rudyvdbrink/CitationDatabase huggingface dataset:
In vivo RyR1 reduction in muscle triggers a core-like myopathy.
Acta neuropathologica communications, 2020

Mutations in the RYR1 gene, encoding the skeletal muscle calcium channel RyR1, lead to congenital myopathies, through expression of a channel with abnormal permeability and/or in reduced amount, but the direct functional whole organism consequences of exclusive reduction in RyR1 amount have never been studied. We have developed and characterized a mouse model with inducible muscle specific RYR1 deletion. Tamoxifen-induced recombination in the RYR1 gene at adult age resulted in a progressive reduction in the protein amount reaching a stable level of 50% of the initial amount, and was associated with a progressive muscle weakness and atrophy. Measurement of calcium fluxes in isolated muscle fibers demonstrated a reduction in the amplitude of RyR1-related calcium release mirroring the reduction in the protein amount. Alterations in the muscle structure were observed, with fibers atrophy, abnormal mitochondria distribution and membrane remodeling. An increase in the expression level of many proteins was observed, as well as an inhibition of the autophagy process. This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease, and accordingly similar alterations were observed in muscle biopsies from Dusty Core Disease patients (a subtype of Central Core Disease), pointing to common pathophysiological mechanisms related to RyR1 reduction.
Adenosine A
Neurobiology of disease, 2020

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of function of the maternally inherited Ube3a neuronal protein, whose main features comprise severe intellectual disabilities and motor impairments. Previous studies with the Ube3a
Epigenetic regulation of brain region-specific microglia clearance activity.
Nature neuroscience, 2018

The rapid elimination of dying neurons and nonfunctional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal or cortical, microglia exhibited high levels of basal clearance activity, which correlated with an elevated degree of cerebellar neuronal attrition. Exposing forebrain microglia to apoptotic cells activated gene-expression programs supporting clearance activity. We provide evidence that the polycomb repressive complex 2 (PRC2) epigenetically restricts the expression of genes that support clearance activity in striatal and cortical microglia. Loss of PRC2 leads to aberrant activation of a microglia clearance phenotype, which triggers changes in neuronal morphology and behavior. Our data highlight a key role of epigenetic mechanisms in preventing microglia-induced neuronal alterations that are frequently associated with neurodegenerative and psychiatric diseases.
Orthopedic surgery-induced cognitive dysfunction is mediated by CX3CL1/R1 signaling.
Journal of neuroinflammation, 2021

Postoperative pain is a common phenomenon after surgery and is closely associated with the development of postoperative cognitive dysfunction (POCD). Persistent pain and systemic inflammation caused by surgery have been suggested as key factors for the development of POCD. Fractalkine (CX3CL1) and its receptor, the CX3C chemokine receptor 1 (CX3CR1), are known to play a key role in pain and inflammation signaling pathways. Recent studies have shown that the regulation of CX3CR1/L1 signaling influences the development of various diseases including neuronal diseases. We determined whether CX3CR1/L1 signaling is a putative therapeutic target for POCD in a mouse model.
A Neurologist's View of Lyme Disease and Other Tick-Borne Infections.
Seminars in neurology, 2019

Tick-borne infections-including tick-borne encephalitis viruses, represented in the United States by rare infections with Powassan and deer tick viruses, and more often Lyme disease-are of increasing importance to neurologists. Lyme neuroborreliosis (LNB) causes all or part of a triad including meningitis, radiculoneuritis, and cranial neuritis. Rarely, parenchymal brain and spinal cord involvement occur, with focal findings on examination and magnetic resonance imaging (MRI). LNB diagnosis requires plausible exposure, objective evidence of nervous system involvement, and, generally, positive two-tier serology. Central nervous system (CNS) LNB is almost always accompanied by abnormal cerebrospinal fluid (CSF) (cells, protein), often with intrathecal antibody production, which is determined by concentration-adjusted comparison of serum and CSF antibody. Measuring CSF antibody in isolation and nucleic acid-based testing of CSF are not useful in LNB and should be avoided. LNB treatment is highly effective with a 2- to 3-week course of antibiotics. Increasing evidence suggests that LNB not involving the CNS parenchyma can be treated successfully with oral doxycycline.
Clinical impact of a high-frequency seizure onset zone in a case of bitemporal epilepsy.
Epileptic disorders : international epilepsy journal with videotape, 2008

