rudyvdbrink/CitationDatabase huggingface dataset:
Endocrine regulation of airway clearance in 
Proceedings of the National Academy of Sciences of the United States of America, 2018

Fluid clearance from the respiratory system during developmental transitions is critically important for achieving optimal gas exchange in animals. During insect development from embryo to adult, airway clearance occurs episodically each time the molt is completed by performance of the ecdysis sequence, coordinated by a peptide-signaling cascade initiated by ecdysis-triggering hormone (ETH). We find that the neuropeptide Kinin (also known as Drosokinin or Leukokinin) is required for normal respiratory fluid clearance or "tracheal air-filling" in
Differential effects of familial parkinson mutations in LRRK2 revealed by a systematic analysis of autophosphorylation.
Biochemistry, 2013

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified in pedigrees of autosomal-dominant familial Parkinson's disease (PARK8). It has been shown that the kinase activity of LRRK2 is required for its neuronal toxicity, although how familial Parkinson mutations affect the function of LRRK2 has not been well characterized. In the present study, we systematically characterized the autophosphorylation of LRRK2 by phosphopeptide mapping and identified Thr1348, Thr1349, and Thr1357 as the major autophosphorylation sites. We found that the autophosphorylation at Thr1357 is downregulated by the Y1699C mutation, possibly through a conformational alteration of the ROC domain. We also found that I2020T mutant LRRK2 undergoes excessive autophosphorylation in cell lysates in vitro at a low concentration of ATP. These results highlight the differential effects of familial mutations in LRRK2 on its conformation and enzymatic properties.
Early-onset cortico-cortical synchronization in the hemiparkinsonian rat model.
Journal of neurophysiology, 2015

Changes in synchronized neuronal oscillatory activity are reported in both cortex and basal ganglia of Parkinson's disease patients. The origin of these changes, in particular their relationship with the progressive nigrostriatal dopaminergic denervation, is unknown. Therefore, in the present study we studied interregional neuronal synchronization in motor cortex and basal ganglia during the development of dopaminergic degeneration induced by a unilateral infusion of 6-hydroxydopamine (6-OHDA) into the rat medial forebrain bundle. We performed serial local field potential recordings bilaterally in the motor cortex and the subthalamic nucleus of the lesioned hemisphere prior to, during, and after development of the nigrostriatal dopaminergic cell loss. We obtained signal from freely moving rats in both resting and walking conditions, and we computed local spectral power, interregional synchronization (using phase lag index), and directionality (using Granger causality). After neurotoxin injection the first change in phase lag index was an increment in cortico-cortical synchronization. We observed increased bidirectional Granger causality in the beta frequency band between cortex and subthalamic nucleus within the lesioned hemisphere. In the walking condition, the 6-OHDA lesion-induced changes in synchronization resembled that of the resting state, whereas the changes in Granger causality were less pronounced after the lesion. Considering the relatively preserved connectivity pattern of the cortex contralateral to the lesioned side and the early emergence of increased cortico-cortical synchronization during development of the 6-OHDA lesion, we suggest a putative compensatory role of cortico-cortical coupling.
Determining Brain Mechanisms that Underpin Analgesia Induced by the Use of Pain Coping Skills.
Pain medicine (Malden, Mass.), 2018

Cognitive behavioral therapies decrease pain and improve mood and function in people with osteoarthritis. This study assessed the effects of coping strategies on the central processing of knee pain in people with osteoarthritis of the knees.
General sexual desire, but not desire for uncommitted sexual relationships, tracks changes in women's hormonal status.
Psychoneuroendocrinology, 2018

Several recent longitudinal studies have investigated the hormonal correlates of both young adult women's general sexual desire and, more specifically, their desire for uncommitted sexual relationships. Findings across these studies have been mixed, potentially because each study tested only small samples of women (Ns = 43, 33, and 14). Here we report results from a much larger (N = 375) longitudinal study of hormonal correlates of young adult women's general sexual desire and their desire for uncommitted sexual relationships. Our analyses suggest that within-woman changes in general sexual desire are negatively related to progesterone, but are not related to testosterone or cortisol. We observed some positive relationships for estradiol, but these were generally only significant for solitary sexual desire. By contrast with our results for general sexual desire, analyses showed no evidence that changes in women's desire for uncommitted sexual relationships are related to their hormonal status. Together, these results suggest that changes in hormonal status contribute to changes in women's general sexual desire, but do not influence women's desire for uncommitted sexual relationships.
Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco-magnetoencephalography.
Human brain mapping, 2010

