rudyvdbrink/CitationDatabase huggingface dataset:
FOXP transcription factors in vertebrate brain development, function, and disorders.
Wiley interdisciplinary reviews. Developmental biology, 2020

FOXP transcription factors are an evolutionarily ancient protein subfamily coordinating the development of several organ systems in the vertebrate body. Association of their genes with neurodevelopmental disorders has sparked particular interest in their expression patterns and functions in the brain. Here, FOXP1, FOXP2, and FOXP4 are expressed in distinct cell type-specific spatiotemporal patterns in multiple regions, including the cortex, hippocampus, amygdala, basal ganglia, thalamus, and cerebellum. These varied sites and timepoints of expression have complicated efforts to link FOXP1 and FOXP2 mutations to their respective developmental disorders, the former affecting global neural functions and the latter specifically affecting speech and language. However, the use of animal models, particularly those with brain region- and cell type-specific manipulations, has greatly advanced our understanding of how FOXP expression patterns could underlie disorder-related phenotypes. While many questions remain regarding FOXP expression and function in the brain, studies to date have illuminated the roles of these transcription factors in vertebrate brain development and have greatly informed our understanding of human development and disorders. This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Nervous System Development > Vertebrates: Regional Development.
Osteoblast specific Y1 receptor deletion enhances bone mass.
Bone, 2011

Neuropeptide Y, Y1 receptors are found in neuronal as well as bone tissue and Y1 signalling has been implicated in the regulation of bone mass. However, the contribution of Y1 receptors located in these different tissues, particularly that of the bone-specific Y1 receptors, to the regulation of bone homeostasis is unclear. Here we demonstrate that osteoblast-specific Y1 receptor deletion resulted in a marked increase in femoral cancellous bone volume, trabecular thickness and trabecular number. This is the result of elevated osteoblast activity as shown by increased mineral apposition rate and bone formation rate, and is associated with an upregulation in the mRNA expression levels of alkaline phosphatase, osteocalcin and dentin matrix protein-1. Furthermore, osteoblastic Y1 receptor deletion also led to increased mineral apposition rate on both the endocortical and the periosteal surfaces resulting in increased femoral diameter. Together these data demonstrate a direct role for the Y1 receptor on osteoblasts in the regulation of osteoblast activity and bone formation in vivo and suggest that targeting Y1 receptor signalling directly in the bone may have potential therapeutic implications for stimulating bone accrual in diseases such as osteoporosis.
Cognitive innovations and the evolutionary biology of expertise.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2017

Animal life can be perceived as the selective use of information for maximizing survival and reproduction. All organisms including bacteria and protists rely on genetic networks to build and modulate sophisticated structures and biochemical mechanisms for perceiving information and responding to environmental changes. Animals, however, have gone through a series of innovations that dramatically increased their capacity to acquire, retain and act upon information. Multicellularity was associated with the evolution of the nervous system, which took over many tasks of internal communication and coordination. This paved the way for the evolution of learning, initially based on individual experience and later also via social interactions. The increased importance of social learning also led to the evolution of language in a single lineage. Individuals' ability to dramatically increase performance via learning may have led to an evolutionary cycle of increased lifespan and greater investment in cognitive abilities, as well as in the time necessary for the development and refinement of expertise. We still know little, however, about the evolutionary biology, genetics and neurobiological mechanisms that underlie such expertise and its development.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.
NRL-Regulated Transcriptome Dynamics of Developing Rod Photoreceptors.
Cell reports, 2016

Gene regulatory networks (GRNs) guiding differentiation of cell types and cell assemblies in the nervous system are poorly understood because of inherent complexities and interdependence of signaling pathways. Here, we report transcriptome dynamics of differentiating rod photoreceptors in the mammalian retina. Given that the transcription factor NRL determines rod cell fate, we performed expression profiling of developing NRL-positive (rods) and NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition in the transcriptome landscape between postnatal days 6 and 10 concordant with rod morphogenesis. Rod-specific temporal DNA methylation corroborated gene expression patterns. De novo assembly and alternative splicing analyses revealed previously unannotated rod-enriched transcripts and the role of NRL in transcript maturation. Furthermore, we defined the relationship of NRL with other transcriptional regulators and downstream cognate effectors. Our studies provide the framework for comprehensive system-level analysis of the GRN underlying the development of a single sensory neuron, the rod photoreceptor.
Primary lateral sclerosis: consensus diagnostic criteria.
Journal of neurology, neurosurgery, and psychiatry, 2020

Primary lateral sclerosis (PLS) is a neurodegenerative disorder of the adult motor system. Characterised by a slowly progressive upper motor neuron syndrome, the diagnosis is clinical, after exclusion of structural, neurodegenerative and metabolic mimics. Differentiation of PLS from upper motor neuron-predominant forms of amyotrophic lateral sclerosis remains a significant challenge in the early symptomatic phase of both disorders, with ongoing debate as to whether they form a clinical and histopathological continuum. Current diagnostic criteria for PLS may be a barrier to therapeutic development, requiring long delays between symptom onset and formal diagnosis. While new technologies sensitive to both upper and lower motor neuron involvement may ultimately resolve controversies in the diagnosis of PLS, we present updated consensus diagnostic criteria with the aim of reducing diagnostic delay, optimising therapeutic trial design and catalysing the development of disease-modifying therapy.
Complexin activates exocytosis of distinct secretory vesicles controlled by different synaptotagmins.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Complexins are SNARE-complex binding proteins essential for the Ca(2+)-triggered exocytosis mediated by synaptotagmin-1, -2, -7, or -9, but the possible role of complexins in other types of exocytosis controlled by other synaptotagmin isoforms remains unclear. Here we show that, in mouse olfactory bulb neurons, synaptotagmin-1 localizes to synaptic vesicles and to large dense-core secretory vesicles as reported previously, whereas synaptotagmin-10 localizes to a distinct class of peptidergic secretory vesicles containing IGF-1. Both synaptotagmin-1-dependent synaptic vesicle exocytosis and synaptotagmin-10-dependent IGF-1 exocytosis were severely impaired by knockdown of complexins, demonstrating that complexin acts as a cofactor for both synaptotagmin-1 and synaptotagmin-10 despite the functional differences between these synaptotagmins. Rescue experiments revealed that only the activating but not the clamping function of complexins was required for IGF-1 exocytosis controlled by synaptotagmin-10. Thus, our data indicate that complexins are essential for activation of multiple types of Ca(2+)-induced exocytosis that are regulated by different synaptotagmin isoforms. These results suggest that different types of regulated exocytosis are mediated by similar synaptotagmin-dependent fusion mechanisms, that particular synaptotagmin isoforms confer specificity onto different types of regulated exocytosis, and that complexins serve as universal synaptotagmin adaptors for all of these types of exocytosis independent of which synaptotagmin isoform is involved.
Biphasic effects of Δ9-tetrahydrocannabinol on brain stimulation reward and motor activity.
The international journal of neuropsychopharmacology, 2013

Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the main psychoactive ingredient of marijuana, has led to equivocal results when tested with the intracranial self-stimulation (ICSS) procedure or the open-field test for motor activity, two behavioural models for evaluating the reward-facilitating and locomotor stimulating effects of drugs of abuse, respectively. Therefore, in the present study, the effects of high and low doses of Δ(9)-THC were compared in the ICSS procedure and the open-field test. Moreover, the involvement of CB(1) receptors in tentative Δ(9)-THC-induced effects was investigated by pre-treating the animals with the CB(1) receptor antagonist SR141716A (rimonabant). The results obtained show that low doses of Δ(9)-THC induce opposite effects from high doses of Δ(9)-THC. Specifically, 0.1 mg/kg Δ(9)-THC decreased ICSS thresholds and produced hyperactivity, whereas 1 mg/kg increased ICSS thresholds and produced hypoactivity. Both effects were reversed by pre-treatment with SR141716A, indicating the involvement of CB(1) receptors on these actions. Altogether, our results indicate that Δ(9)-THC can produce acute activating effects in locomotion that coincide with its reward-facilitating effects in the ICSS paradigm. The present findings provide further support that Δ(9)-THC induces behaviours typical of abuse and substantiate the notion that marijuana resembles other drugs of abuse.
Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson's disease.
Neurobiology of disease, 2020

Continuous compensation of dopamine represents an ideal symptomatic treatment for Parkinson's disease (PD). The feasibility in intracerebroventricular administration (i.c.v.) of dopamine previously failed because of unresolved dopamine oxidation.
Serotonin and depression: pathophysiological mechanism or marketing myth?
Trends in pharmacological sciences, 2008

The notion that impaired serotonin (5-HT) function can lead to clinical depression has a long history but is still controversial. Some have argued that the 5-HT hypothesis has been misused by the pharmaceutical industry to promote a simplistic biological model of depression to market selective serotonin reuptake inhibitors (SSRIs) to medical practitioners and the public. By contrast, there is now substantial evidence that unmedicated depressed patients have abnormalities in brain 5-HT function; however, the relation of these abnormalities to the clinical syndrome is unclear. The best evidence that 5-HT contributes to the pathophysiology of depression comes from studies of tryptophan depletion, which show that lowering brain 5-HT levels can induce acute symptomatic relapse in recovered depressed patients. Clarification of the mechanism of this effect will enable an understanding of how impaired 5-HT activity contributes to the subjective experience of depression.
RAB39B gene mutations are not a common cause of Parkinson's disease or dementia with Lewy bodies.
Neurobiology of aging, 2016

Mutations in Ras-related protein Rab-39B (RAB39B) gene have been linked to X-linked early-onset Parkinsonism with intellectual disabilities. The aim of this study was to address the genetic contribution of RAB39B to Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pathologically confirmed Lewy body dementia (pLBD) cases. A cohort of 884 PD, 399 DLB, and 379 pLBD patients were screened for RAB39B mutations, but no coding variants were found, suggesting RAB39B mutations are not a common cause of PD, DLB, or pLBD in Caucasian population.
Diversity of Gene Expression in Hepatocellular Carcinoma Cells.
Genomics, proteomics & bioinformatics, 2015

Understanding tumor diversity has been a long-lasting and challenging question for researchers in the field of cancer heterogeneity or tumor evolution. Studies have reported that compared to normal cells, there is a higher genetic diversity in tumor cells, while higher genetic diversity is associated with higher progression risks of tumor. We thus hypothesized that tumor diversity also holds true at the gene expression level. To test this hypothesis, we used t-test to compare the means of Simpson's diversity index for gene expression (SDIG) between tumor and non-tumor samples. We found that the mean SDIG in tumor tissues is significantly higher than that in the non-tumor or normal tissues (P<0.05) for most datasets. We also combined microarrays and next-generation sequencing data for validation. This cross-platform and cross-experimental validation greatly increased the reliability of our results.
Social and legal aspects of marriage in women with mental illness in India.
Indian journal of psychiatry, 2015

The institution of marriage in Hindus is regulated by the prevailing social norms and the Hindu Marriage Act (HMA), 1955. Married women with mental illness are heavily discriminated. This paper examines the social and legal aspects of Hindu marriage in women with mental illness. The HMA, 1955 lays down the conditions for a Hindu marriage and also provides matrimonial reliefs: Nullity of marriage, restitution of conjugal rights, judicial separation and divorce. The application of the provisions of HMA in the setting mental illness is difficult and challenging. There is a wide gap between the legislative provisions of HMA, and societal value systems and attitudes towards marriage in Indian society. Societal norms are powerful and often override the legal provisions. The disparities are most glaring in the setting of mental illness in women. This is a reflection of social stigma for mental illness and patriarchal attitude towards women. Concerted efforts are needed to bridge the gap between the legislative provisions of HMA and societal value systems and attitudes toward marriage. Awareness programs regarding the nature and types of mental illness, advances in treatment and information about good outcome of severe mental illness will be helpful. Improvement in moral and religious values will overcome to some extent the negative attitudes and patriarchal mind set toward married women with mental illness.
Audiovisual integrative training for augmenting cognitive- motor functions in older adults with mild cognitive impairment.
BMC geriatrics, 2020

Previous studies indicated that the behavioral performances of older adults could be enhanced by multisensory integration. This pilot study tested the benefits of an audiovisual integrative (AV) training for improving the cognitive and upper limb motor functions in older adults with mild cognitive impairment (MCI).
The Role of Glutamate Neurotransmission in Mismatch Negativity (MMN), A Measure of Auditory Synaptic Plasticity and Change-detection.
Neuroscience, 2021

