Expression and function of $\beta$-1,4-galactosyltransferase during wild-type and T/{\it t\/} -mutant spermatogenesis

In the mouse, gamete recognition is mediated in part by the binding of sperm surface $\beta$1,4 galactosyltransferase (GalTase) to specific oligosaccharide residues on the zona pellucida ZP3. The expression of GalTase on the sperm surface is regulated by alleles within the distal segment of the T/t complex and results in a haploid-specific increase in GalTase expression on spermatids and sperm from t-bearing males, suggesting that differences in sperm GalTase activity may contribute to t-sperm transmission ratio distortion. In this study, the expression of GalTase RNA during wild-type and T/t-mutant spermatogenesis was characterized and the role of GalTase was analyzed in transmission ratio distortion. It was found that spermatogenic cells predominantly express the long form of the GalTase RNA, which encodes the GalTase protein that is preferentially targeted to the cell surface in somatic cells. In wild-type testes, GalTase RNA accumulates during the maturation of primary spermatocytes, reaches peak levels prior to meiosis, and decreases and meiosis. GalTase RNA accumulates to similar levels during the maturation of +/t and t/t primary spermatocytes, but unlike wild-type, the level of GalTase RNA in t-spermatocytes remains elevated during meiotic division. Consequently, spermatids in t-mutant testes inherit higher levels of GalTase RNA than do wild-type spermatids, which likely accounts for the haploid-specific increase in surface GalTase activity characteristic of spermatids from t-bearing mice.^ The functional significance of the increased GalTase activity during t-sperm transmission ratio distortion was determined by examining the distribution of GalTase RNA and surface GalTase protein in haploid spermatids from +/t males. Results show that +- and t-spermatids have similar levels of both GalTase RNA and protein, indicating that transmission ratio distortion in +/t mice is not likely due to haploid-specific differences in sperm surface GalTase activity.^ The presence of GalTase on the surface of an early spermatogenic cells before it is required on the mature sperm to perform its function during gamete binding suggests a separate function for GalTase in Sertoli-germ cell adhesion. Studies indicate that cell surface GalTase partly mediates the initial adhesion of pachytene spermatocytes, but not haploid spermatids, to Sertoli cells. ^

PML tumor suppressor potentiates cell death through inhibition of the NF -kappa B survival pathway

The promyelocytic leukemia protein PML is a growth suppressor essential for induction of apoptosis by diverse apoptotic stimuli. The mechanism by which PML regulates cell death remains unclear. In this study we found that ectopic expression of PML potentiates cell death in the TNFα-resistant tumor line U2OS and significantly sensitized these cells to apoptosis induced by TNFα in a p53-independent manner. Our study demonstrated that both PML and PML/TNFα-induced cell death are associated with DNA fragmentation, activation of caspase-3, -7, -8, and degradation of DFF/ICAD. Furthermore, we found that PML-induced and PML/TNFα-induced cell death could be blocked by the caspase-8 inhibitors crmA and c-FLIP, but not by Bcl-2, the inhibitor of mitochondria-mediated apoptotic pathway. These findings indicate that this cell death event is initiated through the death receptor-dependent apoptosis pathway. Our study further showed that PML recruits NF-kappa B (NF-κB) to the PML nuclear body, blocks NF-κB binding to its cognate enhancer, and represses its transactivation function with the C-terminal region. Therefore PML inhibits the NF-κB survival pathway. Overexpression of NF-κB rescued cell death induced by PML and PML/TNFκ. These results imply that PML is a functional repressor of NF-κB. This notion was further supported by the finding that the PML−/− mouse embryo fibroblasts (MEFs) are more resistant than the wild-type MEFs to TNFκ-induced apoptosis. In conclusion, our studies convincingly demonstrated that PML potentiates cell death through inhibition of the NF-κB survival pathway. Activation of NF-κB frequently occurs during oncogenesis. Our study here suggests that a loss of PML function enhances the NF-κB survival pathway and this event may contribute to tumorigenesis. ^

Tramas intergenéricas en el relato Lucaniano del 'día después' (B.C., VII, 786-846)

La escena del campo de batalla tras el enfrentamiento entre pompeyanos y cesarianos en el libro VII del Bellum Ciuile de Lucano (786-846) deja al descubierto el proceso de refuncionalización del tópico tradicional del día después de la lucha. Desde una perspectiva estilística mostramos que la intersección entre los códigos historiográfico, épico y trágico y la manipulación de diversos motivos literarios y culturales en dicho relato pueden leerse como uno de los principales mecanismos de la poética lucaniana del ciuile nefas.

Tramas intergenéricas en el relato Lucaniano del 'día después' (B.C., VII, 786-846)

La escena del campo de batalla tras el enfrentamiento entre pompeyanos y cesarianos en el libro VII del Bellum Ciuile de Lucano (786-846) deja al descubierto el proceso de refuncionalización del tópico tradicional del día después de la lucha. Desde una perspectiva estilística mostramos que la intersección entre los códigos historiográfico, épico y trágico y la manipulación de diversos motivos literarios y culturales en dicho relato pueden leerse como uno de los principales mecanismos de la poética lucaniana del ciuile nefas.

Tramas intergenéricas en el relato Lucaniano del 'día después' (B.C., VII, 786-846)

La escena del campo de batalla tras el enfrentamiento entre pompeyanos y cesarianos en el libro VII del Bellum Ciuile de Lucano (786-846) deja al descubierto el proceso de refuncionalización del tópico tradicional del día después de la lucha. Desde una perspectiva estilística mostramos que la intersección entre los códigos historiográfico, épico y trágico y la manipulación de diversos motivos literarios y culturales en dicho relato pueden leerse como uno de los principales mecanismos de la poética lucaniana del ciuile nefas.

Table I: Schedule of the drilling operation and lengths of the recovered core material for the boreholes on Vernagtferner in 1979

In 1979 a core drilling project was carried out on Vernagtferner in the Oetztal Alps (Austria). This report describes the field work of the drilling project, the recovered core material and the occurrence of water in the boreholes and compiles the succeding investigation program.