rudyvdbrink/CitationDatabase huggingface dataset:
Id2 is required for specification of dopaminergic neurons during adult olfactory neurogenesis.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Understanding the biology of adult neural stem cells has important implications for nervous system development and may contribute to our understanding of neurodegenerative disorders and their treatment. We have characterized the process of olfactory neurogenesis in adult mice lacking inhibitor of DNA binding 2(-/-) (Id2(-/-)). We found a diminished olfactory bulb containing reduced numbers of granular and periglomerular neurons with a distinct paucity of dopaminergic periglomerular neurons. While no deficiency of the stem cell compartment was detectable, migrating neuroblasts in Id2(-/-) mutant mice prematurely undergo astroglial differentiation within a disorganized rostral migratory stream. Further, when evaluated in vitro loss of Id2 results in decreased proliferation of neural progenitors and decreased expression of the Hes1 and Ascl1 (Mash1) transcription factors, known mediators of neuronal differentiation. These data support a novel role for sustained Id2 expression in migrating neural progenitors mediating olfactory dopaminergic neuronal differentiation in adult animals.
Déjà vecu for news events but not personal events: A dissociation between autobiographical and non-autobiographical episodic memory processing.
Cortex; a journal devoted to the study of the nervous system and behavior, 2017

In déjà vu, the feeling that what we are currently experiencing we have experienced before is fleeting and is not accepted as true. In contrast, in déjà vecu or "recollective confabulation", the sense of déjà vu is persistent and convincing, and patients genuinely believe that they have lived through the current moment at some previous time. In previous reports of cases of déjà vecu, both personal events and non-personal, world events gave rise to this experience. In this paper we describe a patient whose déjà vecu experiences are entirely restricted to non-personal events, suggesting that autobiographical and non-autobiographical episodic memory processing can dissociate. We suggest that this dissociation is secondary to differences in the degree to which personal and emotional associations are formed for these two different types of event, and offer a two-factor theory of déjà vecu.
Genetic and pharmacological regulation of the endocannabinoid CB1 receptor in Duchenne muscular dystrophy.
Nature communications, 2018

The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases. However, the potential role of endocannabinoids in skeletal muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne's muscular dystrophy. In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles. Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice. In conclusion, our study uncovers a PAX7-CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies.
Regulator of Calcineurin 1 helps coordinate whole-body metabolism and thermogenesis.
EMBO reports, 2018

Increasing non-shivering thermogenesis (NST), which expends calories as heat rather than storing them as fat, is championed as an effective way to combat obesity and metabolic disease. Innate mechanisms constraining the capacity for NST present a fundamental limitation to this approach, yet are not well understood. Here, we provide evidence that Regulator of Calcineurin 1 (
Refining the Frommelt Attitude Toward the Care of the Dying Scale (FATCOD-B) for medical students: A confirmatory factor analysis and Rasch validation study.
Palliative & supportive care, 2018

Given the increasing number of patients requiring palliative care and the need for more professionals who are able to provide care for the dying comfortably, assessment of medical attitudes toward end-of-life care is becoming a key aspect of medical education. The present study aimed to establish whether the Frommelt Attitude Toward the Care Of the Dying, Form B (FATCOD-B) meets current psychometric standards of validity for an assessment tool in medical education.
Microglia heterogeneity and neurodegeneration: The emerging paradigm of the role of immunity in Alzheimer's disease.
Journal of neuroimmunology, 2020

Alzheimer's disease (AD) is the most common dementia type affecting nearly 44 million people worldwide. Recent findings point to microglia as a significant contributor to neural development, neuroinflammation, and degeneration. Dysregulated immunoactivity in AD has been broadly studied, and current research on animal models enabled us to identify a new cluster of microglia (disease-associated microglia) alongside previously detected glial populations (e.g., plaque-associated microglia, dark microglia, Human Alzheimer's microglia) associated with neuroinflammation and with macrophagic activity. These distinct populations of glia show a spatial distribution within plaques with unique imaging features and distinct gene expression profile. Novel genetic approaches using single-nuclei RNA sequencing (sn-RNA seq) allowed researchers to identify gene expression profiles from fixed human samples. Recent studies, exposing transcriptomic clusters of disease-related cells and analyzing sequenced RNA from sorted myeloid cells, seem to confirm the hypothesis of the central role of glia in the pathogenesis of Alzheimer's disease. These discoveries may shed light on the effects of microglial activation and differences in gene expression profiles, furthering research towards the development of a cell-specific therapy. In this review, we examine recent studies that guide us towards recognizing the role of diverse populations of glial cells and their possible heterogeneous functional states in the pathogenesis of AD in humans.
Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017

Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca
Dissociable roles of prefrontal subregions in self-ordered working memory performance.
Neuropsychologia, 2008

