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71.
Pyramidal neurons in the piriform cortex of olfactory discrimination trained rats show enhanced intrinsic neuronal excitability
that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the
postburst after hyperpolarization which is generated by repetitive spike firing. The molecular machinery underlying such long-lasting
modulation of intrinsic excitability, as well as its exceptional durability, is yet to be fully described. In this review,
we present recent advancements that reveal the identity of the current that is modulated after learning and the second messenger
system by which enhanced excitability is maintained. We also discuss the significance of such long-lasting modulation to the
local network’s sensitivity to noradrenaline, a major learning-relevant neuromodulator. 相似文献
72.
Bernhard Suter Jean-Fred Fontaine Reha Yildirimman Tamás Raskó Martin H. Schaefer Axel Rasche Pablo Porras Blanca M. Vázquez-álvarez Jenny Russ Kirstin Rau Raphaele Foulle Martina Zenkner Kathrin Saar Ralf Herwig Miguel A. Andrade-Navarro Erich E. Wanker 《Nucleic acids research》2013,41(3):1496-1507
The yeast two-hybrid (Y2H) system is the most widely applied methodology for systematic protein–protein interaction (PPI) screening and the generation of comprehensive interaction networks. We developed a novel Y2H interaction screening procedure using DNA microarrays for high-throughput quantitative PPI detection. Applying a global pooling and selection scheme to a large collection of human open reading frames, proof-of-principle Y2H interaction screens were performed for the human neurodegenerative disease proteins huntingtin and ataxin-1. Using systematic controls for unspecific Y2H results and quantitative benchmarking, we identified and scored a large number of known and novel partner proteins for both huntingtin and ataxin-1. Moreover, we show that this parallelized screening procedure and the global inspection of Y2H interaction data are uniquely suited to define specific PPI patterns and their alteration by disease-causing mutations in huntingtin and ataxin-1. This approach takes advantage of the specificity and flexibility of DNA microarrays and of the existence of solid-related statistical methods for the analysis of DNA microarray data, and allows a quantitative approach toward interaction screens in human and in model organisms. 相似文献
73.
Indrek Saar Jaanus Lahe Kent Langel Johan Runesson Kristin Webling Jaak Järv Jussi Rytkönen Ale Närvänen Tamas Bartfai Kaido Kurrikoff Ülo Langel 《Journal of neurochemistry》2013,127(1):114-123
Neuropeptide galanin and its three G‐protein coupled receptors, galanin receptor type 1–galanin receptor type 3 (GalR1–GalR3), are involved in the regulation of numerous physiological and disease processes, and thus represent tremendous potential in neuroscience research and novel drug lead development. One of the areas where galanin is involved is depression. Previous studies have suggested that activation of GalR2 leads to attenuation of depression‐like behavior. Unfortunately, lack of in vivo usable subtype specific ligands hinders testing the role of galanin in depression mechanisms. In this article, we utilize an approach of increasing in vivo usability of peptide‐based ligands, acting upon CNS. Thus, we have synthesized a series of novel systemically active galanin analogs, with modest preferential binding toward GalR2. We have shown that specific chemical modifications to the galanin backbone increase brain levels upon i.v. injection of the peptides. Several of the new peptides, similar to a common clinically used antidepressant medication imipramine, exerted antidepressant‐like effect in forced swim test, a mouse model of depression, at a surprisingly low dose range (< 0.5 mg/kg). We chose one of the peptides, J18, for more thorough study, and showed its efficacy also in another mouse depression model (tail suspension test), and demonstrated that its antidepressant‐like effect upon i.v. administration can be blocked by i.c.v. galanin receptor antagonist M35. The effect of the J18 was also abolished in GalR2KO animals. All this suggests that systemically administered peptide analog J18 exerts its biological effect through activation of GalR2 in the brain. The novel galanin analogs represent potential drug leads and a novel pharmaceutical intervention for depression.
74.
75.
Dahlia spectabilis (Asteraceae, Coreopsideae), a new species from San Luis Potosí, Mexico, is described and illustrated. The plant is distinguished
by its large habit, big flowering heads, and overall lack of trichomes. It occurs within the natural range for the genus and
is known from only one location where it is under heavy grazing pressure.
