rudyvdbrink/CitationDatabase huggingface dataset:
Don't forget astrocytes when targeting Alzheimer's disease.
British journal of pharmacology, 2019

Astrocytes are essential for CNS health, regulating homeostasis, metabolism, and synaptic transmission. In addition to these and many other physiological roles, the pathological impact of astrocytes ("reactive astrocytes") in acute trauma and chronic disease like Alzheimer's disease (AD) is well established. Growing evidence supports a fundamental and active role of astrocytes in multiple neurodegenerative diseases. With a growing interest in normal astrocyte biology, and countless studies on changes in astrocyte function in the context of disease, it may be a surprise that no therapies exist incorporating astrocytes as key targets. Here, we examine unintentional effects of current AD therapies on astrocyte function and theorize how astrocytes may be intentionally targeted for more efficacious therapeutic outcomes. Given their integral role in normal neuronal functioning, incorporating astrocytes as key criteria for AD drug development can only lead to more effective therapies for the millions of AD sufferers worldwide. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.
Codeine induces increased resistance at the esophagogastric junction but has no effect on motility and bolus flow in the pharynx and upper esophageal sphincter in healthy volunteers: A randomized, double-blind, placebo-controlled, cross-over trial.
Neurogastroenterology and motility, 2021

Chronic opioid use can induce esophageal dysfunction with symptoms resembling achalasia and a manometric pattern of esophagogastric junction-outflow obstruction (EGJ-OO). However, the effect of opioids in acute setting on pharyngeal function and esophageal body contractility has not been investigated.
Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate.
Neuron, 2016

Mutations in several genes encoding centrosomal proteins dramatically decrease the size of the human brain. We show that Aspm (abnormal spindle-like, microcephaly-associated) and Wdr62 (WD repeat-containing protein 62) interact genetically to control brain size, with mice lacking Wdr62, Aspm, or both showing gene dose-related centriole duplication defects that parallel the severity of the microcephaly and increased ectopic basal progenitors, suggesting premature delamination from the ventricular zone. Wdr62 and Aspm localize to the proximal end of the mother centriole and interact physically, with Wdr62 required for Aspm localization, and both proteins, as well as microcephaly protein Cep63, required to localize CENPJ/CPAP/Sas-4, a final common target. Unexpectedly, Aspm and Wdr62 are required for normal apical complex localization and apical epithelial structure, providing a plausible unifying mechanism for the premature delamination and precocious differentiation of progenitors. Together, our results reveal links among centrioles, apical proteins, and cell fate, and illuminate how alterations in these interactions can dynamically regulate brain size.
Experimental basis for a new allosteric model for multisubunit proteins.
Proceedings of the National Academy of Sciences of the United States of America, 2014

Monod, Wyman, and Changeux (MWC) explained allostery in multisubunit proteins with a widely applied theoretical model in which binding of small molecules, so-called allosteric effectors, affects reactivity by altering the equilibrium between more reactive (R) and less reactive (T) quaternary structures. In their model, each quaternary structure has a single reactivity. Here, we use silica gels to trap protein conformations and a new kind of laser photolysis experiment to show that hemoglobin, the paradigm of allostery, exhibits two ligand binding phases with the same fast and slow rates in both R and T quaternary structures. Allosteric effectors change the fraction of each phase but not the rates. These surprising results are readily explained by the simplest possible extension of the MWC model to include a preequilibrium between two tertiary conformations that have the same functional properties within each quaternary structure. They also have important implications for the long-standing question of a structural explanation for the difference in hemoglobin oxygen affinity of the two quaternary structures.
Human subthalamic nucleus in movement error detection and its evaluation during visuomotor adaptation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Monitoring and evaluating movement errors to guide subsequent movements is a critical feature of normal motor control. Previously, we showed that the postmovement increase in electroencephalographic (EEG) beta power over the sensorimotor cortex reflects neural processes that evaluate motor errors consistent with Bayesian inference (Tan et al., 2014). Whether such neural processes are limited to this cortical region or involve the basal ganglia is unclear. Here, we recorded EEG over the cortex and local field potential (LFP) activity in the subthalamic nucleus (STN) from electrodes implanted in patients with Parkinson's disease, while they moved a joystick-controlled cursor to visual targets displayed on a computer screen. After movement offsets, we found increased beta activity in both local STN LFP and sensorimotor cortical EEG and in the coupling between the two, which was affected by both error magnitude and its contextual saliency. The postmovement increase in the coupling between STN and cortex was dominated by information flow from sensorimotor cortex to STN. However, an information drive appeared from STN to sensorimotor cortex in the first phase of the adaptation, when a constant rotation was applied between joystick inputs and cursor outputs. The strength of the STN to cortex drive correlated with the degree of adaption achieved across subjects. These results suggest that oscillatory activity in the beta band may dynamically couple the sensorimotor cortex and basal ganglia after movements. In particular, beta activity driven from the STN to cortex indicates task-relevant movement errors, information that may be important in modifying subsequent motor responses.
Neural stem cell transcriptional networks highlight genes essential for nervous system development.
The EMBO journal, 2009

