rudyvdbrink/CitationDatabase huggingface dataset:
Cortical and corticospinal output modulations during reaching movements with varying directions and magnitudes of interaction torques.
Neuroscience, 2015

The neural command required to coordinate a multi-joint movement is inherently complex. During multi-joint movement of the limb, the force created from movement at one joint may create a torque at a second joint known as an interaction torque. Interaction torques may be assistive or resistive thereby aiding or opposing the motion of the second joint, respectively. For movement to be effectively controlled, the central nervous system should modulate neural output to the muscles to appropriately account for interaction torques. The present study examined the neural output from the primary motor cortex before and during reaching movements that required different combinations of assistive and resistive interaction torques occurring at the shoulder and elbow joints. Using transcranial magnetic stimulation to probe neural output from the primary motor cortex, results indicate that corticospinal output controlling the upper arm is related to resistive interaction torques occurring at the shoulder joint. Further, cortical output to bi-articular muscles is associated with interaction torque and this may be driven by the fact that these muscles are in an advantageous position to control torques produced between inter-connection segments. Humans have a tendency to avoid reaching movements that involve resistive interaction torques and this may be driven by the requirement of increased neural output associated with these movements.
How Clinically Efficient Is Lumacaftor/Ivacaftor for Cystic Fibrosis Patients? An Updated Literature Review.
Cureus, 2020

Cystic fibrosis (CF) is an autosomal recessive illness caused by the defective cystic fibrosis transmembrane conductance regulator (CFTR) gene. These patients suffer from repeated chronic sinuses and lung infections, resulting in frequent hospital admissions and antibiotic (Abx) courses. These are the major contributing factors responsible for a low health-related quality of life (HRQoL) and increasing the disease burden. The introduction and approval of CFTR modulators-lumacaftor (LUM) and ivacaftor (IVA) in 2015 by the US Food and Drug Administration (FDA) reduced the mortality and morbidity rates associated with the disease. In 2018, the FDA approved these drugs from age two and five years with two copies of F5806 del. This literature review aims to present the studies centered on the clinical effects of LUM/IVA. We searched for the relevant articles, from 2016 to 2020, in PubMed Central (PMC), Google Scholars, and Journal of Cystic Fibrosis. LUM/IVA has a broader range of effects. They showed marked improvement in the reduction of pulmonary exacerbations (PEx), Hospitalization rates, Abx use, and modification in forced expiratory volume in one second (FEV1) status of pre-existing severe lung disease. Now, there is a need for an initiative to conduct more clinical trials and studies in the future to assess and evaluate the long-term clinical benefits and safety of LUM/IVA therapy in all age groups.
Lentiviral Interleukin-10 Gene Therapy Preserves Fine Motor Circuitry and Function After a Cervical Spinal Cord Injury in Male and Female Mice.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021

In mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable biomaterial scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, tissue sparing using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2 weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons, axons, and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2 weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce tissue damage and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.
Comparative proteomic analysis of saliva from dogs with and without obesity-related metabolic dysfuntion.
Journal of proteomics, 2019

Dogs develop only some of the components of the human metabolic syndrome (MetS). Thus, in order to study possible MetS-related alterations in dogs, human MetS criteria were adapted to define canine MetS or so-called obesity-related metabolic dysfunction (ORMD). The main objective of this study was to identify changes in the salivary proteome of obese dogs with ORMD in comparison with obese dogs without ORMD which may constitute potential salivary biomarkers for assessing ORMD. In a first phase, 12 adult obese dogs with ORMD (N = 6) and without ORMD (N = 6) were included in the study. Subsequently, and with the aim of validating and strengthening the results, additional 12 obese dogs (6 with and 6 without ORMD) were tested in an independent experiment following the same protocol. Saliva samples were subjected to a quantitative proteomics analysis and the levels of nine salivary proteins were found to be significantly different between groups, among them those which had greatest fold-change were proteins involved in glycolysis and oxidative stress. In conclusion, despite metabolic syndrome to include different combinations of diseases, the observation of differences in salivary proteome suggests a potential of this fluid to understand the pathophysiology of the disease. SIGNIFICANCE: This is the first study evaluating proteomes of saliva in dogs, as a non invasive sample, in order to increase knowledge about the metabolic/physiopathological changes related to obesity-related metabolic dysfunction (ORMD) together with the identification of potential biomarkers for its diagnosis. As approximately 20% of dogs with naturally occurring obesity were described to suffer ORMD associated with insulin resistance and hypoadiponectinemia, the fact that indicate possible links between ORMD and associated diseases.
Stressed-Out T Cells Fragment the Mind.
Trends in immunology, 2020