Resumen Dahlia spectabilis (Asteraceae, Coreopsideae), una especie nueva del estado de San Luis Potosí, México, es descrita e ilustrada. Se distingue por su hábito más grande, su grandes inflorescencias y la falta de tricomas. Ocuriendo dento del rango natural del género, conocida solo por un poblacón, la cual está sufriendo por presión de ganado.相似文献
76.
We present a novel assay for rapid and highly sensitive detection of specific nucleic acid fragments in human serum. In a magnetic modulation biosensing (MMB) system, magnetic beads and fluorescently labeled probes are attached to the target analyte and form a “sandwich” complex. An alternating external magnetic field gradient condenses the magnetic beads (and hence the target molecules with the fluorescently labeled probes) to the detection volume and sets them in a periodic motion, in and out of a laser beam. A synchronous detection enables the removal of background signal from the oscillating target signal without complicated sample preparation. The high sensitivity of the MMB system, combined with the specificity of a sandwich hybridization assay, enables detection of DNA fragments without enzymatic signal amplification. Here, we demonstrate the sensitivity of the assay by directly detecting the EML4‐ALK oncogenic translocation sequence spiked in human serum. The calculated limit of detection is 1.4 pM, which is approximately 150 times better than a conventional plate reader. In general, the MMB‐assisted SHA can be implemented in many other applications for which enzymatic amplification, such as PCR, is not applicable and where rapid detection of specific nucleic acid targets is required. 相似文献
77.
Two alpha-bungarotoxin-sensitive nicotinic receptor subtypes in cockroach neurons are identified as desensitizing (nAChD), selectively inhibitable with 100 nM imidacloprid, and non-desensitizing (nAChN), selectively inhibitable with 100 pM methyllycaconitine. Although the desensitization rate of nAChD receptors is highly variable, pharmacology is largely independent of desensitization rate. Because desensitized states tightly bind agonists, nAChD receptors are potently inhibited by neonicotinoids and specifically measured in radiolabeled imidacloprid binding assays. However, they are not usually detected in binding assays with radiolabeled alpha-bungarotoxin, which has a Kd for the resting state of 21 nM, but binds poorly to desensitized states often present in binding assays. In contrast, nAChN receptors are specifically measured in binding assays with radiolabeled alpha-bungarotoxin, which binds them with a Kd of 1.3 nM. nAChN receptors are activated by neonicotinoids at micromolar concentrations, and allosterically by spinosyn A, with an EC50 of 27 nM. Spinosyn A weakly antagonizes nAChD receptors -23% at 10 microM. The roles of the two nAChR subtypes in insecticide poisoning are discussed. 相似文献
78.
Bullkich Elad Kimmel Eitan Golan Saar 《Biomechanics and modeling in mechanobiology》2019,18(6):1847-1866
Biomechanics and Modeling in Mechanobiology - Ischemia reperfusion injury (IRI) involvement in pressure ulcers (PU) progression via a surge of oxidative stress and inflammatory responses is well... 相似文献
79.
Frenzel H Bohlender J Pinsker K Wohlleben B Tank J Lechner SG Schiska D Jaijo T Rüschendorf F Saar K Jordan J Millán JM Gross M Lewin GR 《PLoS biology》2012,10(5):e1001318
In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A. 相似文献
80.
Santosh S. Atanur Ana Garcia Diaz Klio Maratou Allison Sarkis Maxime Rotival Laurence Game Michael R. Tschannen Pamela J. Kaisaki Georg W. Otto Man Chun John Ma Thomas M. Keane Oliver Hummel Kathrin Saar Wei Chen Victor Guryev Kathirvel Gopalakrishnan Michael R. Garrett Bina Joe Lorena Citterio Giuseppe Bianchi Martin McBride Anna Dominiczak David J. Adams Tadao Serikawa Paul Flicek Edwin Cuppen Norbert Hubner Enrico Petretto Dominique Gauguier Anne Kwitek Howard Jacob Timothy J. Aitman 《Cell》2013