rudyvdbrink/CitationDatabase huggingface dataset:
Prostaglandin E2 elevates calcium in differentiated neuroectodermal stem cells.
Molecular and cellular neurosciences, 2016

Lipid mediator prostaglandin E2 (PGE2) is an endogenous signaling molecule that plays an important role during early development of the nervous system. Abnormalities in the PGE2 signaling pathway have been associated with neurodevelopmental disorders such as autism spectrum disorders. In this study we use ratiometric fura-2AM calcium imaging to show that higher levels of PGE2 elevate intracellular calcium levels in the cell soma and growth cones of differentiated neuroectodermal (NE-4C) stem cells. PGE2 also increased the amplitude of calcium fluctuation in the neuronal growth cones and affected the neurite extension length. In summary, our results show that PGE2 may adversely impact intracellular calcium dynamics in differentiated neuronal cells and possibly affect early development of the nervous system.
Pavlovian Conditioning of Immunological and Neuroendocrine Functions.
Physiological reviews, 2020

The phenomenon of behaviorally conditioned immunological and neuroendocrine functions has been investigated for the past 100 yr. The observation that associative learning processes can modify peripheral immune functions was first reported and investigated by Ivan Petrovic Pavlov and his co-workers. Their work later fell into oblivion, also because so little was known about the immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. With the employment of a taste-avoidance paradigm in rats, this phenomenon was rediscovered 45 yr ago as one of the most fascinating examples of the reciprocal functional interaction between behavior, the brain, and peripheral immune functions, and it established psychoneuroimmunology as a new research field. Relying on growing knowledge about efferent and afferent communication pathways between the brain, neuroendocrine system, primary and secondary immune organs, and immunocompetent cells, experimental animal studies demonstrate that cellular and humoral immune and neuroendocrine functions can be modulated via associative learning protocols. These (from the classical perspective) learned immune responses are clinically relevant, since they affect the development and progression of immune-related diseases and, more importantly, are also inducible in humans. The increased knowledge about the neuropsychological machinery steering learning and memory processes together with recent insight into the mechanisms mediating placebo responses provide fascinating perspectives to exploit these learned immune and neuroendocrine responses as supportive therapies, the aim being to reduce the amount of medication required, diminishing unwanted drug side effects while maximizing the therapeutic effect for the patient's benefit.
Prevention of ventricular catheter obstruction and slit ventricle syndrome by the prophylactic use of the Integra antisiphon device in shunt therapy for pediatric hypertensive hydrocephalus: a 25-year follow-up study.
Journal of neurosurgery. Pediatrics, 2010

This 25-year follow-up study was performed on 120 children with hypertensive hydrocephalus to evaluate the influence of the early prophylactic implantation of the Integra antisiphon device (ASD, Integra Neurosciences Ltd.) on the rate of proximal shunt obstructions and the frequency of symptomatic slit ventricle syndrome (SVS). The adaptability of the ASD to growth, proper positioning of the ASD as a necessity for its successful performance, and the 3 phases of SVS development are discussed.
KCNT1-related epilepsy: An international multicenter cohort of 27 pediatric cases.
Epilepsia, 2020

Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants.
Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor.
Journal of medicinal chemistry, 2009

The discovery of a series of pyrrole-sulfonamides as positive allosteric modulators (PAM) of alpha7 nAChRs is described. Optimization of this series led to the identification of 19 (A-867744), a novel type II PAM with good potency and selectivity. Compound 19 showed acceptable pharmacokinetic profile across species and brain levels sufficient to modulate alpha7 nAChRs. In a rodent model of sensory gating, 19 normalized gating deficits. These results suggest that 19 represents a novel class of molecules capable of allosteric modulation of the alpha7 nAChRs.
The Sigma-2 Receptor and Progesterone Receptor Membrane Component 1 are Different Binding Sites Derived From Independent Genes.
EBioMedicine, 2015

