rudyvdbrink/CitationDatabase huggingface dataset:
Sox17 Promotes Oligodendrocyte Regeneration by Dual Modulation of Hedgehog and Wnt Signaling.
iScience, 2020

Signaling pathways that promote oligodendrocyte development improve oligodendrocyte regeneration and myelin recovery from demyelinating pathologies. Sox factors critically control myelin gene expression and oligodendroglial fate, but little is known about signaling events underlying Sox-mediated oligodendroglial regeneration. In this study of the SoxF member Sox17, we demonstrate that Sox17-induced oligodendrocyte regeneration in adult myelin lesions occurs by suppressing lesion-induced Wnt/beta-catenin signaling which is inhibitory to oligodendrocyte regeneration and by increasing Sonic Hedgehog/Smoothened/Gli2 activity. Hedgehog signaling through Smoothened critically supports adult oligodendroglial viability and is an upstream regulator of beta-catenin. Gli2 ablation in adult oligodendrocyte progenitor cells indicates that Gli2 regulates beta-catenin differentially in wild-type and Sox17-overexpressing white matter. Myelin lesions in Sox17-deficient mice show beta-catenin hyperactivation, regenerative failure, and loss of oligodendrogenesis, despite exogenous Hedgehog stimulation. These studies indicate the benefit of Sox17 signaling targets to enhance oligodendrocyte regeneration after demyelination injury by modulating both Hedgehog and Wnt/beta-catenin signaling.
Disruption of a putative intersubunit electrostatic bond enhances agonist efficacy at the human α1 glycine receptor.
Brain research, 2017

Partial agonists have lower efficacies than compounds considered 'full agonists', eliciting submaximal responses even at saturating concentrations. Taurine is a partial agonist at the glycine receptor (GlyR), a member of the cys-loop ligand-gated ion channel superfamily. The molecular mechanisms responsible for agonism are not fully understood but evidence suggests that efficacy at these receptors is determined by conformational changes that occur early in the process of receptor activation. We previously identified a residue located near the human α1 glycine binding site (aspartate-97; D97) that, when mutated to arginine (D97R), results in GlyR channels opening spontaneously with a high open probability, mimicking the effects of saturating glycine concentrations on wildtype GlyR. This D97 residue is hypothesized to form an electrostatic interaction with arginine-119 on an adjacent subunit, stabilizing the channel in a shut state. Here we demonstrate that the disruption of this putative bond increases the efficacy of partial agonists including taurine, as well as two other β-amino acid partial agonists, β-aminobutyric acid (β-ABA) and β-aminoisobutyric acid (β-AIBA). Even the subtle charge-conserving mutation of D97 to glutamate (D97E) markedly affects partial agonist efficacy. Mutation to the neutral alanine residue in the D97A mutant mimics the effects seen with D97R, indicating that charge repulsion does not significantly affect these findings. Our findings suggest that the determination of efficacy following ligand binding to the glycine receptor may involve the disruption of an intersubunit electrostatic interaction occurring near the agonist binding site.
Neuroscience: Decision, Insight and Intention.
Current biology : CB, 2017

A new study of perceptual decision making in which subjects were asked to report, after indicating their choice, precisely when they felt they had made a decision, supports the idea that conscious awareness occurs when evidence has accumulated beyond some threshold.
A Scalable, Easy-to-Deploy Protocol for Cas13-Based Detection of SARS-CoV-2 Genetic Material.
Journal of clinical microbiology, 2021

The COVID-19 pandemic has created massive demand for widespread, distributed tools for detecting SARS-CoV-2 genetic material. The hurdles to scalable testing include reagent and instrument accessibility, availability of highly trained personnel, and large upfront investment. Here, we showcase an orthogonal pipeline we call CREST (Cas13-based, rugged, equitable, scalable testing) that addresses some of these hurdles. Specifically, CREST pairs commonplace and reliable biochemical methods (PCR) with low-cost instrumentation, without sacrificing detection sensitivity. By taking advantage of simple fluorescence visualizers, CREST allows a binary interpretation of results. CREST may provide a point-of-care solution to increase the distribution of COVID-19 surveillance.
Electrophysiological correlates of visual backward masking in patients with bipolar disorder.
Psychiatry research. Neuroimaging, 2021

