A Mutation in Myo15 Leads to Usher-Like Symptoms in LEW/Ztm-ci2 Rats

The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, an impaired vision can be observed in some animals through behavioral studies. Syndromal deafness as well as retinal degeneration are features of the Usher syndrome in humans. In the present study, the mutation was identified as a base substitution (T->C) in exon 56 of Myo15, leading to an amino acid exchange from leucine (Leu) to proline (Pro) within the carboxy-terminal MyTH4 domain in the proteins' tail region. Myo15 mRNA was expressed in the retina as demonstrated for the first time with the help of in-situ hybridization and PCR. To characterize the visual phenotype, rats were examined by scotopic and photopic electroretinography and, additionally, histological analyses of the retinas were conducted. The complete loss of sight was detected along with a severe degeneration of photoreceptor cells. Interestingly, the manifestation of the disease does not solely depend on the mutation, but also on environmental factors. Since the LEW/Ztm-ci2 rat features the entire range of symptoms of the human Usher syndrome we think that this strain is an appropriate model for this disease. Our findings display that mutations in binding domains of myosin XV do not only cause non-syndromic hearing loss but can also lead to syndromic disorders including retinal dysfunction

Distributed Dynamical Computation in Neural Circuits with Propagating Coherent Activity Patterns

Activity in neural circuits is spatiotemporally organized. Its spatial organization consists of multiple, localized coherent patterns, or patchy clusters. These patterns propagate across the circuits over time. This type of collective behavior has ubiquitously been observed, both in spontaneous activity and evoked responses; its function, however, has remained unclear. We construct a spatially extended, spiking neural circuit that generates emergent spatiotemporal activity patterns, thereby capturing some of the complexities of the patterns observed empirically. We elucidate what kind of fundamental function these patterns can serve by showing how they process information. As self-sustained objects, localized coherent patterns can signal information by propagating across the neural circuit. Computational operations occur when these emergent patterns interact, or collide with each other. The ongoing behaviors of these patterns naturally embody both distributed, parallel computation and cascaded logical operations. Such distributed computations enable the system to work in an inherently flexible and efficient way. Our work leads us to propose that propagating coherent activity patterns are the underlying primitives with which neural circuits carry out distributed dynamical computation

Pan-Americanism; a forecast of the inevitable clash between the United States and Europe's victor,

Bibliography: p. 443-459.Mode of access: Internet

Pan-Germanism.

Bibliography: p.[309]-[314]Mode of access: Internet

The Presbyterian movement in the reign of Queen Elizabeth as illustrated by the Minute book of the Dedham classis, 1582-1589;

"A list of Puritan ministers concerned in the classical movement": p. xxxv-li."A bibliography": p. xxx-xxxiv.Introduction.--Bancroft's 'Dangerous positions.'--Minute book of the Dedham classis, 1582-1589.--Letters and papers illustrative of the 'Minute book.'Mode of access: Internet