The sigma-2 receptor (S2R) is a potential therapeutic target for cancer and neuronal diseases. However, the identity of the S2R has remained a matter of debate. Historically, the S2R has been defined as (1) a binding site with high affinity to 1,3-di-o-tolylguanidine (DTG) and haloperidol but not to the selective sigma-1 receptor ligand (+)-pentazocine, and (2) a protein of 18-21 kDa, as shown by specific photolabeling with [(3)H]-Azido-DTG and [(125)I]-iodoazido-fenpropimorph ([(125)I]-IAF). Recently, the progesterone receptor membrane component 1 (PGRMC1), a 25 kDa protein, was reported to be the S2R (Nature Communications, 2011, 2:380). To confirm this identification, we created PGRMC1 knockout NSC34 cell lines using the CRISPR/Cas9 technology. We found that in NSC34 cells devoid of or overexpressing PGRMC1, the maximum [(3)H]-DTG binding to the S2R (Bmax) as well as the DTG-protectable [(125)I]-IAF photolabeling of the S2R were similar to those of wild-type control cells. Furthermore, the affinities of DTG and haloperidol for PGRMC1 (KI = 472 μM and 350 μM, respectively), as determined in competition with [(3)H]-progesterone, were more than 3 orders of magnitude lower than those reported for the S2R (20-80 nM). These results clarify that PGRMC1 and the S2R are distinct binding sites expressed by different genes.
A novel approach to training attention and gaze in ASD: A feasibility and efficacy pilot study.
Developmental neurobiology, 2018

In addition to the social, communicative and behavioral symptoms that define the disorder, individuals with ASD have difficulty re-orienting attention quickly and accurately. Similarly, fast re-orienting saccadic eye movements are also inaccurate and more variable in both endpoint and timing. Atypical gaze and attention are among the earliest symptoms observed in ASD. Disruption of these foundation skills critically affects the development of higher level cognitive and social behavior. We propose that interventions aimed at these early deficits that support social and cognitive skills will be broadly effective. We conducted a pilot clinical trial designed to demonstrate the feasibility and preliminary efficacy of using gaze-contingent video games for low-cost in-home training of attention and eye movement. Eight adolescents with ASD participated in an 8-week training, with pre-, mid- and post-testing of eye movement and attention control. Six of the eight adolescents completed the 8 weeks of training and all six showed improvement in attention (orienting, disengagement) and eye movement control or both. All game systems remained intact for the duration of training and all participants could use the system independently. We delivered a robust, low-cost, gaze-contingent game system for home use that, in our pilot training sample, improved the attention orienting and eye movement performance of adolescent participants in 8 weeks of training. We are currently conducting a clinical trial to replicate these results and to examine what, if any, aspects of training transfer to more real-world tasks. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 546-554, 2018.
Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons.
Proceedings of the National Academy of Sciences of the United States of America, 2008

Transient forebrain or global ischemia induces delayed neuronal death in vulnerable CA1 pyramidal cells with many features of apoptosis. A brief period of ischemia, i.e., ischemic preconditioning, affords robust protection of CA1 neurons against a subsequent more prolonged ischemic challenge. Here we show that preconditioning acts via PI3K/Akt signaling to block the ischemia-induced cascade involving mitochondrial translocation of Bad, assembly of Bad with Bcl-x(L), cleavage of Bcl-x(L) to form its prodeath fragment, DeltaN-Bcl-x(L), activation of large-conductance channels in the mitochondrial outer membrane, mitochondrial release of cytochrome c and Smac/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low pI), caspase activation, and neuronal death. These findings show how preconditioning acts to prevent the release of cytochrome c and Smac/DIABLO from mitochondria and to preserve the integrity of the mitochondrial membrane. The specific PI3K inhibitor LY294002 administered in vivo 1 h before or immediately after ischemia or up to 120 h later significantly reverses preconditioning-induced protection, indicating a requirement for sustained PI3K signaling in ischemic tolerance. These findings implicate PI3K/Akt signaling in maintenance of the integrity of the mitochondrial outer membrane.
A spatial memory signal shows that the parietal cortex has access to a craniotopic representation of space.
eLife, 2018

Humans effortlessly establish a gist-like memory of their environment whenever they enter a new place, a memory that can guide action even in the absence of vision. Neurons in the lateral intraparietal area (LIP) of the monkey exhibit a form of this environmental memory. These neurons respond when a monkey makes a saccade that brings the spatial location of a stimulus that appeared on a number of prior trials, but not on the present trial, into their receptive fields (RFs). The stimulus need never have appeared in the neuron's RF. This memory response is usually weaker, with a longer latency than the neuron's visual response. We suggest that these results demonstrate that LIP has access to a supraretinal memory of space, which is activated when the spatial location of the vanished stimulus can be described by a retinotopic vector from the center of gaze to the remembered spatial location.
Reduced pupil dilation during action preparation in schizophrenia.
International journal of psychophysiology : official journal of the International Organization of Psychophysiology, 2018

Impairments in cognitive control-the ability to exert control over thoughts and actions and respond flexibly to the environment-are well-documented in schizophrenia. However, the degree to which experimental task performance reflects true cognitive control impairments or more general alterations in effort, arousal and/or task preparedness is unclear. Pupillary responses can provide insight into these latter factors, as the pupil dilates with degree of cognitive effort and response preparation. In the current study, 16 medicated outpatients with schizophrenia (SZP) and 18 healthy controls performed a task that measures the ability to reactively inhibit and modify a planned action-the double-step task. In this task, participants were required to make a saccade to a visual target. Infrequently, the target jumped to a new location and participants were instructed to rapidly inhibit and change their eye movement plan. Applying a race model of performance, we have previously shown that SZP require more time to inhibit a planned action. In the current analysis, we measured pupil dilation associated with task preparation and found that SZP had a shallower increase in pupil size prior to the onset of the trial. Additionally, reduced magnitude of the pupil response was associated with negative symptom severity in patients. Based on primate neurophysiology and cognitive neuroscience work, we suggest that this blunted pupillary response may reflect abnormalities in a general orienting response or reduced motivational significance of a cue signifying the onset of a preparatory period and that these abnormalities might share an autonomic basis with negative symptoms.
Chronic morphine exposure affects contrast response functions of V1 neurons in cats.
Neuroscience, 2012

Opiates disrupt neural functions in many brain areas, including visual cortex. Previous studies have indicated substantial changes of many neuronal response properties induced by chronic morphine exposure in the visual information processing system. However, it remains unclear whether neuronal contrast coding is also affected. To investigate this issue, we measured the contrast response functions (CRFs) of V1 neurons in chronic morphine-treated and saline-treated cats by using extra-cellular single-unit recording techniques. Our results indicated significantly lower contrast sensitivity in morphine-treated cats than in saline-treated cats and V1 neurons in morphine-treated cats exhibited enhanced maximum visual responses, higher baseline responses and lower signal-to-noise ratios compared with saline-treated cats. These findings provide some neurobiological evidence for the morphine-mediated degenerations of the visual cortex, which could underlie the opiate-induced deficits in visual function.
Gender identity better than sex explains individual differences in episodic and semantic components of autobiographical memory and future thinking.
Consciousness and cognition, 2018

A recently tested hypothesis suggests that inter-individual differences in episodic autobiographical memory (EAM) are better explained by individual identification of typical features of a gender identity than by sex. This study aimed to test this hypothesis by investigating sex and gender related differences not only in EAM but also during retrieval of more abstract self-knowledge (i.e., semantic autobiographical memory, SAM, and conceptual self, CS), and considering past and future perspectives. No sex-related differences were identified, but regardless of the sex, feminine gender identity was associated with clear differences in emotional aspects that were expressed in both episodic and more abstract forms of AM, and in the past and future perspectives, while masculine gender identity was associated with limited effects. In conclusion, our results support the hypothesis that inter-individual differences in AM are better explained by gender identity than by sex, extending this assumption to both episodic and semantic forms of AM and future thinking.
Increased plasma donepezil concentration improves cognitive function in patients with dementia with Lewy bodies: An exploratory pharmacokinetic/pharmacodynamic analysis in a phase 3 randomized controlled trial.
Journal of the neurological sciences, 2016

