rudyvdbrink/CitationDatabase huggingface dataset:
Spinal control of motor outputs by intrinsic and externally induced electric field potentials.
Journal of neurophysiology, 2017

Despite numerous studies on spinal neuronal systems, several issues regarding their role in motor behavior remain unresolved. One of these issues is how electric fields associated with the activity of spinal neurons influence the operation of spinal neuronal networks and how effects of these field potentials are combined with other means of modulating neuronal activity. Another closely related issue is how external electric field potentials affect spinal neurons and how they can be used for therapeutic purposes such as pain relief or recovery of motor functions by transspinal direct current stimulation. Nevertheless, progress in our understanding of the spinal effects of electric fields and their mechanisms has been made over the last years, and the aim of the present review is to summarize the recent findings in this field.
Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept).
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Several mouse models of Alzheimer's disease (AD) with abundant β-amyloid and/or aberrantly phosphorylated tau develop memory impairments. However, multiple non-mnemonic cognitive domains such as attention and executive control are also compromised early in AD individuals. Currently, it is unclear whether mutations in the β-amyloid precursor protein (APP) and tau are sufficient to cause similar, AD-like attention deficits in mouse models of the disease. To address this question, we tested 3xTgAD mice (which express APPswe, PS1M146V, and tauP301L mutations) and wild-type control mice on a newly developed touchscreen-based 5-choice serial reaction time test of attention and response control. The 3xTgAD mice attended less accurately to short, spatially unpredictable stimuli when the attentional demand of the task was high, and also showed a general tendency to make more perseverative responses than wild-type mice. The attentional impairment of 3xTgAD mice was comparable to that of AD patients in two aspects: first, although 3xTgAD mice initially responded as accurately as wild-type mice, they subsequently failed to sustain their attention over the duration of the task; second, the ability to sustain attention was enhanced by the cholinesterase inhibitor donepezil (Aricept). These findings demonstrate that familial AD mutations not only affect memory, but also cause significant impairments in attention, a cognitive domain supported by the prefrontal cortex and its afferents. Because attention deficits are likely to affect memory encoding and other cognitive abilities, our findings have important consequences for the assessment of disease mechanisms and therapeutics in animal models of AD.
Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.
Age (Dordrecht, Netherlands), 2016

We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or fibrosis, while the differential effect of aging on HFD-induced renal injury was not remarkable as shown in the liver.
Deletion of REXO1L1 locus in a patient with malabsorption syndrome, growth retardation, and dysmorphic features: a novel recognizable microdeletion syndrome?
BMC medical genetics, 2015

Copy number variations (CNVs) can contribute to genetic variation among individuals and/or have a significant influence in causing diseases. Many studies consider new CNVs' effects on protein family evolution giving rise to gene duplicates or losses. "Unsuccessful" duplicates that remain in the genome as pseudogenes often exhibit functional roles. So, changes in gene and pseudogene number may contribute to development or act as susceptibility alleles of diseases.
Ataxin-1 regulates proliferation of hippocampal neural precursors.
Neuroscience, 2016

Polyglutamine expansion in the protein ATAXIN-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), an inherited neurodegenerative disease characterized by motor deficits, cognitive impairment and depression. Although ubiquitously expressed, mutant ATXN1 causes neurodegeneration primarily in the cerebellum, which is responsible for the observed motor deficits. The role of ATXN1 outside of the cerebellum and the causes of cognitive deficits and depression in SCA1 are less understood. In this study, we demonstrate a novel role of ATXN1 in the hippocampus as a regulator of adult neurogenesis. Adult hippocampal neurogenesis is the process of generating new hippocampal neurons and is linked to cognition and mood. We found that loss of ATXN1 causes a decrease in hippocampal neurogenesis in ATXN1 null (Atxn1(-/-)) mice. This decrease was caused by reduced proliferation of neural precursors in the hippocampus of Atxn1(-/-) mice, and persisted even when Atxn1(-/-) hippocampal neural precursors were removed from their natural environment and grown in vitro, suggesting that ATXN1 affects proliferation in a cell-autonomous manner. Moreover, expression of ATXN1 with a pathological polyglutamine (polyQ) expansion in wild-type neural precursor cells inhibited their proliferation. Our data establish a novel role for ATXN1 in the hippocampus as an intrinsic regulator of precursor cell proliferation, and suggest a mechanism by which polyQ expansion and loss of ATXN1 affect hippocampal function, potentially contributing to cognitive deficits and depression. These results indicate that while depletion of ATXN1 is a promising therapeutic approach to treat the cerebellar aspects of SCA1, this approach should be employed with caution given the potential for side effects on hippocampal function with loss of wild-type ATXN1.
Postictal generalized EEG suppression and postictal immobility: what do we know?
Epileptic disorders : international epilepsy journal with videotape, 2020

