rudyvdbrink/CitationDatabase huggingface dataset:
Markerless motion capture can provide reliable 3D gait kinematics in the sagittal and frontal plane.
Medical engineering & physics, 2014

Estimating 3D joint rotations in the lower extremities accurately and reliably remains unresolved in markerless motion capture, despite extensive studies in the past decades. The main problems have been ascribed to the limited accuracy of the 3D reconstructions. Accordingly, the purpose of the present study was to develop a new approach based on highly detailed 3D reconstructions in combination with a translational and rotational unconstrained articulated model. The highly detailed 3D reconstructions were synthesized from an eight camera setup using a stereo vision approach. The subject specific articulated model was generated with three rotational and three translational degrees of freedom for each limb segment and without any constraints to the range of motion. This approach was tested on 3D gait analysis and compared to a marker based method. The experiment included ten healthy subjects in whom hip, knee and ankle joint were analysed. Flexion/extension angles as well as hip abduction/adduction closely resembled those obtained from the marker based system. However, the internal/external rotations, knee abduction/adduction and ankle inversion/eversion were less reliable.
Structural and functional properties of a probabilistic model of neuronal connectivity in a simple locomotor network.
eLife, 2018

Although, in most animals, brain connectivity varies between individuals, behaviour is often similar across a species. What fundamental structural properties are shared across individual networks that define this behaviour? We describe a probabilistic model of connectivity in the hatchling Xenopus tadpole spinal cord which, when combined with a spiking model, reliably produces rhythmic activity corresponding to swimming. The probabilistic model allows calculation of structural characteristics that reflect common network properties, independent of individual network realisations. We use the structural characteristics to study examples of neuronal dynamics, in the complete network and various sub-networks, and this allows us to explain the basis for key experimental findings, and make predictions for experiments. We also study how structural and functional features differ between detailed anatomical connectomes and those generated by our new, simpler, model (meta-model).
A comparison of four antiepileptic drugs in status epilepticus: experience from India.
The International journal of neuroscience, 2016

We report the efficacy and safety of lorazepam (LOR), phenytoin (PHT), valproate (VPA) and levetiracetam (LEV) as first and second choice antiepileptic drug (AED) in status epilepticus (SE) and their combinations in preventing refractory SE.
Nrf2-Inducers Counteract Neurodegeneration in Frataxin-Silenced Motor Neurons: Disclosing New Therapeutic Targets for Friedreich's Ataxia.
International journal of molecular sciences, 2017

Oxidative stress is actively involved in Friedreich's Ataxia (FA), thus pharmacological targeting of the antioxidant machinery may have therapeutic value. Here, we analyzed the relevance of the antioxidant phase II response mediated by the transcription factor Nrf2 on frataxin-deficient cultured motor neurons and on fibroblasts of patients. The in vitro treatment of the potent Nrf2 activator sulforaphane increased Nrf2 protein levels and led to the upregulation of phase II antioxidant enzymes. The neuroprotective effects were accompanied by an increase in neurites' number and extension. Sulforaphane (SFN) is a natural compound of many diets and is now being used in clinical trials for other pathologies. Our results provide morphological and biochemical evidence to endorse a neuroprotective strategy that may have therapeutic relevance for FA. The findings of this work reinforce the crucial importance of Nrf2 in FA and provide a rationale for using Nrf2-inducers as pharmacological agents.
Glutamate release through connexin 43 by cultured astrocytes in a stimulated hypertonicity model.
Brain research, 2011

We investigated the role of connexin 43 (Cx43) hemichannels in the release of glutamate by astrocytes after hypertonic stimulus. Mechanical, osmotic and oxidative stress, and changes in the extracellular or intracellular Ca(2+) levels induce connexin hemichannels located in the plasma membrane to open and release small ions and molecules with signaling potential such as glutamate, ATP, etc. In our past studies, we primarily found that acute hypertonic stimulus induced the release of glutamate. Since glutamate release was involved with several routes, we studied its release routes by astrocytes incubated in a hypertonic media for various periods. The glutamate release was increased after hypertonic stimulus. Glutamate release in hypertonic stimulus was inhibited by gap junction or Cx43 hemichannel blockers, but not by antagonists of purinergic receptor (P2XnR), glutamate transport inhibitors, intracellular Ca(2+) blockers, and pannexin 1(Panx1) hemichannel. The results suggest that glutamate release by the Cx43 hemichannels is likely to feature in the response of cultured astrocytes to hypertonic stimulus.
The structural basis for an on-off switch controlling Gβγ-mediated inhibition of TRPM3 channels.
Proceedings of the National Academy of Sciences of the United States of America, 2020