Neuronal network oscillations are a unifying phenomenon in neuroscience research, with comparable measurements across scales and species. Cortical oscillations are of central importance in the characterization of neuronal network function in health and disease and are influential in effective drug development. Whilst animal in vitro and in vivo electrophysiology is able to characterize pharmacologically induced modulations in neuronal activity, present human counterparts have spatial and temporal limitations. Consequently, the potential applications for a human equivalent are extensive. Here, we demonstrate a novel implementation of contemporary neuroimaging methods called pharmaco-magnetoencephalography. This approach determines the spatial profile of neuronal network oscillatory power change across the cortex following drug administration and reconstructs the time course of these modulations at focal regions of interest. As a proof of concept, we characterize the nonspecific GABAergic modulator diazepam, which has a broad range of therapeutic applications. We demonstrate that diazepam variously modulates theta (4-7 Hz), alpha (7-14 Hz), beta (15-25 Hz), and gamma (30-80 Hz) frequency oscillations in specific regions of the cortex, with a pharmacodynamic profile consistent with that of drug uptake. We examine the relevance of these results with regard to the spatial and temporal observations from other modalities and the various therapeutic consequences of diazepam and discuss the potential applications of such an approach in terms of drug development and translational neuroscience.
Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats.
Molecules (Basel, Switzerland), 2017

The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status.
Selective activation of p38 mitogen-activated protein kinase in dopaminergic neurons of substantia nigra leads to nuclear translocation of p53 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Activation of the mixed lineage kinase and c-Jun N-terminal kinase (JNK) has been reported in models of PD. Our focus was to discern whether distinct pathways were activated in cell-specific manner within the SNpc. We now demonstrate the selective phosphorylation of p38 MAP kinase within the dopaminergic neurons, whereas JNK activation occurs predominantly in the microglia. p38 activation results in downstream phosphorylation of p53 and increased p53 mediated transcription of Bax and Puma in the ventral midbrain. Treatment with p38 inhibitor, SB239063 protected primary dopaminergic neurons derived from human progenitor cells from MPP(+) mediated cell death and prevented the downstream phosphorylation of p53 and its translocation to the nucleus in vivo, in the ventral midbrain. The increased staining of phosphorylated p38 in the surviving neurons of SNpc in human brain sections from patients with PD and in MPTP treated mice but not in the ventral tegmental area provides further evidence suggesting a role for p38 in the degeneration of dopaminergic neurons of SNpc. We thus demonstrate the cell specific activation of MAP kinase pathways within the SNpc after MPTP treatment emphasizing the role of multiple signaling cascades in the pathogenesis and progression of the disease. Selective inhibitors of p38 may therefore, help preserve the surviving neurons in PD and slow down the disease progression.
Vagus nerve stimulator treatment in adult-onset Rasmussen's encephalitis.
Epilepsy & behavior : E&B, 2011

We describe a patient with adult-onset Rasmussen's encephalitis (RE) responsive to vagus nerve stimulation. This previously healthy woman developed RE in the right hemisphere at the age of 27. Despite antiepileptic drug polytherapy, she continued to experience subcontinuous, simple-partial left-sided motor seizures and slowly progressive cognitive impairment. Resective surgery was not considered owing to the preservation of left motor skills. She was implanted with a vagus nerve stimulator at the age of 41; after 6 months she experienced a greater than 50% reduction in seizure frequency, which persisted over 2 years together with improvement of her neurological and cognitive status.
Evaluating hearing performance with cochlear implants within the same patient using daily randomization and imaging-based fitting - The ELEPHANT study.
Trials, 2020

Prospective research in the field of cochlear implants is hampered by methodological issues and small sample sizes. The ELEPHANT study presents an alternative clinical trial design with a daily randomized approach evaluating individualized tonotopical fitting of a cochlear implant (CI).
Cortical morphometric changes after spinal cord injury.
Brain research bulletin, 2018