Despite representing the leading cause of epilepsy-related mortality, the pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains elusive. In this context, the identification of clinical markers of SUDEP assumes a great importance and has been the target of many studies aimed at stratifying patients' individual risk. Among the potentially most hazardous post-ictal phenomena observed following convulsive seizures in monitored SUDEP cases, postictal generalized EEG suppression and postictal immobility have attracted attention as potential SUDEP risk factors. In this manuscript, we review the current knowledge on postictal generalized EEG suppression and postictal immobility, aiming to identify their pathophysiological mechanisms, reported frequencies and associated clinical factors, and critically evaluate the evidence on their potential relevance as SUDEP risk markers.
The effect of 18F-FDG-PET image reconstruction algorithms on the expression of characteristic metabolic brain network in Parkinson's disease.
Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB), 2017

To evaluate the reproducibility of the expression of Parkinson's Disease Related Pattern (PDRP) across multiple sets of 18F-FDG-PET brain images reconstructed with different reconstruction algorithms.
Subcellular elevation of cytosolic free calcium is required for osteoclast migration.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2014

Osteoclasts are multinucleated cells responsible for the resorption of bone and other mineralized tissues during development, physiological remodeling, and pathological bone loss. Osteoclasts have the ability to resorb substrate while concurrently migrating. However, the subcellular processes underlying migration are not well understood. It has been proposed that, in other cell types, cytosolic free Ca(2+) concentration ([Ca(2+) ]i ) regulates cell protrusion as well as retraction. Integration of these distinct events would require precise spatiotemporal patterning of subcellular Ca(2+) . The large size of osteoclasts offers a unique opportunity to monitor patterns of Ca(2+) during cell migration. We used ratiometric imaging to map [Ca(2+) ]i within rat and mouse osteoclasts. Migration was characterized by lamellipodial outgrowth at the leading edge, along with intermittent retraction of the uropod. Migrating osteoclasts displayed elevation of [Ca(2+) ]i in the uropod, that began prior to retraction. Dissipation of this [Ca(2+) ]i gradient by loading osteoclasts with the Ca(2+) chelator BAPTA abolished uropod retraction, on both glass and mineralized substrates. In contrast, elevation of [Ca(2+) ]i using ionomycin initiated prompt uropod retraction. To investigate downstream effectors, we treated cells with calpain inhibitor-1, which impaired uropod retraction. In contrast, lamellipodial outgrowth at the leading edge of osteoclasts was unaffected by any of these interventions, indicating that the signals regulating outgrowth are distinct from those triggering retraction. The large size of mature, multinucleated osteoclasts allowed us to discern a novel spatiotemporal pattern of Ca(2+) involved in cell migration. Whereas localized elevation of Ca(2+) is necessary for uropod retraction, lamellipod outgrowth is independent of Ca(2+) -a heretofore unrecognized degree of specificity underlying the regulation of osteoclast migration.
Super-Resolution Track-Density Imaging Reveals Fine Anatomical Features in Tree Shrew Primary Visual Cortex and Hippocampus.
Neuroscience bulletin, 2018

Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to study white and gray matter (GM) micro-organization and structural connectivity in the brain. Super-resolution track-density imaging (TDI) is an image reconstruction method for dMRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI (stTDI), a variation of TDI with enhanced contrast for GM structures, to reconstruct direction-encoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging (DTI) method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with stTDI, but not with DTI reconstructions from the same dMRI data. The possible mechanisms underlying the enhanced GM contrast are discussed.
Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2.
American journal of human genetics, 2018

Although mutations in more than 90 genes are known to cause CMT, the underlying genetic cause of CMT remains unknown in more than 50% of affected individuals. The discovery of additional genes that harbor CMT2-causing mutations increasingly depends on sharing sequence data on a global level. In this way-by combining data from seven countries on four continents-we were able to define mutations in ATP1A1, which encodes the alpha1 subunit of the Na
Altered White Matter and Sensory Response to Bodily Sensation in Female-to-Male Transgender Individuals.
Archives of sexual behavior, 2017

