rudyvdbrink/CitationDatabase huggingface dataset:
Mutually exclusive dendritic arbors in C. elegans neurons share a common architecture and convergent molecular cues.
PLoS genetics, 2020

Stress-induced changes to the dendritic architecture of neurons have been demonstrated in numerous mammalian and invertebrate systems. Remodeling of dendrites varies tremendously among neuron types. During the stress-induced dauer stage of Caenorhabditis elegans, the IL2 neurons arborize to cover the anterior body wall. In contrast, the FLP neurons arborize to cover an identical receptive field during reproductive development. Using time-course imaging, we show that branching between these two neuron types is highly coordinated. Furthermore, we find that the IL2 and FLP arbors have a similar dendritic architecture and use an identical downstream effector complex to control branching; however, regulation of this complex differs between stress-induced IL2 branching and FLP branching during reproductive development. We demonstrate that the unfolded protein response (UPR) sensor IRE-1, required for localization of the complex in FLP branching, is dispensable for IL2 branching at standard cultivation temperatures. Exposure of ire-1 mutants to elevated temperatures results in defective IL2 branching, thereby demonstrating a previously unknown genotype by environment interaction within the UPR. We find that the FOXO homolog, DAF-16, is required cell-autonomously to control arborization during stress-induced arborization. Likewise, several aspects of the dauer formation pathway are necessary for the neuron to remodel, including the phosphatase PTEN/DAF-18 and Cytochrome P450/DAF-9. Finally, we find that the TOR associated protein, RAPTOR/DAF-15 regulates mutually exclusive branching of the IL2 and FLP dendrites. DAF-15 promotes IL2 branching during dauer and inhibits precocious FLP growth. Together, our results shed light on molecular processes that regulate stress-mediated remodeling of dendrites across neuron classes.
Hypothesis: Entrapment of lipoprotein particles in the brain causes Alzheimer's disease.
Free neuropathology, 2021

We present for consideration a hypothesis that impaired movement of lipoprotein particles in the extracellular space in the brain in ageing is central to and causes all the key pathophysiological features of Alzheimer's disease (AD). The role of lipoprotein particles is to transport cholesterol from glial cells, where it is synthesised, to neurons, which require cholesterol for synaptic plasticity. The lipoprotein particles have a cholesterol-containing hydrophobic core, in which amyloid-β (Aβ) can be solubilised. The core is surrounded by a hydrophilic surface containing apolipoprotein E (APOE) which, as neurons bear receptors for APOE, determines the destination of the particles. The problem arises because the extracellular space is a narrow cleft, barely wider than the lipoprotein particles themselves, which they have to navigate in order to perform their crucial cholesterol-transporting function. We explain how lipoprotein particles could become trapped in the ageing extracellular matrix and that this primary abnormality results in reduced delivery of cholesterol to neurons leading to impaired synaptic plasticity, crucial for learning and memory. It can also explain extracellular Aβ accumulation, to which a microglial response generates a neurotoxic reaction, and intraneuronal tau aggregation, each of which exacerbate the problem. All these players have been known for many years to be important in Alzheimer's pathogenesis but a single unifying mechanism to explain how they are linked has been lacking. This proposed mechanism, with entrapment of lipoproteins particles as key to the development of AD, can explain the failure of so many clinical trials and points out new directions to be taken.
Prisoners of Addictive Cues: Biobehavioral Markers of Overweight and Obese Adults with Food Addiction.
Nutrients, 2020

Obesity is associated with food and eating addiction (FA), but the biobehavioral markers of this condition are poorly understood. To characterize FA, we recruited 18 healthy controls and overweight/obese adults with (
Automated approach to detecting behavioral states using EEG-DABS.
Heliyon, 2017