Neural stem cells must strike a balance between self-renewal and multipotency, and differentiation. Identification of the transcriptional networks regulating stem cell division is an essential step in understanding how this balance is achieved. We have shown that the homeodomain transcription factor, Prospero, acts to repress self-renewal and promote differentiation. Among its targets are three neural stem cell transcription factors, Asense, Deadpan and Snail, of which Asense and Deadpan are repressed by Prospero. Here, we identify the targets of these three factors throughout the genome. We find a large overlap in their target genes, and indeed with the targets of Prospero, with 245 genomic loci bound by all factors. Many of the genes have been implicated in vertebrate stem cell self-renewal, suggesting that this core set of genes is crucial in the switch between self-renewal and differentiation. We also show that multiply bound loci are enriched for genes previously linked to nervous system phenotypes, thereby providing a shortcut to identifying genes important for nervous system development.
Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning.
Electrophysiological correlates of emotional scene processing in bipolar disorder.
Journal of psychiatric research, 2020

Emotional dysfunction is a core feature of bipolar I disorder (BD). Behavioral data suggest that emotional processing may differ based on history of psychosis, but physiological studies frequently disregard this differentiating feature. Face processing studies indicate that emotion-related components of event-related potentials (ERPs) are abnormal in BD, but fMRI data using emotional scenes are mixed. The current study used ERPs to examine emotional scene perception in BD with and without a history of psychosis (BDP, BDNP). 386 participants from the PARDIP consortium (HC = 181, BDP = 130, BDNP = 75) viewed neutral, pleasant, and unpleasant scenes from the International Affective Picture System (IAPS) during continuous EEG recording. The early posterior negativity (EPN) and late positive potential (LPP) were examined for group and stimulus effects. Analyses were conducted for groups on and off medications to examine associations between medication status, psychosis, and ERP response. Group differences were found between HC and BD in emotional modulation of the EPN and between HC and BDP in the LPP to pleasant images. There was a significant interaction between psychosis history and anticonvulsant status in the EPN, but no other medication associations were found. The relationship between neural/self-reported emotional responses and clinical symptoms were examined with canonical correlations, but no significant associations were found. Results from this large well characterized sample indicate mild deviations in neural reactivity related to medication, mood, and psychosis history. However, processing of emotional scenes appears mostly intact in individuals with BD regardless of symptom severity.
The capillary dysfunction hypothesis of Alzheimer's disease.
Neurobiology of aging, 2013

It is widely accepted that hypoperfusion and changes in capillary morphology are involved in the etiopathogenesis of Alzheimer's disease (AD). This is difficult to reconcile with the hyperperfusion observed in young high-risk subjects. Differences in the way cerebral blood flow (CBF) is coupled with the local metabolic needs during different phases of the disease can explain this apparent paradox. This review describes this coupling in terms of a model of cerebral oxygen availability that takes into consideration the heterogeneity of capillary blood flow patterns. The model predicts that moderate increases in heterogeneity requires elevated CBF in order to maintain adequate oxygenation. However, with progressive increases in heterogeneity, the resulting low tissue oxygen tension will require a suppression of CBF in order to maintain tissue metabolism. The observed biphasic nature of CBF responses in preclinical AD and AD is therefore consistent with progressive disturbances of capillary flow patterns. Salient features of the model are discussed in the context of AD pathology along with potential sources of increased capillary flow heterogeneity.
A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia.
International journal of obesity (2005), 2010

