New approach for inhibiting Rev function and HIV-1 production using the influenza virus NS1 protein.

The Rev protein of HIV-1, which facilitates the nuclear export of HIV-1 pre-mRNAs, has been a target for antiviral therapy. Here we describe a new strategy for inhibiting Rev function and HIV-1 replication. In contrast to previous approaches, we use a wild-type rather than a mutant Rev protein and covalently link this Rev sequence to the NS1 protein of influenza A virus, a protein that inhibits the nuclear export of mRNAs. The NS1 protein contains an RNA-binding domain mutation (RM), so that the only functional RNA-binding domain in the chimeric protein (NS1RM-Rev) is in the Rev protein sequence. In the presence of the NS1RM-Rev chimeric protein, HIV-1 pre-mRNAs were retained in, rather than exported from, the nucleus. In addition, this chimeric protein effectively inhibited Rev function in trans in transfection experiments and effectively inhibited the production of HIV-1 in tissue culture cells transfected with an infectious molecular clone of HIV-1 DNA. The inhibitory activities of the NS1RM-Rev chimera were at least equivalent to those of the Rev M10 mutant protein, which has been considered to be the prototype trans inhibitor of Rev function and is currently in phase I clinical trials for the treatment of AIDS patients. We discuss (i) the potential for increasing the inhibitory activity of NS1-Rev chimeras against HIV-1 and (ii) the need for additional studies to evaluate these chimeras for the treatment of AIDS.

Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain.

The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age-related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.

Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo.

The yeast two-hybrid system and far-Western protein blot analysis were used to demonstrate dimerization of human double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in vivo and in vitro. A catalytically inactive mutant of PKR with a single amino acid substitution (K296R) was found to dimerize in vivo, and a mutant with a deletion of the catalytic domain of PKR retained the ability to dimerize. In contrast, deletion of the two dsRNA-binding motifs in the N-terminal regulatory domain of PKR abolished dimerization. In vitro dimerization of the dsRNA-binding domain required the presence of dsRNA. These results suggest that the binding of dsRNA by PKR is necessary for dimerization. The mammalian dsRNA-binding protein TRBP, originally identified on the basis of its ability to bind the transactivation region (TAR) of human immunodeficiency virus RNA, also dimerized with itself and with PKR in the yeast assay. Taken together, these results suggest that complexes consisting of different combinations of dsRNA-binding proteins may exist in vivo. Such complexes could mediate differential effects on gene expression and control of cell growth.

Osteology, function, and evolution of the Trematopsid (Amphibia: Labyrinthodontia) nasal region / [by] John R. Bolt --.

v.33:no.2(1974)

Collection of Harvard College admission form letter and bills sent to Charles Walker and his son Charles Walker, Jr., 1785-1816

This collection consists primarily of quarter bills and butler's bills from Charles Walker and Charles Walker, Jr.'s years as students at Harvard College, from 1785 to 1789 and from 1815-1816. It includes the following materials from Charles Walker: a form of admission (a printed form letter with manuscript annotations and signatures) from August 1785, quarter bills and butler's bills from 1785 to 1789, and occasional receipts of payment. The documents from Charles Walker, Jr. are less numerous, consisting solely of quarter bills from 1815 and 1816. The bills for father and son include annotations explaining the basis of additional or unusual charges, including fines for absence from lectures and prayers. The form used for the son's quarter bills, issued in 1815 and 1816, separate the amounts owed into the following categories: Steward and Commons, Sizings, Study and Cellar Rent, Instruction, Librarian, Natural History, Episcopal Church, Books, Catalogue and Commencement Dinner, Repairs, Sweepers, Assessments for delinquency in payment of Quarter Bills, Wood, and Fines. All of the bills are printed forms which were then filled out by hand, by either the steward or the butler, and issued to the students. Caleb Gannett was the College steward during both father and son's era. Joshua Paine, William Harris, and Thomas Adams served, successively, as butler during the father's era. Some of the butler's bills are signed by Roger Vose, a student who appears to have been employed by the butler in 1786 and 1787.

Ecosystem structure, function, and composition in rangelands are negatively affected by livestock grazing

Reports of positive or neutral effects of grazing on plant species richness have prompted calls for livestock grazing to be used as a tool for managing land for conservation. Grazing effects, however, are likely to vary among different response variables, types, and intensity of grazing, and across abiotic conditions. We aimed to examine how grazing affects ecosystem structure, function, and composition. We compiled a database of 7615 records reporting an effect of grazing by sheep and cattle on 278 biotic and abiotic response variables for published studies across Australia. Using these data, we derived three ecosystem measures based on structure, function, and composition, which were compared against six contrasts of grazing pressure, ranging from low to heavy, two different herbivores (sheep, cattle), and across three different climatic zones. Grazing reduced structure (by 35%), function (24%), and composition (10%). Structure and function (but not composition) declined more when grazed by sheep and cattle together than sheep alone. Grazing reduced plant biomass (40%), animal richness (15%), and plant and animal abundance, and plant and litter cover (25%), but had no effect on plant richness nor soil function. The negative effects of grazing on plant biomass, plant cover, and soil function were more pronounced in drier environments. Grazing effects on plant and animal richness and composition were constant, or even declined, with increasing aridity. Our study represents a comprehensive continental assessment of the implications of grazing for managing Australian rangelands. Grazing effects were largely negative, even at very low levels of grazing. Overall, our results suggest that livestock grazing in Australia is unlikely to produce positive outcomes for ecosystem structure, function, and composition or even as a blanket conservation tool unless reduction in specific response variables is an explicit management objective.

The leopard's claw : a thrilling story of love and adventure from a European castle through the West African jungle, disclosing a deep insight into the quality and spiritual influence of African social institutions and conditions, and revealing a profound psyschic [sic] interpretation of African inner life, all clustered about the mysterious function and significance of the leopard's claw /

Mode of access: Internet.

Path integral calculation of the three-particle direct and exchange contributions to the pair distribution function and of the third virial coefficient for He4 gas /

Thesis--Illinois.

DDT in the diet of the rat; its effect on DDT storage, liver function, and cell morphology

Bibliography: p. 26-27.

The zeros and maxima of the Airy function and its first derivative to 25 significant figures.

Mode of access: Internet.

Manual of suggestions in form, drawing, and color for the public schools of the state of New York; based upon the official documents issued by the Board of regents and the Department of public instruction in the state of New York, specially arranged to meet the requirements for regents' and uniform examinations in these subjects,

Mode of access: Internet.