While most people take identification with their body for granted, conditions such as phantom limb pain, alien hand syndrome, and xenomelia suggest that the feeling of bodily congruence is constructed and susceptible to alteration. Individuals with xenomelia typically experience one of their limbs as over-present and aversive, leading to a desire to amputate the limb. Similarly, many transgender individuals describe their untreated sexed body parts as incongruent and aversive, and many experience phantom body parts of the sex they identify with (Ramachandran, 2008). This experience may relate to differences in brain representation of the sexed body part, as suggested in xenomelia (McGeoch et al., 2011). We utilized magnetoencephalography imaging to record brain activity during somatosensory stimulation of the breast-a body part that feels incongruent to most presurgical female-to-male (FtM)-identified transgender individuals-and the hand, a body part that feels congruent. We measured the sensory evoked response in right hemisphere somatosensory and body-related brain areas and found significantly reduced activation in the supramarginal gyrus and secondary somatosensory cortex, but increased activation at the temporal pole for chest sensation in the FtM group (N = 8) relative to non-transgender females (N = 8). In addition, we found increased white matter coherence in the supramarginal gyrus and temporal pole and decreased white matter diffusivity in the anterior insula and temporal pole in the FtM group. These findings suggest that dysphoria related to gender-incongruent body parts in FtM individuals may be tied to differences in neural representation of the body and altered white matter connectivity.
A pragmatic effectiveness randomized controlled trial of the duration of psychiatric hospitalization in a trans-diagnostic sample of patients with acute mental illness admitted to a ward with either blue-depleted evening lighting or normal lighting conditions.
Trials, 2019

There is increasing recognition of the need to stabilize sleep-wake cycles in individuals with major mental disorders. As such, clinicians and researchers advocate the use of interventions targeted at sleep and circadian dysrhythmias as an adjunct to the standard treatments offered for acute illness episodes of a broad range of diagnoses. To determine the trans-diagnostic generalizability of chronotherapy, we explore the benefits of admitting individuals with an acute illness episode to a psychiatric inpatient unit where changes in light exposure are integrated into the therapeutic environment.
A systematic review of economic evaluations of treatments for patients with epilepsy.
Epilepsia, 2017

The increasing number of treatment options and the high costs associated with epilepsy have fostered the development of economic evaluations in epilepsy. It is important to examine the availability and quality of these economic evaluations and to identify potential research gaps. As well as looking at both pharmacologic (antiepileptic drugs [AEDs]) and nonpharmacologic (e.g., epilepsy surgery, ketogenic diet, vagus nerve stimulation) therapies, this review examines the methodologic quality of the full economic evaluations included. Literature search was performed in MEDLINE, EMBASE, NHS Economic Evaluation Database (NHS EED), Econlit, Web of Science, and CEA Registry. In addition, Cochrane Reviews, Cochrane DARE and Cochrane Health Technology Assessment Databases were used. To identify relevant studies, predefined clinical search strategies were combined with a search filter designed to identify health economic studies. Specific search strategies were devised for the following topics: (1) AEDs, (2) patients with cognitive deficits, (3) elderly patients, (4) epilepsy surgery, (5) ketogenic diet, (6) vagus nerve stimulation, and (7) treatment of (non)convulsive status epilepticus. A total of 40 publications were included in this review, 29 (73%) of which were articles about pharmacologic interventions. Mean quality score of all articles on the Consensus Health Economic Criteria (CHEC)-extended was 81.8%, the lowest quality score being 21.05%, whereas five studies had a score of 100%. Looking at the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), the average quality score was 77.0%, the lowest being 22.7%, and four studies rated as 100%. There was a substantial difference in methodology in all included articles, which hampered the attempt to combine information meaningfully. Overall, the methodologic quality was acceptable; however, some studies performed significantly worse than others. The heterogeneity between the studies stresses the need to define a reference case (e.g., how should an economic evaluation within epilepsy be performed) and to derive consensus on what constitutes "standard optimal care."
Rare subtypes of BK virus are viable and frequently detected in renal transplant recipients with BK virus-associated nephropathy.
Virology, 2010