The anatomical segregation of executive control processes within the prefrontal cortex remains poorly defined. The present study focused on strategy implementation on two working memory tasks: the CANTAB spatial working memory task and a visuospatial sequence generation task. These measures were administered to a group of frontal lesion patients and a comparison group of healthy subjects. Frontal patients with damage to the right inferior frontal gyrus were impaired on the CANTAB spatial working memory task, compared with healthy controls and patients without damage to this region. This deficit was most strongly related to the pars opercularis subregion (BA44) and was accompanied by poor strategy usage. On the sequence generation task, frontal lesion patients were impaired on a strategy-training phase when the working memory demands of the task were reduced, but had relatively intact performance on other phases of the task. Performance on the training phase was correlated with the amount of damage to the dorsolateral prefrontal cortex (DLPFC: BA46/9). These results support theoretical notions of prefrontal cortical function that emphasise its contribution to executive processes such as mnemonic strategies and monitoring over its role as a short-term memory store. Moreover, we provide evidence for the first time that such functions are dependent on dissociable brain regions within the prefrontal cortex.
The North-South Divide: Substance Use Risk, Care Engagement, and Viral Suppression Among Hospitalized Human Immunodeficiency Virus-Infected Patients in 11 US Cities.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019

Regional variability in human immunodeficiency virus (HIV) care engagement remains underexplored. Multiple logistic models compared HIV outcomes for participants from 5 Southern (n = 557) and 6 non-Southern (n = 670) sites. Southern participants were less likely to experience viral suppression (adjusted odds ratio [aOR], 0.52; 95% confidence interval [CI], .37-.72) and had a higher likelihood of a CD4+ count <200 cells/µL (aOR, 1.53; 95% CI, 1.17-2.00). HIV intervention and social safety net programs should be expanded.
Cux2 acts as a critical regulator for neurogenesis in the olfactory epithelium of vertebrates.
Developmental biology, 2014

Signaling pathways and transcription factors are crucial regulators of vertebrate neurogenesis, exerting their function in a spatial and temporal manner. Despite recent advances in our understanding of the molecular regulation of embryonic neurogenesis, little is known regarding how different signaling pathways interact to tightly regulate this process during the development of neuroepithelia. To address this, we have investigated the events lying upstream and downstream of a key neurogenic factor, the Cut-like homeodomain transcription factor-2 (Cux2), during embryonic neurogenesis in chick and mouse. By using the olfactory epithelium as a model for neurogenesis we have analyzed mouse embryos deficient in Cux2, as well as chick embryos exposed to Cux2 silencing (si) RNA or a Cux2 over-expression construct. We provide evidence that enhanced BMP activity increases Cux2 expression and suppresses olfactory neurogenesis in the chick olfactory epithelium. In addition, our results show that up-regulation of Cux2, either BMP-induced or ectopically over-expressed, reduce Delta1 expression and suppress proliferation. Interestingly, the loss of Cux2 activity, using mutant mice or siRNA in chick, also diminishes neurogenesis, Notch activity and cell proliferation in the olfactory epithelium. Our results suggest that controlled low levels of Cux2 activity are necessary for proper Notch signaling, maintenance of the proliferative pool and ongoing neurogenesis in the olfactory epithelium. Thus, we demonstrate a novel conserved mechanism in vertebrates in which levels of Cux2 activity play an important role for ongoing neurogenesis in the olfactory epithelium.
Spatial uncertainty improves the distribution of visual attention and the availability of sensory information for conscious report.
Experimental brain research, 2020

Picking-up and exploiting spatial and temporal regularities in the occurrence of sensory events is important for goal-directed behaviour. According to the "Predictive Coding Hypothesis" (Friston Philosophical Trans R Soc B 360(1456):815-836, 2005), these regularities are used to generate top-down predictions that are constantly compared with actual sensory events. In a previous study with the Attentional Blink (AB) paradigm, we showed that the temporal and probabilistic uncertainty of T2s that are presented outside the Attentional Blink period, i.e. at least 400 ms after T1, improves the conscious report of T2 that are presented inside the AB. The study of ERP correlated showed that this improvement was associated with a prolonged storage of pre-conscious T2 traces in extra-striate areas (Lasaponara et al. Cortex 71:15-33, 2015). Here, we tested whether variations in the probabilistic cueing of the position of a primary T1 visual target in a 4 × 4 letter array, modulate the retention of memory traces evoked by secondary letter targets (T2) that were presented in other positions of the array. Most important, in each trial, the identity of T2 was specified to participants upon disappearance of the array. We show that high probabilistic cueing facilitates T1 detection and improves the corresponding sensitivity index (d'). In contrast, retention and conscious report of secondary targets (T2) improves when the probabilistic cueing of T1 position is poor. These results suggest that uncertainty in the upcoming position of primary targets boosts the strength of memory traces evoked by secondary targets and improves the possibility that traces of secondary targets gain full access to conscious processing.
Differential effects of testosterone, dihydrotestosterone and estradiol on carotenoid deposition in an avian sexually selected signal.
Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology, 2011

