rudyvdbrink/CitationDatabase huggingface dataset:
Early and persistent abnormal decoding by glial cells at the neuromuscular junction in an ALS model.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Amyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease characterized by progressive loss of motor neurons (MNs) preceded by neuromuscular junction (NMJ) denervation. Despite the importance of NMJ denervation in ALS, the mechanisms involved remain unexplored and ill defined. The contribution of glial cells in the disease has been highlighted, including axonal Schwann cell activation that precedes the decline of motor function and the onset of hindlimb paralysis. Because NMJ denervation occurs early in the process and that perisynaptic Schwann cells (PSCs), glial cells at the NMJ, regulate morphological stability, integrity, and repair of the NMJ, one could predict that PSC functions would be altered even before denervation, contributing to NMJ malfunctions. We tested this possibility using a slowly progressive model of ALS (SOD1(G37R) mice). We observed a normal NMJ organization at a presymptomatic stage of ALS (120 d), but PSC detection of endogenous synaptic activity revealed by intracellular Ca(2+) changes was enhanced compared with their wild-type littermates. This inappropriate PSC decoding ability was associated with an increased level of neurotransmitter release and dependent on intrinsic glial properties related to enhanced muscarinic receptor activation. The alteration of PSC muscarinic receptor functions also persists during the preonset stage of the disease and became dependent on MN vulnerability with age. Together, these results suggest that PSC properties are altered in the disease process in a manner that would be detrimental for NMJ repair. The impairments of PSC functions may contribute to NMJ dysfunction and ALS pathogenesis.
Evaluation of EEG training curricula for non-specialist clinicians: a systematic qualitative review.
Epileptic disorders : international epilepsy journal with videotape, 2021

Neurologists and epileptologists are scarce in sub-Saharan Africa (SSA). Whilst electroencephalograms (EEGs) are becoming more available in the region, interpretation is typically undertaken by non-specialist clinicians with limited or no training. This is a systematic review of the peer-reviewed literature on EEG training of non-specialist clinicians worldwide, assessing the efficacy of the training methodology and the curricula content.
Kinetics of GADD45α, TP53 and CASP3 gene expression in the rat lens in vivo in response to exposure to double threshold dose of UV-B radiation.
Experimental eye research, 2012

The purpose of the present study was to investigate the evolution of expression of mRNA message for the genes for the genome stress sensor GADD45α, the apoptosis initiator TP53 and the apoptosis executor CASP3 in the rat lens in vivo in response to exposure to UVR around 300 nm. Forty six week old female albino Sprague-Dawley rats were unilaterally exposed to double threshold dose for cataract induction, 8 kJ/m(2) (8.9 W/m(2) for 15 min), of UVR (λ(max) = 300 nm). The animals were sacrificed at 1, 5, 24 and 120 h following exposure to UVR-B. For each of the GADD45α, TP53 and CASP3 genes, respectively, mRNA expression in the lenses was measured by quantitative RT-PCR. It was found that expression of mRNA for GADD45α transiently increases between 5 and 24 h after exposure. TP53 is slightly downregulated in exposed lenses at 1 and 5 h after exposure and thereafter the mRNA expression increases with a constant rate of 9.4\ 10(-3) rel. units/h to a 1.8 fold increase at 120 h after exposure. Expression of mRNA for CASP3 is downregulated at 1, 5 and 24 h after in vivo exposure and then increases with a constant rate of 4.7 10(-3) rel. units/h, upto a 1.3 fold upregulation at 120 h. Double threshold dose of UVR, for short delay onset of cataract, in vivo causes a transient upregulation of the stress sensor GADD45α, a concurrent downregulation of TP53 and CASP3, followed by a constant upregulation of TP53 that precedes a constant upregulation of CASP3.
Occupational health physicians have better work conditions for handling sickness certification compared with general practitioners: results from a nationwide survey in Sweden.
Scandinavian journal of public health, 2015