To investigate whether increasing plasma donepezil concentration further improves cognitive function and neuropsychiatric symptoms without compromising safety in patients with dementia with Lewy bodies (DLB).
Legislative Enforcement of Nonconsensual Determination of Neurological (Brain) Death in Muslim Patients: A Violation of Religious Rights.
Journal of religion and health, 2018

Death is defined in the Quran with a single criterion of irreversible separation of the ruh (soul) from the body. The Quran is a revelation from God to man, and the primary source of Islamic knowledge. The secular concept of death by neurological criteria, or brain death, is at odds with the Quranic definition of death. The validity of this secular concept has been contested scientifically and philosophically. To legitimize brain death for the purpose of organ donation and transplantation in Muslim communities, Chamsi-Pasha and Albar (concurring with the US President's Council on Bioethics) have argued that irreversible loss of capacity for consciousness and breathing (apneic coma) in brain death defines true death in accordance with Islamic sources. They have postulated that the absence of nafs (personhood) and nafas (breath) in apneic coma constitutes true death because of departure of the soul (ruh) from the body. They have also asserted that general anesthesia is routine in brain death before surgical procurement. Their argument is open to criticism because: (1) the ruh is described as the essence of life, whereas the nafs and nafas are merely human attributes; (2) unlike true death, the ruh is still present even with absent nafs and nafas in apneic coma; and (3) the routine use of general anesthesia indicates the potential harm to brain-dead donors from surgical procurement. Postmortem general anesthesia is not required for autopsy. Therefore, the conclusion must be that legislative enforcement of nonconsensual determination of neurological (brain) death and termination of life-support and medical treatment violates the religious rights of observant Muslims.
Electroacupuncture analgesia in rat ankle sprain pain model: neural mechanisms.
Neurological research, 2010

Acupuncture, an alternative medical therapy with a long history, is appealing because it can activate endogenous analgesic mechanisms by minimally invasive means. The mechanisms of acupuncture, however, are not well understood yet. The following sentence was removed from our original manuscript. One of the major problems impeding understanding of the acupuncture mechanism is lack of experimental models that mimic various forms of persistent pain that respond to acupuncture in humans.
Urban eye allergy syndrome: a new clinical entity?
Current medical research and opinion, 2008

A significant number of patients present with conjunctivitis that is not strictly speaking of allergic, infectious, or dry eye origin. Patients affected by this pseudo-allergic form of vasomotor or idiopathic conjunctivitis usually live in urban polluted areas and may be affected by a new clinical entity called the 'urban eye allergy syndrome'.
FUS-dependent liquid-liquid phase separation is important for DNA repair initiation.
The Journal of cell biology, 2021

RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). The RBP FUS is implicated in RNA metabolism and DNA repair, and it undergoes reversible liquid-liquid phase separation (LLPS) in vitro. Here, we demonstrate that FUS-dependent LLPS is necessary for the initiation of the DDR. Using laser microirradiation in FUS-knockout cells, we show that FUS is required for the recruitment to DNA damage sites of the DDR factors KU80, NBS1, and 53BP1 and of SFPQ, another RBP implicated in the DDR. The relocation of KU80, NBS1, and SFPQ is similarly impaired by LLPS inhibitors, or LLPS-deficient FUS variants. We also show that LLPS is necessary for efficient γH2AX foci formation. Finally, using superresolution structured illumination microscopy, we demonstrate that the absence of FUS impairs the proper arrangement of γH2AX nanofoci into higher-order clusters. These findings demonstrate the early requirement for FUS-dependent LLPS in the activation of the DDR and the proper assembly of DSB repair complexes.
Electrophysiological Correlates of Semantic Dissimilarity Reflect the Comprehension of Natural, Narrative Speech.
Current biology : CB, 2018