In visual backward masking (VBM), a target is followed by a mask that decreases target discriminability. Schizophrenia patients (SZ) show strong and reproducible masking impairments, which are associated with reduced EEG amplitudes. Patients with bipolar disorder (BP) show masking deficits, too. Here, we investigated the neural EEG correlates of VBM in BP. 122 SZ, 94 unaffected controls, and 38 BP joined a standard VBM experiment. 123 SZ, 94 unaffected controls and 16 BP joined a corresponding EEG experiment, analyzed in terms of global field power. As in previous studies, SZ and BP show strong masking deficits. Importantly and similarly to SZ, BP show decreased global field power amplitudes at approximately 200 ms after the target onset, compared to controls. These results suggest that VBM deficits are not specific for schizophrenia but for a broader range of functional psychoses. Potentially, both SZ and BP show deficient target enhancement.
Predicting the fMRI Signal Fluctuation with Recurrent Neural Networks Trained on Vascular Network Dynamics.
Cerebral cortex (New York, N.Y. : 1991), 2021

Resting-state functional MRI (rs-fMRI) studies have revealed specific low-frequency hemodynamic signal fluctuations (<0.1 Hz) in the brain, which could be related to neuronal oscillations through the neurovascular coupling mechanism. Given the vascular origin of the fMRI signal, it remains challenging to separate the neural correlates of global rs-fMRI signal fluctuations from other confounding sources. However, the slow-oscillation detected from individual vessels by single-vessel fMRI presents strong correlation to neural oscillations. Here, we use recurrent neural networks (RNNs) to predict the future temporal evolution of the rs-fMRI slow oscillation from both rodent and human brains. The RNNs trained with vessel-specific rs-fMRI signals encode the unique brain oscillatory dynamic feature, presenting more effective prediction than the conventional autoregressive model. This RNN-based predictive modeling of rs-fMRI datasets from the Human Connectome Project (HCP) reveals brain state-specific characteristics, demonstrating an inverse relationship between the global rs-fMRI signal fluctuation with the internal default-mode network (DMN) correlation. The RNN prediction method presents a unique data-driven encoding scheme to specify potential brain state differences based on the global fMRI signal fluctuation, but not solely dependent on the global variance.
Acoustic Speech Analytics Are Predictive of Cerebellar Dysfunction in Multiple Sclerosis.
Cerebellum (London, England), 2020

Speech production relies on motor control and cognitive processing and is linked to cerebellar function. In diseases where the cerebellum is impaired, such as multiple sclerosis (MS), speech abnormalities are common and can be detected by instrumental assessments. However, the potential of speech assessments to be used to monitor cerebellar impairment in MS remains unexplored. The aim of this study is to build an objectively measured speech score that reflects cerebellar function, pathology and quality of life in MS. Eighty-five people with MS and 21 controls participated in the study. Speech was independently assessed through objective acoustic analysis and blind expert listener ratings. Cerebellar function and overall disease disability were measured through validated clinical scores; cerebellar pathology was assessed via magnetic resonance imaging, and validated questionnaires informed quality of life. Selected speech variables were entered in a regression model to predict cerebellar function. The resulting model was condensed into one composite speech score and tested for prediction of abnormal 9-hole peg test (9HPT), and for correlations with the remaining cerebellar scores, imaging measurements and self-assessed quality of life. Slow rate of syllable repetition and increased free speech pause percentage were the strongest predictors of cerebellar impairment, complemented by phonatory instability. Those variables formed the acoustic composite score that accounted for 54% of variation in cerebellar function, correlated with cerebellar white matter volume (r = 0.3, p = 0.017), quality of life (r = 0.5, p < 0.001) and predicted an abnormal 9HPT with 85% accuracy. An objective multi-feature speech metric was highly representative of motor cerebellar impairment in MS.
Trauma-induced myasthenia gravis: coincidence or causal relationship?
BMJ case reports, 2021

