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https://www.readbyqxmd.com/read/28230986/design-synthesis-and-evaluation-of-a-novel-series-of-oxadiazine-gamma-secretase-modulators-for-familial-alzheimer-s-disease
#1
Matthew G Bursavich, Bryce A Harrison, Raksha Acharya, Donald E Costa, Emily A Freeman, Hilliary E Hodgdon, Lori A Hrdlicka, Hong Jin, Sudarshan Kapadnis, Jeffrey S Moffit, Deirdre A Murphy, Scott Nolan, Holger Patzke, Cuyue Tang, Melody Wen, Gerhard Koenig, Jean-François Blain, Duane A Burnett
Herein we describe the design, synthesis and evaluation of a novel series of oxadiazine-based gamma secretase modulators obtained via isosteric amide replacement and critical consideration of conforma-tional restriction. Oxadiazine lead 47 possesses good in vitro potency with excellent predicted CNS drug-like properties and desirable ADME/PK profile. This lead compound demonstrated robust Aβ42 reductions and subsequent Aβ37 increases in both rodent brain and CSF at 30 mg/kg dosed orally.
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230822/disordered-redox-metabolism-of-brain-cells-in-rats-exposed-to-low-doses-of-ionizing-radiation-or-uhf-electromagnetic-radiation
#2
A P Burlaka, M O Druzhyna, A V Vovk, S М Lukin
AIM: To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. MATERIALS AND METHODS: The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28228585/fixation-target-representation-in-prefrontal-cortex-during-the-anti-saccade-task
#3
Xin Zhou, Christos Constantinidis
Neurons that discharge strongly during the time period of fixation of a visual target and cease to discharge prior to saccade initiation have been described in the brain stem, superior colliculus, and cortical areas. In subcortical structures, fixation neurons play a reciprocal role with saccadic neurons during the generation of eye movements. Their role in the dorsolateral prefrontal cortex is less obvious and it is not known if they are activated by fixation, inhibit saccade generation, or play a role in more complex functions such as the inhibition of inappropriate responses...
February 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28227864/automatic-segmentation-of-multimodal-brain-tumor-images-based-on-classification-of-super-voxels
#4
M Kadkhodaei, S Samavi, N Karimi, H Mohaghegh, S M R Soroushmehr, K Ward, A All, K Najarian, M Kadkhodaei, S Samavi, N Karimi, H Mohaghegh, S M R Soroushmehr, K Ward, A All, K Najarian, K Ward, S M R Soroushmehr, A All, S Samavi, M Kadkhodaei, H Mohaghegh, K Najarian, N Karimi
Despite the rapid growth in brain tumor segmentation approaches, there are still many challenges in this field. Automatic segmentation of brain images has a critical role in decreasing the burden of manual labeling and increasing robustness of brain tumor diagnosis. We consider segmentation of glioma tumors, which have a wide variation in size, shape and appearance properties. In this paper images are enhanced and normalized to same scale in a preprocessing step. The enhanced images are then segmented based on their intensities using 3D super-voxels...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227807/ecog-data-analyses-to-inform-closed-loop-bci-experiments-for-speech-based-prosthetic-applications
#5
Tejaswy Pailla, Werner Jiang, Benjamin Dichter, Edward F Chang, Vikash Gilja, Tejaswy Pailla, Werner Jiang, Benjamin Dichter, Edward F Chang, Vikash Gilja, Vikash Gilja, Werner Jiang, Tejaswy Pailla, Benjamin Dichter, Edward F Chang
Brain Computer Interfaces (BCIs) assist individuals with motor disabilities by enabling them to control prosthetic devices with their neural activity. Performance of closed-loop BCI systems can be improved by using design strategies that leverage structured and task-relevant neural activity. We use data from high density electrocorticography (ECoG) grids implanted in three subjects to study sensory-motor activity during an instructed speech task in which the subjects vocalized three cardinal vowel phonemes...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227803/ear-eeg-allows-extraction-of-neural-responses-in-challenging-listening-scenarios-a-future-technology-for-hearing-aids
#6
L Fiedler, J Obleser, T Lunner, C Graversen, L Fiedler, J Obleser, T Lunner, C Graversen, J Obleser, C Graversen, L Fiedler, T Lunner
