Description of the first definitive Corythosaurus (Dinosauria, Hadrosauridae) specimens from the Judith River Formation in Montana, USA and their paleobiogeographical significance.

Despite the long history of research in the late Campanian Judith River Formation in northern Montana, most of the vertebrate fossils are represented by fragmentary remains, making precise taxonomic identifications difficult. Contrary to this, the partially contemporaneous Dinosaur Park Formation, Alberta, Canada is known for its tremendous fossil preservation, permitting rigorous studies of dinosaur diversity, evolution, and biostratigraphy. Hadrosaurids comprise one of the most abundant dinosaur clades in the Dinosaur Park Formation, but taxonomic affinities of hadrosaurid specimens remain poorly understood in the Judith River Formation.

Kantis: A new Australopithecus site on the shoulders of the Rift Valley near Nairobi, Kenya.

Most Plio-Pleistocene sites in the Gregory Rift Valley that have yielded abundant fossil hominins lie on the Rift Valley floor. Here we report a new Pliocene site, Kantis, on the shoulder of the Gregory Rift Valley, which extends the geographical range of Australopithecus afarensis to the highlands of Kenya. This species, known from sites in Ethiopia, Tanzania, and possibly Kenya, is believed to be adapted to a wide spectrum of habitats, from open grassland to woodland.

Influence of 3'-azido-2',3'-dideoxyguanosine treatment on telomere length in human telomerase-immortalized human fibroblast cells.

In order to study telomerase activation in normal cells, a telomerase-immortalized fibroblast cell line, hTERT-BJ1, treated with a telomerase inhibitor, 3'-azido-2',3'-dideoxyguanosine (AZddG), is considered to be a good model. Long-term treatment with AZddG resulted in telomere shortening from 10-20 kbp to 5-6 kbp in cultured hTERT BJ1 cells. However, the telomere length then stabilized.

Influence of 3'-azido-2',3'-dideoxyguanosine treatment on amounts of TERT and POT1 in human HL60 cells.

In human cells, TERT (telomerase reverse transcriptase) is involved in the synthesis of telomere DNA, and POT1 (protection of telomeres 1) is believed to be a regulator of telomere length. We have reported that long-term treatment of human HL60 cells with 50 microM 3'-azido-2',3'-dideoxyguanosine (AZddG) caused telomeres to shorten significantly during early passages (up to 40-50 days), but that telomere length was then stabilized at approximately 2 kbp during later passages. Additionally, cell growth rates showed no obvious change during culture in the presence of 50 microM AZddG.

Production of the oocyte maturation-inducing substance of starfish by heat treatment of s-adenosylmethionine.

1-Methyladenine (1-MeA) has been identified as the oocyte maturation-inducing substance (MIS) in starfish, but little is known about its biosynthesis. This study showed that starfish MIS activity was present in a reactant derived from S-adenosylmethionine (SAM) by heat treatment. In vitro MIS production was markedly dependent on the temperature of the SAM solution: it increased as the temperature was raised, and reached a plateau within 5 min upon boiling, although hardly only MIS was observed upon incubation below 20 degrees C.

Telomere shortening in human HL60 cells by treatment with 3'-azido-2',3'-dideoxynucleosides and telomerase inhibition by their 5'-triphosphates.

Telomerase is thought to play an important role in the mechanism of tumor cell immortalization by maintenance of telomere length. To obtain information on the susceptibility of telomerase to nucleoside analogues, the effects of base-modified 3'-azido-2',3'-dideoxynucleoside triphosphates on the enzyme were investigated. It is suggested that the 2-amino group of the nucleotide purine nucleus is important for the inhibitory activity.

Influence of nucleoside analogue treatment on telomere length and TRF2 amount in human HL60 cells.

Long-term treatment with 3'-azido-2',3'-dideoxy-guanosine (AZddG) results in reproducible telomere shortening in cultured human HL60 cells. TRF2 protein has been implicated in the protection of chromosome ends. It binds to double-strand repeats and may have an indirect role in protecting the G-rich overhang by recruiting other telomere-binding proteins to the G-tail or by mediating the formation of the telomeric t-loop.

A new Late Miocene great ape from Kenya and its implications for the origins of African great apes and humans.

Extant African great apes and humans are thought to have diverged from each other in the Late Miocene. However, few hominoid fossils are known from Africa during this period. Here we describe a new genus of great ape (Nakalipithecus nakayamai gen.

3'-Azido-2',3'-dideoxynucleoside 5'-triphosphates inhibit telomerase activity in vitro, and the corresponding nucleosides cause telomere shortening in human HL60 cells.