We report a case of a 55-year-old man presenting with diplopia, masticatory weakness and dysarthria several weeks post multitrauma. The clinical suspicion of myasthenia gravis (MG) was supported with positive acetylcholine receptor antibodies and abnormal repetitive stimulation study. He responded well to pyridostigmine, intravenous immunoglobulin and oral prednisolone. In this report, we describe the timing and progression of MG in our patient, and review the literature pertaining to the relationship between trauma and MG. The search for definitive evidence of causation may be impractical, but should not delay the recognition and management of a treatable condition.
Axon guidance receptors: Endocytosis, trafficking and downstream signaling from endosomes.
Progress in neurobiology, 2021

During the development of the nervous system, axons extend through complex environments. Growth cones at the axon tip allow axons to find and innervate their appropriate targets and form functional synapses. Axon pathfinding requires axons to respond to guidance signals and these cues need to be detected by specialized receptors followed by intracellular signal integration and translation. Several downstream signaling pathways have been identified for axon guidance receptors and it has become evident that these pathways are often initiated from intracellular vesicles called endosomes. Endosomes allow receptors to traffic intracellularly, re-locating receptors from one cellular region to another. The localization of axon guidance receptors to endosomal compartments is crucial for their function, signaling output and expression levels. For example, active receptors within endosomes can recruit downstream proteins to the endosomal membrane and facilitate signaling. Also, endosomal trafficking can re-locate receptors back to the plasma membrane to allow re-activation or mediate downregulation of receptor signaling via degradation. Accumulating evidence suggests that axon guidance receptors do not follow a pre-set default trafficking route but may change their localization within endosomes. This re-routing appears to be spatially and temporally regulated, either by expression of adaptor proteins or co-receptors. These findings shed light on how signaling in axon guidance is regulated and diversified - a mechanism which explains how a limited set of guidance cues can help to establish billions of neuronal connections. In this review, we summarize and discuss our current knowledge of axon guidance receptor trafficking and provide directions for future research.
BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer's disease brain.
Brain : a journal of neurology, 2020

In the phase 3 EPOCH trial (Clinicaltrials.gov; NCT01739348), treatment with the BACE inhibitor verubecestat failed to improve cognition in patients with mild-to-moderate Alzheimer's disease, but was associated with reduced hippocampal volume after 78 weeks as assessed by MRI. The aims of the present exploratory analyses were to: (i) characterize the effect of verubecestat on brain volume by evaluating the time course of volumetric MRI changes for a variety of brain regions; and (ii) understand the mechanism through which verubecestat might cause hippocampal (and other brain region) volume loss by assessing its relationship to measures of amyloid, neurodegeneration, and cognition. Participants were aged 55-85 years with probable Alzheimer's disease dementia and a Mini Mental State Examination score ≥15 and ≤26. MRIs were obtained at baseline and at Weeks 13, 26, 52 and 78 of treatment. MRIs were segmented using Freesurfer and analysed using a tensor-based morphometry method. PET amyloid data were obtained with 18F-flutemetamol (Vizamyl®) at baseline and Week 78. Standardized uptake value ratios were generated with subcortical white matter as a reference region. Neurofilament light chain in the CSF was assessed as a biomarker of neurodegeneration. Compared with placebo, verubecestat showed increased MRI brain volume loss at Week 13 with no evidence of additional loss through Week 78. The verubecestat-related volumetric MRI loss occurred predominantly in amyloid-rich brain regions. Correlations between amyloid burden at baseline and verubecestat-related volumetric MRI reductions were not significant (r = 0.05 to 0.26, P-values > 0.27). There were no significant differences between verubecestat and placebo in changes from baseline in CSF levels of neurofilament light chain at Week 78 (increases of 7.2 and 14.6 pg/ml for verubecestat versus 19.7 pg/ml for placebo, P-values ≥ 0.1). There was a moderate correlation between volumetric MRI changes and cognitive decline in all groups including placebo at Week 78 (e.g. r = -0.45 to -0.55, P < 0.001 for whole brain), but the correlations were smaller at Week 13 and significant only for the verubecestat groups (e.g. r = -0.15 and -0.11, P < 0.04 for whole brain). Our results suggest that the verubecestat-associated MRI brain volume loss is not due to generalized, progressive neurodegeneration, but may be mediated by specific effects on BACE-related amyloid processes.
Unravelling the Immunotoxicity of Polycaprolactone Nanoparticles-Effects of Polymer Molecular Weight, Hydrolysis, and Blends.
Chemical research in toxicology, 2020

