rudyvdbrink/CitationDatabase huggingface dataset:
Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission.
Cell reports, 2016

AMPA receptor (AMPAR) complexes contain auxiliary subunits that modulate receptor trafficking and gating. In addition to the transmembrane AMPAR regulatory proteins (TARPs) and cornichons (CNIH-2/3), recent proteomic studies identified a diverse array of additional AMPAR-associated transmembrane and secreted partners. We systematically surveyed these and found that PORCN and ABHD6 increase GluA1 levels in transfected cells. Knockdown of PORCN in rat hippocampal neurons, which express it in high amounts, selectively reduces levels of all tested AMPAR complex components. Regulation of AMPARs is independent of PORCN's membrane-associated O-acyl transferase activity. PORCN knockdown in hippocampal neurons decreases AMPAR currents and accelerates desensitization and leads to depletion of TARP γ-8 from AMPAR complexes. Conditional PORCN knockout mice also exhibit specific changes in AMPAR expression and gating that reduce basal synaptic transmission but leave long-term potentiation intact. These studies define additional roles for PORCN in controlling synaptic transmission by regulating the level and composition of hippocampal AMPAR complexes.
Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions.
Scientific reports, 2020

There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT
Physiological functions of non-apoptotic caspase activity in the nervous system.
Seminars in cell & developmental biology, 2018

Caspases are cysteine proteases that play important and well-defined roles in apoptosis and inflammation. Increasing evidence point to alternative functions of caspases where restricted and localized caspase activation within neurons allows for a variety of non-apoptotic and non-inflammatory processes required for brain development and function. In this review, we highlight sublethal caspase functions in axon and dendrite pruning, neurite outgrowth and dendrite branches formation, as well as in long-term depression and synaptic plasticity. Importantly, as non-apoptotic activity of caspases is often confined in space and time in neurons, we also discuss the mechanisms that restrict caspase activity in order to maintain the neuronal networks in a healthy and functional state.
Biotin Thiamin Responsive Basal Ganglia Disease in Siblings.
Indian journal of pediatrics, 2018

Biotin Thiamine responsive Basal Ganglia Disease (BTBGD) is a rare treatable autosomal recessive metabolic disorder caused by mutations in SLC19A3 gene. It usually presents with encephalopathy and dystonia; if not treated, can progress to quadriparesis and death. Two Indian siblings born to a consanguineous marriage presented with regression of milestones, epilepsy and dystonia. Neuroimaging showed signal changes in basal ganglia and thalami. Genetic testing showed a homozygous missense substitution p.Gly23Val (c.68G > T) in exon 2 of the SLC19A3 gene. Thus to conclude, any child who presents with neuroregression, epilepsy and dystonia in the background of basal ganglia changes on neuroimaging, a possibility of biotin thiamine responsive basal ganglia disease should be considered.
Identification of amygdala-expressed genes associated with autism spectrum disorder.
Molecular autism, 2020

Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development.
Age moderates the associations between TRAbs, free T3 and outcomes of Graves' disease patients with radioactive iodine treatment.
Clinical endocrinology, 2021

This study aimed to explore whether age moderates the associations between TSH receptor antibodies (TRAbs) with thyroid hormones and remission in patients with Graves' disease (GD) who undergo radioactive iodine (RAI) treatment.
Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice.
Human molecular genetics, 2021

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscular weakness because of the loss of dystrophin. Extracellular Ca2+ flows into the cytoplasm through membrane tears in dystrophin-deficient myofibers, which leads to muscle contracture and necrosis. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) takes up cytosolic Ca2+ into the sarcoplasmic reticulum, but its activity is decreased in dystrophic muscle. Here, we show that an allosteric SERCA activator, CDN1163, ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice. The administration of CDN1163 prevented exercise-induced muscular damage and restored mitochondrial function. In addition, treatment with CDN1163 for 7 weeks enhanced muscular strength and reduced muscular degeneration and fibrosis in mdx mice. Our findings provide preclinical proof-of-concept evidence that pharmacological activation of SERCA could be a promising therapeutic strategy for DMD. Moreover, CDN1163 improved muscular strength surprisingly in wild-type mice, which may pave the new way for the treatment of muscular dysfunction.
Small compounds mimicking the adhesion molecule L1 improve recovery in a zebrafish demyelination model.
Scientific reports, 2021