High-frequency activity has been described as having a role in the initiation of epileptic seizures. The case of a patient with refractory bitemporal epilepsy is presented. Extraoperative monitoring with depth and subdural electrodes revealed an ictal pattern with a build-up of high-frequency (> 80 Hz) activity originating in the cortex, with spread to both hippocampi. This observation was only revealed with the use of high-pass filtering, and represented crucial information that significantly influenced the decision about the side, localization and extent of resection. Removal of the cortex generating high-frequency activity, led to cessation of seizures in this patient. Current knowledge about the role of high-frequency activity and the case presented here support the importance of recording with equipment capable of detecting fast activity during the presurgical invasive monitoring. An active search for a high-frequency seizure onset zone in patients with structurally-unaffected hippocampi may improve the outcome beyond that possible with conventional bandwidth, invasive EEG recordings.
OTOPLAN in Cochlear Implantation for Far-advanced Otosclerosis.
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2020

To evaluate OTOPLAN software in the surgical planning of far-advanced otosclerosis (FAO) candidates to cochlear implant (CI) were considered. We aimed to preliminarily investigate if this software could influence the electrode length choice, or predict surgical difficulties.
Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases.
International journal of molecular sciences, 2020

Pancreatic cancer remains one of the most difficult malignancies to treat. Minimal improvements in patient outcomes and persistently abysmal patient survival rates underscore the great need for new treatment strategies. Currently, there is intense interest in therapeutic strategies that target tyrosine protein kinases. Here, we employed kinome arrays and bioinformatic pipelines capable of identifying differentially active protein tyrosine kinases in different patient-derived pancreatic ductal adenocarcinoma (PDAC) cell lines and wild-type pancreatic tissue to investigate the unique kinomic networks of PDAC samples and posit novel target kinases for pancreatic cancer therapy. Consistent with previously described reports, the resultant peptide-based kinome array profiles identified increased protein tyrosine kinase activity in pancreatic cancer for the following kinases: epidermal growth factor receptor (EGFR), fms related receptor tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR-3), insulin receptor (INSR), ephrin receptor A2 (EPHA2), platelet derived growth factor receptor alpha (PDGFRA), SRC proto-oncogene kinase (SRC), and tyrosine kinase non receptor 2 (TNK2). Furthermore, this study identified increased activity for protein tyrosine kinases with limited prior evidence of differential activity in pancreatic cancer. These protein tyrosine kinases include B lymphoid kinase (BLK), Fyn-related kinase (FRK), Lck/Yes-related novel kinase (LYN), FYN proto-oncogene kinase (FYN), lymphocyte cell-specific kinase (LCK), tec protein kinase (TEC), hemopoietic cell kinase (HCK), ABL proto-oncogene 2 kinase (ABL2), discoidin domain receptor 1 kinase (DDR1), and ephrin receptor A8 kinase (EPHA8). Together, these results support the utility of peptide array kinomic analyses in the generation of potential candidate kinases for future pancreatic cancer therapeutic development.
Which Problem Are We Addressing Today? The Utility of a Multifaceted Formulation Approach to a Complex Case.
American journal of psychotherapy, 2019

A case of a 54-year-old woman with posttraumatic stress disorder, somatic delusions, and borderline personality disorder is presented by using psychodynamic, trauma-informed, and cognitive-behavioral formulations. The usefulness of a multifaceted formulation in the treatment of the case is discussed along with a review of relevant literature.
Repurposing current therapeutics for treating COVID-19: A vital role of prescription records data mining.
Drug development research, 2020

Since its outbreak in late 2019, the SARS-Cov-2 pandemic already infected over 3.7 million people and claimed more than 250,000 lives globally. At least 1 year may take for an approved vaccine to be in place, and meanwhile millions more could be infected, some with fatal outcome. Over thousand clinical trials with COVID-19 patients are already listed in ClinicalTrials.com, some of them for assessing the utility of therapeutics approved for other conditions. However, clinical trials take many months, and are typically done with small cohorts. A much faster and by far more efficient method for rapidly identifying approved therapeutics that can be repurposed for treating COVID-19 patients is data mining their past and current electronic health and prescription records for identifying drugs that may protect infected individuals from severe COVID-19 symptoms. Examples are discussed for applying health and prescription records for assessing the potential repurposing (repositioning) of angiotensin receptor blockers, estradiol, or antiandrogens for reducing COVID-19 morbidity and fatalities. Data mining of prescription records of COVID-19 patients will not cancel the need for conducting controlled clinical trials, but could substantially assist in trial design, drug choice, inclusion and exclusion criteria, and prioritization. This approach requires a strong commitment of health provides for open collaboration with the biomedical research community, as health provides are typically the sole owners of retrospective drug prescription records.
Trends and predictors of exclusive e-cigarette use, exclusive smoking and dual use among youth in Canada.
Addictive behaviors, 2020