Poly-ε-caprolactone (PCL) is a biodegradable polyester that has FDA and CE approval as a medical device. Nonetheless, the lack of toxicity exhibited by the polymer cannot be extrapolated to its nanomaterial conformation. Despite PCL-based NPs being widely studied in the biomedical field for their advantages as controlled drug delivery systems, little data describe PCL NPs' toxicity, particularly immunotoxicity. This work assessed different PCL-based delivery systems intended for protein delivery regarding their immunotoxicity and hemocompatibility. Two different molecular weight PCL polymers were used, as well as blends with chitosan and glucan. Results showed that the presence of NaOH during the production of PCL
Polyphenols of marine red macroalga 
Heliyon, 2019

Chronic hyperglycaemia activates the polyol pathway of glucose metabolism thereby stimulating the activation aldose reductase enzyme that in turn initiates a cascade of deleterious events, eventually, leading to nerve damage or neuropathy. Marine macroalgae and their isolated chemical constituents have been found to possess potential antidiabetic activity and have proved beneficial in the treatment of diabetes. In this study the neuroprotective effect of polyphenols isolated from the red macroalga
Associations between Functional Milestones and Psychiatric Admissions in an Urban Area: Utility of a Cluster-Analytical Approach.
Psychiatria Danubina, 2018

The purpose of the study was to identify homogenous subgroups, based upon achievement of two functional milestones (marriage and employment) and Global Assessment of Functioning (GAF) score in a sample of 848 acute patients admitted to the Psychiatric Emergency Service (PES) of the Città della Salute e della Scienza di Torino, during a 24-months period.
Basal ganglia necrosis: a 'best-fit' approach.
Practical neurology, 2016

A previously well 16-year-old boy developed a rapid-onset hypokinetic syndrome, coupled with a radiological appearance of extensive and highly symmetrical basal ganglia and white matter change. The diagnostic process was challenging and we systematically considered potential causes. After excluding common causes of this clinico-radiological picture, we considered common disorders with this unusual radiological picture and vice versa, before finally concluding that this was a rare presentation of a rare disease. We considered the broad categories of: metabolic; toxic; infective; inflammatory, postinfective and immune-mediated; neoplastic; paraneoplastic and heredodegenerative. Long-term follow-up gave insight into the nature of the insult, confirming the monophasic course. During recovery, and following presumed secondary aberrant reinnervation, his disorder evolved from predominantly hypokinetic to hyperkinetic. Here, we explore the process of finding a 'best-fit' diagnosis: in this case, acute necrotising encephalopathy.
Calcium imaging in the Drosophila olfactory system with a genetic indicator.
Cold Spring Harbor protocols, 2013

Insects show sophisticated odor-mediated behaviors controlled by an olfactory system that is genetically and anatomically simpler than that of vertebrates, providing an attractive system to investigate the mechanistic link between behavior and odor perception. Advances in neuroscience have been facilitated by modern optical imaging technologies--both in instrumentation and in probe design--that permit the visualization of functional neural circuits. Imaging calcium activity in genetically defined populations of neurons provides an important tool for investigating the function of neural circuits. This article describes a two-photon imaging system for monitoring neural activity in the Drosophila antennal lobe. Odor-evoked calcium activity is followed by measuring the specific expression of the calcium-sensitive green fluorescent protein G-CaMP in Drosophila antennae-brain preparations.
Dedication of special issue of JBHS&R in memory of Douglas Longshore.
The journal of behavioral health services & research, 2009

This special issue is dedicated to the memory of Douglas Longshore, who was affiliated with the UCLA Integrated Substance Abuse Programs and RAND. The special issue reflects Longshore's research legacy in the areas of addiction and health services research and his many productive collaborations with other investigators.
A Diagnosis of Multiple Sclerosis Following Whiplash Injury: Is There a True Association?
Cureus, 2021