Demyelination leads to a loss of neurons, which results in, among other consequences, a severe reduction in locomotor function, and underlies several diseases in humans including multiple sclerosis and polyneuropathies. Considerable clinical progress has been made in counteracting demyelination. However, there remains a need for novel methods that reduce demyelination while concomitantly achieving remyelination, thus complementing the currently available tools to ameliorate demyelinating diseases. In this study, we used an established zebrafish demyelination model to test selected compounds, following a screening in cell culture experiments and in a mouse model of spinal cord injury that was aimed at identifying beneficial functions of the neural cell adhesion molecule L1. In comparison to mammalian nervous system disease models, the zebrafish allows testing of potentially promotive compounds more easily than what is possible in mammals. We found that our selected compounds tacrine and duloxetine significantly improved remyelination in the peripheral and central nervous system of transgenic zebrafish following pharmacologically induced demyelination. Given that both molecules are known to positively affect functions other than those related to L1 and in other disease contexts, we propose that their combined beneficial function raises hope for the use of these compounds in clinical settings.
Biological markers for anxiety disorders, OCD and PTSD - a consensus statement. Part I: Neuroimaging and genetics.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2016

Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD).
Brain state dependent postinhibitory rebound in entorhinal cortex interneurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Postinhibitory rebound (PIR) is believed to play an important role in the genesis and maintenance of biological rhythms. While it has been demonstrated during several in vitro studies, in vivo evidence for PIR remains scarce. Here, we report that PIR can be observed in the dorsomedial entorhinal cortex of anesthetized rats, mostly between putatively connected GABAergic interneurons, and that it is more prevalent during the theta (4-6 Hz) oscillation state than the slow (0.5-2 Hz) oscillation state. Functional inhibition was also found to be brain state and postsynaptic cell type dependent but that alone could not explain this brain state dependence of PIR. A theoretical analysis, using two Fitzhugh-Nagumo neurons coupled to an external periodic drive, predicted that the modulation of a faster spiking rate by the slower periodic drive could account for the brain state dependence of PIR. Model predictions were verified experimentally. We conclude that PIR is cell type and brain state dependent and propose that this could impact network synchrony and rhythmogenesis.
A lack of consistent brain alterations in insomnia disorder: An activation likelihood estimation meta-analysis.
Sleep medicine reviews, 2018

Insomnia disorder is a prevalent sleep disorder, which affects about 10% of general population. However, its neural mechanisms are poorly understood. Recently, several structural and functional neuroimaging studies have been conducted in patients with insomnia disorder, but these studies have yielded diverse findings. Here, we aimed to identify consistent patterns of abnormal brain alterations in insomnia disorder by performing a quantitative coordinate-based meta-analysis. Following the preferred reporting for systematic reviews and meta-analyses statement, we searched PubMed database and used reference tracking and finally retrieved 19 eligible studies (six task-based functional magnetic resonance imaging, eight resting-state functional magnetic resonance imaging, three voxel-based morphometry, and two positron emission tomography). We extracted peak coordinates from these studies and tested for convergence using the activation likelihood estimation method. Using this method, we found no significant convergent evidence for combination of structural atrophy and functional disturbances across previous studies (p = 0.914). Inconsistencies across these studies might be related to heterogonous clinical populations, the explorative nature of these studies in combination with small sample sizes, different experimental designs, and various preprocessing and statistical approaches. Future neuroimaging studies on insomnia disorder should include larger well-characterized samples, as well as standard imaging and analysis protocols.
Use of an electronic cognitive aid by a person with Korsakoff syndrome.
Scandinavian journal of occupational therapy, 2013

The purpose of the current study was to evaluate the feasibility and the effectiveness of the use of a customized personal digital assistant (PDA) to support cognitive functioning in a person with Korsakoff syndrome.
Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy.
The EMBO journal, 2018

Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining.
Identifying therapeutic targets for Alzheimer's disease with big data.
Neurodegenerative disease management, 2017

