rudyvdbrink/CitationDatabase huggingface dataset:
Molecular Regulation of Alternative Polyadenylation (APA) within the Drosophila Nervous System.
Journal of molecular biology, 2017

Alternative polyadenylation (APA) is a widespread gene regulatory mechanism that generates mRNAs with different 3'-ends, allowing them to interact with different sets of RNA regulators such as microRNAs and RNA-binding proteins. Recent studies have shown that during development, neural tissues produce mRNAs with particularly long 3'UTRs, suggesting that such extensions might be important for neural development and function. Despite this, the mechanisms underlying neural APA are not well understood. Here, we investigate this problem within the Drosophila nervous system, focusing on the roles played by general cleavage and polyadenylation factors (CPA factors). In particular, we examine the model that modulations in CPA factor concentration may affect APA during development. For this, we first analyse the expression of the Drosophila orthologues of all mammalian CPA factors and note that their expression decreases during embryogenesis. In contrast to this global developmental decrease in CPA factor expression, we see that cleavage factor I (CFI) expression is actually elevated in the late embryonic central nervous system, suggesting that CFI might play a special role in neural tissues. To test this, we use the UAS/Gal4 system to deplete CFI proteins from neural tissue and observe that in this condition, multiple genes switch their APA patterns, demonstrating a role of CFI in APA control during Drosophila neural development. Furthermore, analysis of genes with 3'UTR extensions of different length leads us to suggest a novel relation between 3'UTR length and sensitivity to CPA factor expression. Our work thus contributes to the understanding of the mechanisms of APA control within the developing central nervous system.
The role of the superior parietal lobule in lexical processing of sign language: Insights from fMRI and TMS.
Cortex; a journal devoted to the study of the nervous system and behavior, 2021

There is strong evidence that neuronal bases for language processing are remarkably similar for sign and spoken languages. However, as meanings and linguistic structures of sign languages are coded in movement and space and decoded through vision, differences are also present, predominantly in occipitotemporal and parietal areas, such as superior parietal lobule (SPL). Whether the involvement of SPL reflects domain-general visuospatial attention or processes specific to sign language comprehension remains an open question. Here we conducted two experiments to investigate the role of SPL and the laterality of its engagement in sign language lexical processing. First, using unique longitudinal and between-group designs we mapped brain responses to sign language in hearing late learners and deaf signers. Second, using transcranial magnetic stimulation (TMS) in both groups we tested the behavioural relevance of SPL's engagement and its lateralisation during sign language comprehension. SPL activation in hearing participants was observed in the right hemisphere before and bilaterally after the sign language course. Additionally, after the course hearing learners exhibited greater activation in the occipital cortex and left SPL than deaf signers. TMS applied to the right SPL decreased accuracy in both hearing learners and deaf signers. Stimulation of the left SPL decreased accuracy only in hearing learners. Our results suggest that right SPL might be involved in visuospatial attention while left SPL might support phonological decoding of signs in non-proficient signers.
Validation of the English version of the Mood Rhythm Instrument.
BMC psychology, 2020

Disruption of biological rhythms has been linked to the pathophysiology of mental disorders. However, little is known regarding the rhythmicity of mood symptoms due to the lack of validated clinical questionnaires. A better understanding of the rhythmicity of mood symptoms can help identifying individuals whose severity of mood symptoms follows an altered circadian rhythm. The objective of this study was to validate the English version of the Mood Rhythm Instrument (MRhI), a self-reported measure of self-perceived rhythmicity of mood symptoms and behaviours, in a sample of the general population from Canada.
Molecular definition of group 1 innate lymphoid cells in the mouse uterus.
Nature communications, 2018

Determining the function of uterine lymphocytes is challenging because of the dynamic changes in response to sex hormones and, during pregnancy, to the invading foetal trophoblast cells. Here we provide a genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (ILCs) at mid-gestation. Tissue-resident Eomes
Sex differences and stress across the lifespan.
Nature neuroscience, 2015

Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan.
Characteristics of men accompanying their partners to a specialist antenatal clinic for women with severe mental illness.
Asian journal of psychiatry, 2014

Partners are often enlisted in the care and management of pregnant women with severe mental illness (SMI); however their needs and capacity to provide support is not yet well understood. We aim to describe the psychosocial characteristics, health behaviours and appraisals of parenthood of men accompanying their partners with SMI to a specialist antenatal clinic.
Dietary therapy restores glutamatergic input to orexin/hypocretin neurons after traumatic brain injury in mice.
Sleep, 2018

In previous work, dietary branched-chain amino acid (BCAA) supplementation, precursors to de novo glutamate and γ-aminobutyric acid (GABA) synthesis, restored impaired sleep-wake regulation and orexin neuronal activity following traumatic brain injury (TBI) in mice. TBI was speculated to reduce orexin neuronal activity through decreased regional excitatory (glutamate) and/or increased inhibitory (GABA) input. Therefore, we hypothesized that TBI would decrease synaptic glutamate and/or increase synaptic GABA in nerve terminals contacting orexin neurons, and BCAA supplementation would restore TBI-induced changes in synaptic glutamate and/or GABA.
Non-Coding RNAs as Potential Neuroprotectants against Ischemic Brain Injury.
Brain sciences, 2013

Over the past decade, scientific discoveries have highlighted new roles for a unique class of non-coding RNAs. Transcribed from the genome, these non-coding RNAs have been implicated in determining the biological complexity seen in mammals by acting as transcriptional and translational regulators. Non-coding RNAs, which can be sub-classified into long non-coding RNAs, microRNAs, PIWI-interacting RNAs and several others, are widely expressed in the nervous system with roles in neurogenesis, development and maintenance of the neuronal phenotype. Perturbations of these non-coding transcripts have been observed in ischemic preconditioning as well as ischemic brain injury with characterization of the mechanisms by which they confer toxicity. Their dysregulation may also confer pathogenic conditions in neurovascular diseases. A better understanding of their expression patterns and functions has uncovered the potential use of these riboregulators as neuroprotectants to antagonize the detrimental molecular events taking place upon ischemic-reperfusion injury. In this review, we discuss the various roles of non-coding RNAs in brain development and their mechanisms of gene regulation in relation to ischemic brain injury. We will also address the future directions and open questions for identifying promising non-coding RNAs that could eventually serve as potential neuroprotectants against ischemic brain injury.
Jackson's Parrot: Samuel Beckett, Aphasic Speech Automatisms, and Psychosomatic Language.
The Journal of medical humanities, 2016

This article explores the relationship between automatic and involuntary language in the work of Samuel Beckett and late nineteenth-century neurological conceptions of language that emerged from aphasiology. Using the work of John Hughlings Jackson alongside contemporary neuroscientific research, we explore the significance of the lexical and affective symmetries between Beckett's compulsive and profoundly embodied language and aphasic speech automatisms. The interdisciplinary work in this article explores the paradox of how and why Beckett was able to search out a longed-for language of feeling that might disarticulate the classical bond between the language, intention, rationality and the human, in forms of expression that seem automatic and "readymade".
Women's weight and disordered eating in a large Norwegian community sample: the Nord-Trøndelag Health Study (HUNT).
BMJ open, 2015

An increasing part of the population is affected by disordered eating (DE) even though they do not meet the full eating disorder (ED) criteria. To improve treatment in the range of weight-related disorders, there is a need to improve our knowledge about DE and relevant correlates of weight problems such as underweight, overweight and obesity. However, studies investigating DE and weight problems in a wide range of ages in the general population have been lacking. This paper explores DE, weight problems, dieting and weight dissatisfaction among women in a general population sample.
Establishment and characterization of primary astrocyte culture from adult mouse brain.
Brain research bulletin, 2017