We report a case of a previously well, 25-year-old Caucasian female whose diagnosis of multiple sclerosis (MS) followed significant trauma. Her symptoms and signs developed quickly and satisfied the criteria for rapidly evolving relapsing-remitting MS. She was started on natalizumab (Tysabri) and was stabilized. We discuss the existing literature on traumatic demyelination and possible underlying mechanisms.
Progesterone - Friend or foe?
Frontiers in neuroendocrinology, 2020

Estradiol is the "prototypic" sex hormone of women. Yet, women have another sex hormone, which is often disregarded: Progesterone. The goal of this article is to provide a comprehensive review on progesterone, and its metabolite allopregnanolone, emphasizing three key areas: biological properties, main functions, and effects on mood in women. Recent years of intensive research on progesterone and allopregnanolone have paved the way for new treatment of postpartum depression. However, treatment for premenstrual syndrome and premenstrual dysphoric disorder as well as contraception that women can use without risking mental health problems are still needed. As far as progesterone is concerned, we might be dealing with a two-edged sword: while its metabolite allopregnanolone has been proven useful for treatment of PPD, it may trigger negative symptoms in women with PMS and PMDD. Overall, our current knowledge on the beneficial and harmful effects of progesterone is limited and further research is imperative.
An assessment of the potential miscalibration of cardiovascular disease risk predictions caused by a secular trend in cardiovascular disease in England.
BMC medical research methodology, 2020

A downwards secular trend in the incidence of cardiovascular disease (CVD) in England was identified through previous work and the literature. Risk prediction models for primary prevention of CVD do not model this secular trend, this could result in over prediction of risk for individuals in the present day. We evaluate the effects of modelling this secular trend, and also assess whether it is driven by an increase in statin use during follow up.
Traumatic brain injury in mice induces changes in the expression of the XCL1/XCR1 and XCL1/ITGA9 axes.
Pharmacological reports : PR, 2020

Every year, millions of people suffer from various forms of traumatic brain injury (TBI), and new approaches with therapeutic potential are required. Although chemokines are known to be involved in brain injury, the importance of X-C motif chemokine ligand 1 (XCL1) and its receptors, X-C motif chemokine receptor 1 (XCR1) and alpha-9 integrin (ITGA9), in the progression of TBI remain unknown.
Microglia Tweak Retinogeniculate Pathways during Visual Circuit Refinement.
Neuron, 2020

Cheadle et al. reveal that microglia expressing TWEAK facilitate synapse elimination through a novel, non-phagocytic mechanism in the retinogeniculate pathway during visual circuit development. This mechanism is experience-dependent and occurs through the local binding of TWEAK to postsynaptic Fn14.
Airway relaxation mechanisms and structural basis of osthole for improving lung function in asthma.
Science signaling, 2020

Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin derived from a traditional Chinese medicine, in preclinical models of asthma. In mouse precision-cut lung slices, osthole relaxed preconstricted airways, irrespective of β2-adrenoceptor desensitization. Osthole administered in murine asthma models attenuated airway hyperresponsiveness, a hallmark of asthma. Osthole inhibited phosphodiesterase 4D (PDE4D) activity to amplify autocrine prostaglandin E
Going in circles is the way forward: the role of recurrence in visual inference.
Current opinion in neurobiology, 2020

Biological visual systems exhibit abundant recurrent connectivity. State-of-the-art neural network models for visual recognition, by contrast, rely heavily or exclusively on feedforward computation. Any finite-time recurrent neural network (RNN) can be unrolled along time to yield an equivalent feedforward neural network (FNN). This important insight suggests that computational neuroscientists may not need to engage recurrent computation, and that computer-vision engineers may be limiting themselves to a special case of FNN if they build recurrent models. Here we argue, to the contrary, that FNNs are a special case of RNNs and that computational neuroscientists and engineers should engage recurrence to understand how brains and machines can (1) achieve greater and more flexible computational depth (2) compress complex computations into limited hardware (3) integrate priors and priorities into visual inference through expectation and attention (4) exploit sequential dependencies in their data for better inference and prediction and (5) leverage the power of iterative computation.