Autocrine/paracrine regulation of breast cancer cell proliferation by growth hormone releasing hormone via Ras, Raf, and mitogen-activated protein kinase

Although GHRH has previously been shown to regulate proliferation of breast cancer cells and prevent apoptosis, the intracellular pathways mediating this effect have not been clarified. Exogenous GHRH stimulated a dose-dependent proliferative response within 24 h in MDA-231, as well as in T47D cells and in MCF-7 cells transfected with the GHRH receptor. The proliferation of MDA-MB-231 (MDA-231) cells was associated with an increase in tritiated thymidine uptake. In addition, phosphorylation of MAPK was rapidly stimulated by GHRH. The phosphorylation of MAPK by GHRH was prevented by transfection of the cells with dominant-negative Ras or Raf or by pretreatment of cells with Raf kinase 1 inhibitor. The inhibition of Ras and Raf, as well as the inhibition of MAPK phosphorylation by PD98059, also prevented GHRH-induced cell proliferation. Finally, pretreatment of cells with the somatostatin analog, BIM23014, also prevented GHRH-induced MAPK phosphorylation and cell proliferation. These results indicate that GHRH stimulates dose-dependent cell proliferation of MDA-231 breast cancer cells through a pathway that requires Ras, Raf, and MAPK phosphorylation. The results also provide support for a possible autocrine/paracrine antagonism between GHRH and somatostatin in the regulation of MDA-231 cell population maintenance. Taken together, the studies provide further insight into the possible role of GHRH as a growth factor in breast cancer.     

Recrafting the neighbor-joining method

Background  

The neighbor-joining method by Saitou and Nei is a widely used method for constructing phylogenetic trees. The formulation of the method gives rise to a canonical Θ(n ³) algorithm upon which all existing implementations are based.     

Frasnian vertebrate taphonomy and sedimentology of macrofossil concentrations from the Langsēde Cliff,Latvia

Luk?evi?s, E., Ahlberg, P.E., Stinkulis, ?., Vasi?kova, J. & Zupi??, I. 2011: Frasnian vertebrate taphonomy and sedimentology of macrofossil concentrations from the Langsēde Cliff, Latvia. Lethaia, Vol. 45, pp. 356–370. The siliciclastic sequence of the Upper Devonian of Kurzeme, Western Latvia, is renowned for abundant vertebrate fossils, including the stem tetrapods Obruchevichthys gracilis and Ventastega curonica. During the first detailed taphonomic study of the vertebrate assemblage from the Ogre Formation cropping out at the Langsēde Cliff, Imula River, abundant vertebrate remains have been examined and identified as belonging to one psammosteid, two acanthodian and three sarcopterygian genera; the placoderm Bothriolepis maxima dominates the assemblage. Besides fully disarticulated placoderm and psammosteid plates, separate sarcopterygian scales and teeth, and acanthodian spines, partly articulated specimens including complete distal segments of Bothriolepis pectoral fins, Bothriolepis head shields and sarcopterygian lower jaws have been found. The size distribution of the placoderm bones demonstrates that the individuals within the assemblage are of approximately uniform age. Distinct zones have been traced within the horizontal distribution of the bones. These linear zones are almost perpendicular to the dominant dip azimuth of the cross‐beds and ripple‐laminae and most probably correspond to the depressions between subaqueous dunes. Concavity ratio varies significantly within the excavation area. The degree of fragmentation of the bones and disarticulation of the skeletons suggest that the carcasses were reworked and slightly transported before burial. Sedimentological data suggest deposition in a shallow marine environment under the influence of rapid currents. The fossiliferous bed consists of a basal bone conglomerate covered by a cross‐stratified sandstone with mud drapes, which is in turn overlain by ripple laminated sandstone, indicating the bones were buried by the gradual infilling of a tidal channel. All the Middle–Upper Devonian vertebrate bone‐beds from Latvia are associated with sandy to clayey deposits and have been formed in a sea‐coastal zone during rapid sedimentation episodes, but differ in fossil abundance and degree of preservation. □Agnathans, Devonian, facies analysis, fish, fossil assemblage, palaeoenvironment.     

Tryptophan enhancement of somatic embryogenesis in rice

Cereal embryos can produce two types of callus. One type, termed “embryogenic,” consists of small meristematic-like cells and gives rise to many plants by somatic embryogenesis if placed on a suitable regeneration medium. The other is termed “nonembryogenic” and consists of long tubular cells which gives rise to few or no plants. High concentrations of tryptophan increased the formation of embryogenic callus in three rice cultivars (Oryza sativa L. Calrose 76, Pokkali, and IR 36) but not in four others (Mahsuri, Bg 400-1, H₄, and Giza 159). The best concentration of tryptophan for Pokkali and Calrose 76 was 100 micrograms per milliliter, and for IR 36, 50 micrograms per milliliter. Indoleacetic acid at 100 micrograms per milliliter promoted an effect similar to that of tryptophan on Calrose 76. The difference between japonica (Calrose 76, Giza 159) and indica (Pokkali, IR 36) varieties is not the causal factor for the difference in response to tryptophan. Kinetin does not appear to be a requirement for embryogenic callus formation in Calrose 76. Plant regeneration from Calrose 76 embryogenic callus occurred at low levels in media containing no hormones. 6-benzyladenine, or 2,3,5-triiodobenzoic acid but not indoleacetic acid at 0.1 to 0.5 micrograms per milliliter significantly increased regeneration.     

A tree-based method for the rapid screening of chemical fingerprints

Background  

The fingerprint of a molecule is a bitstring based on its structure, constructed such that structurally similar molecules will have similar fingerprints. Molecular fingerprints can be used in an initial phase of drug development for identifying novel drug candidates by screening large databases for molecules with fingerprints similar to a query fingerprint.     

New sensitive biological assay for 12,13-epoxytrichothecenes.

Germination of Nicotiana sylvestris pollen is inhibited by T2 toxin and diacetoxyscirpenol. Based on this observation, an assay method was developed that is capable of detecting nanogram quantities of these toxins.