Electrocorticographic (ECoG) signals represent cortical electrical dipoles generated by synchronous local field potentials that result from simultaneous firing of neurons at distinct frequencies (brain waves). Since different brain waves correlate to different behavioral states, ECoG signals presents a novel strategy to detect complex behaviors. We developed a program, EEG Detection Analysis for Behavioral States (EEG-DABS) that advances Fast Fourier Transforms through ECoG signals time series, separating it into (user defined) frequency bands and normalizes them to reduce variability. EEG-DABS determines events if segments of an experimental ECoG record have significantly different power bands than a selected control pattern of EEG. Events are identified at every epoch and frequency band and then are displayed as output graphs by the program. Certain patterns of events correspond to specific behaviors. Once a predetermined pattern was selected for a behavioral state, EEG-DABS correctly identified the desired behavioral event. The selection of frequency band combinations for detection of the behavior affects accuracy of the method. All instances of certain behaviors, such as freezing, were correctly identified from the event patterns generated with EEG-DABS. Detecting behaviors is typically achieved by visually discerning unique animal phenotypes, a process that is time consuming, unreliable, and subjective. EEG-DABS removes variability by using defined parameters of EEG/ECoG for a desired behavior over chronic recordings. EEG-DABS presents a simple and automated approach to quantify different behavioral states from ECoG signals.
A distinct transcriptional signature of antidepressant response in hippocampal dentate gyrus granule cells.
Translational psychiatry, 2021

Major depressive disorder is the most prevalent mental illness worldwide, still its pharmacological treatment is limited by various challenges, such as the large heterogeneity in treatment response and the lack of insight into the neurobiological pathways underlying this phenomenon. To decode the molecular mechanisms shaping antidepressant response and to distinguish those from general paroxetine effects, we used a previously established approach targeting extremes (i.e., good vs poor responder mice). We focused on the dentate gyrus (DG), a subregion of major interest in the context of antidepressant mechanisms. Transcriptome profiling on micro-dissected DG granule cells was performed to (i) reveal cell-type-specific changes in paroxetine-induced gene expression (paroxetine vs vehicle) and (ii) to identify molecular signatures of treatment response within a cohort of paroxetine-treated animals. We identified 112 differentially expressed genes associated with paroxetine treatment. The extreme group comparison (good vs poor responder) yielded 211 differentially expressed genes. General paroxetine effects could be distinguished from treatment response-associated molecular signatures, with a differential gene expression overlap of only 4.6% (15 genes). Biological pathway enrichment and cluster analyses identified candidate mechanisms associated with good treatment response, e.g., neuropeptide signaling, synaptic transmission, calcium signaling, and regulation of glucocorticoid secretion. Finally, we examined glucocorticoid receptor (GR)-dependent regulation of selected response-associated genes to analyze a hypothesized interplay between GR signaling and good antidepressant treatment response. Among the most promising candidates, we suggest potential targets such as the developmental gene Otx2 or Htr2c for further investigations into antidepressant treatment response in the future.
Copy number variants in siblings of Mexican origin concordant for schizophrenia or bipolar disorder.
Psychiatry research, 2020

Schizophrenia (SCZ) and bipolar disorder (BD) cause similar symptomatology. A correlation between these disorders has been found. We aimed to explore shared CNVs between SCZ and BD, in 35 sibpairs diagnosed with SCZ and 21 sibpairs diagnosed with BD. CNV calling was performed using data derived of Psycharray, by PennCNV. We did not find any shared CNVs between individuals diagnosed with BD and SCZ, neither with psychotic symptoms in individuals with BD. Nevertheless, we found a significant higher CNV burden in early-onset SCZ. This is one of the first's studies analyzing shared CNVs between SCZ and BD in Mexican population.
Isolation of Rodent Brain Vessels.
Bio-protocol, 2017

The prevalence of neurodegenerative diseases is increasing worldwide. Cerebrovascular disorders and/or conditions known to affect brain vasculature, such as diabetes, are well-known risk factors for neurodegenerative diseases. Thus, the evaluation of the brain vasculature is of great importance to better understand the mechanisms underlying brain damage. We established a protocol for the isolation of brain vessels from rodents. This is a simple, non-enzymatic isolation protocol that allows us to perform comparative studies in different animal models of disease, helping understand the impact of several pathological conditions on brain vasculature and how those alterations predispose to neurodegenerative conditions.
Aging reduces the sensitivity to the reinforcing efficacy of morphine.
Neurobiology of aging, 2021