To study whether occupational health physicians (OPs) have a better work situation regarding handling of sickness certification compared with other physicians, in particular general practitioners (GPs), and to analyze associations between OPs' experiences of assessing and providing a long-term prognosis of patients' work capacity and some potentially interrelated factors.
The functional logic of corticostriatal connections.
Brain structure & function, 2017

Unidirectional connections from the cortex to the matrix of the corpus striatum initiate the cortico-basal ganglia (BG)-thalamocortical loop, thought to be important in momentary action selection and in longer-term fine tuning of behavioural repertoire; a discrete set of striatal compartments, striosomes, has the complementary role of registering or anticipating reward that shapes corticostriatal plasticity. Re-entrant signals traversing the cortico-BG loop impact predominantly frontal cortices, conveyed through topographically ordered output channels; by contrast, striatal input signals originate from a far broader span of cortex, and are far more divergent in their termination. The term 'disclosed loop' is introduced to describe this organisation: a closed circuit that is open to outside influence at the initial stage of cortical input. The closed circuit component of corticostriatal afferents is newly dubbed 'operative', as it is proposed to establish the bid for action selection on the part of an incipient cortical action plan; the broader set of converging corticostriatal afferents is described as contextual. A corollary of this proposal is that every unit of the striatal volume, including the long, C-shaped tail of the caudate nucleus, should receive a mandatory component of operative input, and hence include at least one area of BG-recipient cortex amongst the sources of its corticostriatal afferents. Individual operative afferents contact twin classes of GABAergic striatal projection neuron (SPN), distinguished by their neurochemical character, and onward circuitry. This is the basis of the classic direct and indirect pathway model of the cortico-BG loop. Each pathway utilises a serial chain of inhibition, with two such links, or three, providing positive and negative feedback, respectively. Operative co-activation of direct and indirect SPNs is, therefore, pictured to simultaneously promote action, and to restrain it. The balance of this rival activity is determined by the contextual inputs, which summarise the external and internal sensory environment, and the state of ongoing behavioural priorities. Notably, the distributed sources of contextual convergence upon a striatal locus mirror the transcortical network harnessed by the origin of the operative input to that locus, thereby capturing a similar set of contingencies relevant to determining action. The disclosed loop formulation of corticostriatal and subsequent BG loop circuitry, as advanced here, refines the operating rationale of the classic model and allows the integration of more recent anatomical and physiological data, some of which can appear at variance with the classic model. Equally, it provides a lucid functional context for continuing cellular studies of SPN biophysics and mechanisms of synaptic plasticity.
Navβ4 regulates fast resurgent sodium currents and excitability in sensory neurons.
Molecular pain, 2015

Increased electrical activity in peripheral sensory neurons including dorsal root ganglia (DRG) and trigeminal ganglia neurons is an important mechanism underlying pain. Voltage gated sodium channels (VGSC) contribute to the excitability of sensory neurons and are essential for the upstroke of action potentials. A unique type of VGSC current, resurgent current (INaR), generates an inward current at repolarizing voltages through an alternate mechanism of inactivation referred to as open-channel block. INaRs are proposed to enable high frequency firing and increased INaRs in sensory neurons are associated with pain pathologies. While Nav1.6 has been identified as the main carrier of fast INaR, our understanding of the mechanisms that contribute to INaR generation is limited. Specifically, the open-channel blocker in sensory neurons has not been identified. Previous studies suggest Navβ4 subunit mediates INaR in central nervous system neurons. The goal of this study was to determine whether Navβ4 regulates INaR in DRG sensory neurons.
Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations.
Movement disorders : official journal of the Movement Disorder Society, 2010

Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome.
Perinatal Depression: Embracing Variability toward Better Treatment and Outcomes.
Neuron, 2019

Perinatal depression (PND) is a heterogeneous disorder with differences in timing of onset of depression, which influences symptomology, severity, and treatment efficacy. Researchers must embrace the heterogeneity to bring fruition to a precision medicine approach for women in reproductive mental health care.
Hind limb stepping over obstacles in the horse guided by place-object memory.
Behavioural brain research, 2009