Few studies have examined predictors of exclusive e-cigarette use, exclusive smoking and dual use among youth. We investigated whether frequency of e-cigarette use and cigarette smoking predicted involvement in different usage groups after a 1- and 2-year follow-up among a sample of Canadian youth.
Mitotic and Proliferative Indices in WHO Grade III Meningioma.
Cancers, 2020

Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12-2.31,
Neuroligin-2 as a central organizer of inhibitory synapses in health and disease.
Science signaling, 2020

Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of synaptic adhesion proteins called neuroligins. Neuroligins form transsynaptic bridges with presynaptic neurexins to regulate various aspects of excitatory and inhibitory synaptic transmission. Neuroligin-2 (NLGN2) is the only member that acts exclusively at GABAergic inhibitory synapses. Altered expression and mutations in NLGN2 and several of its interacting partners are linked to cognitive and psychiatric disorders, including schizophrenia, autism, and anxiety. Research on NLGN2 has fundamentally shaped our understanding of the molecular architecture of inhibitory synapses. Here, we discuss the current knowledge on the molecular and cellular functions of mammalian NLGN2 and its role in the neuronal circuitry that regulates behavior in rodents and humans.
Neurodevelopment: a novel role for activity in shaping retinal circuits.
Current biology : CB, 2014

The number of synaptic inputs onto retinal bipolar cells is influenced by transmitter release from neighboring bipolar cells, implicating a new form of population-based retrograde plasticity in the development of these neural circuits.
Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer's disease.
Acta neuropathologica communications, 2020

Previous studies showed that injection of tissue extracts containing amyloid-β (Aβ) aggregates accelerate amyloid deposition in the brain of mouse models of Alzheimer's disease (AD) through prion-like mechanisms. In this study, we evaluated whether brain amyloidosis could be accelerated by blood infusions, procedures that have been shown to transmit prion diseases in animals and humans. Young transgenic mice infused with whole blood or plasma from old animals with extensive Aβ deposition in their brains developed significantly higher levels brain amyloidosis and neuroinflammation compared to untreated animals or mice infused with wild type blood. Similarly, intra-venous injection of purified Aβ aggregates accelerated amyloid pathology, supporting the concept that Aβ seeds present in blood can reach the brain to promote neuropathological alterations in the brain of treated animals. However, an amyloid-enhancing effect of other factors present in the blood of donors cannot be discarded. Our results may help to understand the role of peripheral (amyloid-dependent or -independent) factors implicated in the development of AD and uncover new strategies for disease intervention.
Pnpla3 silencing with antisense oligonucleotides ameliorates nonalcoholic steatohepatitis and fibrosis in Pnpla3 I148M knock-in mice.
Molecular metabolism, 2019

Nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of advanced chronic liver disease. The progression of NAFLD, including nonalcoholic steatohepatitis (NASH), has a strong genetic component, and the most robust contributor is the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 encoding the 148M protein sequence variant. We hypothesized that suppressing the expression of the PNPLA3 148M mutant protein would exert a beneficial effect on the entire spectrum of NAFLD.
The aging brain: A set of functional MRI data acquired at rest and during exposure to tactile or muscle proprioceptive stimulation in healthy young and older volunteers.
Data in brief, 2020

There is a growing interest in understanding functional brain decline with aging. The dataset provides raw anatomical and functional images recorded in a group of 20 young volunteers and in another group of 19 older volunteers during a 10-minute period of resting state followed by four consecutive task-related runs. During each task-related run, the participants were exposed to two types of sensory stimulation: a tactile stimulation consisting in a textured-disk rotation under the palm of their right hand or a muscle proprioceptive stimulation consisting in a mechanical vibration applied to the muscle tendon of their wrist abductor. These two stimulations are known to evoke illusory sensations of hand movement, while the hand remains actually still. Therefore, the dataset is meant to be used to assess age-related functional brain changes during the perception of hand movements based on muscle proprioception or touch individually. It also allows to explore any structural changes or functional resting connectivity alteration with aging. The dataset is a supplement to the research findings in the paper 'Functional brain changes in the elderly for the perception of hand movements: a greater impairment occurs in proprioception than touch published in NeuroImage.
An Overview of the Pathophysiology of Metabolic Changes and Their Sequence of Occurrence in Obese Diabetic Females: A Narrative Review.
Cureus, 2020

