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221.
Stylianos Michalakis Karin Schäferhoff Isabella Spiwoks-Becker Nawal Zabouri Susanne Koch Fred Koch Michael Bonin Martin Biel Silke Haverkamp 《Cellular and molecular life sciences : CMLS》2013,70(10):1831-1847
In the mammalian retina, light signals generated in photoreceptors are passed to bipolar and horizontal cells via synaptic contacts. In various pathological conditions, these second-order neurons extend neurites into the outer nuclear layer (ONL). However, the molecular events associated with this neurite outgrowth are not known. Here, we characterized the morphological synaptic changes in the CNGA3/CNGB1 double-knockout (A3B1) mouse, a model of retinitis pigmentosa. In these mice, horizontal cells looked normal until postnatal day (p) 11, but started growing neurites into the ONL 1 day later. At p28, the number of sprouting processes decreased, but the remaining sprouts developed synapse-like contacts at rod cell bodies, with an ultrastructural appearance reminiscent of ribbon synapses. Hence, neurite outgrowth and ectopic synaptogenesis in the A3B1 retina were precisely timed events starting at p12 and p28, respectively. We therefore performed microarray analysis of retinal gene expression in A3B1 and wild-type mice at those ages to evaluate the genomic response underlying these two events. This analysis identified 163 differentially regulated genes in the A3B1 retina related to neurite outgrowth or plasticity of synapses. The global changes in gene expression in the A3B1 retina were consistent with activation of signaling pathways related to Tp53, Smad, and Stat3. Moreover, key molecules of these signaling pathways could be localized at or in close proximity to outgrowing neurites. We therefore propose that Tp53, Smad, and Stat3 signaling pathways contribute to the synaptic plasticity in the A3B1 retina. 相似文献
222.
Katharina Mamasuew Stylianos Michalakis Heinz Breer Martin Biel Joerg Fleischer 《Cellular and molecular life sciences : CMLS》2010,67(11):1859-1869
Localized to the vestibule of the nasal cavity, neurons of the Grueneberg ganglion (GG) respond to cool ambient temperatures. The molecular mechanisms underlying this thermal response are still elusive. Recently, it has been suggested that cool temperatures may activate a cyclic guanosine monophosphate (cGMP) pathway in the GG, which would be reminiscent of thermosensory neurons in Caenorhabditis elegans. In search for other elements of such a cascade, we have found that the cyclic nucleotide-gated ion channel CNGA3 was strongly expressed in the GG and that expression of CNGA3 was confined to those cells that are responsive to coolness. Further experiments revealed that the response of GG neurons to cool temperatures was significantly reduced in CNGA3-deficient mice compared to wild-type conspecifics. The observation that a cGMP-activated non-selective cation channel significantly contributes to the coolness-evoked response in GG neurons strongly suggests that a cGMP cascade is part of the transduction process. 相似文献
223.
Habitat use by Sage Grouse ( Centrocercus urophasianus hens with broods was examined at Jackass Creek and Hart Mountain, Oregon, from 1989 through 1991. Sage Grouse hens initially selected low sagebrush ( Artemisia spp.) cover types during early brood-rearing, big sagebrush cover types later in the brood-rearing period, and ultimately concentrated use in and near lakebeds and meadows. Areas used by Sage Grouse broods typically had greater forb frequency than did random sites. Hens at Jackass Creek selected sites with forb cover similar to that generally available at Hart Mountain, but home ranges were larger at Jackass Creek because of lower availability of suitable brood-rearing habitat. Differences in habitat use by broods on the two areas were reflected in dietary differences; at Hart Mountain, chicks primarily ate forbs and insects, whereas at Jackass Creek most of the diet was sagebrush. Larger home ranges, differences in diets, and differences in availability of forb-rich habitats possibly were related to differences in abundance and productivity between areas. 相似文献
224.
Martin Niss 《Archive for History of Exact Sciences》2011,65(6):625-658
This is the last in a series of three papers on the history of the Lenz–Ising model from 1920 to the early 1970s. In the first paper, I studied the invention of the model in the 1920s, while in the second paper, I documented a quite sudden change in the perception of the model in the early 1960s when it was realized that the Lenz–Ising model is actually relevant for the understanding of phase transitions. In this article, which is self-contained, I study how this realization affected attempts to understand critical phenomena, which can be understood as limiting cases of (first-order) phase transitions, in the epoch from circa 1965 to 1970, where these phenomena were recognized as a research field in its own right. I focus on two questions: What kinds of insight into critical phenomena was the employment of the Lenz–Ising model thought to give? And how could a crude model, which the Lenz–Ising model was thought to be, provide this understanding? I document that the model played several roles: At first, it played a role analogous to experimental data: hypotheses about real systems, in particular relations between critical exponents and what is now called the hypothesis of scaling, which was advanced by Benjamin Widom and others, were confronted with numerical results for the model, in particular the model’s so-called critical exponents. A positive result of a confrontation was seen as positive evidence for this hypothesis. The model was also used to gain insight into specific aspects of critical phenomena, for example that diverse physical systems exhibit similar behavior close to a critical point. Later, a more systematic program of understanding critical phenomena emerged that involved an explicit formulation of what it means to understand critical phenomena, namely, the elucidation of what features of the Hamiltonian of models lead to what kinds of behavior close to critical points. Attempts to accomplish this program culminated with the so-called hypothesis of universality, put forward independently by Robert B. Griffiths and Leo P. Kadanoff in 1970. They divided critical phenomena into classes with similar critical behavior. I also study the crucial role of the Lenz–Ising model in the development and justification of these ideas. 相似文献
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One part of the microsomal galactosyl-transferase activity of splenic cells of rats can by solubilized by the action of Triton X-100 and Tween 20. Its purification on a Sephadex G-200 column and by electrophoresis on a polyacrylamide gel leads to a solution of high specific enzymic activity. 相似文献
229.
AA Pezzulo XX Tang MJ Hoegger MH Alaiwa S Ramachandran TO Moninger PH Karp CL Wohlford-Lenane HP Haagsman M van Eijk B Bánfi AR Horswill DA Stoltz PB McCray MJ Welsh J Zabner 《Nature》2012,487(7405):109-113
Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain. To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo, when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO(3)(-) transport. Without CFTR, airway epithelial HCO(3)(-) secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions. 相似文献
230.
Ritter S Nölleke C Hahn C Reiserer A Neuzner A Uphoff M Mücke M Figueroa E Bochmann J Rempe G 《Nature》2012,484(7393):195-200
Quantum networks are distributed quantum many-body systems with tailored topology and controlled information exchange. They are the backbone of distributed quantum computing architectures and quantum communication. Here we present a prototype of such a quantum network based on single atoms embedded in optical cavities. We show that atom-cavity systems form universal nodes capable of sending, receiving, storing and releasing photonic quantum information. Quantum connectivity between nodes is achieved in the conceptually most fundamental way-by the coherent exchange of a single photon. We demonstrate the faithful transfer of an atomic quantum state and the creation of entanglement between two identical nodes in separate laboratories. The non-local state that is created is manipulated by local quantum bit (qubit) rotation. This efficient cavity-based approach to quantum networking is particularly promising because it offers a clear perspective for scalability, thus paving the way towards large-scale quantum networks and their applications. 相似文献