Minicells: versatile vectors for targeted drug or si/shRNA cancer therapy

Effective cancer therapy continues to be a daunting challenge due mainly to considerable tumor cell heterogeneity, drug-resistance, and dose-limiting toxicity of therapeutics. Here we review a versatile nano-cellular (minicell) delivery vehicle that can be packaged with therapeutically effective concentrations of chemotherapeutic drugs, siRNAs or shRNAs and can be targeted to tumors via minicell-surface attached bispecific antibodies. A range of minicell-based therapeutics have shown highly effective tumor stabilization/regression in the murine xenograft model and in case studies in canines with late-stage endogenous tumors. Repeat intravenous dosing shows absence of toxicity or immunogenicity in both species. The minicell-based therapeutic has potential applications in personalized cancer medicine.     

Effects of plant height and row spacing on kenaf forage potential with multiple harvests

Kenaf (Hibiscus cannabinus L.) forage potential can be enhanced through its regrowth capacity and higher production in narrow rows. A field experiment was conducted in Matamoros, Coahuila, Mexico, during 2 growing seasons (2004 and 2005) to study the effects of plant height and row spacing on kenaf forage potential with multiple harvests. This study evaluated the effects of (1) 2 plant heights at cutting (1.0-1.2 m and 1.8-2.0 m) and (2) 4 inter row spacings (0.19, 0.38, 0.57 and 0.76 m) using a 2 x 4 factorial arrangement of treatments in a completely randomized block design with 4 replications. Dry matter (DM) and crude protein (CP) yields, DM partitioning, neutral detergent fiber (NDF) and CP concentrations were determined. Heights at cutting × row spacing interactions were not significant for the monitored variables (p>0.05). Kenaf response to treatments was only relevant for main effects (p≤0.05). Row spacing and plant height affected DM and CP yields (p≤0.05), whereas only plant height affected chemical composition and DM partitioning (p≤0.05). Dry matter (17.0%-26.0%), and CP (12.4%-15.6%) yields were higher (p≤0.05) when plant heights had reached 1.8 to 2.0 m. Row spacing reduction from 0.76 m to 0.38 and 0.19 m increased DM yield (20.4-33.4%) and CP yield (24.2-38.5%) (p≤0.05). Kenaf forage potential increases when planted in narrow rows and harvested 2 or 3 times during the growing season.     

A1 toxicity in yeast. A role for Mg?

We have established conditions in which soluble Al is toxic to the yeast Saccharomyces cerevisiae. The major modifications to a standard synthetic medium were lowering the pH and the concentration of Mg ions. Alterations to the PO4, Ca, or K concentration had little effect on toxicity. Organic acids known to chelate Al reduced its toxicity, suggesting that Al3+ is the toxic Al species. The unique ability of Mg ions to ameliorate Al toxicity led us to investigate the hypothesis that Al inhibits Mg uptake by yeast. Yeast cells accumulate Mg, Co, Zn, Ni, and Mn ions via the same transport system (G.F. Fuhrmann, A. Rothstein [1968] Biochim Biophys Acta 163: 325-330). Al3+ inhibited the accumulation of 57Co2+ by yeast cells more effectively than Ga, La, or Mg. In addition, a mutant yeast strain with a defect in divalent cation uptake proved to be more sensitive to Al than a wild-type strain. Taken together, these results suggest that Al may cause Mg deficiency in yeast by blocking Mg transport. We discuss the relevance of yeast as a model for the study of Al toxicity in plant systems.     

Characterization of a Glomus intraradices gene encoding a putative Zn transporter of the cation diffusion facilitator family

A full-length cDNA (GintZnT1) encoding a putative Zn transporter was isolated from the extraradical mycelium of Glomus intraradices. Based on its sequence analysis, GintZnT1 was classified as a member of the cation diffusion facilitator (CDF) family of heavy metal transporters. Functional analysis of GintZnT1 was performed by heterologous expression in yeast mutants defective in different CDFs. Although Zn sensitivity of the mutants was not reverted, an effect of GintZnT1 on the labile regulatory Zn pool was detected by using a Zn-regulated beta-galactosidase reporter gene. GintZnT1 expression was studied in the extraradical mycelium obtained from a symbiotic root organ culture. Gin +/- ZnT1 was up-regulated in the extraradical mycelium of G. intraradices upon short-time exposure to Zn and when the mycelia were developed in 75 microM Zn supplemented plates. These data suggest a role of GintZnT1 in Zn compartmentalization and in the protection of G. intraradices against Zn stress.     

Infants' exploration of scented toys: effects of prior experiences

To evaluate breastfed infants' responses to scented objects, we videotaped the facial and bodily reactions of sixty-three infants as they explored, in succession, three toys that were identical in appearance but different in their characteristic odor. Two of the toys were scented with odorants previously shown to be transmitted to human milk, one with ethanol and the other with vanilla, whereas the third toy was unscented. Each videotape was subjected to frame-by-frame analysis to measure a variety of behaviors that are considered either to be exploratory in nature in that they lead to perceptual information about the object or to reflect the infants' hedonic reaction. Analyses of these behaviors revealed that the infants looked more and vocalized less in the presence of the vanilla-scented toy and spent less time manipulating the ethanol-scented toy when compared with the unscented toy. Moreover, differential exposure to the odors of ethanol and vanilla, as indicated by differential consumption of alcohol by a parent or use of vanilla-scented product by the mother, was related to differential responses to these odors. These findings suggest that human infants are able to detect and retain information about the chemical features of their environment.