Obesity and diabetes both mediate their effects through insulin resistance and frequently co-exist. Insulin resistance is one of the key factors in the development of the metabolic syndrome. Adult females tend to develop obesity more frequently than males. One of the factors causing this difference is the pattern of changes that occur as females age from pre-menopausal to the post-menopausal stage, causing a change in the pattern of accumulation of fats. Several studies have explored and described the association between obesity and metabolic syndrome and their effect on type II diabetes. We conducted our literature search using PubMed and Google Scholar as our primary databases. We selected a total of 49 articles for review after applying the inclusion and exclusion criteria and removing the duplicate articles. We chose the full-text articles that were published in the English language only. The selected studies were randomized controlled trials and review papers. The reviewed articles showed that visceral fat, central obesity, and fasting blood sugar of post-menopausal is higher than in pre-menopausal women and needs adequate management. More studies are needed in the future to explore the patterns of the metabolic changes in obese females to provide early and better management of diabetes and prevent related complications.
Opioid-Mediated HIV-1 Immunopathogenesis.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2020

Despite the ability of combination antiretroviral therapy to dramatically suppress viremia, the brain continues to be a reservoir of HIV-1 low-level replication. Adding further complexity to this is the comorbidity of drug abuse with HIV-1 associated neurocognitive disorders and neuroHIV. Among several abused drugs, the use of opiates is highly prevalent in HIV-1 infected individuals, both as an abused drug as well as for pain management. Opioids and their receptors have attained notable attention owing to their ability to modulate immune functions, in turn, impacting disease progression. Various cell culture, animal and human studies have implicated the role of opioids and their receptors in modulating viral replication and virus-mediated pathology both positively and negatively. Further, the combinatorial effects of HIV-1/HIV-1 proteins and morphine have demonstrated activation of inflammatory signaling in the host system. Herein, we summarized the current knowledge on the role of opioids on peripheral immunopathogenesis, viral immunopathogenesis, epigenetic profiles of the host and viral genome, neuropathogenesis of SIV/SHIV-infected non-human primates, blood-brain-barrier, HIV-1 viral latency, and viral rebound. Overall, this review provides recent insights into the role of opioids in HIV-1 immunopathogenesis. Graphical abstract.
Mini-Review - Teaching Writing in the Undergraduate Neuroscience Curriculum: Its Importance and Best Practices.
Neuroscience letters, 2020

In neuroscience and other scientific disciplines, instructors increasingly appreciate the value of writing. Teaching students to write well helps them succeed in school, not only because they perform better on assessments but also because well-structured writing assignments improve learning. Moreover, the ability to write well is an essential professional skill, because good clear writing in conjunction with good clear thinking results in increased success in fellowship applications, grant proposals, and publications. However, teaching writing in neuroscience classrooms is challenging for several reasons. Students may not initially recognize the importance of writing, teachers may lack training in the pedagogy of writing instruction, and both teachers and students must commit substantial time and effort to writing if progress is to be made. Here, we detail effective strategies for teaching writing to undergraduates, including scaffolding of teaching assignments, both within a class and across a curriculum; use of different types of writing assignments; early integration of writing into courses; peer review and revision of assignments; mentoring by student tutors; and use of defined rubrics. We also discuss how these strategies can be utilized effectively in the context of multicultural classrooms and labs.
Protective actions of exercise-related FNDC5/Irisin in memory and Alzheimer's disease.
Journal of neurochemistry, 2020

The proportion of elderly populations is rapidly booming, and human lifespan has considerably increased in the past century because of scientific and medical advances. However, the winds of change brought by the 21st century made sedentarism one of the factors that renders the brain vulnerable to age-related chronic diseases, such as Alzheimer's disease (AD). Conversely, physical exercise has been shown to stimulate molecular mechanisms beneficial to cognition. Here, we review evidence showing the positive effects of physical exercise in the brain. We further discuss recent evidence that irisin, a myokine stimulated by physical exercise derived from fibronectin type III domain-containing protein 5 (FNDC5) transmembrane protein, has neuroprotective actions in the brain. Lastly, we highlight the importance of the crosstalk between the periphery and the brain in cognition and the therapeutic potential of FNDC5/irisin in AD.