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https://www.readbyqxmd.com/read/29149702/an-hplc-tandem-mass-spectrometry-for-quantification-of-et-26-hcl-and-its-major-metabolite-in-plasma-and-application-to-a-pharmacokinetic-study-in-rats
#1
Xu Chen, Wensheng Zhang, Sandy Rios, Miriam B Morkos, Xiaoli Ye, Gen Li, Xuehua Jiang, Zhijun Wang, Ling Wang
ET-26-HCl is a new analog of etomidate, a short-acting anesthetic drug, with less adrenal cortex inhibition. The pharmacokinetics of ET-26-HCl in rats needs to be determined for future clinical trials in human subjects. In order to facilitate the pharmacokinetic study, a liquid chromatography based tandem mass spectrometric (HPLC-MS/MS) method was developed and validated for quantification of ET-26-HCl and its major metabolite, ET-26-acid. These two compounds and gabapentin (internal standard) were extracted using a protein precipitation method with methanol and detected by Multiple Reaction Monitoring of m/z transition of 275...
November 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29149617/decoding-early-and-late-cortical-contributions-to-individuation-of-attended-and-unattended-objects
#2
Claire K Naughtin, Jason B Mattingley, Angela D Bender, Paul E Dux
To isolate a visual stimulus as a unique object with a specific spatial location and time of occurrence, it is necessary to first register (individuate) the stimulus as a distinct perceptual entity. Recent investigations into the neural substrates of object individuation have suggested it is subserved by a distributed neural network, but previous manipulations of individuation load have introduced extraneous visual confounds, which might have yielded ambiguous findings, particularly in early cortical areas...
November 8, 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/29149614/risky-business-the-circuits-that-impact-stress-induced-decision-making
#3
Amy F T Arnsten, Daeyeol Lee, Christopher Pittenger
How does stress promote risky decision-making? Friedman et al. find that stress disrupts inhibition of striatal circuits by prefrontal cortex, rendering animals insensitive to potential losses. This may help explain how stress contributes to substance abuse and how it can disinhibit automatic behaviors, such as tics in Tourette syndrome.
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29149443/migration-of-interneuron-precursors-in-the-nascent-cerebellar-cortex
#4
Annika K Wefers, Christian Haberlandt, Lachezar Surchev, Christian Steinhäuser, Ronald Jabs, Karl Schilling
The cerebellum arguably constitutes one of the best characterized central nervous circuits, and its structure, cellular function, and histogenesis have been described in exceptional quantitative detail. A notable exception to this is the development of its inhibitory interneurons, and in particular the extensive migrations of future basket and stellate cells. Here, we used acute slices from 8-day-old mice to assess the migration of Pax2-EGFP-tagged precursors of these cells en route to the molecular layer during their transit through the nascent cerebellar cortex...
November 17, 2017: Cerebellum
https://www.readbyqxmd.com/read/29149327/focused-time-lapse-analysis-reveals-novel-aspects-of-human-fertilization-and-suggests-new-parameters-of-embryo-viability
#5
G Coticchio, M Mignini Renzini, P V Novara, M Lain, E De Ponti, D Turchi, R Fadini, M Dal Canto
STUDY QUESTION: Can focused application of time-lapse microscopy (TLM) lead to a more detailed map of the morphokinetics of human fertilization, revealing novel or neglected aspects of this process? SUMMARY ANSWER: Intensive harnessing of TLM reveals novel or previously poorly characterised phenomena of fertilization, such as a cytoplasmic wave (CW) preceding pronuclear formation and kinetics of pronuclear chromatin polarization, thereby suggesting novel non-invasive biomarkers of embryo quality...
November 15, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29149290/discovering-the-3-utr-mediated-regulation-of-alpha-synuclein
#6
Domenica Marchese, Teresa Botta-Orfila, Davide Cirillo, Juan Antonio Rodriguez, Carmen Maria Livi, Rubén Fernández-Santiago, Mario Ezquerra, Maria J Martí, Elias Bechara, Gian Gaetano Tartaglia
Recent evidence indicates a link between Parkinson's Disease (PD) and the expression of a-synuclein (SNCA) isoforms with different 3' untranslated regions (3'UTRs). Yet, the post-transcriptional mechanisms regulating SNCA expression are unknown. Using a large-scale in vitro/in silico screening we identified RNA-binding proteins (RBPs) that interact with SNCA 3' UTRs. We identified two RBPs, ELAVL1 and TIAR, that bind with high affinity to the most abundant and translationally active 3' UTR isoform (575 nt)...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29149249/human-accelerated-regions-and-other-human-specific-sequence-variations-in-the-context-of-evolution-and-their-relevance-for-brain-development
#7
Anastasia Levchenko, Alexander Kanapin, Anastasia Samsonova, Raul Gainetdinov
The review discusses, in a format of a timeline, the studies of different types of genetic variants, present in Homo sapiens, but absent in all other primate, mammalian or vertebrate species, tested so far. The main characteristic of these variants is that they are found in regions of high evolutionary conservation. These sequence variations include single nucleotide substitutions (called human accelerated regions), deletions and segmental duplications. The rationale for finding such variations in the human genome is that they could be responsible for traits, specific to our species, of which the human brain is the most remarkable...