TRPM3 channels play important roles in the detection of noxious heat and in inflammatory thermal hyperalgesia. The activity of these ion channels in somatosensory neurons is tightly regulated by µ-opioid receptors through the signaling of Gβγ proteins, thereby reducing TRPM3-mediated pain. We show here that Gβγ directly binds to a domain of 10 amino acids in TRPM3 and solve a cocrystal structure of this domain together with Gβγ. Using these data and mutational analysis of full-length proteins, we pinpoint three amino acids in TRPM3 and their interacting partners in Gβ
Time-of-day effects on prospective memory.
Behavioural brain research, 2019

Cognitive performance fluctuates during the course of a day. Different cognitive functions show optimal performance at different times of the day, known as the 'time-of-day effect'. While this effect has been observed for a number of cognitive domains including declarative memory, it is presently unclear whether performance fluctuations are also seen in prospective memory, i.e. memory for intentions to be realized in the future. The present study examined time-of-day effects in four different prospective memory tasks with varying degrees of complexity, taking into account circadian preference (i.e. morningness-eveningness/chronotype) and attentional resources (in one of the tasks). In a pilot study (n = 48) and a main experiment (n = 39), prospective memory was compared between morning groups (˜09:00) and evening groups (˜21:00) of young adults. We found time-of-day effects, with better performance in the evening than in the morning, in a simple one-item prospective memory task (Red Pencil Task, p = .02), a classical event-based prospective memory task including the detection of cue syllables in a lexical decision ongoing task (Syllable Detection Task, p < .048), and a rather naturalistic complex planning task for breakfast preparation (Dresden Breakfast Task, including time-based prospective memory (p = .026) and event-based prospective memory (p = .054)). These time-of-day effects were neither modulated by circadian preference nor by attentional resources. Another simple one-item prospective memory task was not affected by time of day (Color Task, p = .14). Ongoing task performance in the Syllable Detection Task and the Dresden Breakfast Task, overall, did not differ significantly between morning and evening groups. These findings provide tentative evidence for time-of-day effects in prospective memory of young adults, with better performance in the evening hours.
Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes.
Stem cell reports, 2015

In glioblastoma multiforme (GBM), brain-tumor-initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM.
Neurobiological degeneracy: A key property for functional adaptations of perception and action to constraints.
Neuroscience and biobehavioral reviews, 2016

A crucial aspect of understanding human behavior relates to how perception and action sub-systems are integrated during coordinated and controlled movement in goal-directed activity. Here we discuss how a neurobiological system property, degeneracy (i.e., many coordinative structures to achieve one function), can help us understand how skilled individuals functionally adapt perception and action to interacting constraints during performance. Since most research investigating degeneracy has been conducted in neuroanatomy, genetics and theoretical neurobiology, here we clarify how degeneracy is exhibited in perceptual-motor systems. Using an ecological dynamics framework, we highlight how degeneracy underpins the functional role of movement coordination variability in performance of multi-articular tasks. Following that, we discuss how degenerate neurobiological systems are able to exploit system stability and flexibility in their movement coordination. Third, we show how better coupling of information and movement could lead individuals to explore functionally degenerate behaviors. Last, we explore how degeneracy can support pluri-potentiality (i.e., one coordinative structure for many perceptual-motor functions) as a way toward innovation or refinement in performance.
Moringa oleifera induced potentiation of serotonin release by 5-HT(3) receptors in experimental ulcer model.
Phytomedicine : international journal of phytotherapy and phytopharmacology, 2011

moringa oleifera (Moringaceae), a perennial plant is widely cultivated throughout the world. Extensive pharmacological studies revealed its promising role in modulation of various disorders like antispasmodic, diuretic, abortifacient, antimicrobial antibacterial, antitubercular, antiviral, antifertility, depressant, anti-inflammatory and anticancer property which promoted us to conduct the study to elucidate its role on experimental gastric ulceration.
Re: Woolsey TA, van der Loos H. 1970. The structural organization of layer IV in the somatosensory region (S I) of mouse cerebral cortex. Brain Res. 17: 205-242.
Brain research, 2016

