641 research outputs found
Neurotransmitter Vesicle Release from Human Model Neurons (NT2) is Sensitive to Botulinum Toxin A
No full textBotulinum neurotoxins (BoNTs) internalize into nerve terminals and block the release of neurotransmitters into the synapse. BoNTs are widely used as a therapeutic agent for treatment of movement disorders and recently gained more attention as a biological weapon. Consequently, there is strong interest to develop a cell-based assay platform to screen the toxicity and bioactivity of the BoNTs. In this study, we present an in vitro screening assay for BoNT/A based on differentiated human embryonal carcinoma stem (NT2) cells. The human NT2 cells fully differentiated into mature neurons that display immunoreactivity to cytoskeletal markers (beta III-tubulin and MAP2) and presynaptic proteins (synapsin and synaptotagmin I). We showed that the human NT2 cells undergo a process of exo-endocytotic synaptic vesicle recycling upon depolarization with high K+ buffer. By employing an antibody directed against light chain of BoNT/A, we detected internalized toxin as a punctate staining along the neurites of the NT2 neurons. Using well-established methods of synaptic vesicle exocytosis assay (luminal synaptotagmin I and FM1-43 imaging) we show that pre-incubation with BoNT/A resulted in a blockade of vesicle release from human NT2 neurons in a dose-dependent manner. Moreover, this blocking effect of BoNT/A was abolished by pre-adsorbing the toxin with neutralizing antibody. In a proof of principle, we demonstrate that our cell culture assay for vesicle release is sensitive to BoNT/A and the activity of BoNT/A can be blocked by specific neutralizing antibodies. Overall our data suggest that human NT2 neurons are suitable for large scale screening of botulinum bioactivity.Federal Ministry for Education and Research (BMBF) [0313732
Dr. Gerd J. Horten Professor of History - Concordia University Portland
No full textGerd Horten, author of the book \u27Radio Goes to War: The Cultural Politics of Propaganda during World War II\u27, discusses World War II propaganda and censorship. Recorded by Phil Sedgwick.
Video uploaded by Phil Sedgwick under Standard YouTube Licensehttps://commons.cu-portland.edu/humfacultymedia/1000/thumbnail.jp
Endogenous Fixprices and Sticky Price Adjustment of Risk-averse Firms
No full textA risk-averse price-setting firm which knows the quantity demanded at the status quo price but has imperfect information otherwise may choose not to change it although an otherwise identical risk-neutral firm would do so, provided the variance of the firm's subjective probability distribution over quantities demanded as a function of price displays a kink at the status quo. This is equivalent to risk aversion of order one. When no such endogenous fixprice exists, the size of price adjustment still tends to zero as risk aversion tends to infinity, and to any arbitrarily small menu cost there exists a degree of risk aversion so that the firm will not adjust.fixed prices, price adjustment, risk aversion, menu cost
Treating gastro-oesophageal reflux disease (GERD) with sense
No full textGastro-esophageal reflux disease (GERD) is a common disorder that affects an estimated 5 % to 7 % of the global population. Management of GERD often poses a number of challenges. In this article, the author presents a number of management modalities for this condition.peer-reviewe
La place de la guerre de 1914-1918 dans l'histoire culturelle de l'Allemagne
No full textThe place of the 1914-1918 war in the cultural history of Germany, Gerd Krumeich.
Through his study of war accounts and memories, the author analyses the impact of the war experience on German culture in its individual as well as its collective aspects. That impact brought about the continuation and the diffusion of militarism and nationalism in much of the German society of the 1920s and 1930s.Krumeich Gerd. La place de la guerre de 1914-1918 dans l'histoire culturelle de l'Allemagne. In: Vingtième Siècle, revue d'histoire, n°41, janvier-mars 1994. La guerre de 1914-1918. Essais d'histoire culturelle. pp. 9-17
Differences in cerebral response to esophageal acid stimuli and psychological anticipation in GERD subtypes-An fMRI study
No full textBackground: To evaluate whether there are differences in the cerebral response to intraesophageal acid and psychological anticipation stimuli among subtypes of gastroesophageal reflux disease (GERD)
Augmenting a pH Medical Study with Wearable Video for Treatment of GERD
No full textIn this paper we present an augmentation to the wearable computers typically used to determine if a patient is a candidate for surgery to correct problems associated with Gastroesophageal Reflux Disease (GERD). A wearable camera was used by the first author while participating in a 24–hour stomach acid pH study. After the study’s conclusion, an examination of the captured video and pH record revealed some results that allowed the first author to avoid many of the activities that result in symptoms related to GERD. 1 GERD and Medical Testing Gastroesophageal Reflux Disease is a medical condition that affects 2 % of the adult population of the United States. GERD refers to the reflux of stomach acid into the esophagus and can lead to complications such as esophageal cancer and lung damage. The most common symptom of GERD is heartburn. Typical treatments for GERD include diet modification and medication; however, for some patients these treatments may prove ineffective, and the patient may be evaluated for more drastic measures such as surgery. If surgery to correct GERD is considered an option, the patient usually undergoes a 24 – or 48–hour pH study to measure the percentage of time that the patient is in reflux during normal daily activities. In the 24–hour study, a pH probe is inserted into the subject’s nose and lowered through the esophagus to a position above the stomach. Since the probe is attached to a line that is retained in the patient’s nose and throat, several pH sensors can be placed at varying locations along the patient’s esophagus. The probe is attached to a wearable computer which records the patient’s pH levels for 24 hours. The patient typically uses the wearable computer to record times of meals, periods spent in a supine position (e.g. sleeping), and occurrences of symptoms. The first author suffered from severe and relatively un
Linguistics and Life. Autobiographical snapshots
No full textAnhand einer Reihe von autobiographischen „Selfies“ wird ein Leben als eine Folge von aufgeschnappten Meinungen konfrontiert. Vor allem mit dem, was Gerd Antos in und mit der Linguistik im Laufe sejner Karriere dazugelernt hat. Linguistik sozusagen als ein lebenslanges learning by doing.Through a series of autobiographical snapshots the author confronts his life as a sequence of picked‑up views. The emphasis will be on the new things Gerd Antos learned with and within linguistics over the course of his career. Linguistics as a life‑long ‘learning by doing’ as it were
Looking at Developmental Neurotoxicity Testing from the Perspective of an Invertebrate Embryo
No full textDevelopmental neurotoxicity (DNT) of chemical compounds disrupts the formation of a normal brain. There is impressive progress in the development of alternative testing methods for DNT potential in chemicals, some of which also incorporate invertebrate animals. This review briefly touches upon studies on the genetically tractable model organisms of Caenorhabditis elegans and Drosophila melanogaster about the action of specific developmental neurotoxicants. The formation of a functional nervous system requires precisely timed axonal pathfinding to the correct cellular targets. To address this complex key event, our lab developed an alternative assay using a serum-free culture of intact locust embryos. The first neural pathways in the leg of embryonic locusts are established by a pair of afferent pioneer neurons which use guidance cues from membrane-bound and diffusible semaphorin proteins. In a systematic approach according to recommendations for alternative testing, the embryo assay quantifies defects in pioneer navigation after exposure to a panel of recognized test compounds for DNT. The outcome indicates a high predictability for test-compound classification. Since the pyramidal neurons of the mammalian cortex also use a semaphorin gradient for neurite guidance, the assay is based on evolutionary conserved cellular mechanisms, supporting its relevance for cortical development
- …