Advances in brain-computer interface research have recently empowered the development of wearable sensors to record mobile electroencephalography (EEG) as an unobtrusive and easy-to-use alternative to conventional scalp EEG. One such mobile solution is to record EEG from the ear canal, which has been validated for auditory steady state responses and discrete event related potentials (ERPs). However, it is still under discussion where to place recording and reference electrodes to capture best responses to auditory stimuli...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227566/somatosensory-encoding-with-cuneate-nucleus-microstimulation-detection-of-artificial-stimuli
#7
Srihari Y Sritharan, Andrew G Richardson, Pauline K Weigand, Ivette Planell-Mendez, Xilin Liu, Hongjie Zhu, Milin Zhang, Jan Van der Spiegel, Timothy H Lucas, Srihari Y Sritharan, Andrew G Richardson, Pauline K Weigand, Ivette Planell-Mendez, Xilin Liu, Hongjie Zhu, Milin Zhang, Jan Van der Spiegel, Timothy H Lucas, Srihari Y Sritharan, Andrew G Richardson, Milin Zhang, Jan Van der Spiegel, Pauline K Weigand, Xilin Liu, Timothy H Lucas, Hongjie Zhu, Ivette Planell-Mendez
The sense of touch and proprioception are critical to movement control. After spinal cord injury, these senses may be restored with direct, electrical microstimulation of the brain as part of a complete sensorimotor neuroprosthesis. The present study was designed to test, in part, the hypothesis that the cuneate nucleus (CN) of the brainstem is a suitable site to encode somatosensory information. Two rhesus macaques were implanted with microelectrode arrays providing chronic access to the CN. The monkeys were trained on an active touch oddity task to detect vibrotactile stimuli...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227297/features-of-cerebral-oxygenation-detects-brain-injury-in-premature-infants
#8
John M O'Toole, Mmoloki Kenosi, Daragh Finn, Geraldine B Boylan, Eugene M Dempsey, John M O'Toole, Mmoloki Kenosi, Daragh Finn, Geraldine B Boylan, Eugene M Dempsey, Daragh Finn, Eugene M Dempsey, Mmoloki Kenosi, John M Otoole, Geraldine B Boylan
Babies born prematurely can develop brain injury within days after birth. Early identification of high-risk infants enables appropriate clinical care to mitigate potential lifelong disabilities. Near infra-red spectroscopy is an established technology that can provide continuous measurements of cerebral oxygen saturation (rcSO2) over this critical period. We develop a feature set of the rcSO2 signal for the purpose of detecting brain injury. Our feature set contains amplitude, spectral, and fractal dimension features within 5 frequency bands...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226853/generalized-binary-noise-stimulation-enables-time-efficient-identification-of-input-output-brain-network-dynamics
#9
Yuxiao Yang, Maryam M Shanechi, Yuxiao Yang, Maryam M Shanechi, Yuxiao Yang, Maryam M Shanechi
Identification of input-output (IO) dynamics of brain networks in response to electrical stimulation is essential for devising closed-loop therapies for neurological disorders such as major depression. A critical component for accurate IO identification is the stimulation input design. The time available for open-loop stimulation to perform system identification is typically limited. While our prior design of a binary noise (BN) modulated input pattern satisfies the requirements for optimal identification and clinical safety, it does not incorporate any prior information about the underlying network...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226809/comparison-of-eeg-spatial-filters-for-movement-related-cortical-potential-detection
#10
Fatemeh Karimi, Jonathan Kofman, Natalie Mrachcz-Kersting, Dario Farina, Ning Jiang, Fatemeh Karimi, Jonathan Kofman, Natalie Mrachcz-Kersting, Dario Farina, Ning Jiang, Jonathan Kofman, Dario Farina, Natalie Mrachcz-Kersting, Fatemeh Karimi, Ning Jiang
Movement related cortical potential (MRCP), a slow cortical potential from scalp electroencephalogram (EEG), has been the used in real-time brain-computer-interface (BCI) systems designed for neurorehabilitation applications. Detecting MPCPs in real time with high accuracy is essential for a reliable BCI system in these applications. In this study, we investigated the effect of four spatial filters on MRCP detection during executed and imagined dorsiflexion of healthy participants. Our analysis indicated that, in both executed and imagined movement datasets, none of the methods investigated significantly improved trial-to-trial consistency of MRCP...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226454/optimization-of-electrospun-fibrous-membranes-for-in-vitro-modeling-of-blood-brain-barrier