An animal that has stepped over an obstacle with its forelimbs uses a memory of the obstacle to guide the hind limbs so that they also clear the obstacle, even in situations in which long pauses are introduced between forelimb and hind limb stepping. To further clarify the features of hind limb obstacle clearance memory, the present study examined hind limb obstacle clearance in the horse. A rider guided horses over obstacles and paused the horse over obstacles in tests that examined the relationship between forelimb and hind limb stepping, with the following results. First, the horses displayed memory for an obstacle as measured by hind limb lifting over the obstacle for durations lasting as long as 15 min. The response was not dependent upon ongoing visualization of the obstacle, as limb lifting was unaffected by visual occlusion with blinders, a blindfold, or by removing the obstacle during the pause. Second, previous experience of stepping over an obstacle led to pause-related hind limb lifting at the object's previous location even on trials for which there was no obstacle and so no preceding forelimb lifting. Third, whereas a horse would lift its hind limbs to clear two successively presented obstacles, replacing an obstacle before the horse after the forelimbs had cleared the obstacle prevented subsequent hind limb lifting at the obstacle's previous location. Taken together the results show that hind limb obstacle clearance is guided by a place-object memory. The results are discussed in relation to the differential sensory and memonic control of forelimb and hind limb stepping with the suggestion that place-object memory can guide hind stepping as well as overshadow working memory from front leg stepping.
Neurotransmitters and Motoneuron Contacts of Multifunctional and Behaviorally Specialized Turtle Spinal Cord Interneurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

The spinal cord can appropriately generate diverse movements, even without brain input and movement-related sensory feedback, using a combination of multifunctional and behaviorally specialized interneurons. The adult turtle spinal cord can generate motor patterns underlying forward swimming, three forms of scratching, and limb withdrawal (flexion reflex). We previously described turtle spinal interneurons activated during both scratching and swimming (multifunctional interneurons), interneurons activated during scratching but not swimming (scratch-specialized interneurons), and interneurons activated during flexion reflex but not scratching or swimming (flexion reflex-selective interneurons). How multifunctional and behaviorally specialized turtle spinal interneurons affect downstream neurons was unknown. Here, we recorded intracellularly from spinal interneurons activated during these motor patterns in turtles of both sexes
The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable.
Neurobiology of aging, 2016

Late-onset Alzheimer's disease (LOAD) can present heterogeneously, with several subtypes recognized, including dysexecutive AD. One way to identify people with dysexecutive AD is to consider the difference between memory and executive functioning, which we refer to as the executive prominent/memory prominent spectrum. We aimed to determine if this spectrum was heritable. We used neuropsychological and genetic data from people with mild LOAD (Clinical Dementia Rating 0.5 or 1.0) from the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative. We cocalibrated the neuropsychological data to obtain executive functioning and memory scores and used their difference as a continuous phenotype to calculate its heritability overall and by chromosome. Narrow-sense heritability of the difference between memory and executive functioning scores was 0.68 (standard error 0.12). Single nucleotide polymorphisms on chromosomes 1, 2, 4, 11, 12, and 18 explained the largest fraction of phenotypic variance, with signals from each chromosome accounting for 5%-7%. The chromosomal pattern of heritability differed substantially from that of LOAD itself.
Observation of Autoregulation Indices During Ventricular CSF Drainage After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study.
Neurocritical care, 2015

Cerebral autoregulation is increasingly recognized as a factor that requires evaluation when managing poor grade aneurysmal subarachnoidal hemorrhage (aSAH) patients. In this single center pilot study, we investigated whether intraventricular intracranial pressure (ICP) derived when extraventricular drain (EVD) is open can be used to calculate dynamic autoregulation estimates in ICU aSAH patients.
A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats.
Neuron, 2017

Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing.
Pitch perception deficits in nonverbal learning disability.
Research in developmental disabilities, 2016

