Prevention of chemotherapy-induced alopecia in rodent models

Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy. We observed in experiments using different rodent models that localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein response in hair follicles and effectively prevented alopecia from adriamycin, cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support the presumption that such localized hair-saving treatment does not negatively affect chemotherapy efficacy.     

Effects of malate supplementation on acid-base balance and productive performance in growing/finishing bull calves fed a high-grain diet

This study investigated the effects of malate supplementation on blood acid-base balance and serum lactate levels in a 137-day feedlot experiment with bull calves. Animals were allotted to one of two experimental groups: (1) A control group (no supplementation), and (2) a group receiving a salt of DL-malic acid. Blood pH, pCO2, HCO3-, base excess, serum L-lactate and productivity parameters were evaluated. Our data reveal that under the conditions of the present experiment malate supplementation did not have any significant effect on productivity parameters by comparison with non-supplemented animals. As regards acid-base balance, no significant effects attributable only to malate were observed. In conclusion, the time-course and the overall means of serum L-lactate for both groups in both growing and finishing periods (0.44 +/- 0.04 mmol/l and 0.39 +/- 0.02 mmol/l, respectively, for control animal; and 0.54 +/- 0.03 mmol/l and 0.49 +/- 0.01 mmol/l, respectively, for supplemented animals) suggests that malate does not have any beneficial effects in animals fed a diet of similar characteristics to that given in this study.     

Synthesis and biological properties of beta-turned Abeta(31-35) constrained analogues

A series of constrained pentapeptide analogues of the fragment Abeta(31-35) has been prepared using solid phase synthesis protocols. The results of conformational studies and surface plasmon resonance (SPR) experiments seem to indicate that the affinity of these constrained analogues for immobilized Abeta(25-35) peptide could be related to their ability to adopt a Leu34N-Ile31O beta-turn-like folded conformation.     

Design, synthesis and antiproliferative properties of oligomers with chromophore units linked by amide backbones

The preparation of oligomers made up of several chromophore units as compounds with potential fluorescent and antiproliferative properties is described. Specifically, chromophore units with protected-amino groups and one carboxylic group are described, together with methods to assemble these units using peptide chemistry. Some of these compounds have antiproliferative activity.     

Specific detection of RNA on ultra-thin sections

In this paper, we describe a specific method for ultrastructural detection of RNA. Our method is based in the bromination "in situ" of uridine residues in the RNA, which allows the detection of brominated RNA with specific antibodies against bromo-deoxyuridine. With this method we can achieve high specificity and resolution, and it can be applied to Epon or acrylic resin embedded material.     

Stable long-term indigo production by overexpression of dioxygenase genes using a chromosomal integrated cascade expression circuit

In our laboratory we have analyzed different factors to maximize the yield in heterologous protein expression for long-term cultivation, by combination of an efficient cascade expression system and stable integration in the bacterial chromosome. In this work, we have explored this system for the production of indigo dye as a model for biotechnological production, by expressing in Escherichia coli the thnA1A2A3A4 genes from Sphingomonas macrogolitabida strain TFA, which encode the components of a tetralin dioxygenase activity. We compared Ptac, and the Pm-based cascade expression circuit in a multicopy plasmid and stably integrated into the bacterial chromosome. Plasmid-based expression systems resulted in instability of indigo production when serially diluted batch experiments were performed without a selective pressure. This problem was solved by integrating the expression module in the chromosome. Despite the gene dosage reduction, the synergic effect of the cascade expression system produced comparable expression to the dioxygenase activity in the plasmid configuration but could be stably maintained for at least 5 days. Here, we show that the cascade amplification circuit integrated in the chromosome could be an excellent system for tight control and stable production of recombinant products.     

Fibulin-1C and Fibulin-1D splice variants have distinct functions and assemble in a hemicentin-dependent manner

Fibulins are a family of extracellular glycoproteins associated with basement membranes and elastic fibers in vertebrates. Conservation of the fibulin-1 gene throughout metazoan evolution includes fibulin-1C and fibulin-1D alternate splice variants, although little is known about variant specific functions that would justify this striking structural conservation. We have therefore investigated the structure, localization and loss-of-function phenotype specific to both fibulin-1 variants in C. elegans. We find that fibulin-1C has specific roles during pharynx, intestine, gonad and muscle morphogenesis, being required to regulate cell shape and adhesion, whereas fibulin-1D assembles in flexible polymers that connect the pharynx and body-wall-muscle basement membranes. The assembly of fibulin-1C and fibulin-1D in multiple locations is dependent upon the presence of hemicentin, a recently described extracellular member of the immunoglobulin superfamily. We suggest that the distinct developmental roles and hemicentin-dependent assembly for fibulin-1 splice variants demonstrated here may be relevant to fibulin-1 and possibly other fibulin family members in non-nematode species.