The modulation of the induction of ornithine decarboxylase by spermine,spermidine and diamines

Extremely low concentrations of putrescine, spermidine and spermine added to the extracellular medium of cultures of mammalian cells inhibit the induction of ornithine decarboxylase activity despite 100- to 1,000-fold greater intracellular polyamine concentrations. The diamines, 1,2-diaminoethane, 1,3-diaminopropane, 1,5-diaminopentane, 1,7-diaminoheptane, 1,10-diaminodecane, 1,12-diaminododecane also inhibit ornithine decarboxylase at all concentrations tested (greater than 10^?6 M). In contrast, 10^?6 M to 10 ^?3 M 1,8-diaminooctane, the alkyl analog of spermidine, enhances ornithine decarboxylase activity. The concentraton of putrescine required to inhibit the activity of ornithine decarboxylase by 50% is a characteristic of each cell line; however, it varies by as much as 1,000-fold among the five cell lines we have tested (L1210 leukemic, H35 hepatoma, N18 neuroblastoma, W256 carcinosarcoma and 3T3 fibroblasts). The antizyme to ornithine decarboxylase can be induced in all these cells by high (di)(poly)amine concentrations. Based on these and other experiments we suggest a working hypothesis: that the polyamines regulate ornithine decarboxylase activity through two different sites that may be interrelated; a sensitive membrane-mediated site that responds to minute fluctuations of extracellular polyamine levels and a coarse site which may be intracellular or membrane associated that responds to larger fluctuations of intracellular polyamine levels. The consequences of such a control mechanism operating within the whole organism are discussed.     

Neutralization of BDNF Attenuates the in vitro Protective Effects of Olfactory Ensheathing Cell-Conditioned Medium on Scratch-Insulted Retinal Ganglion Cells

Transplantation of olfactory ensheathing cells (OECs) becomes one of the promising strategies in restoring lost functions of injured central nervous system. Elevated level of expressed brain-derived neurotrophic factor (BDNF) was revealed in the previous studies to be related to the protective effects of OECs on injured cortical and brain stem neurons as well as retinal ganglion cells (RGCs), but no evidence has been obtained to demonstrate whether transplanted OECs protect injured central neurons directly by their secreted BDNF. In the present study, the effects of BDNF neutralization on the neuroprotection of adult OEC-conditioned medium (OEC-CM) on scratch-insulted RGCs were examined. The results showed that OEC-CM protected cultured RGCs from scratch insult, and neutralization of BDNF by BDNF neutralizing antibody attenuated such neuroprotection of the medium. It is thus concluded that neurotrophic factors including BDNF secreted by OECs can protect injured OECs in vitro and BDNF plays a major role in such a protection of OECs.     

Synergistic actions between the SRP RNA and translating ribosome allow efficient delivery of the correct cargos during cotranslational protein targeting

During cotranslational protein targeting by the Signal Recognition Particle (SRP), the correct cargo accelerates stable complex assembly between the SRP and SRP receptor (FtsY) by several orders of magnitude, thus enabling rapid and faithful cargo delivery to the target membrane. The molecular mechanism underlying this cargo-induced rate acceleration has been unclear. Here we show that the SRP RNA allows assembly of the SRP-FtsY complex to be specifically stimulated by a correct cargo, and, reciprocally, a correct cargo enables the SRP RNA to optimize its electrostatic interactions with FtsY. These results combined with recent structural work led us to suggest a "conformational selection" model that explains the synergistic action of the SRP RNA with the cargo in accelerating complex assembly. In addition to its previously proposed role in preventing the premature dissociation of SRP and FtsY, we found that the SRP RNA also plays an active role in ensuring the formation of productive assembly intermediates, thus guiding the SRP and FtsY through the most efficient pathway of assembly.     