As a major class of glial cells, astrocytes have been indicated to play multi-roles in physiological and pathological brain. Astrocyte cultures derived from postnatal mouse brains have been extensively used to characterize their biological properties. However, the inability to culture adult mouse primary astrocytes has long stymied studies of function in adult brain. Here, we developed a protocol to successfully establish highly enriched astrocyte cultures from the brains of adult mouse. Cortical tissues were collected to prepare cell suspension by enzymatic digestion and mechanical dissociation, and then plated onto vessels pre-coated with gelatin and matrigel and cultured in DMEM medium containing 20% fetal bovine serum (FBS). Forskolin (FSK) and glial-derived neurotrophic factor (GDNF) were use to promote astrocyte proliferation and survival respectively. These adult astrocyte cultures were identified by immunocytochemical, immunobloting and PCR analysis. Furthermore, biological and functional analysis indicated that they possess the biochemical and physiological properties of astrocytes, suggestive of a useful cell model for astroglial studies in adult brain.
Human glioblastoma-associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples.
Glia, 2016

Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) to CD11b(+) microglia isolated from non-tumor samples. Hierarchical clustering and principal component analysis showed a clear separation of the two sample groups and we identified 334 significantly regulated genes in hGAMs. In comparison to human control microglia hGAMs upregulated genes associated with mitotic cell cycle, cell migration, cell adhesion, and extracellular matrix organization. We validated the expression of several genes associated with extracellular matrix organization in samples of human control microglia, hGAMs, and the hGAMs-depleted fraction via qPCR. The comparison to murine GAMs (mGAMs) showed that both cell populations share a significant fraction of upregulated transcripts compared with their respective controls. These genes were mostly related to mitotic cell cycle. However, in contrast to murine cells, human GAMs did not upregulate genes associated to immune activation. Comparison of human and murine GAMs expression data to several data sets of in vitro-activated human macrophages and murine microglia showed that, in contrast to mGAMs, hGAMs share a smaller overlap to these data sets in general and in particular to cells activated by proinflammatory stimulation with LPS + INFγ or TNFα. Our findings provide new insights into the biology of human glioblastoma-associated microglia/monocytes and give detailed information about the validity of murine experimental models. GLIA 2016 GLIA 2016;64:1416-1436.
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
Molecular psychiatry, 2017

Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.
Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from South-Eastern Spain.
Environment international, 2015

Childrens exposure to neurotoxic compounds poses a major problem to public health because oftheir actively developing brain that makes them highly vulnerable. However, limited information is available on neuropsychological effects in children associated with pre- and postnatal exposures to pesticides.
Precision Revisited: Targeting Microcephaly Kinases in Brain Tumors.
International journal of molecular sciences, 2019

Glioblastoma multiforme and medulloblastoma are the most frequent high-grade brain tumors in adults and children, respectively. Standard therapies for these cancers are mainly based on surgical resection, radiotherapy, and chemotherapy. However, intrinsic or acquired resistance to treatment occurs almost invariably in the first case, and side effects are unacceptable in the second. Therefore, the development of new, effective drugs is a very important unmet medical need. A critical requirement for developing such agents is to identify druggable targets required for the proliferation or survival of tumor cells, but not of other cell types. Under this perspective, genes mutated in congenital microcephaly represent interesting candidates. Congenital microcephaly comprises a heterogeneous group of disorders in which brain volume is reduced, in the absence or presence of variable syndromic features. Genetic studies have clarified that most microcephaly genes encode ubiquitous proteins involved in mitosis and in maintenance of genomic stability, but the effects of their inactivation are particularly strong in neural progenitors. It is therefore conceivable that the inhibition of the function of these genes may specifically affect the proliferation and survival of brain tumor cells. Microcephaly genes encode for a few kinases, including CITK, PLK4, AKT3, DYRK1A, and TRIO. In this review, we summarize the evidence indicating that the inhibition of these molecules could exert beneficial effects on different aspects of brain cancer treatment.
Is 'object-centred neglect' a homogeneous entity?
Brain and cognition, 2013