Mismatch negativity (MMN) is an electrophysiological signature that occurs in response to unexpected stimuli. It is often referred to as a measure of memory-based change detection, because the elicitation of a prediction error response relies on the formation of a prediction, which in turn, is dependent upon intact memory of previous auditory stimulation. As such, the MMN is altered in conditions in which memory is affected, such as Alzheimer's disease, schizophrenia and healthy aging. The most prominent pharmacological finding for MMN strengthens the link between MMN and synaptic plasticity, as glutamate N-methyl-d-aspartate receptor (NMDA-R) antagonists reduce the MMN response. However, recent data has begun to demonstrate that the link between NMDA-R function and MMN is not as clear as once thought, with low dose and low affinity NMDA-R antagonists observed to facilitate MMN.
Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life.
The American journal of psychiatry, 2018

Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume.
Pro-resolving lipid mediator lipoxin A
Cell reports, 2021

The chronic neuro-inflammatory character of multiple sclerosis (MS) suggests that the natural process to resolve inflammation is impaired. This protective process is orchestrated by specialized pro-resolving lipid mediators (SPMs), but to date, the role of SPMs in MS remains largely unknown. Here, we provide in vivo evidence that treatment with the SPM lipoxin A
A Review of Fluid Biomarkers for Alzheimer's Disease: Moving from CSF to Blood.
Neurology and therapy, 2017

A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal degeneration, tau phosphorylation with tangle formation, and Aβ aggregation with deposition of the peptide into plaques. The core AD CSF biomarkers have been validated clinically in numerous studies, and found to have a very high diagnostic performance to identify AD, both in the dementia and in the mild cognitive impairment stages of the disease. CSF Aβ42 has also been found to show very high concordance with amyloid PET to identify brain amyloid deposition. The synaptic protein neurogranin is a novel candidate CSF biomarker for AD and prodromal AD. High CSF neurogranin predicts future cognitive decline and seems to be more specific for AD than, for example, T-tau. Importantly, technical developments have given ultrasensitive measurement techniques that allow measurement of brain-specific proteins such as tau and neurofilament light (NFL) in blood samples. Both plasma tau and NFL are increased in AD, and a recent study showed that plasma NFL has a diagnostic performance comparable to the core AD CSF biomarkers, and predicted future cognitive decline. Future large longitudinal clinical studies are warranted to determine the potential for plasma tau and NFL to serve as first-in-line screening tools for neurodegeneration in primary care.
Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor.
Toxicology and applied pharmacology, 2008

The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in activation of the channel and has been shown to be reversible for several ligands. Commonly used tear gasses CN, CR and CS are also pungent chemicals, and in this study we show that they are extremely potent and selective activators of the human TRPA1 receptor. To our knowledge, these are the most potent TRPA1 agonists known to date. The identification of the molecular target for these tear gasses may open up possibilities to alleviate the effects of tear gasses via treatment with TRPA1 antagonists. In addition these results may contribute to the basic knowledge of the TRPA1 channel that is gaining importance as a pharmacological target.
Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys.
Proceedings of the National Academy of Sciences of the United States of America, 2013

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.
An overview of measuring impulsive behavior in mice.
Current protocols in mouse biology, 2014

Impulsive behavior is a key constituent of many psychiatric illnesses, with maladaptive response control being a feature of disorders such as ADHD, schizophrenia, mania, and addiction. In order to understand the neurological underpinnings of impulsivity, a number of behavioral tasks have been developed for use with animal models. Data from studies with rats and other animals have led to the idea of the existence of dissociable components of impulsivity, which in turn informs studies of human disorders and potentially the development of specific therapies. Increasingly, mouse models are being used to investigate the known genetic contribution to psychiatric disorders in which abnormal response control leads to altered impulsive behaviors. In order to maximize the potential of these mouse models, it is important that researchers take into account the non-unitary nature of response control and impulsivity. In this article, we briefly review the tasks available to behavioral neuroscientists and how these can be used in order to tease apart the contribution of a specific genetic lesion into the discrete aspects of impulsive behavior.
Modeling the Mechanical Parameters of Glaucoma.
Tissue engineering. Part B, Reviews, 2019

Glaucoma is a major eye disease characterized by a progressive loss of retinal ganglion cells (RGCs). Biomechanical forces as a result of hydrostatic pressure and strain play a role in this disease. Decreasing intraocular pressure is the only available therapy so far, but is not always effective and does not prevent blindness in many cases. There is a need for drugs that protect RGCs from dying in glaucoma; to develop these, we need valid glaucoma and drug screening models. Since