Identification of a nonneuronal isoform of synaptotagmin.

Synaptotagmins, which have been found exclusively in neuroendocrine or exocrine tissues, have been implicated in the regulation of secretory vesicle fusion with the plasma membrane. The present paper describes a synaptotagmin isoform (synaptotagmin-5) which exhibits 49% amino acid identity to synaptotagmin-1 and -2. Synaptotagmin-5 mRNA is expressed in rat kidney, adipose tissue, lung, and heart, as well as at higher levels in brain and PC12 cells. Antiserum specific for the synaptotagmin-5 isoform recognizes a protein of about 50 kDa which is about 6-fold more abundant in brain synaptic vesicles than in whole brain membranes.

Alternative splicing generates a second isoform of the catalytic A subunit of the vacuolar H(+)-ATPase.

We have identified a second isoform of the catalytic A subunit of the vacuolar H+ pump in chicken osteoclasts. In this isoform (A2) a 72-bp cassette replaces a 90-bp cassette present in the classical A1 isoform. The A1-specific cassette encodes a region of the protein that contains one of the three ATP-binding consensus sequences (the P-loop) identified in this polypeptide, as well as the pharmacologically relevant Cys254. In contrast, the A2-specific cassette does not contain any of these features. These two isoforms, which appear to be ubiquitously expressed, are encoded by a single gene and are generated by alternative splicing of two mutually exclusive exons. The alternative RNA processing involves the recognition of a single site, the boundary between the A2- and A1-specific exons, as either acceptor (in A1) or donor (in A2) splice site.

Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein.

The beta-amyloid precursor protein (beta-APP), from which the beta-A4 peptide is derived, is considered to be central to the pathogenesis of Alzheimer disease (AD). Transgenic mice expressing the 751-amino acid isoform of human beta-APP (beta-APP751) have been shown to develop early AD-like histopathology with diffuse deposits of beta-A4 and aberrant tau protein expression in the brain, particularly in the hippocampus, cortex, and amygdala. We now report that beta-APP751 transgenic mice exhibit age-dependent deficits in spatial learning in a water-maze task and in spontaneous alternation in a Y maze. These deficits were mild or absent in 6-month-old transgenic mice but were severe in 12-month-old transgenic mice compared to age-matched wild-type control mice. No other behavioral abnormalities were observed. These mice therefore model the progressive learning and memory impairment that is a cardinal feature of AD. These results provide evidence for a relationship between abnormal expression of beta-APP and cognitive impairments.

Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors.

Calcium/phospholipid-dependent protein kinase (protein kinase C, PKC) has been suggested to play a role in the sensitivity of gamma-aminobutyrate type A (GABAA) receptors to ethanol. We tested a line of null mutant mice that lacks the gamma isoform of PKC (PKC gamma) to determine the role of this brain-specific isoenzyme in ethanol sensitivity. We found that the mutation reduced the amount of PKC gamma immunoreactivity in cerebellum to undetectable levels without altering the levels of the alpha, beta I, or beta II isoforms of PKC. The mutant mice display reduced sensitivity to the effects of ethanol on loss of righting reflex and hypothermia but show normal responses to flunitrazepam or pentobarbital. Likewise, GABAA receptor function of isolated brain membranes showed that the mutation abolished the action of ethanol but did not alter actions of flunitrazepam or pentobarbital. These studies show the unique interactions of ethanol with GABAA receptors and suggest protein kinase isoenzymes as possible determinants of genetic differences in response to ethanol.

Isolation of a differentially regulated splicing isoform of human NF-E2.

The transcription factor NF-E2 (nuclear factor erythroid 2), interacting via DNA motifs within regulatory regions of several hematopoietic genes, is thought to mediate the enhancer activity of the globin locus control regions. By screening a human fetal liver cDNA library with probes derived from mouse NF-E2, we have isolated a splicing variant of the NF-E2 gene (fNF-E2) that differs in the 5' untranslated region from the previously reported cDNA (aNF-E2). The fNF-E2 isoform is transcribed from an alternative promoter located in the 3' end of the first intron and joined by alternative splicing to the second and third exons, which are shared by both RNA isoforms. Although the two forms produce the same protein, they are expressed in different ratios during development. fNF-E2 is more abundant in the fetal liver and less abundant in the adult bone marrow compared to the previously described form. Their distribution apparently follows the differential expression of fetal and adult hemoglobins.

A classified catalogue of theological and religious books, comprising a large collection of standard works, American and foreign; old and rare works, and recent publications, to September 1, 1871. Also an addenda of miscellaneous literature, works of reference, &c. For sale by Smith, English & Co., booksellers and importers ...

Interleaved.

The pastrycook & confectioner's guide : for hotels, restaurants, and the trade in general adapted also for family use : including a large variety of modern recipes for bread, cakes, fancy biscuits, ice creams and water ices, jellies, pies, puddings and custards, joints, meat pies and dishes, poultry and game, ornamental sugar work & butter-work etc. : with useful hints and instructions /

"To build an ice-house": p. [57]-58.

Translation of documents presented by William R. Hearst before the Special Committee appointed pursuant to S. Res. 7, a resolution relative to the alleged payment of large sums of money by the government of Mexico to influence the official action of certain United States Senators.

David A. Reed, Chairman.

The Dominion of Canada ; containing a historical sketch of the preliminaries and organization of confederation ; also the vast improvements made ... for the past eighty years under the provincial names. With a large amount of statistical information. /

"Furnished to subscribers only."

Capacity testing in large canals of the Central Valley Project /

Mode of access: Internet.

Boyer's French dictionary: comprising all the additions and improvements of the latest Paris and London editions, with a very large number of useful words and phrases, now first selected from the modern dictionaries of Boiste, Wailly, Catineau, and others; with the pronunciation of each word, according to the dictionary of the Abbé Tardy: to which are prefixed, rules for the pronunciation of French vowels, diphthongs, and final consonants, chiefly collected from the prosody of the Abbé d'Olivet, with a table of French verbs, &c.

Acompañado de: An English-French dictionary, designed as a second part to the Boston edition of Boyer's French dictionary, with Tardy's pronunciation.

Patriotic recitations and readings, containing a large number of the most effective, eloquent, instructive and brilliant selections for Fourth of July, Decoration, Arbor and Labor Day, Washington and Lincoln's birthdays, and all other holiday celebrations.

Mode of access: Internet.

The American orator : with an appendix containing the Declaration of Independence, with the fac-similes of the autographs of the signers; the Constitution of the United States; Washington's Farewell Address; and fac-similes of the autographs of a large number of distinguished individuals /

Mode of access: Internet.

Radford's cyclopedia of cement construction; a general reference work on up-to-date practice in the manufacture and testing of cements; the selection of concreting materials, tools, and machinery; the proportioning, mixing, and depositing of concrete, and its application to all types and reinforced; together with analysis of the principles of constructive design, cost estimating, and the allied branches of stone and brick masonry and steel construction; based on the practical experience of a large staff of experts in actual construction work ...

"Prepared under the supervision of William A. Radford, editor-in-chief ... Alfred Sidney Johnson ... editor in charge."

The Chapin genealogy : containing a very large proportion of the descendants of Dea. Samuel Chapin, who settled in Springfield, Mass. in 1642 /

Mode of access: Internet.