The nonverbal learning disability (NLD) is a neurological dysfunction that affects cognitive functions predominantly related to the right hemisphere such as spatial and abstract reasoning. Previous evidence in healthy adults suggests that acoustic pitch (i.e., the relative difference in frequency between sounds) is, under certain conditions, encoded in specific areas of the right hemisphere that also encode the spatial elevation of external objects (e.g., high vs. low position). Taking this evidence into account, we explored the perception of pitch in preadolescents and adolescents with NLD and in a group of healthy participants matched by age, gender, musical knowledge and handedness. Participants performed four speeded tests: a stimulus detection test and three perceptual categorization tests based on colour, spatial position and pitch. Results revealed that both groups were equally fast at detecting visual targets and categorizing visual stimuli according to their colour. In contrast, the NLD group showed slower responses than the control group when categorizing space (direction of a visual object) and pitch (direction of a change in sound frequency). This pattern of results suggests the presence of a subtle deficit at judging pitch in NLD along with the traditionally-described difficulties in spatial processing.
PARP Inhibitor Affects Long-term Heat-stress Response via Changes in DNA Methylation.
Neuroscience, 2019

Resilience to stress can be obtained by adjusting the stress-response set point during postnatal sensory development. Recent studies have implemented epigenetic mechanisms to play leading roles in improving resilience. We previously found that better resilience to heat stress in chicks can be achieved by conditioning them to moderate heat stress during their critical developmental period of thermal control establishment, 3 days posthatch. Furthermore, the expression level of corticotropin-releasing hormone (CRH) was found to play a direct role in determining future resilience or vulnerability to heat stress by alterations in its DNA-methylation and demethylation pattern. Here we demonstrate how intraperitoneal injection of poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) influences the DNA methylation pattern, thereby affecting the long-term heat-stress response. Single PARPi administration, induced a reduction in both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), without affecting body temperature. The accumulated effect of three PARPi doses brought about a long-term decrease in 5mC% and 5hmC%. These changes coincided with a reduction in body temperature in non-conditioned chicks, similar to that occurring in moderately conditioned heat-stress-resilient chicks. The observed changes in DNA methylation can be explained by decreased activity of the enzyme DNA methyltransferase as a result of the PARPi injection. Furthermore, evaluation of the DNA-methylation pattern along the CRH intron showed a reduction in 5mC% as a result of PARPi treatment, alongside a reduction in CRH mRNA expression. Thus, PARPi treatment can affect DNA methylation, which can alter hypothalamic-pituitary-adrenal (HPA) axis anchors such as CRH, thereby potentially enhancing long-term resilience to heat stress.
Subthalamic Nucleus and Sensorimotor Cortex Activity During Speech Production.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019

The sensorimotor cortex is somatotopically organized to represent the vocal tract articulators such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed LFP recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 human subjects (1 female) with Parkinson's disease during implantation of deep-brain stimulation (DBS) electrodes while they read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high-gamma (60-150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulators involved in the production of the initial consonants were topographically represented by high-gamma activity. We found that STN high-gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high-gamma activity varied along the ventral-dorsal trajectory of the electrodes, with greater high-gamma power recorded in the dorsal locations of the STN. Interestingly, the majority of significant articulator-discriminative activity in the STN occurred before that in sensorimotor cortex. These results demonstrate that articulator-specific speech information is contained within high-gamma activity of the STN, but with different spatial and temporal organization compared with similar information encoded in the sensorimotor cortex.
Saccade-target selection of dyslexic children when reading Chinese.
Vision research, 2014

This study investigates the eye movements of dyslexic children and their age-matched controls when reading Chinese. Dyslexic children exhibited more and longer fixations than age-matched control children, and an increase of word length resulted in a greater increase in the number of fixations and gaze durations for the dyslexic than for the control readers. The report focuses on the finding that there was a significant difference between the two groups in the fixation landing position as a function of word length in single-fixation cases, while there was no such difference in the initial fixation of multi-fixation cases. We also found that both groups had longer incoming saccade amplitudes while the launch sites were closer to the word in single fixation cases than in multi-fixation cases. Our results suggest that dyslexic children's inefficient lexical processing, in combination with the absence of orthographic word boundaries in Chinese, leads them to select saccade targets at the beginning of words conservatively. These findings provide further evidence for parafoveal word segmentation during reading of Chinese sentences.