Telomerase adds telomeric DNA repeats to the ends of linear chromosomal DNA. 3'-Azido-3'-deoxythymidine 5'-triphosphate (AZTTP) is a known telomerase inhibitor. To obtain more selective and potent inhibitors that can be employed as tools for studying telomerase, we investigated the telomerase-inhibitory effects of purine nucleosides bearing a 3'-down azido group: 3'-azido-2',3'-dideoxyguanosine (AZddG) 5'-triphosphate (AZddGTP), 3'-azido-2',3'-dideoxy-6-thioguanosine (AZddSG) 5'-triphosphate (AZddSGTP), 3'-azido-2',3'-dideoxyadenosine (AZddA) 5'-triphosphate (AZddATP) and 3'-azido-2',3'-dideoxy-2-aminoadenosine (AZddAA) 5'-triphosphate (AZddAATP).

Telomerase inhibition by 3'-azido-2', 3'-dideoxynucleoside 5'-triphosphates and telomere shortening in human cultured cells by the corresponding nucleosides.

Telomerase is believed to be a good target for the development of antitumor agents. In this study, 3'-azido-2',3'-dideoxy-2-aminoadenosine (AZddAA), 3'-azido-2',3'-dideoxyadenosine (AZddA), 9-(3-azido-2,3-dideoxy-beta-D-ribofuranosyl)-2-aminopurine (AZddAP), 3'-azido-2-chloro-2',3'-dideoxyadenosine (AZddClA) and their triphosphate derivatives were synthesized. Telomerase assay studies showed that the 2-amino group plays an important role in the inhibitory activity of these compounds.

Influence of long-term treatment with cytosine arabinoside on telomere length in human HL60 cells.

Immortal tumor cells employ a telomere length maintenance mechanism to escape the normal limits on proliferation. We investigated whether treatment with cytosine arabinoside (AraC), whose triphosphate derivative AraCTP might partially inhibit the synthesis of C-rich telomere strands, is effective for inducing telomere shortening in human HL60 cells. Long-term treatment with 0.

Telomere shortening in human HL60 cells by treatment with deoxyguanosine analogs.

Telomerase is a cellular endogenous reverse transcriptase thought to play an important role in the maintenance of telomere length. We investigated the effects of 3'-azido-2',3'-dideoxyguanosine (AZddG) and carbocyclic oxetanocin G (C.OXT-G), of which the triphosphate derivatives AZddGTP and C.

Synthetic nucleosides and nucleotides. 43. Inhibition of vertebrate telomerases by carbocyclic oxetanocin g (C.OXT-G) triphosphate analogues and influence of C.OXT-G treatment on telomere length in human HL60 cells.

Telomerase, responsible for telomere synthesis, is expressed in approximately 90% of human tumor cells but seldom in normal somatic cells. In this study, inhibition by carbocyclic oxetanocin G triphosphate (C. OXT-GTP) and its analogues was investigated in order to clarify the susceptibility of telomerase to various nucleotide analogues.

Inhibition of vertebrate telomerases by the triphosphate derivatives of some biologically active nucleosides.

In order to clarify the effect of the base moiety of nucleotide analogs on telomerase inhibition, triphosphate derivatives of biologically active nucleosides, 3'-azido-3'-deoxythymidine (AZT), 2'-deoxy-2'-fluoroarafuranosylthymine (FaraT), acycloguanosine (ACG) and their guanine or thymine counterparts (AZdG, FaraG and ACT, respectively) were investigated. In all of the present cases, guanine derivatives showed more potent inhibition than their thymine counterparts.

Inhibition of vertebrate telomerases by the triphosphate derivatives of carbocyclic oxetanocin analogs.

Telomerase is a cellular endogenous reverse transcriptase that uses its internal RNA as a template for extension of the telomere repeat, thus maintaining telomere length. In order to clarify the susceptibility of telomerase to triphosphate derivatives of carbocyclic oxetanocins, inhibition by 9-[trans-trans-2,3-bis(hydroxymethyl)cyclobutyl]guanine triphosphate (C.OXT-GTP) and its methylene analog, 9-(cis-3-hydroxymethyl-2-methylenecyclobutyl)guanine triphosphate (m-C.

Inhibition of human telomerase by nucleotide analogues bearing a hydrophobic group.

Telomerase, which synthesizes telomeric DNA in eukaryotic cells, is classified as a reverse transcriptase. To clarify the susceptibility of telomerase to nucleoside 5'-triphosphates bearing a hydrophobic group on the base moiety, we studied the inhibitory effects of 2',3'-dideoxy-5-styryluridine 5'-triphosphate analogues and 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino)purine 5'-triphosphate analogues on telomerase activity using a quantitative 'stretch PCR' assay. 2',3'-Dideoxy-5-styryluridine 5'-triphosphate (StddUTP) showed more potent inhibition than 2',3'-dideoxythymidine 5'-triphosphate (ddTTP).