Nilüfer Ertekin-Taner is a Professor of Neuroscience and Neurology at the Mayo Clinic, Jacksonville, FL, USA. A neurogeneticist and board-certified behavioral neurologist, she received her medical degree from Hacettepe University Medical School in Ankara, Turkey and her doctorate degree in Molecular Neuroscience from Mayo Graduate School. She completed her residency training in the Department of Neurology at Mayo Clinic in Rochester (MN, USA) and fellowship in Behavioral Neurology at Mayo Clinic in Jacksonville. Her laboratory aims to discover and characterize genetic factors underlying the complex genetics of Alzheimer's disease (AD) and related neurodegenerative conditions. Her earlier work contributed to the establishment of the endophenotype approach in genetic studies of AD and pioneered the use of amyloid β peptide levels as an endophenotype in AD genetic research. Her laboratory currently uses biological traits such as gene expression levels and cognitive scores and leverages combined genome, transcriptome and epigenetic data to uncover genetic risk factors for neurodegenerative conditions. She is the principal investigator of numerous NIH and foundation grants. She leads multiple collaborative projects aimed at gene and pathway discoveries in AD and other neurodegenerative diseases, as a part of the NIH initiatives Accelerating Medicines Partnership AD (AMP-AD) and Molecular Mechanisms of the Vascular Etiology of AD (M
Coenzyme Q10 Influences on the Levels of TNF-α and IL-10 and the Ratio of Bax/Bcl2 in a Menopausal Rat Model Following Lumbar Spinal Cord Injury.
Journal of molecular neuroscience : MN, 2018

The roles of the immune response and apoptosis as potential mediators of secondary damage in spinal cord injury (SCI) are being investigated. Research is also being done to determine the effects of female gonadal steroids, which decrease during menopause, and antioxidants, such as coenzyme Q10 (CoQ10) on SCI. We hypothesized that in the absence of female gonadal steroids, which provide protection following an SCI, CoQ10 could modulate the expression of cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-10, besides aquaporin-4 (AQP4) water channels in the CNS, which participate in neuroinflammation, as well as the Bax and Bcl2 proteins that are involved in apoptosis at the site of injury. The spinal cord was compressed at the level of the T10 vertebrae and rats were treated by 10 mg/kg/day CoQ10 for 3 weeks after surgery. The TNF-α and IL-10 expressions were studied using an ELISA. Western blot was used to investigate the Bax/Bcl-2 ratio, AQP4. The level of TNF-α significantly decreased following the administration of CoQ10 compared with the level of IL-10. When the treatment group was compared with the OVX-SCI group, the ratio of Bax/Bcl2 significantly decreased in the groups (P < 0.01). Based on our findings, CoQ10 could be used to compensate for the absence of the neuroprotection effects provided by female gonadal steroids via reducing the inappropriate effects of the two main pathways of secondary damage in SCI apoptosis.
Neural stem cells, the subventricular zone and radiotherapy: implications for treating glioblastoma.
Journal of neuro-oncology, 2016

Over the past decade, advances in neuroscience have suggested that neural stem cells resident in specific regions of the adult brain may be involved in development of both primary and recurrent glioblastoma. Neurogenesis and malignant transformation occurs in the subventricular zone adjacent to the lateral ventricles. This region holds promise as a potential target for therapeutic intervention with radiotherapy. However, irradiation of a larger brain volume is not without risk, and significant side effects have been observed. The current literature remains contradictory regarding the efficacy of deliberate intervention with radiation to the subventricular zone. This critical review discusses the connection between neural stem cells and development of glioblastoma, explores the behavior of tumors associated with the subventricular zone, summarizes the discordant literature with respect to the effects of irradiation, and reviews other targeted therapies to this intriguing region.
r-tPA with loading dose of clopidogrel and aspirin therapies for capsular warning syndrome attributed to middle cerebral artery atherosclerotic stenosis: A CARE-compliant case report.
Medicine, 2020

The capsular warning syndrome (CWS) is a rare and special type of transient ischemic attacks (TIAs) syndrome. The pathophysiology of CWS is very complicate, and intracranial atherosclerotic stenosis (ICAS) is rare cause. Moreover, the effective and standard therapy has not yet been established.
Microtubules in neurons as information carriers.
Journal of neurochemistry, 2014

Microtubules in neurons consist of highly dynamic regions as well as stable regions, some of which persist after bouts of severing as short mobile polymers. Concentrated at the plus ends of the highly dynamic regions are microtubule plus end tracking proteins called +TIPs that can interact with an array of other proteins and structures relevant to the plasticity of the neuron. It is also provocative to ponder that short mobile microtubules might similarly convey information with them as they transit within the neuron. Thus, beyond their known conventional functions in supporting neuronal architecture and organelle transport, microtubules may act as 'information carriers' in the neuron.
Boosting maintenance in working memory with temporal regularities.
Journal of experimental psychology. Learning, memory, and cognition, 2018