The mechanisms for how saturated fat and sugar-based beverages contribute to human obesity are poorly understood. This paper describes a series of experiments developed to examine the response of hypothalamic neuropeptides to diets rich in sugar and fat, using three different diets: a high-fat high-sugar (HFHS) choice diet with access to chow, saturated fat and a 30% sugar solution; a high-fat (HF) choice diet with access to chow and saturated fat; or to a high-sugar (HS) choice diet with access to chow and a sugar solution.
Neuroinvasion of SARS-CoV-2 in human and mouse brain.
bioRxiv : the preprint server for biology, 2020

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate
HIV/AIDS-related stigma in South African alcohol-serving venues and its potential impact on HIV disclosure, testing and treatment-seeking behaviours.
Global public health, 2015

Alcohol-serving venues in South Africa are sites for high-risk behaviours that may lead to HIV transmission. Prevention and treatment interventions are sorely needed in these settings, but HIV-related stigma may limit their effectiveness. This study explored expressions of stigma among alcohol-serving venue patrons in Cape Town and examined the potential impact of stigma on HIV disclosure, testing and treatment-seeking behaviours. A total of 92 in-depth interviews with male and female, black and coloured patrons were conducted. Transcripts were analysed via memo-writing and diagramming techniques. Many participants mentioned knowing other patrons living with HIV/AIDS (PLWH), and this visibility of HIV impacted expressions of HIV-related stigma. Participants discussed four forms of HIV-related stigma in the venues: fearing PLWH, fearing HIV acquisition, blaming others for spreading HIV and isolating PLWH. HIV visibility and expressions of HIV-related stigma, particularly fear of isolation, influenced participants' willingness to disclose their status. HIV-related stigma in the venues also appeared to indirectly influence testing and treatment-seeking behaviour outside the venue. Results suggest that efforts to change norms and reduce expressions of HIV-related stigma in alcohol-serving venues are necessary to successfully deliver tailored HIV prevention interventions and increase uptake of HIV testing and care in this important social setting.
Apathy in rapid eye movement sleep behaviour disorder is common and under-recognized.
European journal of neurology, 2018

Apathy is an important neuropsychiatric feature of Parkinson's disease (PD), which often emerges before the onset of motor symptoms. Patients with rapid eye movement sleep behaviour disorder (RBD) have a high probability of developing PD in future. Neuropsychiatric problems are common in RBD, but apathy has not previously been detailed in this key prodromal population.
Optopatcher--an electrode holder for simultaneous intracellular patch-clamp recording and optical manipulation.
Journal of neuroscience methods, 2013

Optogenetics has rapidly become a standard method in neuroscience research. Although significant progress has been made in the development of molecular tools, refined techniques for combined light delivery and recording in vivo are still lacking. For example, simultaneous intracellular recording and light stimulation have only been possible by using two separate positioning systems. To overcome this limitation, we have developed a glass pipette holder which contains an additional port for the insertion of an optical fiber into the pipette. This device, which we called "optopatcher" allows whole cell patch-clamp recording simultaneously with direct projection of light from the recording pipette. The holder spares the use of an additional manipulator and, importantly, enables accurate, stable and reproducible illumination. In addition, replacement of standard pipettes is done as easily as with the available commercial holders. Here we used the optopatcher in vivo to record the membrane potential of neurons from different cortical layers in the motor cortex of transgenic mice expressing channelrhodopsin-2 under the Thy1 promoter. We demonstrate the utility of the optopatcher by recording LFP and intracellular responses to light stimulation.
A brief guide to the science and art of writing manuscripts in biomedicine.
Journal of translational medicine, 2020