The immune system is increasingly recognized to play an integral role in regulating stress responses. In a recent article in Cell, Fan et al. demonstrate a novel mechanism through which stress drives mitochondrial fragmentation-induced xanthine accumulation in mouse CD4
Issues in data expansion in understanding criticality in biological systems.
The European physical journal. E, Soft matter, 2018

At the point of a second-order phase transition also termed as a critical point, systems display long-range order and their macroscopic behaviors are independent of the microscopic details making up the system. Due to these properties, it has long been speculated that biological systems that show similar behavior despite having very different microscopics, may be operating near a critical point. Recent methods in neuroscience are making it possible to explore whether criticality exists in neural networks. Despite being large in size, many datasets are only a minute sample of the neural system and methods have to be developed to expand these datasets to study criticality. In this work we develop an analytical method of expanding a dataset to the large N limit to make statements about the critical nature of the dataset. We show that different ways of expanding the dataset while keeping its variance and mean fixed yield different results regarding criticality. This hence casts doubts on the established procedures for deducing criticality of biological systems through expansion of finite-sized datasets.
Amphetamine effects in appetitive acquisition depend on the modality of the stimulus rather than its relative validity.
Progress in neuro-psychopharmacology & biological psychiatry, 2008

Amphetamine has been shown previously to increase the apportioning of associative strength to weak predictors in appetitive Pavlovian conditioning procedures such as latent inhibition and overshadowing. Manipulating the likelihood with which different conditioned stimuli (CSs) predict subsequent delivery of an unconditioned stimulus (UCS) is an alternative method by which the associability of CSs can be influenced. The present experiment tested effects of D-amphetamine (0.5 mg/kg or 1.5 mg/kg administered 15 min prior to conditioning) in appetitive acquisition under partial versus continuous reinforcement of alternative CSs with sucrose pellet UCS delivery. Specifically, male Wistar rats were conditioned to light and tone CSs that were followed by the UCS on 100% or 50% of trials in a cross-over design. It was predicted that amphetamine would disrupt rats' ability to select appropriately the most valid CSs for learning which would be expressed as increased conditioning to weaker, 50% valid CSs. Contrary to prediction, differential responding based on relative validity was preserved under amphetamine, for both light and tone stimuli. Instead, the results showed that responding to light CSs was generally reduced under amphetamine. Conditioning to tone CSs was higher and unaffected by amphetamine. Thus, results demonstrate that amphetamine effects are determined by the properties of the CS used for learning.
Reflections on observing faces in art.
American journal of medical genetics. Part C, Seminars in medical genetics, 2021

The experience of art provides the visitor of a museum or gallery with the opportunity to contemplate and share the human condition both from the physical and psychological point of view. Because of the accessibility and the number of museums throughout Europe, classical European art as both sculpture and painting, affords the viewer the opportunity to experience life from one part of the world over centuries of history. These museums occasionally exhibit pieces showing a person with a human disorder and physical differences. On viewing such artwork, practitioners of health care, especially dysmorphologists, usually find themselves observing such pieces within the context of their practice. In this essay, the coauthors reflect on paintings and sculptures which remind us of our patients with similar physical and medical conditions. Various works of art also provide the opportunity to observe and view the human face from many vantage points and times in history. Several paintings are cited to illustrate the central themes of the Commentary: the human circumstance of disease and differences and the skill of observing and describing the human face.
Functional positional eye and eyelid movements.
Journal of neurology, 2020

Positional manoeuvres are an important part of the neurological examination, particularly in patients with vertigo where the presence and characteristics of provoked nystagmus can help differentiate central from peripheral neurological disorders.
β-Adrenergic Receptors/Epac Signaling Increases the Size of the Readily Releasable Pool of Synaptic Vesicles Required for Parallel Fiber LTP.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

The second messenger cAMP is an important determinant of synaptic plasticity that is associated with enhanced neurotransmitter release. Long-term potentiation (LTP) at parallel fiber (PF)-Purkinje cell (PC) synapses depends on a Ca
Adiposity covaries with signatures of asymmetric feedback learning during adaptive decisions.
Social cognitive and affective neuroscience, 2020