Music cognition research has provided evidence for the benefit of temporally regular structures guiding attention over time. The present study investigated whether maintenance in working memory can benefit from an isochronous rhythm. Participants were asked to remember series of 6 letters for serial recall. In the rhythm condition of Experiment 1A, a wood block sound was presented 6 times with a regular stimulus-onset-asynchrony during the delay between encoding and recall. In the silent condition, no sound was presented. The presence of the regular rhythm resulted in improved memory performance (Experiment 1A.), an effect also observed under articulatory suppression (Experiment 2), suggesting that temporal regularities can enhance maintenance in working memory including attentional refreshing. Experiment 1B confirmed this interpretation by showing that the presentation of a nonisochronous rhythm did not result in improved memory performance in comparison to a silent condition. The findings are discussed in relation to current working memory models and the theoretical framework of dynamic attending. (PsycINFO Database Record
Plasma Xanthine Oxidoreductase Activity Is Associated with a High Risk of Cardiovascular Disease in a General Japanese Population.
International journal of environmental research and public health, 2021

The purpose of this study was to investigate the association between xanthine oxidoreductase (XOR) activity and a high risk of cardiovascular disease (CVD) in a general Japanese population. The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture. The cardiovascular risk was calculated using the Framingham Risk Score (FRS). A total of 1605 of the 1631 participants (98.4%) had detectable XOR activity. Multiple regression analysis demonstrated that XOR activity was independently associated with body mass index (β = 0.26,
Implementing Self-collection of Biological Specimens With a Diverse Sample.
Field methods, 2013

Collecting saliva is the most noninvasive way to detect changing levels of cortisol (Adam & Kumari, 2009; Soo-Quee Koh & Choon-Huat Koh, 2007), a stress hormone of interest to behavioral and health scientists, where there are benefits from multiple samples taken over a period of days. Various self-collection strategies have been employed, ranging from treated cards to cotton swabs and passive drool methods. The current study investigates the effectiveness of a variety of reminder techniques in encouraging adherence with procedures requiring 4 samples per day on 3 separate days of passive drool collection among African American and European American young adults. The findings suggest that direct texts were associated with the greatest level of adherence, while phone reminders were most effective when controlling for total number of contacts. Results indicate that both traditional and novel reminder methods can positively influence adherence, even with challenging populations.
Thiol-Based Potent and Selective HDAC6 Inhibitors Promote Tubulin Acetylation and T-Regulatory Cell Suppressive Function.
ACS medicinal chemistry letters, 2015

Several new mercaptoacetamides were synthesized and studied as HDAC6 inhibitors. One compound, 2b, bearing an aminoquinoline cap group, was found to show 1.3 nM potency at HDAC6, with >3000-fold selectivity over HDAC1. 2b also showed excellent efficacy at increasing tubulin acetylation in rat primary cortical cultures, inducing a 10-fold increase in acetylated tubulin at 1 μM. To assess possible therapeutic effects, compounds were assayed for their ability to increase T-regulatory (Treg) suppressive function. Some but not all of the compounds increased Treg function, and thereby decreased conventional T cell activation and proliferation in vitro.
Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.
Nature communications, 2018

Learning and memory depend on neuronal plasticity originating at the synapse and requiring nuclear gene expression to persist. However, how synapse-to-nucleus communication supports long-term plasticity and behavior has remained elusive. Among cytonuclear signaling proteins, γCaMKII stands out in its ability to rapidly shuttle Ca
Aggressive somatotrophinomas lacking clinical symptoms: neurosurgical management.
Neurosurgical review, 2018

We report our experience about somatotrophinomas without clinical manifestation of acromegaly having radiological- and surgical-verified invasion of the cavernous sinus. We present the clinical, radiological and hormonal status of three patients affected by invasive GH-secreting pituitary adenomas without clinical signs and symptoms of acromegaly with elevation of serum IGF-1 from a series of 142 pituitary adenomas operated in our institute with the aid of intraoperative magnetic resonance imaging (MRI). Total tumor removal was possible in two of the three cases; the patients show normal hormonal status and no recurrence at long-term follow-up. In the third case, due to the different features of the tumor, complete resection was not possible and a multimodal treatment was performed that allowed regularization of the hormonal status and control of the residual tumor. GH-secreting adenomas without clinical manifestation of acromegaly are uncommon lesions. Total microsurgical excision can be curative. However, in case of partial removal, a tailored adjuvant treatment should be considered to preserve the quality of life of the patient and avoid regrowth of the lesion. In not resectable tumors, preoperative medical treatment with somatostatin analogues is always an option.