify an effective combination therapy for the most aggressive form of MB.
Region-specific role of growth differentiation factor-5 in the establishment of sympathetic innervation.
Neural development, 2016

Nerve growth factor (NGF) is the prototypical target-derived neurotrophic factor required for sympathetic neuron survival and for the growth and ramification of sympathetic axons within most but not all sympathetic targets. This implies the operation of additional target-derived factors for regulating terminal sympathetic axon growth and branching.
Successful antidepressant chronotherapeutics enhance fronto-limbic neural responses and connectivity in bipolar depression.
Psychiatry research, 2015

The identification of antidepressant response predictors in bipolar disorder (BD) may provide new potential enhancements in treatment selection. Repeated total sleep deprivation combined with light therapy (TSD+LT) can acutely reverse depressive symptoms and has been proposed as a model antidepressant treatment. This study aims at investigating the effect of TSD+LT on effective connectivity and neural response in cortico-limbic circuitries during implicit processing of fearful and angry faces in patients with BD. fMRI and Dynamic Causal Modeling (DCM) were combined to study the effect of chronotherapeutics on neural responses in healthy controls (HC, n = 35) and BD patients either responder (RBD, n = 26) or non responder (nRBD, n = 11) to 3 consecutive TSD+LT sessions. Twenty-four DCMs exploring connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), Amygdala (Amy), fusiform gyrus and visual cortex were constructed. After treatment, patients significantly increased their neural responses in DLPFC, ACC and insula. nRBD showed lower baseline and endpoint neural responses than RBD. The increased activity in ACC and in medial prefrontal cortex, associated with antidepressant treatment, was positively associated with the improvement of depressive symptomatology. Only RBD patients increased intrinsic connectivity from DLPFC to ACC and reduced the modulatory effect of the task on Amy-DLPFC connection. A successful antidepressant treatment was associated with an increased functional activity and connectivity within cortico-limbic networks, suggesting the possible role of these measures in providing possible biomarkers for treatment efficacy.
Altered cortical excitability in persistent idiopathic facial pain.
Cephalalgia : an international journal of headache, 2019

Persistent idiopathic facial pain is a refractory and disabling condition of unknown mechanism and etiology. It has been suggested that persistent idiopathic facial pain patients have not only peripheral generators of pain, but also central nervous system changes that would contribute to the persistence of symptoms. We hypothesized that persistent idiopathic facial pain would have changes in brain cortical excitability as measured by transcranial magnetic stimulation compared to healthy controls.
Suicide in a rural area of coastal Kenya.
BMC psychiatry, 2018

Suicide accounts for approximately 1.4% of deaths globally and is the 15th leading cause of death overall. There are no reliable data on the epidemiology of completed suicide in rural areas of many developing countries, yet suicide is an indicator of the sustainable development goals on health.
Brn3a and Brn3b knockout mice display unvaried retinal fine structure despite major morphological and numerical alterations of ganglion cells.
The Journal of comparative neurology, 2019

Ganglion cells (GCs), the retinal output neurons, receive synaptic inputs from bipolar and amacrine cells in the inner plexiform layer (IPL) and send information to the brain nuclei via the optic nerve. Although GCs constitute less than 1% of the total retinal cells, they occur in numerous types and are the first neurons formed during retinal development. Using Brn3a and Brn3b mutant mice in which the alkaline phosphatase gene was knocked-in (Badea et al. [Neuron] 2009;61:852-864; Badea and Nathans [Vision Res] 2011;51:269-279), we studied the general effects after gene removal on the retinal neuropil together with the consequences of lack of development of large numbers of GCs onto the remaining retinal neurons of the same class. We analyzed the morphology, number, and general architecture of various neuronal types presynaptic to GCs, searching for changes secondary to the decrement in the number of their postsynaptic partners, as well as the morphology and distribution of retinal astrocytes, for their strong topographical relation to GCs. We found that, despite GC losses, retinal organization in Brn3 null mice is remarkably similar to that of wild-type controls. J. Comp. Neurol. 527:187-211, 2019. © 2016 Wiley Periodicals, Inc.