#11
V Pensabene, S W Crowder, D A Balikov, J B Lee, H J Sung, V Pensabene, S W Crowder, D A Balikov, J B Lee, H J Sung, V Pensabene, D A Balikov, S W Crowder, J B Lee, H J Sung
The blood-brain barrier (BBB) plays a critical role in brain homeostasis at the cellular and global level. Mimicking the selective permeability and transport properties of the BBB to specific molecules and cells remains a significant challenge towards the development of a physiologically relevant in vitro BBB model. In this study, we developed electrospun poly (ε-caprolactone) (PCL) and polyethylene glycol (PEG) copolymer membranes that supported different cellular components of the neurovascular unit including human-derived endothelial cells, pericytes and astrocytes...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225154/human-butyrylcholinesterase-efficacy-against-nerve-agent-exposure
#12
Beth A Reed, Carol L Sabourin, David E Lenz
Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without immediate medical intervention. Current therapies mitigate the cholinergic crisis caused by nerve agents but do not fully prevent long-term health concerns, for example, brain damage following seizures. Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger being investigated as an antidote for OP nerve agent poisoning. HuBChE sequesters OP nerve agent in the bloodstream preventing the nerve agent from reaching critical target organ systems...
February 22, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28225044/comparison-of-dp3-signals-evoked-by-comfortable-3d-images-and-2d-images-an-event-related-potential-study-using-an-oddball-task
#13
Peng Ye, Xiang Wu, Dingguo Gao, Haowen Liang, Jiahui Wang, Shaozhi Deng, Ningsheng Xu, Juncong She, Jun Chen
The horizontal binocular disparity is a critical factor for the visual fatigue induced by watching stereoscopic TVs. Stereoscopic images that possess the disparity within the 'comfort zones' and remain still in the depth direction are considered comfortable to the viewers as 2D images. However, the difference in brain activities between processing such comfortable stereoscopic images and 2D images is still less studied. The DP3 (differential P3) signal refers to an event-related potential (ERP) component indicating attentional processes, which is typically evoked by odd target stimuli among standard stimuli in an oddball task...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225024/rheb1-deletion-in-myeloid-cells-aggravates-ova-induced-allergic-inflammation-in-mice
#14
Kai Li, Yue Zhang, Kang Yan Liang, Song Xu, Xue Juan Zhou, Kang Tan, Jun Lin, Xiao Chun Bai, Cui Lan Yang
The small GTPase ras homolog enriched in brain (Rheb) is a downstream target of tuberous sclerosis complex 1/2 (TSC1/2) and an upstream activator of the mechanistic target of rapamycin complex 1 (mTORC1), the emerging essential modulator of M1/M2 balance in macrophages. However, the role and regulatory mechanisms of Rheb in macrophage polarization and allergic asthma are not known. In the present study, we utilized a mouse model with myeloid cell-specific deletion of the Rheb1 gene and an ovalbumin (OVA)-induced allergic asthma model to investigate the role of Rheb1 in allergic asthma and macrophage polarization...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224622/slc2a3-single-nucleotide-polymorphism-and-duplication-influence-cognitive-processing-and-population-specific-risk-for-attention-deficit-hyperactivity-disorder
#15
Sören Merker, Andreas Reif, Georg C Ziegler, Heike Weber, Ute Mayer, Ann-Christine Ehlis, Annette Conzelmann, Stefan Johansson, Clemens Müller-Reible, Indrajit Nanda, Thomas Haaf, Reinhard Ullmann, Marcel Romanos, Andreas J Fallgatter, Paul Pauli, Tatyana Strekalova, Charline Jansch, Alejandro Arias Vasquez, Jan Haavik, Marta Ribasés, Josep Antoni Ramos-Quiroga, Jan K Buitelaar, Barbara Franke, Klaus-Peter Lesch
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory-inhibitory balance impacting both brain development and activity-dependent neural plasticity...