Unhealthy weight gain relates, in part, to how people make decisions based on prior experience. Here we conducted post hoc analysis on an archival data set to evaluate whether individual differences in adiposity, an anthropometric construct encompassing a spectrum of body types, from lean to obese, associate with signatures of asymmetric feedback learning during value-based decision-making. In a sample of neurologically healthy adults (N = 433), ventral striatal responses to rewards, measured using fMRI, were not directly associated with adiposity, but rather moderated its relationship with feedback-driven learning in the Iowa gambling task, tested outside the scanner. Using a biologically inspired model of basal ganglia-dependent decision processes, we found this moderating effect of reward reactivity to be explained by an asymmetrical use of feedback to drive learning; that is, with more plasticity for gains than for losses, stronger reward reactivity leads to decisions that minimize exploration for maximizing long-term outcomes. Follow-up analysis confirmed that individual differences in adiposity correlated with signatures of asymmetric use of feedback cues during learning, suggesting that reward reactivity may especially relate to adiposity, and possibly obesity risk, when gains impact future decisions more than losses.
The active second-generation proteasome inhibitor oprozomib reverts the oxaliplatin-induced neuropathy symptoms.
Biochemical pharmacology, 2020

Oxaliplatin-induced neuropathy (OXAIN) is a major adverse effect of this antineoplastic drug, widely used in the treatment of colorectal cancer. Although its molecular mechanisms remain poorly understood, recent evidence suggest that maladaptive neuroplasticity and oxidative stress may participate to the development of this neuropathy. Given the role played on protein remodeling by ubiquitin-proteasome system (UPS) in response to oxidative stress and in neuropathic pain, we investigated whether oxaliplatin might cause alterations in the UPS-mediated degradation pathway, in order to identify new pharmacological tools useful in OXAIN. In a rat model of OXAIN (2.4 mg kg
Effect of Aging on Daily Rhythms of Lactate Metabolism in the Medial Prefrontal Cortex of Male Mice.
Neuroscience, 2020

Aging is associated with reduced amplitude and earlier timing of circadian (daily) rhythms in sleep, brain function, and behavior. We examined whether age-related circadian dysfunction extends to the metabolic function of the brain, particularly in the prefrontal cortex (PFC). Using enzymatic amperometric biosensors, we recorded lactate concentration changes in the PFC in Young (7 mos) and Aged (19 mos) freely-behaving C57BL/6N male mice. Both Young and Aged mice displayed diurnal and circadian rhythms of lactate, with the Aged rhythm slightly phase advanced. Under constant conditions, the Aged rhythm showed a reduced amplitude not seen in the Young mice. We simultaneously observed a relationship between arousal state and PFC lactate rhythm via electroencephalography, which was modified by aging. Finally, using RT-qPCR, we found that aging affects the daily expression pattern of Glucose Transporter 1 (GLUT-1).
Clearance of intracellular tau protein from neuronal cells via VAMP8-induced secretion.
The Journal of biological chemistry, 2020

In Alzheimer's disease (AD), tau, a microtubule-associated protein (MAP), becomes hyperphosphorylated, aggregates, and accumulates in the somato-dendritic compartment of neurons. In parallel to its intracellular accumulation in AD, tau is also released in the extracellular space, as revealed by its increased presence in cerebrospinal fluid (CSF). Consistent with this, recent studies, including ours, have reported that neurons secrete tau, and several therapeutic strategies aim to prevent the intracellular tau accumulation. Previously, we reported that late endosomes were implicated in tau secretion. Here, we explore the possibility of preventing intracellular tau accumulation by increasing tau secretion. Using neuronal models, we investigated whether overexpression of the vesicle-associated membrane protein 8 (VAMP8), an R-SNARE found on late endosomes, could increase tau secretion. The overexpression of VAMP8 significantly increased tau secretion, decreasing its intracellular levels in the neuroblastoma (N2a) cell line. Increased tau secretion by VAMP8 was also observed in murine hippocampal slices. The intracellular reduction of tau by VAMP8 overexpression correlated to a decrease of acetylated tubulin induced by tau overexpression in N2a cells. VAMP8 staining was preferentially found on late endosomes in N2a cells. Using total internal reflection fluorescence (TIRF) microscopy, the fusion of VAMP8-positive vesicles with the plasma membrane was correlated to the depletion of tau in the cytoplasm. Finally, overexpression of VAMP8 reduced the intracellular accumulation of tau mutants linked to frontotemporal dementia with parkinsonism and α-synuclein by increasing their secretion. Collectively, the present data indicate that VAMP8 could be used to increase tau and α-synuclein clearance to prevent their intracellular accumulation.
Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms.
Journal of inherited metabolic disease, 2021

Metabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably glucose transporter type 1 deficiency syndrome, succinic semialdehyde dehydrogenase deficiency, pyruvate dehydrogenase complex deficiency, nonketotic hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders. The ketogenic diet (KD) has been successfully utilized to treat such conditions to varying degrees. While the mechanisms underlying the clinical efficacy of the KD in IEM remain unclear, it is likely that the proposed heterogeneous targets influenced by the KD work in concert to rectify or ameliorate the downstream negative consequences of genetic mutations affecting key metabolic enzymes and substrates-such as oxidative stress and cell death. These beneficial effects can be broadly grouped into restoration of impaired bioenergetics and synaptic dysfunction, improved redox homeostasis, anti-inflammatory, and epigenetic activity. Hence, it is conceivable that the KD might prove useful in other metabolic disorders that present with epileptic seizures. At the same time, however, there are notable contraindications to KD use, such as fatty acid oxidation disorders. Clearly, more research is needed to better characterize those metabolic epilepsies that would be amenable to ketogenic therapies, both experimentally and clinically. In the end, the expanded knowledge base will be critical to designing metabolism-based treatments that can afford greater clinical efficacy and tolerability compared to current KD approaches, and improved long-term outcomes for patients.
[Neuroscience on Cognitive Control of Behavior: Functional Division among Prefrontal Areas].
Brain and nerve = Shinkei kenkyu no shinpo, 2019

The prefrontal cortex is greatly developed in primates and is considered to play an important role in cognitive control of behavior. In the visual and motor systems, research into the functional division between cortical areas has advanced. The prefrontal cortex has also been shown to be divided into several areas which have different anatomical connections with other brain sites. However, the functional division among prefrontal cortical areas has been less well studied. Knowledge of the functional division is expected to help in understanding the cognitive control of complex behaviors in terms of more elementary processes.
White matter microstructure and structural networks in treatment-resistant schizophrenia patients after commencing clozapine treatment: A longitudinal diffusion imaging study.
Psychiatry research, 2021

This study investigates changes on white matter microstructure and neural networks after 6 months of switching to clozapine in schizophrenia patients compared to controls, and whether any changes are related to clinical variables. T1 and diffusion-weighted MRI images were acquired at baseline before commencing clozapine and after 6 months of treatment for 22 patients with treatment-resistant schizophrenia and 23 controls. The Tract-based spatial statistics approach was used to compare changes over time between groups in fractional anisotropy (FA). Changes in structural network organisation weighted by FA and number of streamlines were assessed using graph theory. Patients displayed a significant reduction of FA over time (p<0.05) compared to controls in the genu and body of the corpus callosum and bilaterally in the anterior and superior corona radiata. There was no correlation between FA change in patients and changes in clinical variables or serum level of clozapine. There was no changes in structural network organisation between groups (F(7,280)=2.80;p = 0.187). This longitudinal study demonstrated progressive focal FA abnormalities in key anterior tracts, but preserved brain structural network organisation in patients. The FA reduction was independent of any clinical measures and may reflect progression of the underlying pathophysiology of this malignant form of schizophrenia illness.
Estimated and projected burden of multiple sclerosis attributable to smoking and childhood and adolescent high body-mass index: a comparative risk assessment.
International journal of epidemiology, 2021

Smoking and childhood and adolescent high body-mass index (BMI) are leading lifestyle-related risk factors of global premature morbidity and mortality, and have been associated with an increased risk of developing multiple sclerosis (MS). This study aims to estimate and project the proportion of MS incidence that could be prevented with elimination of these risk factors.
VCP/p97 regulates Beclin-1-dependent autophagy initiation.
Nature chemical biology, 2021

Autophagy is an essential cellular process that removes harmful protein species, and autophagy upregulation may be able to protect against neurodegeneration and various pathogens. Here, we have identified the essential protein VCP/p97 (VCP, valosin-containing protein) as a novel regulator of autophagosome biogenesis, where VCP regulates autophagy induction in two ways, both dependent on Beclin-1. Utilizing small-molecule inhibitors of VCP ATPase activity, we show that VCP stabilizes Beclin-1 levels by promoting the deubiquitinase activity of ataxin-3 towards Beclin-1. VCP also regulates the assembly and activity of the Beclin-1-containing phosphatidylinositol-3-kinase (PI3K) complex I, thus regulating the production of PI(3)P, a key signaling lipid responsible for the recruitment of downstream autophagy factors. A decreased level of VCP, or inhibition of its ATPase activity, impairs starvation-induced production of PI(3)P and limits downstream recruitment of WIPI2, ATG16L and LC3, thereby decreasing autophagosome formation, illustrating an important role for VCP in early autophagy initiation.