November 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29149149/decreased-regional-grey-matter-volume-in-women-with-chronic-whiplash-associated-disorders-relationships-with-cognitive-deficits-and-disturbed-pain-processing
#8
Iris Coppieters, Robby De Pauw, Karen Caeyenberghs, Lieven Danneels, Jeroen Kregel, Astrid Pattyn, Mira Meeus, Barbara Cagnie
BACKGROUND: Patients with chronic whiplash-associated disorders (CWAD) are characterized by pain of traumatic origin, cognitive deficits, and central sensitization (CS). Previous neuroimaging studies revealed altered grey matter volume (GMV) in mild traumatic brain injury patients and chronic pain conditions also characterized by CS. It can therefore be hypothesized that GMV alterations also play a role in the persistent complaints of CWAD. However, brain alterations remain poorly investigated in these patients...
November 2017: Pain Physician
https://www.readbyqxmd.com/read/29149028/changes-of-cerebral-and-or-peripheral-adenosine-a%C3%A2-receptor-and-igf-i-concentrations-under-extended-sleep-duration-in-rats
#9
Mounir Chennaoui, Pierrick J Arnal, Rodolphe Dorey, Fabien Sauvet, Sylvain Ciret, Thierry Gallopin, Damien Leger, Catherine Drogou, Danielle Gomez-Merino
Extended sleep improves sustained attention and reduces sleep pressure in humans. Downregulation of adenosine A₁ receptor (A₁R) and modulation of the neurotrophic factor insulin growth factor-1 (IGF-I) in brain structures controlling attentional capacities could be involved. In the frontal cortex and hippocampus of rats, we measured adenosine A₁R and IGF-I protein concentrations after photoperiod-induced sleep extension. Two groups of twelve rats were adapted over 14 days to a habitual (CON) 12:12 light-dark (LD) schedule and an extended (EXT) 16:8 LD schedule...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29148909/inhibition-of-gaba-transporters-fails-to-afford-significant-protection-following-focal-cerebral-ischemia
#10
Maria Ek Lie, Emma K Gowing, Rasmus P Clausen, Petrine Wellendorph, Andrew N Clarkson
Brain ischemia triggers excitotoxicity and cell death, yet no neuroprotective drugs have made it to the clinic. While enhancing GABAergic signaling to counterbalance excitotoxicity has shown promise in animal models, clinical studies have failed. Blockade of GABA transporters (GATs) offers an indirect approach to increase GABA inhibition to lower the excitation threshold of neurons. Among the GATs, GAT1 is known to promote neuroprotection, while the protective role of the extrasynaptic transporters GAT3 and BGT1 is elusive...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29148542/prrt2-dependent-dyskinesia-cerebellar-paroxysmal-and-persistent
#11
Lieke Kros, Chris I De Zeeuw
In an elegant publication in Cell Research, Tan and colleagues showed that ablation of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal kinesigenic dyskinesia. PRRT2 turns out to downregulate the presynaptic SNARE complex in granule cell axons, which in turn controls the activity patterns of Purkinje cells, the sole output of the cerebellar cortex.
November 17, 2017: Cell Research
https://www.readbyqxmd.com/read/29148122/altered-frontal-interhemispheric-and-fronto-limbic-structural-connectivity-in-unmedicated-adults-with-obsessive-compulsive-disorder
#12
Xiaofu He, Emily Steinberg, Mihaela Stefan, Martine Fontaine, H Blair Simpson, Rachel Marsh
BACKGROUND: Previous diffusion tensor imaging (DTI) studies of obsessive-compulsive disorder (OCD) have primarily used voxel- or tract-based methods to assess white matter microstructure in medicated patients. This is the first probabilistic tractography study to assess the structural connectivity of all major white matter tracts in unmedicated adults with OCD without comorbid psychopathology. We hypothesized that OCD compared to healthy participants would show reduced integrity in frontal interhemispheric and fronto-limbic tracts...
November 16, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/29148040/the-endocranial-shape-of-australopithecus-africanus-surface-analysis-of-the-endocasts-of-sts-5-and-sts-60
#13
Amélie Beaudet, Jean Dumoncel, Frikkie de Beer, Stanley Durrleman, Emmanuel Gilissen, Anna Oettlé, Gérard Subsol, John Francis Thackeray, José Braga
Assessment of global endocranial morphology and regional neuroanatomical changes in early hominins is critical for the reconstruction of evolutionary trajectories of cerebral regions in the human lineage. Early evidence of cortical reorganization in specific local areas (e.g. visual cortex, inferior frontal gyrus) is perceptible in the non-human South African hominin fossil record. However, to date, little information is available regarding potential global changes in the early hominin brain. The introduction of non-invasive imaging techniques opens up new perspectives for the study of hominin brain evolution...
