rudyvdbrink/CitationDatabase huggingface dataset:
Ascending dorsal column sensory neurons respond to spinal cord injury and downregulate genes related to lipid metabolism.
Scientific reports, 2021

Regeneration failure after spinal cord injury (SCI) results in part from the lack of a pro-regenerative response in injured neurons, but the response to SCI has not been examined specifically in injured sensory neurons. Using RNA sequencing of dorsal root ganglion, we determined that thoracic SCI elicits a transcriptional response distinct from sciatic nerve injury (SNI). Both SNI and SCI induced upregulation of ATF3 and Jun, yet this response failed to promote growth in sensory neurons after SCI. RNA sequencing of purified sensory neurons one and three days after injury revealed that unlike SNI, the SCI response is not sustained. Both SCI and SNI elicited the expression of ATF3 target genes, with very little overlap between conditions. Pathway analysis of differentially expressed ATF3 target genes revealed that fatty acid biosynthesis and terpenoid backbone synthesis were downregulated after SCI but not SNI. Pharmacologic inhibition of fatty acid synthase, the enzyme generating palmitic acid, decreased axon growth and regeneration in vitro. These results support the notion that decreased expression of lipid metabolism-related genes after SCI, including fatty acid synthase, may restrict axon regenerative capacity after SCI.
Impact of vitamin D supplementation on adiposity in African-Americans.
Nutrition & diabetes, 2015

African-Americans have higher rates of obesity-associated chronic diseases. Serum 25-hydroxyvitamin D (25(OH)D) shows an inverse association with obesity status. We investigated whether vitamin D supplementation changes body mass index (BMI).
TGFβ regulates persistent neuroinflammation by controlling Th1 polarization and ROS production via monocyte-derived dendritic cells.
Glia, 2016

Intracerebral levels of Transforming Growth Factor beta (TGFβ) rise rapidly during the onset of experimental autoimmune encephalomyelitis (EAE), a mouse model of Multiple Sclerosis (MS). We addressed the role of TGFβ responsiveness in EAE by targeting the TGFβ receptor in myeloid cells, determining that Tgfbr2 was specifically targeted in monocyte-derived dendritic cells (moDCs) but not in CNS resident microglia by using bone-marrow chimeric mice. TGFβ responsiveness in moDCs was necessary for the remission phase since LysM(Cre) Tgfbr2(fl/fl) mice developed a chronic form of EAE characterized by severe demyelination and extensive infiltration of activated moDCs in the CNS. Tgfbr2 deficiency resulted in increased moDC IL-12 secretion that skewed T cells to produce IFN-γ, which in turn enhanced the production of moDC-derived reactive oxygen species that promote oxidative damage and demyelination. We identified SNPs in the human NOX2 (CYBB) gene that associated with the severity of MS, and significantly increased CYBB expression was recorded in PBMCs from both MS patients and from MS severity risk allele rs72619425-A carrying individuals. We thus identify a novel myeloid cell-T cell activation loop active in the CNS during chronic disease that could be therapeutically targeted. GLIA 2016;64:1925-1937.
Response compliance and predictors thereof in studies using the experience sampling method.
Psychological assessment, 2019

Intensive repeated measurement techniques, such as the experience sampling method (ESM), put high demands on participants and may lead to low response compliance, which, in turn, may affect data quality. Therefore, the objective of this study was to investigate ESM compliance and predictors thereof based on a pooled dataset of 10 ESM studies with a total of 92,394 momentary assessments from 1,717 individuals with different mental health conditions. All included studies used an ESM paper-and-pencil diary protocol of 4 to 6 study days with 10 random time assessments per day. Analyses were conducted using multilevel mixed-effects logistic regression models. Results indicated overall acceptable compliance with an average response rate of 78% (95% CI [0.74, 0.82]). However, compliance declined across days (p < .001), reaching a low on the 5th day with 73% (95% CI [0.68, 0.77]). Compliance also varied significantly across assessments depending on the time within a day (p < .001), with highest compliance between 12 p.m. and 1.30 p.m. (83%; 95% CI [0.80, 0.86]) and lowest compliance between 7.30 a.m. and 9 a.m. (56%; 95% CI [0.50, 0.62]). Persons with psychosis were less compliant than healthy participants (70% vs. 83%, respectively; p < .001). Also females (p = .002) and older participants (p < .001) were slightly more compliant. The findings suggest acceptable compliance in an ESM protocol of 4 to 6 study days with a high frequency of 10 assessments per day despite fluctuations across and within study days. Further evidence on compliance and its predictors in different ESM protocols is needed, especially in clinical populations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice.
Molecular psychiatry, 2020

Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C->A substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.
Different mechanisms are responsible for dishabituation of electrophysiological auditory responses to a change in acoustic identity than to a change in stimulus location.
Neurobiology of learning and memory, 2013