Deterministic extinction effect of parasites on host populations

 Experimental studies have shown that parasites can reduce host density and even drive host population to extinction. Conventional mathematical models for parasite-host interactions, while can address the host density reduction scenario, fail to explain such deterministic extinction phenomena. In order to understand the parasite induced host extinction, Ebert et al. (2000) formulated a plausible but ad hoc epidemiological microparasite model and its stochastic variation. The deterministic model, resembles a simple SI type model, predicts the existence of a globally attractive positive steady state. Their simulation of the stochastic model indicates that extinction of host is a likely outcome in some parameter regions. A careful examination of their ad hoc model suggests an alternative and plausible model assumption. With this modification, we show that the revised parasite-host model can exhibit the observed parasite induced host extinction. This finding strengthens and complements that of Ebert et al. (2000), since all continuous models are likely break down when all population densities are small. This extinction dynamics resembles that of ratio-dependent predator-prey models. We report here a complete global study of the revised parasite-host model. Biological implications and limitations of our findings are also presented. Received: 30 October 2001 / Revised version: 11 February 2002 / Published online: 17 October 2002 Work is partially supported by NSF grant DMS-0077790 Mathematics Subject Classification (2000): 34C25, 34C35, 92D25. Keywords or phrases: Microparasite model – Ratio-dependent predator-prey model – Host extinction – Global stability – Biological control     

3,3′,4,4′,5-Pentachlorobiphenyl influences mitochondrial apoptosis pathway in granulosa cells

3,3′,4,4′,5-Polychlorinated biphenyl (PCB126) is a persistent organic environmental pollutant which can affect various biological activities of organisms, such as immunity, neurological function, and reproduction. In our study, we aimed to investigate the effects of PCB126 on granulosa cells (GCs). GCs were collected from ovaries in PMSG-treated mice, after 24 hours culture. GCs were then incubated with 10 pg/mL, 100 pg/mL, and 10 ng/mL of PCB126 for another 24 hours. Following these steps, exposed GCs were collected for further experimentation. Our data showed that the number of GCs in the 10 ng/mL PCB126 decreased. Meanwhile, pyknotic nuclei and condensed chromatin increased, while the apoptotic cells in the 10 ng/mL PCB126 group were significantly increased. Furthermore, the expression of the apoptotic executive protein caspase-3 increased after PCB126 treatment. The expression of Bax, Bcl-2, and Bim related to the mitochondrial apoptosis pathway were also influenced to different degrees. Thus, our data suggested that PCB126 affect the GCs apoptosis, and mitochondrial apoptosis pathway was involved in this process.     

Vocal divergence is concordant with genomic evidence for strong reproductive isolation in grasshopper mice (Onychomys)

Behavioral barriers to gene flow often evolve faster than intrinsic incompatibilities and can eliminate the opportunity for hybridization between interfertile species. While acoustic signal divergence is a common driver of premating isolation in birds and insects, its contribution to speciation in mammals is less studied. Here we characterize the incidence of, and potential barriers to, hybridization among three closely related species of grasshopper mice (genus Onychomys). All three species use long‐distance acoustic signals to attract and localize mates; Onychomys arenicola and Onychomys torridus are acoustically similar and morphologically cryptic whereas Onychomys leucogaster is larger and acoustically distinct. We used genotyping‐by‐sequencing (GBS) to test for evidence of introgression in 227 mice from allopatric and sympatric localities in the western United States and northern Mexico. We conducted laboratory mating trials for all species pairs to assess reproductive compatibility, and recorded vocalizations from O. arenicola and O. torridus in sympatry and allopatry to test for evidence of acoustic character displacement. Hybridization was rare in nature and, contrary to prior evidence for O. torridus/O. arenicola hybrids, only involved O. leucogaster and O. arenicola. In contrast, laboratory crosses between O. torridus and O. arenicola produced litters whereas O. leucogaster and O. arenicola crosses did not. Call fundamental frequency in O. torridus and O. arenicola was indistinguishable in allopatry but significantly differentiated in sympatry, a pattern consistent with reproductive character displacement. These results suggest that assortative mating based on a long‐distance signal is an important isolating mechanism between O. torridus and O. arenicola and highlight the importance of behavioral barriers in determining the permeability of species boundaries.