November 16, 2017: Journal of Anatomy
https://www.readbyqxmd.com/read/29147678/a-haplotype-associated-with-enhanced-mineralocorticoid-receptor-expression-facilitates-the-stress-induced-shift-from-cognitive-to-habit-learning
#14
Lisa Wirz, Martin Reuter, Jan Wacker, Andrea Felten, Lars Schwabe
Stress induces a shift from hippocampus-dependent "cognitive" toward dorsal striatum-dependent "habit" memory. However, not all individuals are susceptible to this shift under stress. Based on pharmacological studies indicating a critical role of the mineralocorticoid receptor (MR) in the stress-induced bias toward dorsal striatal learning, we hypothesized that MR gene variants contribute to these individual differences. In two experiments, healthy participants were genotyped, exposed to a stressor or control manipulation and performed a learning task that can be solved using hippocampal or dorsal striatal systems, while electroencephalography (EEG; Experiment I) or functional magnetic resonance imaging (fMRI; Experiment II) measurements were taken...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29147586/corticospinal-plasticity-in-bilateral-primary-motor-cortices-induced-by-paired-associative-stimulation-to-the-dominant-hemisphere-does-not-differ-between-young-and-older-adults
#15
Daina S E Dickins, Marc R Kamke, Martin V Sale
Older adults have been shown to exhibit a reduction in the lateralization of neural activity. Although neuroplasticity induced by noninvasive brain stimulation has been reported to be attenuated in the targeted motor cortex of older adults, it remains possible that the plasticity effects may instead manifest in a more distributed (bilateral) network. Furthermore, attention, which modulates neuroplasticity in young adults, may influence these effects. To address these questions, plasticity was induced in young (19-32 years) and older (65-78 years) adults using transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29147492/alterations-in-adult-hippocampal-neurogenesis-aberrant-protein-s-nitrosylation-and-associated-spatial-memory-loss-in-streptozotocin-induced-diabetes-mellitus-type-2-mice
#16
Aneeqa Noor, Saadia Zahid
Objectives: Epidemiological and biochemical studies conducted over the past two decades have established a strong link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). However, the exact mechanisms through which aberrations in insulin signaling associated with T2DM contribute to cognitive decline are not yet known. Materials and Methods: In an effort to explore possible molecular links between T2DM and AD, the present study investigated the status of neurodegeneration, adult hippocampal neurogenesis, and nitrosative stress induced protein S-nitrosylation in streptozotocin (STZ) induced mice models of T2DM...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29147147/collective-behavior-of-large-scale-neural-networks-with-gpu-acceleration
#17
Jingyi Qu, Rubin Wang
In this paper, the collective behaviors of a small-world neuronal network motivated by the anatomy of a mammalian cortex based on both Izhikevich model and Rulkov model are studied. The Izhikevich model can not only reproduce the rich behaviors of biological neurons but also has only two equations and one nonlinear term. Rulkov model is in the form of difference equations that generate a sequence of membrane potential samples in discrete moments of time to improve computational efficiency. These two models are suitable for the construction of large scale neural networks...
December 2017: Cognitive Neurodynamics
https://www.readbyqxmd.com/read/29147143/analyzing-text-recognition-from-tactually-evoked-eeg
#18
A Khasnobish, S Datta, R Bose, D N Tibarewala, A Konar
Tactual exploration of objects produce specific patterns in the human brain and hence objects can be recognized by analyzing brain signals during tactile exploration. The present work aims at analyzing EEG signals online for recognition of embossed texts by tactual exploration. EEG signals are acquired from the parietal region over the somatosensory cortex of blindfolded healthy subjects while they tactually explored embossed texts, including symbols, numbers, and alphabets. Classifiers based on the principle of supervised learning are trained on the extracted EEG feature space, comprising three features, namely, adaptive autoregressive parameters, Hurst exponents, and power spectral density, to recognize the respective texts...
December 2017: Cognitive Neurodynamics
https://www.readbyqxmd.com/read/29146502/protracted-motivational-dopamine-related-deficits-following-adolescence-sugar-overconsumption
#19
Fabien Naneix, Florence Darlot, Véronique De Smedt-Peyrusse, Jean-Rémi Pape, Etienne Coutureau, Martine Cador
Adolescence represents a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system during adolescence might constitute an important factor of vulnerability to pathological development. Increasing evidences suggest that adolescent overconsumption of sweet palatable foods impact reward-based processes. However, the neurobiological bases of these deficits remain poorly understood. Previous studies have demonstrated motivational deficits for palatable foods after sweet diet exposure during adolescence that might involve the dopamine (DA) system, a central actor in incentive processes...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29146468/tdcs-changes-in-motor-excitability-are-specific-to-orientation-of-current-flow
#20
Vishal Rawiji, Matteo Ciocca, André Zacharia, David Soares, Dennis Truong, Marom Bikson, John Rothwell, Sven Bestmann
BACKGROUND: Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the folded cortex results in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. METHODS: Here we test this idea by using Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP) to measure changes in corticospinal excitability following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus...
November 7, 2017: Brain Stimulation
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