People routinely hear and understand speech at rates of 120-200 words per minute [1, 2]. Thus, speech comprehension must involve rapid, online neural mechanisms that process words' meanings in an approximately time-locked fashion. However, electrophysiological evidence for such time-locked processing has been lacking for continuous speech. Although valuable insights into semantic processing have been provided by the "N400 component" of the event-related potential [3-6], this literature has been dominated by paradigms using incongruous words within specially constructed sentences, with less emphasis on natural, narrative speech comprehension. Building on the discovery that cortical activity "tracks" the dynamics of running speech [7-9] and psycholinguistic work demonstrating [10-12] and modeling [13-15] how context impacts on word processing, we describe a new approach for deriving an electrophysiological correlate of natural speech comprehension. We used a computational model [16] to quantify the meaning carried by words based on how semantically dissimilar they were to their preceding context and then regressed this measure against electroencephalographic (EEG) data recorded from subjects as they listened to narrative speech. This produced a prominent negativity at a time lag of 200-600 ms on centro-parietal EEG channels, characteristics common to the N400. Applying this approach to EEG datasets involving time-reversed speech, cocktail party attention, and audiovisual speech-in-noise demonstrated that this response was very sensitive to whether or not subjects understood the speech they heard. These findings demonstrate that, when successfully comprehending natural speech, the human brain responds to the contextual semantic content of each word in a relatively time-locked fashion.
Loss of the mu opioid receptor on different genetic backgrounds leads to increased bromodeoxyuridine labeling in the dentate gyrus only after repeated injection.
Neuroscience, 2012

The endogenous opioid system is involved in various physiological processes, including neurogenesis in the dentate gyrus (DG) of the hippocampus. In the current study, we investigated the role of the mu opioid receptor (MOR-1) on DG neurogenesis and measured glucocorticoid levels following several injection paradigms to supplement the neurogenesis experiments. MOR-1 knockout (KO) mice on C57BL/6 and 129S6 backgrounds were injected with bromodeoxyuridine (BrdU) using either a single injection or two different repeated injection protocols and then sacrificed at different time points. The total number of BrdU and proliferating cell nuclear antigen (PCNA) positive cells in the DG is significantly increased in MOR-1 KO mice compared with wild type (WT) on both strains after repeated injection, but not after a single injection. Plasma corticosterone (CORT) levels increased similarly in MOR-1 KO and WT mice following both single and repeated injection, indicating that the stress response is activated following any injection protocol, but that the mechanism responsible for the increase in BrdU labeling in MOR-1 KO mice is CORT-level independent. Finally, WT 129S6 mice, independent of genotype, showed higher levels of plasma CORT compared with WT C57BL/6 mice in both noninjected controls and following injection at two separate time points; these levels were inversely correlated with low numbers of BrdU cells in the DG in 129S6 mice compared with C57BL/6 mice. In summary, these data demonstrate that loss of MOR-1 increases BrdU labeling in the DG independent of CORT levels, but only following a repeated injection, illustrating the capability of injection paradigms to influence cell-proliferative responses in a genotype-dependent manner.
The status of neurology fellowships in the United States: clinical needs, educational barriers, and future outlooks.
BMC medical education, 2021

The need for subspecialty-trained neurologists is growing in parallel with increasing disease burden. However, despite the immense burden of neurological diseases, like headache and neurodegenerative disorders, recruitment into these subspecialties remains insufficient in the United States. In this manuscript, a group of educators from the American Academy of Neurology's A.B. Baker Section on Neurological Education sought to review and discuss the current landscape of neurology fellowships in the United States, the factors driving fellowship recruitment and the educational barriers. Moreover, suggestions to potentially improve recruitment for under-selected fellowships, which can contribute towards an alignment between neurological education and neurological needs, and future educational scenarios are discussed.