Diabetes, growth or clotting disorders are among the spectrum of human diseases related to protein absence or malfunction. Since these pathologies cannot be yet regularly treated by gene therapy, the administration of functional proteins produced ex vivo is required. As both protein extraction from natural producers and chemical synthesis undergo inherent constraints that limit regular large-scale production, recombinant DNA technologies have rapidly become a choice for therapeutic protein production. The spectrum of organisms exploited as recombinant cell factories has expanded from the early predominating Escherichia coli to alternative bacteria, yeasts, insect cells and especially mammalian cells, which benefit from metabolic and protein processing pathways similar to those in human cells. Up to date, around 650 protein drugs have been worldwide approved, among which about 400 are obtained by recombinant technologies. Other 1300 recombinant pharmaceuticals are under development, with a clear tendency towards engineered versions with improved performance and new functionalities regarding the conventional, plain protein species. This trend is exemplified by the examination of the contemporary protein-based drugs developed for cancer treatment.

No abstract

The biomass variation and the reproduction of the natural Gracilaria gracilis bed in Bahía Bustamante (Patagonia, Argentina) were analyzed for 2 years, with the aim of determining the present situation of the population for an updated status overview; establishing the relevant features of the temporal variation in both biomass and reproductive states in relation to environmental factors, epiphytes and associated algae; and assessing carpospore availability for future spore-culture development. Field measurements and sampling were performed monthly between March 2006 and February 2008. In both years, G. gracilis biomass presented marked seasonal variations, with a minimum in winter and a maximum in late spring and in summer. During both years, coexistence of the three life-cycle phases was found, with dominance of tetrasporophytes. Two data sets from individuals originated from sexual reproduction (tetraspores and carpospores) and from asexual reproduction by thallus fragmentation were analyzed separately. In the fragmentation fraction, tetrasporophyte frequencies remained higher than those for gametophytes. However, in the spore-originated fraction, a generation ratio close to 0.5 was observed. Female gametophytes bearing cystocarps were always present, with a maximum in summer and autumn. Biological data were related to environmental factors by means of canonical correspondence analysis (CCA). The first year was characterized by higher biomass values of G. gracilis and Undaria pinnatifida, lower epiphytism, larger Gracilaria thalli and greater proportion of mature tetrasporophytes and gametophytes. The second year was characterized by a high proportion of Gracilaria vegetative thalli and high epiphyte density. The best time to obtain spores from cystocarpic thalli would be in summer and early autumn.

The growth, lipid accumulation and bioproducts of the marine diatom Halamphora coffeaeformis were evaluated in a hybrid two-stage culture using seawater enriched with nutrients and without vitamins. The influence of dissolved and internal nutrients on growth and lipid accumulation was also analyzed. Total lipid content increased in the declining phase up to 33.4% ash-free dry weight, due to an increase in neutral lipids, which reached 87% of total lipids. The observed delay in triacylglycerol (TAG) accumulation could be explained by the accumulation of large internal pools of nitrogen in H. coffeaeformis. TAG, frustules (silica-containing cell wall) and soluble exopolysaccharides are analyzed and proposed as bioproducts of commercial interest. A biorefinery approach for the economic and environmentally sustainable production of biodiesel from the hybrid two-stage culture of H. coffeaeformis is suggested.

No abstract

Stroke remains a leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures in the hyper-acute phase of ischemic stroke is still a primary interest for translational research on stroke diagnosis, prognosis, and treatment. Data integration from high-throughput -omics techniques has become crucial to unraveling key interactions among different molecular elements in complex biological contexts, such as ischemic stroke. Thus, we used advanced data integration methods for a multi-level joint analysis of transcriptomics and proteomics datasets obtained from mouse brains at 2 h after cerebral ischemia. By modeling net-like correlation structures, we identified an integrated network of genes and proteins that are differentially expressed at a very early stage after stroke. We validated 10 of these deregulated elements in acute stroke, and changes in their expression pattern over time after cerebral ischemia were described. Of these, CLDN20, GADD45G, RGS2, BAG5, and CTNND2 were next evaluated as blood biomarkers of cerebral ischemia in mice and human blood samples, which were obtained from stroke patients and patients presenting stroke-mimicking conditions. Our findings indicate that CTNND2 levels in blood might potentially be useful for distinguishing ischemic strokes from stroke-mimicking conditions in the hyper-acute phase of the disease. Furthermore, circulating GADD45G content within the first 6 h after stroke could also play a key role in predicting poor outcomes in stroke patients. For the first time, we have used an integrative biostatistical approach to elucidate key molecules in the initial stages of stroke pathophysiology and highlight new notable molecules that might be further considered as blood biomarkers of ischemic stroke.

Seasonal variation of agar from specimens of a commercially exploited population of Gracilaria gracilis (Stackhouse) Steentoft, Irvine & Farnham in the Patagonian coast of Argentina was studied. For each seasonal harvest, random samples of plants were pooled for subsequent polysaccharide extraction at different water temperatures and agar physico-chemical properties and composition were determined.Both spring and summer plants yielded 30% and 41% of agar, respectively, which differed slightly in their at rest rheological behavior. Spring and summer plants produced strong gels (238 and 218 g cm -2 , respectively), but the latter gels had nil adhesiveness. In autumn plants, agar yield decayed to 19%, though the product still maintained similar gel strength (210 g cm -2 ). Adhesiveness in this product was at least an order of magnitude higher than in the others, concomitant with a peak in the formation of tetraspores and carpospores. This suggests a biological role for the galactan in the initial attachment of spores to the substrate. But since fall corresponds to the settling of reproductive structures, caution should be taken to harvest the algae once spores have been shed from mother plants.

No abstract