A two-fold (C2) symmetric inhibitor of the protease of human immunodeficiency virus type-1 (HIV-1) has been designed on the basis of the three-dimensional symmetry of the enzyme active site. The symmetric molecule inhibited both protease activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against HIV-1 protease than against related enzymes, and appeared to be stable to degradative enzymes. The 2.8 angstrom crystal structure of the inhibitor-enzyme complex demonstrated that the inhibitor binds to the enzyme in a highly symmetric fashion.

Amylin is a 37-amino acid peptide first isolated, purified, and characterized from the amyloid deposits in the pancrease of type 2 diabetics. It is synthesized and secreted primarily from pancreatic beta cells along with insulin. The ability of amylin to potently reduce insulin-stimulated incorporation of glucose into glycogen in skeletal muscle requires both an intact 2Cys-7Cys disulfide bond and a COOH-terminal amide. Amylin has structural and functional relationships to two other messenger proteins, calcitonin and CGRP. Amylin has relatively potent calcitonin-like activity on bone metabolism and weaker CGRP-like activity on the vasculature. CGRP is a slightly weaker agonist than amylin for metabolic responses. Although rat calcitonins are weak, teleost fish calcitonins are very potent agonists for amylin's metabolic effects. This group of peptides appears to act on a family of related G protein-coupled receptors; several variant calcitonin receptors have recently been cloned and expressed. These receptors appear to be coupled to adenylyl cyclase in many instances; recent evidence supports the view that amylin's effects on skeletal muscle occur, at least in large part, through activation of the cAMP pathway.

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ABSIRACT Total RNA, prepared from immature or mature mouse testes or from spermatogenic cells separated on the basis of sedimentation velocity, was translated in vitro. Mouse protamine-like histone could be identified as an in vitro translational product when [3]arginine was used as the label. The mRNA for protamine-like histone was detected only after meiosis; the appearance of a peak of radioactivity comigrating with protamine-like histone occurred only when RNA from mature testes or late spermatid cell fractions was translated. Phosphoglycerate kinase-2 (ATP:3-phospho Dglycerate 1-phosphotransferase, EC 2.7.2.3) was identified as an in vitro translational product by affinity chromatography followed by two-dimensional gel electrophoresis or by specific immunoprecipitation when [35Sjmethionine was the labeL The mRNA for phosphoglycerate kinase-2 was detected only in mature testes or late spermatid cell fractions. These translational assays for protamine-like histone and phosphoglycerate kinase-2 mRNAs suggest that these messages are transcribed after meiosis.it is usually considered that sperm function depends little or not at all on the genotype of the sperm but mainly or only on the diploid genotype of the male, and that all four products of meiosis form functional sperm (1). Thus, it has been generally assumed that postmeiotic (i.e., haploid) gene transcription does not occur. There are two lines of argument for the alternative view in mammals First, although Mendelian transmission ratios require gamete equivalence, this could be accomplished in other ways than eliminating postmeiotic gene transcription. The large intercellular bridges connecting all spermatids allow a sharing of gene products and would contribute greatly to gametic equivalence (2). Second, the appearance of sperm specific proteins after meiosis requires new transcription or the use of stored mRNA. There is little evidence for the use of stored mRNA in mammalian embryogenesis, in contrast to the situation in lower vertebrates (3, 4). The situation remains to be explored for mammalian gametogenesis.Evidence for postmeiotic RNA synthesis was first provided by Monesi (5), who demonstrated that early mouse spermatids exposed to short pulses of [3H]uridine showed a small peak of incorporation when examined by autoradiography. Quantitative autoradiographic studies showed that the rate of RNA synthesis per cell decreased only 75% during meiosis in the ram testis; i.e., the RNA synthesis/DNA ratio was essentially unchanged (6). The newly synthesized RNA from separated, postmeiotic spermatogenic cells has been characterized by size and by the percentage of the RNA transcripts that contain poly(A) tracts (7,8). By these criteria, synthesis of putative mRNA remains at about the same level in early postmeiotic as compared to late premeiotic cells.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact...