5-Halo-6-alkoxy-5,6-dihydro-pyrimidine Nucleosides: Antiviral Nucleosides or Nucleoside Prodrugs?

Abstract

5-Halo-6-alkoxy-5,6-dihydro derivatives of azidothymidine (AZT) and ethyldeoxyuridine (EDU) were developed and evaluated using in vitro and in vivo models. Although most of these 5,6-dihydro derivatives served as prodrugs in improving sitespecific delivery and pharmacokinetic parameters, some unique characteristics were exhibited.     

Synthesis and Anti-Hiv Activity of 3′-0-Formyl Derivatives of Thymidine and 2′-Deoxyuridine

Abstract

Reaction of the 5′-O-t-butyldimethylsilyl derivatives of thymidine and 2′-deoxyuridine with the Vilsmeier reagent (POCI₃/DMF), and removal of the t–butyldimethylsilyl protecting group, afforded 3′-O-formylthymidine (5) and 3′-O-formyl-2′-deoxyuridine (6), respectively. In vitro evaluation, determined as the ability of the test compound to inhibit HIV induced cytopathogenicity in CEM cells, indicated that 5 was moderately active, whereas 6 was inactive.     

Basis for information transmission with biosignals for development of technical communication aids for handicapped patients]

For the design of communication aids controlled by biosignals for the handicapped, an analysis of the aspects of the significance of information is mandatory. The definition of information in its five aspects statistics, syntax, semantics, pragmatics and apobetics, enables us to conclude that the transmission of information is possible only with voluntarily influenceable biosignal components. The voluntary influencing of the biosignal may be interpreted as a modulation of the amplitude density of the Fourier integral. By calculating the highest possible statistical information content of a biosignal, it is possible to estimate the technical complexity of a biosignal-based communication system. The construction of efficient communication aids is possible when many biosignal components that can be readily and rapidly controlled voluntarily are to be found.     

A New Entodiniomorphid Ciliate,Troglocorys cava n. g., n. sp., from the Wild Eastern Chimpanzee (Pan troglodytes schweinfurthii) from Uganda

ABSTRACT. Troglocorys cava n. g., n. sp. is described from the feces of wild eastern chimpanzee, Pan troglodytes schweinfurthii, in Uganda. This new species has a spherical body with a frontal lobe, a long vestibulum, a cytoproct located at the posterior dorsal side of the body, an ovoid macronucleus, a contractile vacuole near the cytoproct, and a large concavity on the left surface of the body. Buccal ciliature is non‐retractable and consists of three ciliary zones: an adoral zone surrounding the vestibular opening, a dorso‐adoral zone extending transversely at the basis of the frontal lobe, and a vestibular zone longitudinally extending in a gently spiral curve to line the surface of the vestibulum. Two non‐retractable somatic ciliary zones comprise arches over the body surface: a short dorsal ciliary arch extending transversely at the basis of the frontal lobe and a wide C‐shaped left ciliary arch in the left concavity. Because of the presence of three ciliary zones in the non‐retractable buccal ciliature, the present genus might be a member of the family Blepharocorythidae, but the large left concavity and the C‐shaped left ciliary arch are unique, such structures have never been described from other blepharocorythids.     

Internal transcribed spacer polymorphism in Pseudo-nitzschia multistriata (Bacillariophyceae) in the Gulf of Naples: recent divergence or intraspecific hybridization?

The planktonic diatom Pseudo-nitzschia multistriata is a potentially toxic species recorded during late summer-autumn in the Gulf of Naples (Tyrrhenian Sea, Italy). We analysed the genetic structure by amplifying the internal transcribed spacer (ITS-1-5.8S-ITS-2) region of the ribosomal DNA of 44 strains isolated along 2 years. Polymorphism in the ITS region was detected by direct sequencing and the PCR-products from selected strains were thus cloned to assess intra-strain ITS variability. Strains clustered into three main types: type A and B - differing by 0.6% sequence divergence - and type A/B, showing both A and B variants within the same genome. The three types showed no differences in the large subunit sequences (LSU) of the rDNA, ultrastructure of the valve, secondary structure of ITS-1 and ITS-2, ploidy level and they were sexually compatible. Based on the results of these multiple approaches, we can state that the three ITS-types belong to the same reproductive unit (or "species" sensu Mayr [(1942). Systematics and the Origin of Species. Columbia University Press, New York]). We suggest that ITS polymorphism in P. multistriata may be related to the contemporary occurrence of different but still inbreeding populations which either diverged recently or originated in different geographic areas and became sympatric in the studied area.     

Negotiation of parental care when the stakes are high: experimental handicapping of one partner during incubation leads to short-term generosity

1. Most game theoretical models of biparental care predict that a reduction in care by one partner should not be fully compensated by increased work of its mate but this may not be true for incubating birds because a reduction in care could cause the entire brood to fail.
2. I performed the first handicapping experiment of both males and females during incubation, by placing small lead weights on the tails of male and female northern flickers Colaptes auratus , a woodpecker in which males do most of the incubation.
3. Females responded to the acute stressor (handling and handicapping) by tending to abandon more readily than males and staying away from the nest longer in the first incubation bout. Among pairs that persisted, both males and females compensated fully for a handicapped partner, keeping the eggs covered nearly 100% of the time.
4. Partners did not retaliate by forcing their handicapped mate to sit on the eggs with a long incubation bout length subsequent to having a long bout length themselves. Instead, during the 24 h immediately after handicapping, males behaved generously by relieving handicapped females early.
5. Such generosity was probably not energetically sustainable as these male partners took on less incubation in the 72 h following handicapping compared to female partners of handicapped males. Males and females are probably generous in the short-term because of the high cost of nest failure during incubation but maintaining increased work loads in the longer term is probably limited by body condition and abandonment thresholds consistent with game theory models.     

Expression of Trichoderma reesei cellulases CBHI and EGI in Ashbya gossypii

To explore the potential of Ashbya gossypii as a host for the expression of recombinant proteins and to assess whether protein secretion would be more similar to the closely related Saccharomyces cerevisiae or to other filamentous fungi, endoglucanase I (EGI) and cellobiohydrolase I (CBHI) from the fungus Trichoderma reesei were successfully expressed in A. gossypii from plasmids containing the two micron sequences from S. cerevisiae, under the S. cerevisiae PGK1 promoter. The native signal sequences of EGI and CBHI were able to direct the secretion of EGI and CBHI into the culture medium in A. gossypii. Although CBHI activity was not detected using 4-methylumbelliferyl-β-d-lactoside as substrate, the protein was detected by Western blot using monoclonal antibodies. EGI activity was detectable, the specific activity being comparable to that produced by a similar EGI producing S. cerevisiae construct. More EGI was secreted than CBHI, or more active protein was produced. Partial characterization of CBHI and EGI expressed in A. gossypii revealed overglycosylation when compared with the native T. reesei proteins, but the glycosylation was less extensive than on cellulases expressed in S. cerevisiae.