Neuroimaging studies suggest that spinal cord injury (SCI) may lead to significant anatomical alterations in the human sensorimotor system. In particular, voxel-based morphometry (VBM) of cortical volume has revealed a significant gray and white matter atrophy bilaterally in the primary sensory cortex (S1). By contrast, some structural studies failed to detect changes in gray matter volume (GMV) in the primary motor cortex (M1) following SCI, whereas others have reported a substantial decrease of GMV also in M1. In addition to direct degeneration of the sensorimotor cortex, SCI can also lead to atrophy of the non-sensorimotor cortex, such as anterior cingulate cortex, insular cortex, middle frontal gyrus and supplementary motor area. These findings suggest that SCI can cause remote atrophy of brain gray matter in the salient network. Furthermore, pain-related remodelling may occur in SCI. In fact, structural changes in SCI are also related to the presence and degree of below-level pain. We performed a systematic review of the neuroimaging studies showing morphometric cortical changes and subsequent functional reorganization in humans with SCI. Literature search was conducted using PubMed and Embase. We identified 12 articles matching the inclusion criteria and 195 patients were included in these studies. The wide range of disease duration, rehabilitation training, drug intervention, and different research methodology, especially the identification of region of interest and the statistical approach to correct for multiple comparisons, may have contributed to some inconsistencies between the reviewed studies. Nevertheless, neuroimaging biomarkers can assess the extent of neural damage, elucidate the mechanisms of neural repair, and predict clinical outcome. A better understanding of the structural and functional changes that occur at cortical level following SCI may be useful in tracking potential treatment induced changes and identifying potential therapeutic targets, thus developing evidence-based rehabilitation therapies.
Morphology and functions of astrocytes cultured on water-repellent fractal tripalmitin surfaces.
Biomaterials, 2014

In the brain, astrocytes play an essential role with their multiple functions and sophisticated structure, as surrounded by a fractal environment which has not been available in our traditional cell culture. Water-repellent fractal tripalmitin (PPP) surfaces can imitate the fractal environment in vivo, so the morphology and biochemical characterization of astrocytes on these surfaces are examined. Water-repellent fractal PPP surface can induce astrocytes to display sophisticated morphology with smaller size of cell area, longer and finer filopodium-like processes, and higher morphological complexity. The super water-repellent fractal PPP surface with water contact angle of 150°∼160° produces the maximal effects compared with other surfaces at lower water contact angles. The trends of characteristic protein expression, including that of nestin, vimentin, GFAP and glutamine synthetase, for astrocytes cultured on super water-repellent fractal PPP surfaces approximate more to in vivo pattern. The super water-repellent PPP surface also render astrocytes to perform more pronounced promotion of neurogenesis by increasing the release of nerve growth factor in a co-culture system. Altogether, our results suggest that the super water-repellent fractal PPP surface facilitates the astrocytes to mimic their in vivo performance, thus provides a closer-to-natural culture environment for experimental assessment of glial structure and functions.
Nerve Injury Diminishes Opioid Analgesia through Lysine Methyltransferase-mediated Transcriptional Repression of μ-Opioid Receptors in Primary Sensory Neurons.
The Journal of biological chemistry, 2016

The μ-opioid receptor (MOR, encoded by Oprm1) agonists are the mainstay analgesics for treating moderate to severe pain. Nerve injury causes down-regulation of MORs in the dorsal root ganglion (DRG) and diminishes the opioid effect on neuropathic pain. However, the epigenetic mechanisms underlying the diminished MOR expression caused by nerve injury are not clear. G9a (encoded by Ehmt2), a histone 3 at lysine 9 methyltransferase, is a key chromatin regulator responsible for gene silencing. In this study, we determined the role of G9a in diminished MOR expression and opioid analgesic effects in animal models of neuropathic pain. We found that nerve injury in rats induced a long-lasting reduction in the expression level of MORs in the DRG but not in the spinal cord. Nerve injury consistently increased the enrichment of the G9a product histone 3 at lysine 9 dimethylation in the promoter of Oprm1 in the DRG. G9a inhibition or siRNA knockdown fully reversed MOR expression in the injured DRG and potentiated the morphine effect on pain hypersensitivity induced by nerve injury. In mice lacking Ehmt2 in DRG neurons, nerve injury failed to reduce the expression level of MORs and the morphine effect. In addition, G9a inhibition or Ehmt2 knockout in DRG neurons normalized nerve injury-induced reduction in the inhibitory effect of the opioid on synaptic glutamate release from primary afferent nerves. Our findings indicate that G9a contributes critically to transcriptional repression of MORs in primary sensory neurons in neuropathic pain. G9a inhibitors may be used to enhance the opioid analgesic effect in the treatment of chronic neuropathic pain.
Activation of calcineurin underlies altered trafficking of α2 subunit containing GABAA receptors during prolonged epileptiform activity.
Neuropharmacology, 2015