Telomerase-inhibitory effects of sugar-modified nucleotide analogs.

Telomerase is an endogenous reverse transcriptase that uses its internal RNA moiety as a template for the synthesis of telomere repeats, thus maintaining telomere length. To study the susceptibility of telomerase to sugar-modified nucleotide analogs, inhibition by arabinofuranosylguanine 5'-triphosphate (araGTP), 3'-azido-2',3'-dideoxyguanosine 5'-triphosphate (AZdGTP), 2',3'-dideoxy-2'-fluoroarabino-furanosylguanine 5'-triphosphate (FaraGTP), and their thymine counterparts was investigated. Among these compounds, all dGTP analogs showed potent inhibitory activity against human telomerase.

Telomerase-inhibitory effects of the triphosphate derivatives of some biologically active nucleosides.

Telomerase is a ribonucleoprotein reverse transcriptase that uses its internal RNA moiety as a template for synthesis of telomere repeats. To clarify the susceptibility of telomerase to HIV-1 reverse transcriptase inhibitors (RT), we investigated the inhibitory effects of 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP), which is known to be a potent HIV-1 RT inhibitor, and acyclovir triphosphate (ACVTP). Lineweaver-Burk plot analyses showed that the inhibition mode of these compounds was competitive with the substrate dNTP counterpart.

Molecular action mode of Hippospongic acid A, an inhibitor of gastrulation of starfish embryos.

Hippospongic acid A (HA-A) is a novel natural triterpene metabolite that exhibits inhibitory activity against the gastrulation of starfish embryos isolated from a marine sponge, Hippospongia sp. We succeeded in chemically synthesizing the natural enantiomer and the racemate HA-A. In this study, we examined its action mode in vitro.

Kohamaic acid A, a novel sesterterpenic acid, inhibits activities of DNA polymerases from deuterostomes.

We previously found and isolated a novel natural product, designated kohamaic acid A (KA-A), which inhibited the first cleavage of fertilized sea urchin eggs. In this paper, we report that this compound could selectively inhibit the activities of DNA polymerases (pol. alpha, beta, gamma, delta and epsilon ) only from species in the deuterostome branch in the animal kingdom, like sea urchin, fish and mammals, but not from protostomes including insects (fruit fly, Drosophila melanogaster) and mollusks (octopus and oyster).

A sulphoquinovosyl diacylglycerol is a DNA polymerase epsilon inhibitor.

Sulphoquinovosyl diacylglycerol (SQDG) was reported as a selective inhibitor of eukaryotic DNA polymerases alpha and beta [Hanashima, Mizushina, Ohta, Yamazaki, Sugawara and Sakaguchi (2000) Jpn. J. Cancer Res.

Synthesis and antiherpesvirus activities of 5-alkyl-2-thiopyrimidine nucleoside analogues.

Twenty 5-alkyl-2-thiopyrimidine nucleosides were newly synthesized and examined for antiviral activities against herpes simplex virus (HSV), varicella-zoster virus (VZV) and human cytomegalovirus (HCMV). In this study, 2'-deoxy-5-alkyl-2-thiocytidine analogues had lower 50% effective concentration (EC50) values against HSV-1, and 2'-deoxy-5-alkyl-2-thiouridine analogues showed lower EC50 against VZV than their congeners of arabinoside form. Among the compounds examined, 2'-deoxy-5-ethyl and 5-propyl-2-thiocytidine (TN-53 and TN-54) were most potent and selective anti-HSV compounds.

Tissue-specific expression of rhamnose-binding lectins in the steelhead trout (Oncorhynchus mykiss).

Tissue-specific expression of three L-rhamnose-binding lectins, named STL1, STL2, and STL3, in the steelhead trout (Oncorhynchus mykiss) was investigated. STL2 and STL3 mRNAs were restricted in the oocytes. In contrast, STL1 mRNA was detected only in the liver.

Distribution and molecular evolution of rhamnose-binding lectins in Salmonidae: isolation and characterization of two lectins from white-spotted Charr (Salvelinus leucomaenis) eggs.

L-Rhamnose-binding lectins were isolated from white-spotted charr (Salvelinus leucomaenis) eggs to understand the distribution and molecular evolution of the lectins in Salmonidae. Only two L-rhamnose-binding lectins, named WCL1 and WCL3, were isolated from white-spotted charr eggs, though three lectins, named STL1, STL2, and STL3, had been obtained from steelhead trout (Oncorhynchus mykiss) eggs. The cDNAs of WCL1 and WCL3 included 1,245 and 838 bp nucleotides with open reading frames of 933 and 651 nucleotides, respectively, and encoded for the complete amino acid sequences of mature proteins consisted of 288 (WCL1) and 195 (WCL3) residues, and signal sequences of 23 and 22 residues, respectively.