February 22, 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28223923/embryonic-and-postnatal-expression-of-aryl-hydrocarbon-receptor-mrna-in-mouse-brain
#16
Eiki Kimura, Chiharu Tohyama
Aryl hydrocarbon receptor (AhR), a member of the basic helix-loop-helix-Per-Arnt-Sim transcription factor family, plays a critical role in the developing nervous system of invertebrates and vertebrates. Dioxin, a ubiquitous environmental pollutant, avidly binds to this receptor, and maternal exposure to dioxin has been shown to impair higher brain functions and dendritic morphogenesis, possibly via an AhR-dependent mechanism. However, there is little information on AhR expression in the developing mammalian brain...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28223922/gut-microbiota-a-potential-regulator-of-neurodevelopment
#17
REVIEW
Paola Tognini
During childhood, our brain is exposed to a variety of environmental inputs that can sculpt synaptic connections and neuronal circuits, with subsequent influence on behavior and learning processes. Critical periods of neurodevelopment are windows of opportunity in which the neuronal circuits are extremely plastic and can be easily subjected to remodeling in response to experience. However, the brain is also more susceptible to aberrant stimuli that might lead to altered developmental trajectories. Intriguingly, postnatal brain development is paralleled by the maturation of the gut microbiota: the ecosystem of symbionts populating our gastro-intestinal tract...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#18
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28223234/advanced-glycation-end-products-produced-systemically-and-by-macrophages-a-common-contributor-to-inflammation-and-degenerative-diseases
#19
REVIEW
Kyunghee Byun, YongCheol Yoo, Myeongjoo Son, Jaesuk Lee, Goo-Bo Jeong, Young Mok Park, Ghasem Hosseini Salekdeh, Bonghee Lee
Advanced glycation end products (AGEs) and their receptor have been implicated in the progressions of many intractable diseases, such as diabetes and atherosclerosis, and are also critical for pathologic changes in chronic degenerative diseases, such as Alzheimer's disease, Parkinson's disease, and alcoholic brain damage. Recently activated macrophages were found to be a source of AGEs, and the most abundant form of AGEs, AGE-albumin excreted by macrophages has been implicated in these diseases and to act through common pathways...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222691/how-to-improve-patient-education-on-deep-brain-stimulation-in-parkinson-s-disease-the-care-monitor-study
#20
Lars Dinkelbach, Bettina Möller, Karsten Witt, Alfons Schnitzler, Martin Südmeyer
BACKGROUND: The introduction of deep brain stimulation (DBS) about 25 years ago provided one of the major breakthroughs in the treatment of Parkinson's disease (PD). However, a high percentage of patients are reluctant to undergo DBS. Previous research revealed that the critical step on the patient's path to DBS is the decision whether to undergo further diagnostic assessment for surgery at a specialized DBS-center. The aims of the current study were to evaluate how effective the combination of an outpatient DBS screening tool, STIMULUS, with specially developed educational material was to enhance patient education on DBS and to identify motivational aspects which influenced the patients' willingness to undergo further assessment...
February 21, 2017: BMC Neurology
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