The US geriatric population is growing and using more opioids than ever before. The purpose of this study was to determine whether aging influenced the reinforcing efficacy of morphine in male and female rats using a rodent intravenous self-administration paradigm. Male and female aged (20-24 months) and young (2-4 months) Wistar rats were tested at 2 doses of morphine (0.75 mg/kg/infusion and 0.25 mg/kg/infusion). During 10 days of self-administration, aged rats took significantly less morphine than their younger counterparts at the 0.25 mg/kg/infusion dose. Aged males also earned significantly fewer infusions on a progressive ration reinforcement schedule at this dose, suggesting that the reinforcing efficacy of morphine is decreased for this group at this dose. These effects dissipated when a separate group of animals had access to the 0.75 mg/kg/infusion dose for both sexes. Our results indicate that morphine is less reinforcing at lower doses in aged male, but not female rats. This research has potential clinical implications for the chronic treatments involving opioids in aged individuals.
Neural Circuits: When Neurons 'Remember' Their Connectivity.
Current biology : CB, 2018

Loss of neurons due to injury or neurodegeneration can lead to dramatically altered neural circuits, resulting in reduced or lost function. One mechanism to preserve function could be to re-establish the stereotypic connectivity among the remnant neurons. In the mammalian retina, such a selective re-wiring has now been described.
Longitudinal Associations of Mental Disorders With Physical Diseases and Mortality Among 2.3 Million New Zealand Citizens.
JAMA network open, 2021

Excess risk of physical disease and mortality has been observed among individuals with psychiatric conditions, suggesting that ameliorating mental disorders might also be associated with ameliorating the later onset of physical disability and early mortality. However, the temporal association between mental disorders and physical diseases remains unclear, as many studies have relied on retrospective recall, used cross-sectional designs or prospective designs with limited follow-up periods, or given inadequate consideration to preexisting physical illnesses.
IKCa agonist (NS309)-elicited all-or-none dehydration response of human red blood cells is cell-age dependent.
Cell calcium, 2011

Elevated [Ca(2+)](i) in human red blood cells (RBCs) activates IK1 K(+) channels leading to cell dehydration. NS309, a powerful IK1 agonist, has been shown to activate IK1 channels even at sub-physiological [Ca(2+)](i) levels. An intriguing feature of this response is its all-or-none nature, with responsive cells dehydrating fully and refractory cells retaining normal volume. We investigated the mechanism of this response suspecting cell-age involvement. We expected the younger cells, with the more vigorous plasma membrane Ca(2+) pumps (PMCA), to be the refractory cells because of their lower [Ca(2+)](i). Osmotic fragility measurements and density separation through phthalate oil were used to monitor red cell dehydration. The fraction of glycosilated haemoglobin (Hb A1c) was used to estimate the mean age of density fractionated cells. The results showed that inhibition of the PMCA by vanadate abolished the all-or-none response, that the mean age of the responsive cells was young, contrary to expectations, and that pump inhibition subsequent to an all-or-none response caused the refractory cells to dehydrate fully, suggesting that the all-or-none response resulted from a reduced efficiency of NS309 to increase the Ca(2+) sensitivity of IK1 channels in aged RBCs.
Spatiotemporal Proteomic Analysis of Stress Granule Disassembly Using APEX Reveals Regulation by SUMOylation and Links to ALS Pathogenesis.
Molecular cell, 2020