BK virus-associated nephropathy (BKVN) occurs in up to 5% of kidney transplants and is a significant cause of graft loss. Four major subtypes of BKV have been described, with the vast majority of individuals persistently infected with BKV Type I (>80% of the population). Sequencing of BKV isolates subcloned from BKVN patients revealed a high percentage of variants in the urine (40%) in the VP1 subtyping region. In vitro analysis of several viral variants revealed that all variants recovered from the urine of BKVN patients produced infectious viral particles and were replication competent in cell culture while some of the variants induced cytopathic changes in infected cells when compared to the major BKV subtype, VP1 Type I. These results suggest that rare BKV VP1 variants are more frequently associated with disease and that some variants could be more cytopathic than others in renal transplant recipients.
Transient reduction of visual distraction following electrical stimulation of the prefrontal cortex.
Cognition, 2015

The ability to overcome distraction is critical to a number of goal-directed behaviors, but information that is not relevant to our goals often captures our attention and distracts us from the task at hand. Neuroimaging work has demonstrated that activity in specific regions of the lateral prefrontal cortex (PFC) is related to the suppression of distracting information, implicating PFC as a critical node in the goal-directed control network. In the current work we asked whether applying transcranial direct-current stimulation (tDCS) to PFC would influence the likelihood of attentional capture by salient, task-irrelevant visual information encountered during visual search. Our results showed that anodal stimulation, relative to sham or cathodal stimulation, led to a transient decrease in attentional capture lasting approximately 15 min after stimulation. This provides causal evidence that PFC is involved in goal-directed control over distraction, and provides a basis for using PFC stimulation as a causal tool to understand deficits in goal-directed control in both neurologically healthy and impaired populations.
Reduced number of axonal mitochondria and tau hypophosphorylation in mouse P301L tau knockin neurons.
Neurobiology of disease, 2016

Expression of the frontotemporal dementia-related tau mutation, P301L, at physiological levels in adult mouse brain (KI-P301L mice) results in overt hypophosphorylation of tau and age-dependent alterations in axonal mitochondrial transport in peripheral nerves. To determine the effects of P301L tau expression in the central nervous system, we examined the kinetics of mitochondrial axonal transport and tau phosphorylation in primary cortical neurons from P301L knock-in (KI-P301L) mice. We observed a significant 50% reduction in the number of mitochondria in the axons of cortical neurons cultured from KI-P301L mice compared to wild-type neurons. Expression of murine P301L tau did not change the speed, direction of travel or likelihood of movement of mitochondria. Notably, the angle that defines the orientation of the mitochondria in the axon, and the volume of individual moving mitochondria, were significantly increased in neurons expressing P301L tau. We found that murine tau phosphorylation in KI-P301L mouse neurons was diminished and the ability of P301L tau to bind to microtubules was also reduced compared to tau in wild-type neurons. The P301L mutation did not influence the ability of murine tau to associate with membranes in cortical neurons or in adult mouse brain. We conclude that P301L tau is associated with mitochondrial changes and causes an early reduction in murine tau phosphorylation in neurons coupled with impaired microtubule binding of tau. These results support the association of mutant tau with detrimental effects on mitochondria and will be of significance for the pathogenesis of tauopathies.
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism.
Epilepsy & behavior : E&B, 2008

Human succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of GABA metabolism associated with motor impairment and epileptic seizures. Similarly, mice with targeted deletion of the Aldh5a1 gene (Aldh5a1(-/-)) exhibit SSADH deficiency and seizures early in life. These seizures begin as absence seizures the second week of life, but evolve into generalized convulsive seizures that increase in severity and become lethal during the fourth postnatal week. The seizures are alleviated and survival is prolonged when the mutant animals are weaned onto a ketogenic diet (KD). The persistence of spontaneous, recurrent, generalized tonic-clonic seizures in KD-treated adult Aldh5a1(-/-) mice allowed us to quantify their daily (circadian) distribution using a novel behavioral method based on the detection of changes in movement velocity. Adult KD-treated Aldh5a1(-/-) mice exhibited a seizure phenotype characterized by fits of wild running clonus accompanied by jumping and bouncing. These hypermotor seizures were largely spontaneous and occurred daily in a nonrandom pattern. The seizure rhythm showed a peak shortly after dark phase onset (2008 hours) with near-24-hour periodicity. Age-matched wild-type littermates showed no evidence of abnormal motor behavior. These new data suggest that generalized tonic-clonic seizures in Aldh5a1(-/-) mice are more frequent during a specific time of day and will provide useful information to clinicians for the treatment of seizures associated with human SSADH deficiency.