Publishing articles in international scientific journals is the primary method for the communication of validated research findings and ideas. Journal articles are commonly used as a major input for evaluations of researchers and institutions. Few articles have been published previously about the different aspects needed for writing high-quality articles. In this manuscript, we provide an updated and brief guide for the multiple dimensions needed for writing manuscripts in the health and biological sciences, from current, international and interdisciplinary perspectives and from our expertise as authors, peer reviewers and editors. We provide key suggestions for writing major sections of the manuscript (e.g. title, abstract, introduction, methods, results and discussion), for submitting the manuscript and bring an overview of the peer review process and  of the post-publication impact of the articles.
Mice use robust and common strategies to discriminate natural scenes.
Scientific reports, 2018

Mice use vision to navigate and avoid predators in natural environments. However, their visual systems are compact compared to other mammals, and it is unclear how well mice can discriminate ethologically relevant scenes. Here, we examined natural scene discrimination in mice using an automated touch-screen system. We estimated the discrimination difficulty using the computational metric structural similarity (SSIM), and constructed psychometric curves. However, the performance of each mouse was better predicted by the mean performance of other mice than SSIM. This high inter-mouse agreement indicates that mice use common and robust strategies to discriminate natural scenes. We tested several other image metrics to find an alternative to SSIM for predicting discrimination performance. We found that a simple, primary visual cortex (V1)-inspired model predicted mouse performance with fidelity approaching the inter-mouse agreement. The model involved convolving the images with Gabor filters, and its performance varied with the orientation of the Gabor filter. This orientation dependence was driven by the stimuli, rather than an innate biological feature. Together, these results indicate that mice are adept at discriminating natural scenes, and their performance is well predicted by simple models of V1 processing.
Pseudo-Brown syndrome: a potential ophthalmologic sequela after a transcaruncular-transconjunctival approach for orbital fracture repair.
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 2012

To prospectively assess the incidence of orthoptic anomalies and, more specifically, the possible development of pseudo-Brown syndrome related to inferior oblique muscle (IO) myotomy after the transcaruncular-transconjunctival approach for orbital fracture repair and its effect on the possible development of annoying diplopia.
Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017.
Annals of the rheumatic diseases, 2020

To report the level and trends of prevalence, incidence and years lived with disability (YLDs) for osteoarthritis (OA) in 195 countries and territories from 1990 to 2017 by age, sex and Socio-demographic index (SDI; a composite of sociodemographic factors).
Human hepatocytes and hematolymphoid dual reconstitution in treosulfan-conditioned uPA-NOG mice.
The American journal of pathology, 2014

Human-specific HIV-1 and hepatitis co-infections significantly affect patient management and call for new therapeutic options. Small xenotransplantation models with human hepatocytes and hematolymphoid tissue should facilitate antiviral/antiretroviral drug trials. However, experience with mouse strains tested for dual reconstitution is limited, with technical difficulties such as risky manipulations with newborns and high mortality rates due to metabolic abnormalities. The best animal strains for hepatocyte transplantation are not optimal for human hematopoietic stem cell (HSC) engraftment, and vice versa. We evaluated a new strain of highly immunodeficient nonobese diabetic/Shi-scid (severe combined immunodeficiency)/IL-2Rγc(null) (NOG) mice that carry two copies of the mouse albumin promoter-driven urokinase-type plasminogen activator transgene for dual reconstitution with human liver and immune cells. Three approaches for dual reconstitution were evaluated: i) freshly isolated fetal hepatoblasts were injected intrasplenically, followed by transplantation of cryopreserved HSCs obtained from the same tissue samples 1 month later after treosulfan conditioning; ii) treosulfan conditioning is followed by intrasplenic simultaneous transplantation of fetal hepatoblasts and HSCs; and iii) transplantation of mature hepatocytes is followed by mismatched HSCs. The long-term dual reconstitution was achieved on urokinase-type plasminogen activator-NOG mice with mature hepatocytes (not fetal hepatoblasts) and HSCs. Even major histocompatibility complex mismatched transplantation was sustained without any evidence of hepatocyte rejection by the human immune system.
Blink Reflex May Help Discriminate Alzheimer Disease From Vascular Dementia.
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 2015

Dementia has several different etiologies, and vascular dementia (VaD) is considered the second leading cause of dementia after Alzheimer disease (AD). Various studies used blink reflex in different spectrum of neurological diseases as a complementary diagnostic test. We performed blink test in AD, VaD, and mixed dementia to investigate different usefulness of blink reflex in differentiating these types of dementia.