Ion channel genes and human neurological disease: Recent progress, prospects, and challenges

What do epilepsy, migraine headache, deafness, episodic ataxia, periodic paralysis, malignant hyperthermia, and generalized myotonia have in common? These human neurological disorders can be caused by mutations in genes for ion channels. Many of the channel diseases are “paroxysmal disorders” whose principal symptoms occur intermittently in individuals who otherwise may be healthy and active. Some of the ion channels that cause human neurological disease are old acquaintances previously cloned and extensively studied by channel specialists. In other cases, however, disease-gene hunts have led the way to the identification of new channel genes. Progress in the study of ion channels has made it possible to analyze the effects of human neurological disease-causing channel mutations at the level of the single channel, the subcellular domain, the neuronal network, and the behaving organism.

Chimeric plant calcium/calmodulin-dependent protein kinase gene with a neural visinin-like calcium-binding domain.

Calcium, a universal second messenger, regulates diverse cellular processes in eukaryotes. Ca2+ and Ca2+/calmodulin-regulated protein phosphorylation play a pivotal role in amplifying and diversifying the action of Ca(2+)-binding domain was cloned and characterized from lily. The cDNA clone contains an open reading frame coding for a protein of 520 amino acids. The predicted structure of CCaMK contains a catalytic domain followed by two regulatory domains, a calmodulin-binding domain and a visinin-like Ca(2+)-binding domain. The amino-terminal region of CCaMK contains all 11 conserved subdomains characteristic of serine/threonine protein kinases. The calmodulin-binding region of CCaMK has high homology (79%) to alpha subunit of mammalian Ca2+/calmodulin-dependent protein kinase. The calmodulin-binding region is fused to a neural visinin-like domain that contains three Ca(2+)-binding EF-hand motifs and a biotin-binding site. The Escherichia coli-expressed protein (approximately 56 kDa) binds calmodulin in a Ca(2+)-dependent manner. Furthermore, 45Ca-binding assays revealed that CCaMK directly binds Ca2+. The CCaMK gene is preferentially expressed in developing anthers. Southern blot analysis revealed that CCaMK is encoded by a single gene. The structural features of the gene suggest that it has multiple regulatory controls and could play a unique role in Ca2+ signaling in plants.

Frozen flowers. March 1952 [Dr. Elzada Clover and botany students]

On negative sleeve: Dr. Elzada Clover, associate professor of botany, (second from right) distributes frozen water lily buds to botany students at the U of M. Students are (left and right) Mrs. Benson Murray, N.Y.; Oka Nichols, Crawfordsville, Ind.; and Nancy Pridmore, Oxford, Mich. Frozen flowers are kept in regular cardboard containers with transparent tops

A shorte introduction of grammar /

Facsimile reprint of edition London, 1567.

A shorte introduction of grammar,

T.-p. reads: ... A shorte introdvction of grammar generally to be vsed: compiled and set forth, for the bringing vp of all those that intende to attaine the knowledge of the Latine tongue. 1567.

The sett and weaving of tartans /

Cover title.

The new American cook book.

Illustrated lining-papers in colors.

Missa sacratissimi rosarii Beatissimae Virginis Mariae : priuilegiata a domino nostro Papa Paulo III. et Gregorio Decimotertio : cum missis de S. Angelo Custode, de S. Gregorio papa conf. & Ecclesiae doctore, de Sancto Carolo episcopo, ac de Sanctis Quindecim Auxiliatoribus.

Woodcut Giunta lily and small ill. on t.p. Initials. Printed in red and black throughout.

The works of Anatole France in an English translation.

Imprint varies slightly.

Descriptio Britanniae, Scotiae, Hyberniae, et Orchadum ex libro Pauli Iouii ... de imperiis, et gentibus cogniti orbis, cum eius operis prohoemio ...

Incluye dos obras históricas sobre Inglaterra por Georges Lily: h. 45-54, Virorum aliquot in Britannia, qui nostro seculo eruditione, & doctrina clari, memorabilesque suerunt, Elogia; h. 57-60 A Bruto Britannicae gentis authore, omnium in quos variante fortuna Britanniae imperium traslata. Incluye una crónica de reyes ingleses, h. 61-125 con título en página: Anglorum regum chronicum.

The Rumford complete cook book,

Advertising matter: p. 239-241.

The accidence; or, First rudiments of the Latin tongue, for the useof youth.

Mode of access: Internet.

"The ladies!" a shining constellation of wit and beauty,

The diurnal of Mrs. Elizth Pepys.--The mystery of Stella.--My lady Mary.--The golden vanity.--The Walpole beauty.--A bluestocking at court.--The Darcys of Rosing.