Recent studies have demonstrated that carotenoid-based traits are under the control of testosterone (T) by up-regulation of carotenoid carriers (lipoproteins) and/or tissue-specific uptake of carotenoids. T can be converted to dihydrotestosterone (DHT) and estradiol (E2), and variation in conversion rate may partly explain some contradictory findings in the literature. Moreover, most studies on the effect of T on sexual signals have focused on the male sex only, while in many species females show the same signal, albeit to a lesser extent. We studied the effects of T, DHT, and E2 treatment in male and female diamond doves Geopelia cuneata in which both sexes have an enlarged red eye ring, which is more pronounced in males. We first showed that this periorbital ring contains very high concentration of carotenoids, of which most are lutein esters. Both T and DHT were effective in enhancing hue, UV-chroma and size in both sexes, while E2 was ineffective. However, E2 dramatically increased the concentration of circulating lipoproteins. We conclude that in both sexes both color and size of the secondary sexual trait are androgen dependent. The action of androgens is independent of lipoproteins regulation. Potential mechanisms and their consequences for trade-off are discussed.
High density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor.
The Journal of cell biology, 2014

Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3',5'-monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 × 10(5) GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces "molecule noise." Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons.
Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 2014

While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression.
Proverb interpretation changes in aging.
Brain and cognition, 2008

Recent investigations have emphasized the involvement of fronto-subcortical networks to proverb comprehension. Although the prefrontal cortex is thought to be affected by normal aging, relatively little work has been carried out to investigate potential effects of aging on proverb comprehension. In the present investigation participants in three age groups were assessed on a proverb comprehension task and a range of executive function tasks. The older group showed impairment in selecting correct interpretations from alternatives. They also showed executive function deficits, as reflected by reduced working memory and deficient set shifting and inhibition abilities. The findings of the present investigation showed proverb comprehension deficits in normal aging which appeared to be related to reduced executive skills.
Impact of brain arousal and time-on-task on autonomic nervous system activity in the wake-sleep transition.
BMC neuroscience, 2018

Autonomic nervous system (ANS) activity has been shown to vary with the state of brain arousal. In a previous study, this association of ANS activity with distinct states of brain arousal was demonstrated using 15-min EEG data, but without directly controlling for possible time-on-task effects. In the current study we examine ANS-activity in fine-graded EEG-vigilance stages (indicating states of brain arousal) during two conditions of a 2-h oddball task while controlling for time-on-task. In addition, we analyze the effect of time-on-task on ANS-activity while holding the level of brain arousal constant.
Anxiety disorders and anxiety-related traits and serotonin transporter gene-linked polymorphic region (5-HTTLPR) in adolescents: case-control and trio studies.
Psychiatric genetics, 2014

The role of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in anxiety disorder and anxiety-related traits is controversial. Besides this study, few studies have evaluated the triallelic genotype in adolescents. The aim of this study was to investigate whether anxiety disorders and anxiety-related traits are associated with 5-HTTLPR (biallelic and triallelic) in adolescents, integrating both case-control-based and family-based designs in a community sample. This is a cross-sectional community study of 504 individuals and their families: 225 adolescents (129 adolescents with anxiety disorder and 96 controls) and their biological families. We assessed psychiatric diagnosis using the Kiddie Schedule for Affective Disorders and Schizophrenia. The Temperament and Character Inventory and the Resnick Behavioral Inhibition Scale were used to evaluate harm avoidance and behavioral inhibition. DNA was extracted from saliva and genotyped, including biallelic and triallelic 5-HTTLPR classification, by PCR-RFLP followed by agarose gel electrophoresis. We were not able to find any associations between 5-HTTLPR and anxiety-related phenotypes in both case-control and trio analyses. Further investigation and meta-analytic studies are needed to better clarify the inconsistent results with regard to the association between 5-HTTLPR and anxiety-related phenotypes in adolescents.
Loss of PINK1 function decreases PP2A activity and promotes autophagy in dopaminergic cells and a murine model.
Neurochemistry international, 2011

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK1-silenced MN9D cells, which suggests that PP2A plays an important role in the PINK1-knockdown-induced autophagic pathway. Furthermore, phosphorylation of Bcl-2 at S87 increased in PINK1-silenced cells and was negatively regulated by additional treatment with C2-ceramide, which indicates that Bcl-2 may be downstream of PP2A inactivation in response to PINK1 dysfunction. Immunoprecipitation also revealed dissociation of the Bcl-2/Beclin1 complex in PINK1-silenced cells, which was reversed by additional treatment with C2-ceramide, and correlated with changes in level of autophagy and S87 phosphorylation of Bcl-2. Finally, Western blots for cleaved caspase-9 and flow cytometry results for active caspase-3 revealed that PP2A inactivation is involved in the protective effect of autophagy on PINK1-silenced cells. Our findings show that downregulation of PP2A activity in PINK1-silenced cells promotes the protective effect of autophagy through phosphorylation of Bcl-2 at S87 and blockage of the caspase pathway. These results may have implications for identifying the mechanism of PD.
Ascending beta oscillation from finger muscle to sensorimotor cortex contributes to enhanced steady-state isometric contraction in humans.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2014

β-Band corticomuscular coherence is suggested as an electrophysiological mechanism that contributes to sensorimotor functioning in the maintenance of steady-state contractions. Converging evidence suggests that not only the descending corticospinal pathway but the ascending sensory feedback pathway is involved in the generation of β-band corticomuscular coherence. The present study aimed to investigate which pathway, descending vs. ascending, contributes more to the stability of muscle contraction, especially for human intrinsic hand muscles.