Repeated exposure to an auditory stimulus leads to habituation of the electrophysiological and immediate-early-gene (IEG) expression response in the auditory system. A novel auditory stimulus reinstates this response in a form of dishabituation. This has been interpreted as the start of new memory formation for this novel stimulus. Changes in the location of an otherwise identical auditory stimulus can also dishabituate the IEG expression response. This has been interpreted as an integration of stimulus identity and stimulus location into a single auditory object, encoded in the firing patterns of the auditory system. In this study, we further tested this hypothesis. Using chronic multi-electrode arrays to record multi-unit activity from the auditory system of awake and behaving zebra finches, we found that habituation occurs to repeated exposure to the same song and dishabituation with a novel song, similar to that described in head-fixed, restrained animals. A large proportion of recording sites also showed dishabituation when the same auditory stimulus was moved to a novel location. However, when the song was randomly moved among 8 interleaved locations, habituation occurred independently of the continuous changes in location. In contrast, when 8 different auditory stimuli were interleaved all from the same location, a separate habituation occurred to each stimulus. This result suggests that neuronal memories of the acoustic identity and spatial location are different, and that allocentric location of a stimulus is not encoded as part of the memory for an auditory object, while its acoustic properties are. We speculate that, instead, the dishabituation that occurs with a change from a stable location of a sound is due to the unexpectedness of the location change, and might be due to different underlying mechanisms than the dishabituation and separate habituations to different acoustic stimuli.
Assessment of anxiety-like behaviors in female rats bred for differences in kindling susceptibility and amygdala excitability.
Brain research, 2008

Two rat lines bred for kindling susceptibility were previously observed to engage in different behavioral strategies in tests of emotionality. In order to extend past research on defensive behaviors in these strains which largely used males, Fast- and Slow-kindling females were assessed for anxiety-like behaviors in a number of aversive paradigms. Fast rats entered and spent more time in the open arms and spent less time in the closed arms of the elevated plus-maze (EPM) compared to Slow animals. Fast rats had higher conditioned suppression ratios across testing days, defecated less often during conditioning, and successfully disinhibited suppression during extinction in the conditioned emotional response (CER) paradigm compared to Slow-kindlers. In order to pursue these differences in emotional reactivity between the strains and differentiate negative affect from motivational, learning, and impulsive explanations, a separate group of animals were assessed in the light-enhanced acoustic startle chamber, a test of anxiety. When initially exposed to a bright-light, Slow rats significantly increased their startle response while this was not observed in the Fast strain. In combination with previous research on these strains, the present data tentatively suggest that Fast and Slow animals utilize different neural systems in tests of fear and anxiety which may have been co-selected with the direct selection of amygdala-kindling susceptibility.
Resting-state connectivity of the amygdala predicts response to cognitive behavioral therapy in obsessive compulsive disorder.
Biological psychology, 2015

Obsessive-compulsive disorder (OCD) is a psychiatric disorder which is characterized by recurrent intrusive thoughts (obsessions) and ritualized, repetitive behaviors or mental acts (compulsions). The gold standard for the treatment of OCD is cognitive behavioral therapy (CBT) with exposure and response prevention. This is the first study exploring the predictive value of resting-state functional connectivity for the outcome of CBT.
Conserved alternative splicing and expression patterns of arthropod N-cadherin.
PLoS genetics, 2009

Metazoan development requires complex mechanisms to generate cells with diverse function. Alternative splicing of pre-mRNA not only expands proteomic diversity but also provides a means to regulate tissue-specific molecular expression. The N-Cadherin gene in Drosophila contains three pairs of mutually-exclusive alternatively-spliced exons (MEs). However, no significant differences among the resulting protein isoforms have been successfully demonstrated in vivo. Furthermore, while the N-Cadherin gene products exhibit a complex spatiotemporal expression pattern within embryos, its underlying mechanisms and significance remain unknown. Here, we present results that suggest a critical role for alternative splicing in producing a crucial and reproducible complexity in the expression pattern of arthropod N-Cadherin. We demonstrate that the arthropod N-Cadherin gene has maintained the three sets of MEs for over 400 million years using in silico and in vivo approaches. Expression of isoforms derived from these MEs receives precise spatiotemporal control critical during development. Both Drosophila and Tribolium use ME-13a and ME-13b in "neural" and "mesodermal" splice variants, respectively. As proteins, either ME-13a- or ME-13b-containing isoform can cell-autonomously rescue the embryonic lethality caused by genetic loss of N-Cadherin. Ectopic muscle expression of either isoform beyond the time it normally ceases leads to paralysis and lethality. Together, our results offer an example of well-conserved alternative splicing increasing cellular diversity in metazoans.
Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course.
Multiple sclerosis (Houndmills, Basingstoke, England), 2020

To provide clinicians who treat multiple sclerosis (MS) patients with evidence-based or expert opinion-based recommendations for promoting exercise and lifestyle physical activity across disability levels.
Comments on defining the targets, mechanisms, and active ingredients of rehabilitation.
Rehabilitation psychology, 2015

Hart and Ehde (2015) provide a cogent framework for conceptualizing rehabilitation psychology interventions, within a broader classification of rehabilitation treatments. The tripartite structure of treatment seems simple and straightforward but, with further consideration, reveals a depth of complexity and richness.
Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders.
Antibodies (Basel, Switzerland), 2017