Axoplasmically transported proteins synthesized in neuronal somata labeled by radioactively labeled amino acids (tritium), following local targeted injections for tracing of pathways in the central nervous system using autoradiography. Results from a number of neuronal systems, including: the rat olfactory bulb; cortico-thalamic projections in the mouse; commissural connections of the rat hippocampus; and retinal projections in the monkey and chick are documented. Pathway origins are clear, as the number and distribution of the labeled cells and the normal structure of the injection site is preserved. Light and electron microscopic autoradiography shows that proteins are transported, at two rates: rapid transport (>100mm/day) of fewer proteins accumulating in axon terminals; and, slow transport (1-5mm/day) of the bulk of labeled proteins distributed along the length of axons. Different survival times can be selected to evaluate terminal projection field(s) or pathways from origin to termination. The clarity of autoradiographic labeling of pathways and their terminations is comparable to other techniques (such as the Nauta-Gygax and the Fink-Heimer methods and the electron microscopy of terminal degeneration). Labeled amino acids do not label molecules in fibers of passage and there is no retrograde transport of labeled material from the axon terminals. The functional polarity of fiber pathways can be easily established. We summarize the merits of this technique is based upon an established physiological properties of neurons that are summarized in contrast to currently used techniques dependent upon pathological changes in neurons, axons, or axonal terminals.
Virtual reality video game improves high-fidelity memory in older adults.
Scientific reports, 2021

Therapeutic interventions have not yet been shown to demonstrate restorative effects for declining long-term memory (LTM) that affects many healthy older adults. We developed a virtual reality (VR) spatial wayfinding game (Labyrinth-VR) as a cognitive intervention with the hypothesis that it could improve detailed, high-fidelity LTM capability. Spatial navigation tasks have been used as a means to achieve environmental enrichment via exposure to and learning about novel and complex information. Engagement has been shown to enhance learning and has been linked to the vitality of the LTM system in the brain. In the current study, 48 older adults (mean age 68.7 ± 6.4 years) with average cognitive abilities for their age were randomly assigned to 12 h of computer game play over four weeks in either the Labyrinth-VR or placebo control game arms. Promptly before and after each participant's treatment regimen, high-fidelity LTM outcome measures were tested to assess mnemonic discrimination and other memory measures. The results showed a post-treatment gain in high-fidelity LTM capability for the Labyrinth-VR arm, relative to placebo, which reached the levels attained by younger adults in another experiment. This novel finding demonstrates generalization of benefits from the VR wayfinding game to important, and untrained, LTM capabilities. These cognitive results are discussed in the light of relevant research for hippocampal-dependent memory functions.
Burst Firing in Bee Gustatory Neurons Prevents Adaptation.
Current biology : CB, 2018

Animals detect changes in the environment using modality-specific, peripheral sensory neurons. The insect gustatory system encodes tastant identity and concentration through the independent firing of gustatory receptor neurons (GRNs) that spike rapidly at stimulus onset and quickly adapt. Here, we show the first evidence that concentrated sugar evokes a temporally structured burst pattern of spiking involving two GRNs within the gustatory sensilla of bumblebees. Bursts of spikes resulted when a sucrose-activated GRN was inhibited by another GRN at a frequency of ∼22 Hz during the first 1 s of stimulation. Pharmacological blockade of gap junctions abolished bursting, indicating that bee GRNs have electrical synapses that produce a temporal pattern of spikes when one GRN is activated by a sugar ligand. Bursting permitted bee GRNs to maintain a high rate of spiking and to exhibit the slowest rate of adaptation of any insect species. Feeding bout duration correlated with coherent bursting; only sugar concentrations that produced bursting evoked the bumblebee's feeding reflex. Volume of solution imbibed was a direct function of time in contact with food. We propose that gap junctions among GRNs enable a sustained rate of GRN spiking that is necessary to drive continuous feeding by the bee proboscis.
Altered hippocampal interneuron activity precedes ictal onset.
eLife, 2018