The nature of object-centred (allocentric) neglect and the possibility of dissociating it from egocentric (subject-centred) forms of neglect are controversial. Originally, allocentric neglect was described by Gainotti, D'Erme, Monteleone & Silveri (1986) and Gainotti, Messerli, & Tissot (1972) in patients who reproduced all the elements of a multi-object scene, but left unfinished the left side of one or more of them. More recently, however, Karnath, Mandler, and Clavagnier (2011) have claimed that the severity of allocentric neglect worsens when a complex 'object' shifts from an ipsilesional to a contralesional egocentric position. On the basis of these and of other clinical data, showing that allocentric and egocentric neglect are strongly associated, they have questioned the possibility of dissociating these two forms of neglect, suggesting that egocentric and allocentric neglect constitute different manifestations of the same disturbed system. Since these statements were inconsistent with the clinical findings which had prompted the construct of object-centred neglect, we checked in a group of right brain-damaged patients, who had copied the original multi-object scene, if the degree of neglect for the left side of figures varied as a function of their position on the horizontal axis. Furthermore, we reviewed all papers where copies of other multi-object scenes had been reported. Results of both studies failed to confirm the assumption of a relationship between spatial location of the stimulus and severity of object-centred neglect. This discrepancy between our data and those obtained by Karnath et al. (2011) could be due to the characteristics of stimuli and of procedures used to evaluate 'object-centred' neglect. If the stimulus is complex and the task requires its thorough exploration, the spatial location of the stimulus will influence the severity of 'object-centred neglect'. If, on the contrary, the stimulus is simple and can be identified with few eye fixations, the spatial location of the stimulus should not influence the severity of 'object-centred neglect'. In any case, our data confirm the possibility of dissociating allocentric from egocentric neglect.
Dual-task Interference Disrupts Parkinson's Gait Across Multiple Cognitive Domains.
Neuroscience, 2018

Gait dysfunction, a hallmark of Parkinson's disease, contributes to a relatively high incidence of falling. Gait function is further diminished during the performance of a motor-cognitive task (i.e., dual-task). It is unclear if Parkinson's disease-related dual-task deficits are related to a specific area of cognitive function or are the result of a more global decline in executive function. The aim of this project was to systematically evaluate gait performance to determine if gait dysfunction is restricted to certain types of executive function or a global phenomenon in individuals with Parkinson's disease. Twenty-three individuals with mild-moderate Parkinson's disease completed a series of dual-task conditions in which gait was paired with cognitive tasks requiring: working memory (0, 1, and 2-back), attention and problem solving (serial-7 subtraction), verbal memory (digit recall), semantic memory (Controlled Oral Word Association) and information processing speed (visual Stroop test). The results demonstrate that individuals with mild-moderate Parkinson's disease have a generalized worsening of spatial-temporal gait parameters regardless of the specific cognitive demand being performed concurrently. Overall, gait velocity decreased (p < 0.01) and stride and stance time both increased (p < 0.01) across all cognitive conditions. The attention and problem solving task resulted in the greatest number of gait parameter decrements. Results indicated that performance on cognitive tasks remained unchanged from single-task to dual-task conditions. Diminished gait performance under dual-task conditions across different cognitive function domains suggests a global Parkinson's disease-related deficit in information processing and regulation of gait.
Validation of the Korean version of the Connor-Davidson Resilience Scale-2 in firefighters and rescue workers.
Comprehensive psychiatry, 2015

Resilience has been considered as a protective factor against stress. Evaluating resilience in firefighters and rescue workers, who are frequently exposed to traumatic events, is important and relevant. This study examined the psychometric properties of the Korean version of the Connor-Davidson Resilience Scale-2 (CD-RISC2).
Unexpected events induce motor slowing via a brain mechanism for action-stopping with global suppressive effects.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression.