Urban form and function have been studied extensively in urban planning geographical information science. However, gaining a greater understanding of how they merge to define the morphology remains substantial scientific challenge. Toward this goal, paper addresses opportunities presented by emergence crowdsourced data gain novel insights into spaces. We are focusing particular on harvested from social media other open-source volunteered datasets (e.g. trajectory OpenStreetMap data). These...

The GABA(A) receptor is an important target for a variety of general anesthetics (Franks and Lieb, 1994) benzodiazepines such as diazepam. Specific point mutations in the selectively abolish regulation by (Rudolph et al., 1999; McKernan 2000) anesthetic ethers (Mihic 1997; Krasowski 1998; Koltchine 1999), suggesting existence discrete binding sites on these drugs. Using different molecular size (isoflurane > halothane chloroform) together with complementary mutagenesis specific amino acid...

General anesthetic drugs interact with many receptors in the nervous system, but only a handful of these interactions are critical for producing anesthesia. Over last 20 years, neuropharmacologists have revealed that one most important target sites general anesthetics is GABAA receptor. In this review we will discuss what known about – receptor interactions.

A component of cerebrospinal fluid in excessively sleepy people activates an inhibitory signaling pathway and mimics the actions sedative-hypnotics.

Place can be generally defined as a location that has been assigned meaning through human experience, and such it is of multidisciplinary scientific interest. Up to this point place studied primarily within the context social sciences theoretical construct. The availability large amounts user-generated content, e.g. in form media feeds or Wikipedia contributions, allows us for first time computationally analyze quantify shared place. By aggregating references activities urban spaces we...

GABAA receptors are ligand-gated anion channels that important regulators of neuronal inhibition. Mutations in several genes encoding receptor subunits have been identified patients with various types epilepsy, ranging from mild febrile seizures to severe epileptic encephalopathy. Using whole-genome sequencing, we a novel de novo missense variant GABRA5 (c.880G > C, p.V294L) patient early-onset epilepsy and developmental delay. Targeted resequencing 279 additional 19 rare variants nine...

Background The intravenous anesthetic etomidate is optically active and exists in two mirror-image enantiomeric forms. However, although the R(+) isomer used as a clinical anesthetic, quantitative information on relative potencies of S(-) isomers lacking. These data could be to test relevance putative molecular targets. Methods concentrations for half-maximal effect (EC50) needed induce loss righting reflex tadpoles (Rana temporaria) were determined both enantiomers. effects...

Objective Some central hypersomnolence syndromes are associated with a positive allosteric modulator of γ‐aminobutyric acid (GABA)‐A receptors in cerebrospinal fluid. Negative modulators GABA‐A receptors, including clarithromycin, have been reported to reduce sleepiness these patients. We sought systematically assess the effects clarithromycin on objective vigilance and subjective sleepiness. Methods This was 5‐week, randomized, placebo‐controlled, double‐blind, crossover trial 500mg...

Abstract Patch-clamp recording has enabled single-cell electrical, morphological and genetic studies at unparalleled resolution. Yet it remains a laborious low-throughput technique, making largely impractical for large-scale measurements such as cell type connectivity characterization of neurons in the brain. Specifically, technique is critically limited by ubiquitous practice manually replacing patch-clamp pipettes after each recording. To circumvent this limitation, we developed simple,...

1 N1E-115 mouse neuroblastoma cells were studied under voltage clamp in the whole-cell patch-clamp configuration. Peak currents induced by bath application of 5-hydroxytryptamine (5-HT) inwardly rectifying, reversed at 0.4 ± 0.2 mV (mean s.e.mean), and approximately half-inhibited (at μm 5-HT) 2 nM 5-HT3 selective antagonist MDL-72222 (3-tropanyl-3,5-dichlorobenzoate). inward activated a low concentration 5-HT holding potential −50 potentiated volatile general anaesthetics. At their human...

γ-Aminobutyric acid type A (GABA_A )receptors are targets for allosteric modulation by general anesthetics. Mutation of Ser270 within the second transmembrane domain GABA_Areceptor α subunit can ablate receptor anesthetic ether isoflurane. To investigate further function this critical amino residue, we made multiple substitutions at and analyzed concentration-dependent gating GABA regulation isoflurane in each mutant receptor. There is a strong negative correlation...

The macrolide antibiotic clarithromycin can enhance central nervous system excitability, possibly by antagonism of GABA-A receptors. Enhancement GABA signaling has recently been demonstrated in a significant proportion patients with hypersomnias, so we sought to determine whether might provide symptomatic benefit these patients. We performed retrospective review all treated for hypersomnia, whom cerebrospinal fluid enhanced receptor activity vitro excess controls, excluding those hypocretin...

Abstract Background Transitions into conscious states are partially mediated by inactivation of sleep networks and activation arousal networks. Pharmacologic hastening emergence from general anesthesia has largely focused on activating subcortical monoaminergic networks, with little attention antagonizing the γ-aminobutyric acid type A receptor (GABAAR). As GABAAR mediates clinical effects many common anesthetics, authors hypothesized that negative modulators would hasten emergence, possibly...

Previous studies have shown that propofol and sevoflurane enhance the function of gamma-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate same molecular pathways. In addition, little about receptor in presence both sevoflurane. The aim this study was to better understand interactions with GABAA receptor.Wild-type alpha1, beta(2), gamma(2s) GABA(A) subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass...

Background Potentiation of the activity gamma-aminobutyric acid type A (GABA(A)) receptor channel by volatile anesthetic agents is usually studied in vitro at room temperature. Systematic variation temperature can be used to assess relevance this general anesthesia and characterize modulation its behavior normal body Methods GABA(A) halothane, sevoflurane, isoflurane, methoxyflurane was six temperatures range 10-37 degrees C using whole-cell patch-clamp technique mouse fibroblast cells...

The gamma-aminobutyric acid type A receptor (GABAA-R) beta subunits are critical targets for the actions several intravenous general anesthetics, but precise nature of anesthetic binding sites unknown. In addition, little is known about role fourth transmembrane (M4) segment plays in function. aim this study was to better define propofol site on GABAA-R by conducting a tryptophan scan M4 beta2 subunit.Seven mutations were introduced into C-terminal end subunit. subunit complementary DNAs...