Although failure of GABAergic inhibition is a commonly hypothesized mechanism underlying seizure disorders, the series of events that precipitate a rapid shift from healthy to ictal activity remain unclear. Furthermore, the diversity of inhibitory interneuron populations poses a challenge for understanding local circuit interactions during seizure initiation. Using a combined optogenetic and electrophysiological approach, we examined the activity of identified mouse hippocampal interneuron classes during chemoconvulsant seizure induction in vivo. Surprisingly, synaptic inhibition from parvalbumin- (PV) and somatostatin-expressing (SST) interneurons remained intact throughout the preictal period and early ictal phase. However, these two sources of inhibition exhibited cell-type-specific differences in their preictal firing patterns and sensitivity to input. Our findings suggest that the onset of ictal activity is not associated with loss of firing by these interneurons or a failure of synaptic inhibition but is instead linked with disruptions of the respective roles these interneurons play in the hippocampal circuit.
Distinct retinohypothalamic innervation patterns predict the developmental emergence of species-typical circadian phase preference in nocturnal Norway rats and diurnal nile grass rats.
The Journal of comparative neurology, 2012

How does the brain develop differently to support nocturnality in some mammals, but diurnality in others? To answer this question, one might look to the suprachiasmatic nucleus (SCN), which is entrained by light via the retinohypothalamic tract (RHT). However, because the SCN is more active during the day in all mammals studied thus far, it alone cannot determine circadian phase preference. In adult Norway rats (Rattus norvegicus), which are nocturnal, the RHT also projects to the ventral subparaventricular zone (vSPVZ), an adjacent region that expresses an in-phase pattern of SCN-vSPVZ neuronal activity. In contrast, in adult Nile grass rats (Arvicanthis niloticus), which are diurnal, an anti-phase pattern of SCN-vSPVZ neuronal activity is expressed. We hypothesized that these species differences result in part from a weak or absent RHT-to-vSPVZ projection in grass rats. Here, using a developmental comparative approach, we assessed species differences in behavior, hypothalamic activity, and RHT anatomy. We report that a robust retina-to-vSPVZ projection develops in Norway rats around the end of the second postnatal week when nocturnal wakefulness and the in-phase pattern of neuronal activity emerge. In grass rats, however, such a projection does not develop and the emergence of the anti-phase pattern during the second postnatal week is accompanied by increased diurnal wakefulness. When considered within the context of previously published reports on RHT projections in a variety of species, the current findings suggest that how and when the retina connects to the hypothalamus differentially shapes brain and behavior to produce animals that occupy opposing temporal niches.
How to Classify the Pituitary Neuroendocrine Tumors (PitNET)s in 2020.
Cancers, 2020

Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, "aggressive" and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as "high risk" tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.
Primary progressive multiple sclerosis: current therapeutic strategies and future perspectives.
Expert review of neurotherapeutics, 2017

Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system with heterogeneous features. Primary progressive (PP) MS is a rare disease subtype characterized by continuous disability worsening from onset. No disease-modifying therapy is currently approved for PP MS due to the negative or inconsistent results of clinical trials conducted on a wide range of interventions, which are reviewed in the present paper. Areas covered: The features and results of randomized trials of disease-modifying treatments for PP MS are discussed, including immunosuppressants, immunomodulators, monoclonal antibodies, and putative neuroprotective agents. Expert commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. Other emerging treatment strategies include cell metabolism modulation and inflammatory pathways inhibition, which are being investigated in several ongoing phase II and III placebo-controlled trials. Future PP MS trials will need to systematically include efficacy endpoints other than physical disability alone, such as cognition, quality of life, advanced MRI measures and molecular biomarkers.
The autistic neuron: troubled translation?
Cell, 2008

Autism is a complex genetic disorder, but single-gene disorders with a high prevalence of autism offer insight into its pathogenesis. Recent evidence suggests that some molecular defects in autism may interfere with the mechanisms of synaptic protein synthesis. We propose that aberrant synaptic protein synthesis may represent one possible pathway leading to autistic phenotypes, including cognitive impairment and savant abilities.