Stress granules (SGs) are cytoplasmic assemblies of proteins and non-translating mRNAs. Whereas much has been learned about SG formation, a major gap remains in understanding the compositional changes SGs undergo during normal disassembly and under disease conditions. Here, we address this gap by proteomic dissection of the SG temporal disassembly sequence using multi-bait APEX proximity proteomics. We discover 109 novel SG proteins and characterize distinct SG substructures. We reveal dozens of disassembly-engaged proteins (DEPs), some of which play functional roles in SG disassembly, including small ubiquitin-like modifier (SUMO) conjugating enzymes. We further demonstrate that SUMOylation regulates SG disassembly and SG formation. Parallel proteomics with amyotrophic lateral sclerosis (ALS)-associated C9ORF72 dipeptides uncovered attenuated DEP recruitment during SG disassembly and impaired SUMOylation. Accordingly, SUMO activity ameliorated C9ORF72-ALS-related neurodegeneration in Drosophila. By dissecting the SG spatiotemporal proteomic landscape, we provide an in-depth resource for future work on SG function and reveal basic and disease-relevant mechanisms of SG disassembly.
Sibship size, birth order and psychotic experiences: Evidence from 43 low- and middle-income countries.
Schizophrenia research, 2018

Sibship size and birth order may be contributing factors to the multifactorial etiology of psychosis. Specifically, several studies have shown that sibship size and birth order are associated with schizophrenia. However, there are no studies on their association with psychotic experiences (PE).
Calcium channel antibodies in patients with absence epilepsy.
The International journal of neuroscience, 2014

Autoimmunity has aroused interest in the last years as a contributory mechanism of epilepsy, especially in epilepsies with unknown cause or therapy resistance. Since the relationship of absence epilepsy (AE) with calcium channels is well established, we aimed to investigate related antibodies in patients diagnosed with AE. Consecutive patients with typical absence seizures having either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) with generalized spike and wave discharges on electroencephalography (EEG) were included after their consent. The patients were diagnosed according to the International League Against Epilepsy (ILAE) 2010 criteria. Antibodies against P-Q type voltage gated calcium channels (VGCC) and T-type VGCC subunit Cav3.2 (encoded by the CACNA1H gene) were investigated by RIA and ELISA, respectively. We searched for these antibodies in 32 patients with AE and 53 patients with focal epilepsy of unknown cause (FEOUC) as the disease control group; furthermore, 30 healthy persons served as the healthy controls. Eleven patients (34.3%) with AE had CAE and the remaining patients had JAE. Only a 47-year-old female FEOUC patient, who also had systemic lupus erythematosus with normal MRI scans showed antibodies against P-Q type VGCC, whereas no antibody positivity could be found in other FEOUC and AE patients and healthy controls. Our results might suggest that calcium channel antibodies do not play an important role in the pathophysiology of AE. Further studies with larger groups of other epileptic syndromes are needed to confirm our results.
Add-on benzodiazepine treatment in patients with major depressive disorder - results from a European cross-sectional multicenter study.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2020

Since many patients with major depressive disorder (MDD) do not satisfactorily respond to initial antidepressant monotherapy, add-on treatment strategies with other psychiatric compounds are often established. The present European multicenter cross-sectional study comprising 1410 MDD in- and outpatients investigated the prescription pattern of benzodiazepines as add-on treatment in the psychopharmacotherapy of MDD. Analyses of variance, chi-squared tests, and logistic regression analyses were conducted to examine differences in socio-demographic, clinical, and treatment characteristics between benzodiazepine users and non-users. The prescription rate for adjunctive benzodiazepine treatment amounted to 31.35%. The most often administered benzodiazepines were lorazepam (11.13%), clonazepam (6.74%), and alprazolam (6.60%). Benzodiazepine users exhibited more severe depressive symptoms expressed by a higher mean Montgomery and Åsberg Depression Rating Scale total score at study entry (26.92 ± 11.07 vs 23.55 ± 11.23, p<.0001) and at the beginning of the current major depressive episode (35.74 ± 8.08 vs 33.31 ± 7.40, p<.0001). Furthermore, they were characterized by a higher proportion of patients receiving additional augmentation/combination medications with antidepressants (40.95% vs 24.28%, p<.0001), antipsychotics (41.63% vs 18.39%, p<.0001), and low-potency antipsychotics (10.18% vs 4.75%, p<.0001). Moreover, benzodiazepine prescription was associated with older age, unemployment, inpatient treatment, suicide risk, psychotic and melancholic features, comorbid panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder. Taken together, our findings indicate that benzodiazepine augmentation in MDD is first of all established in severe/difficult-to-treat conditions and serves as predictor for the use of additional augmentation/combination treatment strategies.
Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity.
eLife, 2020