The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells. After having demonstrated outstanding therapeutic efficacy in multiple models of autoimmunity, inflammation and transplantation, and safety in phase-I studies in humans, selective CD28 antagonists are currently in early clinical development for the treatment of systemic lupus erythematous and rheumatoid arthritis. Here, we review the available proof of concept studies for CD28 antagonists in autoimmunity, with a special focus on the mechanisms of action.
Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications.
Neurosurgical focus, 2010

Although numerous studies have been carried out to investigate the pathophysiology of mild traumatic brain injury (mTBI), there are still no standard criteria for the diagnosis and treatment of this peculiar condition. The dominant theory that diffuse axonal injury is the main neuropathological process behind mTBI is being revealed as weak at best or inconclusive, given the current literature and the fact that neuronal injury inherent to mTBI improves, with few lasting clinical sequelae in the vast majority of patients. Clinical and experimental evidence suggests that such a course, rather than being due to cell death, is based on temporal neuronal dysfunction, the inevitable consequence of complex biochemical and neurochemical cascade mechanisms directly and immediately triggered by the traumatic insult. This report is an attempt to summarize data from a long series of experiments conducted in the authors' laboratories and published during the past 12 years, together with an extensive analysis of the available literature, focused on understanding the biochemical damage produced by an mTBI. The overall clinical implications, as well as the metabolic nature of the post-mTBI brain vulnerability, are discussed. Finally, the application of proton MR spectroscopy as a possible tool to monitor the full recovery of brain metabolic functions is emphasized.
A new automated implementation of the Posturo-Locomotion-Manual (PLM) method for movement analysis in patients with parkinson's disease.
Acta neurologica Scandinavica, 2011

The Posturo-Locomotion-Manual (PLM) test, which uses an optoelectronic laboratory system, has here been further developed into an automated, more user-friendly, standardized tool for movement analysis named the QbTestMotus. This paper compares the accuracy of QbTestMotus to the PLM test, in particular the automated data analysis.
Recurrent Implication of Striatal Cholinergic Interneurons in a Range of Neurodevelopmental, Neurodegenerative, and Neuropsychiatric Disorders.
Cells, 2021

Cholinergic interneurons are "gatekeepers" for striatal circuitry and play pivotal roles in attention, goal-directed actions, habit formation, and behavioral flexibility. Accordingly, perturbations to striatal cholinergic interneurons have been associated with many neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The role of acetylcholine in many of these disorders is well known, but the use of drugs targeting cholinergic systems fell out of favor due to adverse side effects and the introduction of other broadly acting compounds. However, in response to recent findings, re-examining the mechanisms of cholinergic interneuron dysfunction may reveal key insights into underlying pathogeneses. Here, we provide an update on striatal cholinergic interneuron function, connectivity, and their putative involvement in several disorders. In doing so, we aim to spotlight recurring physiological themes, circuits, and mechanisms that can be investigated in future studies using new tools and approaches.
Parma consensus statement on metabolic disruptors.
Environmental health : a global access science source, 2015

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.
Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide.
Molecular psychiatry, 2018

Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.
Identifying a melanogenesis-related candidate gene by a high-quality genome assembly and population diversity analysis in Hypsizygus marmoreus.
Journal of genetics and genomics = Yi chuan xue bao, 2021

Hypsizygus marmoreus is one of the most important edible fungi in Basidiomycete division and includes white and gray strains. However, very limited knowledge is known about the genomic structures and the genetic basis for the white/gray diversity of this mushroom. Here, we report the near-complete high-quality H. marmoreus genome at the chromosomal level. Comparative genomics analysis indicates that chromosome structures were relatively conserved, and variations in collinearity and chromosome number were mainly attributed by chromosome split/fusion events in Aragicales, whereas the fungi genome experienced many genomic chromosome fracture, fusion, and genomic replication events after the split of Aragicales from Basidiomycetes. Resequencing of 57 strains allows us to classify the population into four major groups and associate genetic variations with morphological features, indicating that white strains were not originated independently. We further generated genetic populations and identified a cytochrome P450 as the candidate causal gene for the melanogenesis in H. marmoreus based on bulked segregant analysis (BSA) and comparative transcriptome analysis. The high-quality H. marmoreus genome and diversity data compiled in this study provide new knowledge and resources for the molecular breeding of H. marmoreus as well as the evolution of Basidiomycete.
Mortality after temporal lobe epilepsy surgery.
Epilepsia, 2012

To report mortality, after a longer interval, in a cohort of patients with drug-resistant epilepsy treated by temporal lobe surgery between 1975 and 1995. A previous audit of these patients ending December 1, 1997 observed a standardized mortality ratio (SMR) of 4.5.
Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury.
Neurosurgery, 2009

Injured peripheral nerves regenerate at very slow rates. Therefore, proximal injury sites such as the brachial plexus still present major challenges, and the outcomes of conventional treatments remain poor. This is in part attributable to a progressive decline in the Schwann cells' ability to provide a supportive milieu for the growth cone to extend and to find the appropriate target. These challenges are compounded by the often considerable delay of regeneration across the site of nerve laceration. Recently, low-frequency electrical stimulation (as brief as an hour) has shown promise, as it significantly accelerated regeneration in animal models through speeding of axon growth across the injury site.