Fast inhibitory signalling in the mammalian brain is mediated by gamma-aminobutyric acid type A receptors (GABAARs), which are targets for anti-epileptic therapy such as benzodiazepines. GABAARs undergo tightly regulated trafficking processes that are essential for maintenance and physiological modulation of inhibitory strength. The trafficking of GABAARs to and from the membrane is altered during prolonged seizures such as in Status Epilepticus (SE) and has been suggested to contribute to benzodiazepine pharmacoresistance in patients with SE. However, the intracellular signalling mechanisms that cause this modification in GABAAR trafficking remain poorly understood. In this study, we investigate the surface stability of GABAARs during SE utilising the low Mg(2+) model in hippocampal rat neurons. Live-cell imaging of super ecliptic pHluorin (SEP)-tagged α2 subunit containing GABAARs during low Mg(2+) conditions reveals that the somatic surface receptor pool undergoes down-regulation dependent on N-methyl-d-aspartate receptor (NMDAR) activity. Analysis of the intracellular Ca(2+) signal during low Mg(2+) using the Ca(2+)-indicator Fluo4 shows that this reduction of surface GABAARs correlates well with the timeline of intracellular Ca(2+) changes. Furthermore, we show that the activation of the phosphatase calcineurin was required for the decrease in surface GABAARs in neurons undergoing epileptiform activity. These results indicate that somatic modulation of GABAAR trafficking during epileptiform activity in vitro is mediated by calcineurin activation which is linked to changes in intracellular Ca(2+) concentrations. These mechanisms could account for benzodiazepine pharmacoresistance and the maintenance of recurrent seizure activity, and reveal potential novel targets for the treatment of SE.
Re-Opening the Critical Window for Estrogen Therapy.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

A decline in estradiol (E2)-mediated cognitive benefits denotes a critical window for the therapeutic effects of E2, but the mechanism for closing of the critical window is unknown. We hypothesized that upregulating the expression of estrogen receptor α (ERα) or estrogen receptor β (ERβ) in the hippocampus of aged animals would restore the therapeutic potential of E2 treatments and rejuvenate E2-induced hippocampal plasticity. Female rats (15 months) were ovariectomized, and, 14 weeks later, adeno-associated viral vectors were used to express ERα, ERβ, or green fluorescent protein (GFP) in the CA1 region of the dorsal hippocampus. Animals were subsequently treated for 5 weeks with cyclic injections of 17β-estradiol-3-benzoate (EB, 10 μg) or oil vehicle. Spatial memory was examined 48 h after EB/oil treatment. EB treatment in the GFP (GFP + EB) and ERβ (ERβ + EB) groups failed to improve episodic spatial memory relative to oil-treated animals, indicating closing of the critical window. Expression of ERβ failed to improve cognition and was associated with a modest learning impairment. Cognitive benefits were specific to animals expressing ERα that received EB treatment (ERα + EB), such that memory was improved relative to ERα + oil and GFP + EB. Similarly, ERα + EB animals exhibited enhanced NMDAR-mediated synaptic transmission compared with the ERα + oil and GFP + EB groups. This is the first demonstration that the window for E2-mediated benefits on cognition and hippocampal E2 responsiveness can be reinstated by increased expression of ERα.
Why communities must be at the centre of the Coronavirus disease 2019 response: Lessons from Ebola and human immunodeficiency virus in Africa.
African journal of primary health care & family medicine, 2020

As the Coronavirus disease 2019 (COVID-19) pandemic has spread globally, with no effective treatment or vaccine yet available, governments in many countries have put in place social interventions to control the outbreak. The various lockdown measures may have devastating impacts on economies and livelihoods. This approach risks undermining public trust in government responses and therefore undermines efforts to promote behaviour change, which is key to the success of social interventions. Important lessons can be drawn from past Ebola outbreaks and the human immunodeficiency virus pandemic on how communities should be central to COVID-19 responses. Communities are complex and only their members can inform public health experts about their lived realities, the community's understanding of the outbreak and what will work locally to reduce transmission. The public should be encouraged to take positive actions to ensure their own health and well-being, rather than made to feel powerless. Communities should be supported to develop their own response plans, community leaders should be recognised as vital assets, community representatives should have equal inclusion in strategic meetings and greater empathy should be built into decision-making processes.
The "Saltin-Grimby Physical Activity Level Scale" and its application to health research.
Scandinavian journal of medicine & science in sports, 2015

The use of a four-level questionnaire to assess leisure time physical activity (PA) and its validation is reviewed in this paper. This questionnaire was first published in 1968 and has then been used by more than 600,000 subjects, especially in different population studies in the Nordic countries. A number of modifications to the questionnaire have been published. These are mostly minor changes, such as adding practical examples of activities to illustrate the levels of PA. Some authors have also added duration requirements that were not included for all levels of PA in the original version. The concurrent validity, with respect to aerobic capacity and movement analysis using objective measurements has been shown to be good, as has the predictive validity with respect to various risk factors for health conditions and for morbidity and mortality.