Internal state alters sensory behaviors to optimize survival strategies. The neuronal mechanisms underlying hunger-dependent behavioral plasticity are not fully characterized. Here we show that feeding state alters
Hematologic parameters in coronavirus infection (COVID-19) and their clinical implications.
Discoveries (Craiova, Romania), 2020

Coronaviruses are a class of enveloped RNA viruses that cause infections of the respiratory tract, characterized by fever, tiredness, dry cough, diarrhea, loss of smell or taste, chest pain and shortness of breath. Many patients with mysterious pneumonia were distinguished in December 2019 in Wuhan. The pneumonia of obscure origin was found to be ascribed to a novel coronavirus and described as novel coronavirus pneumonia (NCP). The Chinese authorities initially reported the wave of mysterious pneumonia on December 31st, 2019 and it was declared as an outbreak of international concern on January 30th, 2020. A systematic search of relevant research was conducted, and a total of 58 primary research articles were identified, analyzed, and debated to better understand the hematologic profile in COVID-19 (Coronavirus disease) infection and its clinical implications. All the findings in this article manifest a true impression of the current interpretation of hematological findings of the SARS-COV-2 disease. Pathophysiology of COVID-19 disease can be better interpreted by taking into consideration the hematologic parameters. Clinical implications of the hematologic profile of COVID-19 patients including cytokine storm, coagulation profile, and thrombophilic complications are under-recognized. Therefore, this review focuses on the coagulation profile, cytokine storm, and its treatment options. The role of pre-existing thrombophilia in COVID-19 patients and how it could result in the poor prognosis of the disease is also debated. The recent data suggests that hypercoagulability could be the potential cause of fatalities due to COVID-19. Potential effects of tocilizumab, metronidazole, and ulinastatin in suppressing cytokine storm may help to treat SARS-COV-2 infection. This review also highlights the significance of thrombophilia testing in SARS-CoV-2 patients depending on the clinical features and especially in pregnant women.
Visual selection and response selection without effector selection in tasks with circular arrays.
Attention, perception & psychophysics, 2021

Charles Eriksen and colleagues conducted influential visual-search experiments with circular arrays for which the responses were either vocal naming or unimanual left-right switch movements. These methods have the advantages of the stimuli being equidistant from a centered fixation point and allowing study of visual selection and response selection when effector selection is not required, as in the more typical case in which responses are key presses of distinct fingers. Other researchers have used similar spatial arrangements, but with aimed movements of the limb or of a mouse-controlled cursor to study effects of stimulus identification, visual search, spatial stimulus-response compatibility, response-effect compatibility, and practice/transfer in isolation and jointly. We systematically review studies in these areas that include visual selection and response selection and execution, and examine implications of their results for the role of effector selection. Also, we illustrate that as one moves from simpler to more complex tasks, the results are consistent with a basic information-processing framework in which stimulus identification and selection of a target response location are distinct from selecting, planning, and moving an effector to the targeted location.
Assessing upper limb function in multiple sclerosis using an engineered glove.
European journal of neurology, 2020

The importance of upper limb function in multiple sclerosis (MS) is increasingly recognized, especially for the evaluation of patients with progressive MS with reduced mobility. Two sensor-engineered gloves, able to measure quantitatively the timing of finger opposition movements, were previously used to assess upper limb disability in MS. The aims of the present study were: (1) to confirm the association between glove-derived variables and standard measures of MS disability in a larger cohort; (2) to assess the correlation with quantitative magnetic resonance imaging (MRI) and quality of life (QoL) measures; and (3) to determine if the glove-derived variables offer advantages over the standard measure for assessing upper limb function in MS, namely, the Nine-Hole Peg Test (9HPT).